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Fifth edition, 2015

Medical eligibility
criteria for
contraceptive use

COCs Barrier methods IUDs Fertility
awareness-based methods Lactational
amenorrhoea Patch Female surgical
sterilization Intrauterine devices CICs
Coitus interruptus Copper IUD for
emergency contraception POCs Patch

A WHO family planning cornerstone
Male surgical sterilization Ring ECPs
COCs Barrier methods IUDs Fertility
awareness-based methods Lactational
amenorrhoea Patch Female surgical
sterilization Intrauterine devices CICs
Coitus interruptus Copper IUD for
emergency contraception POCs Patch
Male surgical sterilization Ring ECPs
COCs Barrier methods IUDs Fertility
awareness-based methods Lactational
amenorrhoea Patch Female surgical
sterilization Intrauterine devices CICs
Coitus interruptus Copper IUD for
emergency contraception POCs Patch
Male surgical sterilization Ring ECPs
COCs Barrier methods IUDs Fertility
awareness-based methods Lactational
amenorrhoea Patch Female surgical
sterilization Intrauterine devices CICs
Coitus interruptus Copper IUD for
emergency contraception POCs Patch
Male surgical sterilization Ring ECPs

Medical eligibility criteria
for contraceptive use

Fifth edition 2015

WHO Library Cataloguing-in-Publication Data

Medical eligibility criteria for contraceptive use -- 5th ed.

1.Contraception – methods. 2.Family Planning Services. 3.Eligibility
Determination – standards. 4.Quality Assurance, Health Care. 5.Health Services
Accessibility. I.World Health Organization.

ISBN 978 92 4 154915 8 (NLM classification: WP 630)

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Table of contents
Acknowledgements..................................................................................................................................1
Guideline Development Group..................................................................................................................1
Abbreviations............................................................................................................................................3
EXECUTIVE SUMMARY..............................................................................................................................5
Introduction............................................................................................................................................6
Guideline development methods.............................................................................................................6
Summary of reviewed recommendations................................................................................................6
PART I. DEVELOPMENT OF THE MEDICAL ELIGIBILITY CRITERIA FOR CONTRACEPTIVE USE
Background..........................................................................................................................................15
Methods...............................................................................................................................................17
Dissemination and evaluation ..............................................................................................................21
Recommendations for combined hormonal contraceptives among breastfeeding women.....................28
Recommendations for combined hormonal contraceptives among postpartum women.........................34
Recommendations for combined hormonal contraceptives among women with
superficial venous disorders..............................................................................................................38
Recommendations for combined hormonal contraceptives among women with dyslipidaemias............42
Recommendations for progestogen-only contraceptives and levonorgestrel-releasing
intrauterine devices among breastfeeding women.............................................................................47
Recommendations for safety of depot medroxyprogesterone acetate delivered subcutaneously............61
Recommendations for safety of Sino-implant (II)...................................................................................67
Recommendations for use of emergency contraceptive pills, including adding the condition of
obesity and the new method, ulipristal acetate..................................................................................72
Recommendations for intrauterine devices among women with increased risk for
sexually transmitted infections..........................................................................................................77
Recommendations for use of progesterone-releasing vaginal ring........................................................79
Recommendations for use of hormonal contraception among women at high risk of HIV,
women living with HIV, and women living with HIV using antiretroviral therapy...................................82
PART II. USING THE RECOMMENDATIONS
Background..........................................................................................................................................99
How to use this document..................................................................................................................104
Using the categories in practice..........................................................................................................105
Programmatic implications.................................................................................................................106
Clients with special needs..................................................................................................................106
Summary of changes within the MEC fifth edition...............................................................................107
TABLES
Combined hormonal contraceptives....................................................................................................111
Progestogen-only contraceptives........................................................................................................157
Emergency contraceptive pills............................................................................................................186
Intrauterine devices ...........................................................................................................................189
Copper-bearing IUD for emergency contraception...............................................................................211
Barrier methods..................................................................................................................................214
Fertility awareness-based methods....................................................................................................226
Lactational amenorrhoea method.......................................................................................................229
Coitus interruptus...............................................................................................................................231
Female surgical sterilization...............................................................................................................232
Male surgical sterilization...................................................................................................................243
Summary table ..................................................................................................................................248
Annex 1. Declarations of interest ........................................................................................................265
Annex 2. Systematic reviews...............................................................................................................267

.

USA). (University of Latvia. Brazil). External Peer Review Group Zimbabwe). WHO is Vries. Jean-Jacques Amy •• United States National Institutes of Health (NIH) – Alicia (European Society for Contraception and Reproductive Armstrong. Julie Williams very grateful for the suggestions provided by colleagues who •• International Confederation of Midwives (ICM) – Maria peer-reviewed the earlier drafts of the guideline as members of Papadopoulou the External Peer Review Group. Caitlin Kennedy (Johns Hopkins University. Dominican Republic). Zambia). Vinit Sharma University. Philip Hannaford (University of Aberdeen. USA). Nonkosi Tlale (UNFPA. James Shelton United Kingdom of Great Britain and Northern Ireland [United Kingdom]). China). Hospital. – Maria Alarcos Cieza Moreno Carolyn Westhoff (Columbia University. Tran Son Thach (University of Adelaide. Halley Riley (CDC). Tsungai Chipato (University of Zimbabwe. and Education. Herbert Peterson (University of North Carolina. •• International Federation of Gynecology and Obstetrics (FIGO) – Hamid Rushwan Guideline Development Group •• United Nations Population Fund (UNFPA) – Sennen Hounton •• United States Food and Drug Administration (FDA) – Lisa Richard Adanu (University of Ghana. United WHO Secretariat Kingdom). Eliya Zulu (African Institute for Kenya). WHO headquarters Francesca Martínez (Institut Universitari Dexeus. Lembit Ragu Chile). South Africa). Wu Shangchun (National Research Institute for Family Planning. Anna Altshuler (Stanford University. Ghana). Vivian Brache Maria del Carmen Cravioto (National Institute of Nutrition (Profamilia. the Philippines). Medical eligibility criteria for contraceptive use . Roger Chou (Oregon Health Sciences University. 9–12 March 2014 and 24–25 Rachel Peragallo Urrutia (University of North Carolina. USA). Sharon Cameron (University of Edinburgh. USA). WHO convened three Development [USAID]). Department of Management of Noncommunicable Diseases. Department of HIV – Rachel Baggaley Maria Ascunsion Silvestre (University of the Philippines. USA). Jacqueline Conard (Ministry of Education. Karima Gholbzouri Australia). Helle Karro (Tartu University. Lebanon). Tara Jatlaoui (CDC). USA) the members of the Guideline Development Group and the Kathryn Curtis (CDC). Suneeta Mittal (Fortis Memorial Research Institute. Estonia). Mohammed Eslami (Ministry of Health (Jhpiego. Violence & Injury Prevention Finland). Kavita Nanda (FHI Evidence Secretariat for their contributions throughout the 360). Belgium). Islamic Republic of Iran). Latvia). Blumenthal (Stanford University. Bulbul Sood Beirut. Thailand). Chelsea Polis (United States Agency for International development of these recommendations. The names of the participants in each group are listed below. Caroline Phiri Chibawe Salvador Zubiran. USA). Pisake Lumbiganon (Khon Kaen University. Naomi Tepper (CDC). Disability. Lesotho). USA). USA). Elizabeth Sullivan (University of Sydney. Eliana Amaral Soule (State University of Campinas. India). consultations (13–16 May 2013. Spain) Department of Essential Medicines and Health Products Olav Meirik (Institute Chileno de Medicina Reproductiva. Trent MacKay Health. Australia). Islamic Republic of Iran). Morocco). United Development Policy. All members of the Partners Guideline Development Group and the Evidence Secretariat •• European Medicines Agency (EMA) – Peter Arlett. Thailand). September 2014) to finalize the fifth edition of the Medical eligibility criteria for contraceptive use. Roy Jacobstein (EngenderHealth. Regine Sitruk-Ware (Population Council. Alison Edelman (Oregon Health Sciences USA). Remy Coeytaux (Duke University. Mexico). Belgium). Paul (Hôpital Universitaire de Paris – Hôtel Dieu. – Nicola Magrini. •• USAID – Patricia MacDonald. Parnian Andalib United States of America [USA]). Marc Dhont (Ghent University (Ministry of Health. Ilze Viberga (Ministry of Health. Andy Gray (University of KwaZulu-Natal. Kenya). Marja-Riitta Taskinen (University of Helsinki. Anna Glasier (University of Edinburgh. India). . Gathari Gichuhi (Jhpiego.Executive summary | 1 Acknowledgements Evidence Secretariat Erin Berry-Bibee (United States Centers for Disease Control The World Health Organization (WHO) would like to thank and Prevention [CDC]). Corinne de participated in at least one of the three consultations. Faysel El-Kak (American University of (UNFPA Asia Pacific Regional Office. France). Kingdom).

The GRADE tables and expertise on GRADE methodology were provided by Roger Chou. Monica Dragoman. Venkatraman Chandra. Writing The first draft of the guideline was written by Erin Berry-Bibee. peer reviewers and WHO Secretariat staff. Rachel Peragallo Urrutia and Daniel Westreich. Rajat Khosla. Tara Jatlaoui. Monica Dragoman. Evan Myers. Marleen Temmerman.uk). Philip Hannaford. Theresa Ryle provided coordination and logistic support. Mary Lyn Gaffield. Keri Barnett-Howell (volunteer). Monica Dragoman. United Kingdom (greenink. Technical and copy-editing were provided by Jura Editorial Services (jura-eds. Statistical expertise for meta-analyses was provided by Rochelle Fu. The 14 systematic reviews providing summarized evidence for the guidance were co-authored by Erin Berry-Bibee. Vic Hasselblad. Sharon Phillips. Mario Festin. Sharon Phillips. Kathryn Curtis. Caron Kim. Mary Lyn Gaffield. Shannon Carr (volunteer). Theresa Ryle.co. Caron Kim. Petrus Steyn. Elizabeth Raymond. Remy Coeytaux. Petrus Steyn. Child and Adolescent Health Funding – Nigel Rollins The development of this guideline was financially supported by Department of Reproductive Health and Research – Moazzam the National Institutes of Health (NIH) and United States Agency Ali.com) and Green Ink. Drafts were reviewed and input was provided by members of the Guideline Development Group. Kavita Nanda. Newborn. Maria Rodriguez. Halley Riley.Executive summary Department of Maternal. Chelsea Polis. Mouli. for International Development (USAID). . Naomi Tepper. Kathryn Curtis. Abigail Norris Turner.2 | Medical eligibility criteria for contraceptive use . Teodora Wi WHO regional offices WHO Regional Office for Africa – Léopold Ouedraogo WHO Regional Office for the Eastern Mediterranean – Ramez Mahaini (unable to attend) WHO Regional Office for Europe – Gunta Lazdane WHO Regional Office for the Americas (Pan American Health Organization) – Suzanne Serruya WHO Regional Office for South-East Asia – Arvind Mathur WHO Regional Office for the Western Pacific – Wen Chunmei Overall coordination WHO Department of Reproductive Health and Research – Mary Lyn Gaffield. Halley Riley and Naomi Tepper. Caron Kim. Tara Jatlaoui. Mary Lyn Gaffield.

Assessment. Medical eligibility criteria for contraceptive use . UN United Nations Development and Evaluation UNDP United Nations Development Programme GRC Guidelines Review Committee UNFPA United Nations Population Fund GSG Guideline Steering Group UNICEF United Nations Children’s Fund HbA1c glycated haemoglobin UPA ulipristal acetate HDL high-density lipoprotein USAID United States Agency for International I initiation Development ICPD International Conference on Population and VTE venous thromboembolism Development WHO World Health Organization . comparator. outcome DMPA depot medroxyprogesterone acetate POC progestogen-only contraceptive DMPA-IM depot medroxyprogesterone acetate – POI progestogen-only injectable intramuscular POP progestogen-only pill DMPA-SC depot medroxyprogesterone acetate – PRISMA Preferred reporting items for systematic reviews subcutaneous and meta-analyses DVT deep vein thrombosis PVR progesterone-releasing vaginal ring ECP emergency contraceptive pill RCT randomized controlled trial EE ethinyl estradiol SI (I)/SI (II) Sino-implant (I) / Sino-implant (II) E-IUD emergency intrauterine device SLE systemic lupus erythematosus EMA European Medicines Agency SPR Selected practice recommendations for ETG etonogestrel contraceptive use (WHO publication) FAB fertility awareness-based methods STER sterilization (male and female) FDA United States Food and Drug Administration STI sexually transmitted infection GDG Guideline Development Group SVT superficial venous thrombosis GRADE Grading Recommendations. intervention.Executive summary | 3 Abbreviations IUD intrauterine device ART antiretroviral therapy LAM lactational amenorrhoea method ARV antiretroviral (medication) LDL low-density lipoprotein ß-hCG beta-human chorionic gonadotropin LNG levonorgestrel BF breastfeeding LNG-IUD levonorgestrel-releasing intrauterine device BMD bone mineral density MEC Medical eligibility criteria for contraceptive use BMI body mass index (WHO publication) C continuation MI myocardial infarction CD4 cluster of differentiation 4 NA not applicable CDC United States Centers for Disease Control and NET-EN norethisterone enanthate Prevention NIH National Institutes of Health (United States of CHC combined hormonal contraception America) CI coitus interruptus NNRTI non-nucleoside reverse transcriptase inhibitor CIC combined injectable contraceptive NRTI nucleoside/nucleotide reverse transcriptase CIRE Continuous Identification of Research Evidence inhibitor COC combined oral contraceptive (pill) OC oral contraceptive (pill) CRPD United Nations Convention on the Rights of P combined contraceptive patch Persons with Disabilities PE pulmonary embolism Cu-IUD copper-bearing intrauterine device PI protease inhibitor CVR combined contraceptive vaginal ring PID pelvic inflammatory disease CYP3A4 cytochrome P450 3A4 enzyme PICO population.

Executive summary .4 | Medical eligibility criteria for contraceptive use .

obesity. dyslipidaemias. This is the fifth edition of the MEC – the repeat use of ECPs. copper-IUD for emergency contraception (E-IUD). coitus interruptus (CI). These conditions and characteristics quality of care in family planning. The safety of the method 2 A condition where the advantages of using the method should be weighed along with the benefits of preventing generally outweigh the theoretical or proven risks unintended pregnancy. fertility awareness-based methods (FAB). provided. The MEC aims to provide guidance to methods: low-dose (≤ 35 mcg ethinyl estradiol) combined1 national family planning and reproductive health programmes oral contraceptives (COCs). Several tools and job aids are available from WHO and Target audience other sources to help providers use these recommendations in practice. and 1 A condition for which there is no restriction for the use secondarily. experience of various types of providers and the resources available at the service delivery point will have to be taken into consideration. family planning programme managers and the This document covers the following family planning scientific community. The guidance in this document is intended for interpretation at emergency contraceptive pills (ECPs). The intended audience for this publication includes policy- makers. puerperal sepsis. 1 “Combined” refers to a combination of ethinyl estradiol and a pro- gestogen. venous thromboembolism. While it is unlikely that the classification of categories progesterone-releasing vaginal ring (PVR). the level of clinical knowledge and and male sterilization (STER). increased risk of sexually latest in the series of periodic updates. norethisterone enanthate (NET-EN). contraceptive methods are placed into one of four numbered Introduction categories. among others: age. severe liver disease. more than one condition may need to be considered together to determine This document is part of the process for improving the contraceptive eligibility. high risk of HIV infection. Medical eligibility criteria for contraceptive use . In particular. The recommendations contained within this risk if the contraceptive method is used. for contraceptive use (MEC). superficial published in 1996. Part I outweigh the advantages of using the method describes how the recommendations were developed and Part II contains the recommendations and describes how 4 A condition which represents an unacceptable health to use them. document are based on the latest clinical and epidemiological data. history of severe cardiovascular disease. . methods for use in the context of specific health conditions migraines. 3 A condition where the theoretical or proven risks usually This fifth edition of the MEC is divided into two parts. whether the contraceptive method worsens the medical condition or creates additional health risks. Depending upon the individual. whether the medical circumstance makes the of the contraceptive method contraceptive method less effective. the first edition of which was breastfeeding status. past (WHO) guidance on the safety of various contraceptive ectopic pregnancy. living with HIV. transmitted infections. use of antiretroviral therapy. acetate (DMPA). it is very (BARR). barrier methods in this document would change during this process. combined injectable contraceptives (CICs). services. combined patch (P). It is not meant to serve as the actual guidelines but progestogen-only pills (POPs). Medical eligibility criteria include. use of CYP3A4 inducer. copper-bearing country and programme levels. combined in the preparation of guidelines for delivery of contraceptive vaginal ring (CVR). lactational likely that the application of these categories at country level amenorrhoea method (LAM). weeks/months postpartum. depot medroxyprogesterone rather as a reference. and female will vary.Executive summary | 5 Executive summary For each medical condition or medically relevant characteristic. presents current World Health Organization venous disorders. levonorgestrel-releasing IUDs diversity of situations and settings in which contraceptives are (LNG-IUDs). In the MEC. in a manner that reflects the intrauterine devices (Cu-IUDs). and characteristics. rape. MEC categories for contraceptive eligibility primarily. levonorgestrel (LNG) and etonogestrel (ETG) implants. the safety of each contraceptive method is determined by several considerations in the context of the medical condition or medically relevant characterstics.

references and citations that appear in For this revision process. convened by WHO edition of the MEC (2009). that remained unchanged. the inclusion of four new contraceptive methods in the fifth as needed.2: Methods. should new evidence necessitate reconsideration edition. The GRADE approach was applied to assess the benefits of preventing unintended pregnancy. consisted of 68 individuals representing a wide range in many cases the recommendations that were published of stakeholders. the WHO Secretariat updated the evidence statements. For each contraceptive method. Other than the potential benefits and risks of its use with respect to each of recommendations shown in Table 1. and this provided the an approach towards values and preferences that prioritized basis for the formulation of recommendations (see central the availability of a wide range of contraceptive options.2 To formulate recommendations using the four MEC categories for Fourteen topics (encompassing over 575 recommendations) contraceptive eligibility. particularly warranted for issues where the evidence base at the request of the Guidelines Review Committee. Therefore. 2014. or evidence emerging since that on 14–15 May 2013. all other recommendations the medical conditions or medically relevant physiologic or were confirmed by the GDG and did not undergo formal review personal characteristics assessed (such as age. 3–7 (Table 1.1). In the interim. Therefore. section 2. For some topics. multiple outcomes of interest GDG reached its decisions through consensus. which entailed and/or contraceptive methods were examined. WHO will guidance was issued following the publication of the fourth continue to monitor the body of evidence informing these edition. A summary of the smoking status). Assessment. 93–96. For such recommendations MEC to develop the fifth edition.Executive summary Guideline development methods Updated evidence. In many instances. An explanation of the process followed to select and or guidance on interpretation of the numerical classification. may change rapidly. (b) two topics for which interim this document in four years.gradeworkinggroup. the GDG considered the section 1.org/index. either no new evidence has been identified since the publication of the fourth The Guideline Development Group (GDG). paying particular attention to the suggestions for improving this guidance. breastfeeding. WHO also invites comments and scientific evidence. and (d) two topics to provide greater clarity for the of existing recommendations. revise the guidance in the fourth edition of the the GDG with no changes made. Such updates may be recommendations in the fourth edition relating to these topics. pp. MEC (see Table 1). either a single assessment or a range (see final added clarification statements to provide further explanation column).6. the GDG prioritized the review of: the contraceptive method tables in Part II. strength and consistency of the data. the GDG presented. GRADE assessments of the quality of evidence are any disagreements. (c) contraceptive eligibility recommendations for recommendations and will convene additional consultations. prioritize these topics is included in Part I of the document. WHO encourages research to address key unresolved issues related to establishing medical eligibility The GDG considered the overall quality of the available criteria for contraceptive use. according to the Grading Recommendations. and applied the quality of the available evidence. Development Summary of reviewed recommendations and Evaluation (GRADE) approach to evidence review. Their mandate was to review and. where in the fourth edition have been reviewed and confirmed by appropriate. reproductive health. The column). For these discussion.6 | Medical eligibility criteria for contraceptive use . 9–12 March 2014 and 24–25 September publication confirms previous research findings. debate and consultation with experts to reconcile topics. (a) six topics identified as important to the field and/or those topics with new evidence that may warrant a change in the WHO will initiate a review of the recommendations in existing recommendation. changes between the fourth and fifth editions of this document is available in Part II. These interim recommendations will recommendations for a total of 14 topics were reviewed for the be made available on the WHO’s web pages for sexual and fifth edition of the MEC. the GDG considered potential harms were reviewed by the GDG during the 2014 revision of the related to contraceptive use. pp. the GRADE evidence profiles. 2 Further information is available at the website of the GRADE work- ing group: http://www. For certain recommendations. for the updated fifth edition of the MEC.htm .

When a range is presented. Recommendations for CHC use among breastfeeding women < 6 weeks postpartum Breastfeeding women < 6 weeks postpartum should not use CHCs (MEC Category 4). Topics reviewed for the Medical eligibility criteria for contraceptive use (MEC). Very low Superficial venous Women with SVT can generally use CHCs (MEC Category 2). for VTE ≥ 21 days to 42 days Women who are ≥ 21 days to 42 days postpartum without other risk Range: Low to very low postpartum without factors for VTE can generally use CHCs (MEC Category 2). risk factors for VTE > 42 days postpartum Women who are > 42 days postpartum can use CHCs without restriction (MEC Category 1). Recommendations for CHC use among women with superficial venous disorders Varicose veins Women with varicose veins can use CHCs without restriction (MEC Category 1). factors for venous thromboembolism (VTE) < 21 days postpartum Women who are < 21 days postpartum with other risk factors for VTE with other risk factors should not use CHCs (MEC Category 4). moderate and high. section 1. 8–82) for outcomes explored. Recommendations for combined hormonal contraceptive (CHC) use by age group (CHCs include combined oral contraceptives. ≥ 40 years Women 40 years and older can generally use CHCs (MEC Category 2).Executive summary | 7 Table 1. 3. the range reflects the GRADE quality assessment across important outcomes and/or across contraceptive methods. 2. Recommendations for CHC use among postpartum women < 21 days postpartum Women who are < 21 days postpartum and do not have other risk factors without other risk for VTE generally should not use CHCs (MEC Category 3). ≥ 6 weeks to <6 months Breastfeeding women ≥ 6 weeks to < 6 months postpartum (primarily Range: Low to very low postpartum breastfeeding) generally should not use CHCs (MEC Category 3). combined patch and combined vaginal ring) < 40 years Women from menarche through 40 years of age can use CHCs without Range: Low to very low restriction (MEC Category 1). ≥ 6 months postpartum Breastfeeding women ≥ 6 months postpartum can generally can use CHCs (MEC Category 2). combined injectable contraceptives.4: Reviewed recommendations (p. . Medical eligibility criteria for contraceptive use . other risk factors for VTE ≥ 21 days to 42 days Women who are ≥ 21 days to 42 days postpartum with other risk factors postpartum with other for VTE generally should not use CHCs (MEC Category 3). 4. thrombosis (SVT) a GRADE assessment includes the quality categories of very low. See the specific GRADE table in Part I. low. fifth edition GRADE ASSESSMENT TOPIC MEC RECOMMENDATION OF QUALITY OF EVIDENCEa 1.

and LNG and ETG implants without restriction (MEC Category 1). Range: Low to very low ≥ 6 weeks to < 6 Breastfeeding women who are ≥ 6 weeks to < 6 months months months postpartum postpartum can use POPs. reviewed for without other known risk factors can generally use CHCs (MEC Category 2). clarity as requested by the cardiovascular risk GRC factors 6. See the specific GRADE table in Part I. Breastfeeding women who are < 6 weeks postpartum generally should not use progestogen-only injectables (POIs) (DMPA or NET-EN) (MEC Category 3). ≥ 6 months postpartum Breastfeeding women who are ≥ 6 months postpartum can use POPs. moderate and high. low. 8. Very low ≥ 4 weeks postpartum Breastfeeding women who are ≥ 4 weeks postpartum can use an LNG-IUD without restriction (MEC Category 1). very low a GRADE assessment includes the quality categories of very low. Recommendations for Sino-implant (II) – new method added to the guideline All recommendations Recommendations for Sino-implant (II) will follow the current Range: Moderate to recommendations for LNG implants. 6b. Puerperal sepsis Breastfeeding (and non-breastfeeding) women with puerperal sepsis should not have an LNG-IUD inserted (MEC Category 4). Recommendations for use of subcutaneously-administered depot medroxyprogesterone acetate (DMPA-SC) – new method added to the guideline All recommendations Recommendations for DMPA-SC will follow the current recommendations Very low for DMPA-IM (intramuscular). ≥ 48 hours to < 4 weeks Breastfeeding women who are ≥ 48 hours to < 4 weeks postpartum postpartum generally should not have an LNG-IUD inserted (MEC Category 3). . Recommendations for CHC use among women with known dyslipidaemias Known dyslipidaemias Women with known dyslipidaemias without other known cardiovascular Very low. Recommendations for progestogen-only contraceptive (POC) and levonorgestrel-releasing intrauterine device (LNG-IUD) use among breastfeeding women 6a. implants and injectables) < 6 weeks postpartum Breastfeeding women who are < 6 weeks postpartum can generally use progestogen-only pills (POPs) and levonorgestrel (LNG) and etonogestrel (ETG) implants (MEC Category 2).Executive summary GRADE ASSESSMENT TOPIC MEC RECOMMENDATION OF QUALITY OF EVIDENCEa 5. and LNG and ETG implants without restriction (MEC Category 1). section 1. POIs. When a range is presented.4: Reviewed recommendations (p. 7. POC use among breastfeeding women (POCs include progestogen-only pills. LNG-IUD use among breastfeeding women < 48 hours postpartum Breastfeeding women who are < 48 hours postpartum can generally use LNG-IUDs (MEC Category 2).8 | Medical eligibility criteria for contraceptive use . POIs. the range reflects the GRADE quality assessment across important outcomes and/or across contraceptive methods. 8–82) for outcomes explored.

Women who are breastfeeding can generally use UPA for ECPs (MEC Category 2). Repeat use of ECP There are no restrictions on repeated use for COCs. can generally use COCs. the range reflects the GRADE quality assessment across important outcomes and/or across contraceptive methods. low. Recommendations for emergency contraceptive pills (ECPs) – ulipristal acetate (UPA) as a new method added to the guideline and obesity as a new condition for ECP use Pregnancy For pregnant women. LNG or UPA for ECPs without Moderate restriction (MEC Category 1). Rape There are no restrictions for use of COCs. Past ectopic pregnancies Women who have experienced past ectopic pregnancies can use COCs. Obesity Women who are obese can use COCs. LNG or UPA for ECPs (MEC Category 1). including cardiovascular disease ischaemic heart disease. cerebrovascular attack or other thromboembolic conditions. Severe liver disease Women with severe liver disease. so quality of generally should not have an IUD inserted until appropriate testing and evidence not evaluated treatment occur (MEC Category 3).4: Reviewed recommendations (p. a GRADE assessment includes the quality categories of very low. LNG or UPA for ECPs in cases of rape (MEC Category 1). reviewed for clarity as IUD continuation Women at increased risk of STIs can generally continue use of either Cu. ECP use is not applicable. including jaundice (a personal characteristic and sign of liver disease prior to diagnosis). When a range is presented. moderate and high. . LNG or UPA for ECPs (MEC Category 2). using GRADE process. Use of CYP3A4 inducer Women using CYP3A4 inducers can use COCs. LNG or UPA for ECPs without restriction (MEC Category 1). Medical eligibility criteria for contraceptive use . Breastfeeding Breastfeeding women can use combined oral contraceptive pills (COCs) or LNG for ECPs without restriction (MEC Category 1). Very low Migraines Women with migraines can generally use COCs.requested by the GRC IUD or LNG-IUD (MEC Category 2). section 1. LNG or UPA for ECPs (MEC Category 2). Intrauterine device (IUD) use for women with increased risk of sexually transmitted infections (STIs) IUD initiation Many women with increased risk of STIs can generally undergo either copper-bearing IUD (Cu-IUD) or LNG-IUD initiation (MEC Category 2). No new evidence Some women at increased risk (very high individual likelihood) of STIs identified. History of severe Women with history of severe cardiovascular disease.Executive summary | 9 GRADE ASSESSMENT TOPIC MEC RECOMMENDATION OF QUALITY OF EVIDENCEa 9. can generally use COCs. 10. LNG or UPA for ECPs without restriction (MEC Category 1). See the specific GRADE table in Part I. LNG or UPA for ECPs (MEC Category 2). 8–82) for outcomes explored.

12. Women who already have an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation). POPs. 12c. CICs. Women living with Women living with severe or advanced HIV clinical disease (WHO stage severe or advanced HIV 3 or 4) can use the following hormonal contraceptive methods without clinical disease restriction: COCs. moderate and high. low Women at high risk of acquiring HIV can generally use LNG-IUDs (MEC Category 2).Executive summary GRADE ASSESSMENT TOPIC MEC RECOMMENDATION OF QUALITY OF EVIDENCEa 11. low. CICs.10 | Medical eligibility criteria for contraceptive use . and LNG and ETG implants (MEC Category 1). combined injectable contraceptives (CICs). the range reflects the GRADE quality assessment across important outcomes and/or across contraceptive methods. combined contraceptive patches and rings. When a range is presented. and LNG and ETG implants (MEC Category 1). Recommendations for use of progesterone-releasing vaginal ring – new method added to the guideline Breastfeeding and ≥ 4 Women who are actively breastfeeding and are ≥ 4 weeks postpartum weeks postpartum can use the progesterone-releasing vaginal ring without restrictions Low (MEC Category 1). section 1. low Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) generally should not initiate use of the LNG-IUD (MEC Category 3) until their illness has improved to asymptomatic or mild HIV clinical disease (WHO stage 1 or 2). 8–82) for outcomes explored. and women living with HIV using antiretroviral therapy (ART) 12a. women living with HIV. Range: Moderate to very (WHO stage 3 or 4) POIs (DMPA and NET-EN). See the specific GRADE table in Part I. . POPs. Women living with asymptomatic or mild HIV clinical disease (WHO stage 1 or 2) can generally use the LNG-IUD (MEC Category 2). and LNG and ETG implants (MEC Category 1). Women living with Women living with asymptomatic or mild HIV clinical disease (WHO stage asymptomatic or mild 1 or 2) can use the following hormonal contraceptive methods without HIV clinical disease restriction: COCs. Recommendations for use of hormonal contraception for women at high risk of HIV infection. POPs.4: Reviewed recommendations (p. (WHO stage 1 or 2) POIs (DMPA and NET-EN). a GRADE assessment includes the quality categories of very low. combined contraceptive patches and rings. 12b. combined contraceptive patches and rings. Range: Moderate to very POIs (DMPA and NET-EN). Women at high risk Women at high risk of acquiring HIV can use the following hormonal of HIV infection contraceptive methods without restriction: COCs.

Assessment. moderate and high. GRC: Guidelines Review Committee. NET-EN: norethisterone enanthate. CHC: combined hormonal contraceptive.Executive summary | 11 GRADE ASSESSMENT TOPIC MEC RECOMMENDATION OF QUALITY OF EVIDENCEa 12d.4: Reviewed recommendations (p. SVT: superficial venous thrombosis. POIs (DMPA and NET-EN). Cu-IUD: copper-bearing IUD. Women taking any NRTI can generally use the LNG-IUD (MEC Category 2). . COC: combined oral contraceptive. and LNG and ETG implants (MEC Category 2). provided that their HIV clinical disease is asymptomatic or mild (WHO Stage 1 or 2). POC: progesterone-only contraceptive. low. Medical eligibility criteria for contraceptive use . Women taking any NRTI who already have had an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation). Women taking any NNRTI who already have had an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation). POPs. Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) and taking any NRTI generally should not initiate use of the LNG-IUD (MEC Category 3 for initiation) until their illness has improved to asymptomatic or mild HIV clinical disease. the range reflects the GRADE quality assessment across important outcomes and/or across contraceptive methods. VTE: venous thromboembolism. POP: progesterone-only pill. ETG: etonogestrel. Development and Evaluation. GRADE: Grading Recommendations. Range: Low to very Low transcriptase inhibitors POPs. See the specific GRADE table in Part I. Women living with HIV using antiretroviral therapy (ART) Nucleoside/nucleotide Women taking any NRTI can use all hormonal contraceptive methods reverse transcriptase without restriction: COCs. DMPA: depot medroxyprogesterone acetate. provided that their HIV clinical disease is asymptomatic or mild (WHO Stage 1 or 2). SC: subcutaneous. Women using efavirenz or nevirapine can use DMPA without restriction containing ART (MEC Category 1). NNRTIs containing Women using the newer NNRTIs containing etravirine and rilpivirine etravirine and rilpivirine can use all hormonal contraceptive methods without restriction (MEC Category 1). NRTI: nucleoside/nucleotide reverse transcriptase inhibitor. IUD: intrauterine device. ARV: antiretroviral (medication). and LNG and ETG implants (MEC Category 1). CICs. Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) and taking any NNRTI generally should not initiate use of the LNG-IUD (MEC Category 3 for initiation) until their illness has improved to asymptomatic or mild HIV clinical disease. NNRTI: non-nucleoside/nucleotide reverse transcriptase inhibitor. combined contraceptive patches and rings. Non-nucleoside/ Women using NNRTIs containing either efavirenz or nevirapine can nucleotide reverse generally use COCs. section 1. CIC: combined injectable contraceptive. When a range is presented. Women taking any NNRTI can generally use the LNG-IUD (MEC Category 2). combined contraceptive patches and inhibitor (NRTI) rings. CICs. ART: antiretroviral therapy. a GRADE assessment includes the quality categories of very low. LNG: levonorgestrel. IM: intramuscular. 8–82) for outcomes explored. (NNRTIs) containing efavirenz or nevirapine. NET-EN. POI: progresterone-only injectable.

POI: progresterone-only injectable. GRC: Guidelines Review Committee. provided that their HIV clinical disease is asymptomatic or mild (WHO Stage 1 or 2). DMPA: depot medroxyprogesterone acetate. NET-EN: norethisterone enanthate. Women taking an RI who already have had an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation). CHC: combined hormonal contraceptive. IUD: intrauterine device.g. 8–82) for outcomes explored. GRADE: Grading Recommendations. low. Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) and taking an RI generally should not initiate use of the LNG-IUD (MEC Category 3 for initiation) until their illness has improved to asymptomatic or mild HIV clinical disease. ARV: antiretroviral (medication). Women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) and taking any PI generally should not initiate use of the LNG-IUD (MEC Category 3 for initiation) until their illness has improved to asymptomatic or mild HIV clinical disease. VTE: venous thromboembolism. POP: progesterone-only pill. ritonavir and ARVs ritonavir) can generally use COCs.4: Reviewed recommendations (p. section 1. Women taking any PI who already have had an LNG-IUD inserted and Range: Low to very Low who develop severe or advanced HIV clinical disease need not have their IUD removed (MEC Category 2 for continuation).Executive summary GRADE ASSESSMENT TOPIC MEC RECOMMENDATION OF QUALITY OF EVIDENCEa 12d. Cu-IUD: copper-bearing IUD. When a range is presented.g. CIC: combined injectable contraceptive. moderate and high. IM: intramuscular. SC: subcutaneous. Women taking any PI can generally use the LNG-IUD (MEC Category 2).g. ritonavir and ARVs boosted with (e. CICs. See the specific GRADE table in Part I. ART: antiretroviral therapy. Raltegravir (integrase Women using the integrase inhibitor raltegravir can use all hormonal inhibitor) contraceptive methods without restriction (MEC Category 1). NNRTI: non-nucleoside/nucleotide reverse transcriptase inhibitor. NRTI: nucleoside/nucleotide reverse transcriptase inhibitor. LNG: levonorgestrel. POC: progesterone-only contraceptive. Women taking an RI can generally use the LNG-IUD (MEC Category 2). SVT: superficial venous thrombosis. COC: combined oral contraceptive. Assessment. Development and Evaluation.12 | Medical eligibility criteria for contraceptive use . and LNG and ETG implants (MEC Category 2). . POPs. a GRADE assessment includes the quality categories of very low. combined contraceptive patches boosted with ritonavir) and rings. provided that their HIV clinical disease is asymptomatic or mild (WHO Stage 1 or 2). the range reflects the GRADE quality assessment across important outcomes and/or across contraceptive methods. Women living with HIV using antiretroviral therapy (ART) (continued) Protease inhibitors Women using protease inhibitors (e. Women using protease inhibitors (e. ETG: etonogestrel. ritonavir and ARVs boosted with ritonavir) can use DMPA without restriction (MEC Category 1). NET-EN.

fifth edition . Part I Development of the Medical eligibility criteria for contraceptive use.

.

Decision-making tool for family planning clients and sterilization. fertility awareness-based methods. family planning services by providing policy.g.1 Overview and scope of the guidelines evidence-based recommendations (primarily targeted towards policy-makers and programme managers) and two that focus Over the past 40 years. decision-makers and the scientific community with use (SPR) – provides guidance regarding “how” to use recommendations that can be used for developing or revising contraceptive methods safely and effectively. Because country situations and programme environments vary so greatly. and The goal of this document is to improve access to. hypertension) or characteristics method.g. current sexual health care.1. towards health-care providers). family planning services for clients.Part I | 15 1. counselling and services: barrier methods. schedules for interpreted and used in a broader context of reproductive and administration and novel delivery systems. needs. and 1. national guidelines on medical eligibility criteria used in the Practical tools for front-line providers of contraceptive provision of all hormonal contraceptives. and quality of. Selected practice recommendations for contraceptive makers. provides guidance regarding “who” can use contraceptive methods safely. male and female 3. However. These evidence. rather. Medical eligibility criteria for contraceptive use (MEC) – the access to. age). while reflecting upon local values and preferences. on long-standing theoretical concerns that have never been substantiated or on the personal preference Evidence-based recommendations for provision of or bias of service providers. and emergency contraception. and review of the recommendations allows for consideration of 4. method by certain health conditions (e. . (e. However. it is expected that national programmes will use these recommendations for updating or developing their own contraceptive eligibility guidelines according to national health policies. longer in wide use. These four documents. lactational amenorrhoea method. it is inappropriate to set firm international guidelines on criteria for contraceptive use. priorities and resources. coitus interruptus. are policies and health-care practices in some countries are based updated periodically to reflect changes in the medical and on scientific studies of contraceptive products that are no scientific knowledge. there have been significant advances on application of the recommendations (primarily targeted in the development of new contraceptive technologies. Medical eligibility criteria for contraceptive use . Family planning: a global handbook for providers – offers multiple methods that could be used safely by people with evidence-based information on service delivery.1 Background There are a total of four WHO guidance documents (cornerstones) pertaining to contraception. two that focus on 1. All four cornerstones are best including changes in formulations and dosing. providers – counselling tool that supports both provider and based recommendations do not indicate a “best” method that client in the process of choosing a contraceptive method. should be used given a particular medical context. These outdated policies or contraception: practices often result in limitations to both the quality of. 2. listed below. intrauterine devices.

They are reviewed and updated in a Process for assuring that the timely manner. 2004 sterilization Intrauterine devices CICs Coitus interruptus Copper IUD for emergency contraception POCs Patch Male surgical sterilization Ring ECPs COCs Barrier methods IUDs Fertility awareness-based methods Lactational amenorrhoea Patch Female surgical sterilization Intrauterine devices CICs Coitus interruptus Copper IUD for emergency contraception POCs Patch Male surgical sterilization Ring ECPs Reproductive Health and Research Family and Community Health World Health Organization. The four cornerstones of family planning guidance Medical eligibility SELECTED PRACTICE criteria for RECOMMENDATIONS contraceptive use FOR CONTRACEPTIVE USE COCs ECPs CICs POPs DMPA NET-EN NOR Cu-IUDs LNG-IUD NFP COCs ECPs COCs Barrier methods IUDs Fertility Emergency contraception COCs POPs awareness-based methods Lactational NFP male sterilization COCs NOR CICs amenorrhoea Patch Female surgical DMPA female sterilization sterilization Intrauterine devices CICs barrier methods Cu-IUDs Coitus interruptus Copper IUD for LNG-IUD POPs emergency contraception POCs Patch NOR NFP Fourth edition. 2. 2004 COCs ECPs CICs POPs DMPA NET-EN NOR Cu-IUDs LNG-IUD NFP COCs ECPs Emergency contraception COCs POPs A WHO FAMILY PLANNING CORNERSTONE NFP male sterilization COCs NOR CICs DMPA female sterilization barrier methods Cu-IUDs LNG-IUD POPs NOR NFP COCs NET-EN ECPs female sterilization barrier methods natural family planning emergency contraception DMPA NOR POPs NET-EN barrier methods lactational amenorrhea natural family planning female sterilization COCs barrier methods lactational amenorrhea Medical eligibility criteria Selected practice for contraceptive use recommendations for contraceptive use These are evidence-based guidance and consensus-driven guidelines. Provide electronic updates on WHO’s reproductive health web site Decision-making tool for family Family planning: a global (www. 4.int/reproductivehealth) planning clients and providers handbook for providers as appropriate and determine the need to convene an expert working These are tools that incorporate the Medical eligibility criteria.who. They will be updated as the guidelines are updated or as other evidence warrants. Determine whether the newly synthesized evidence is sufficient to warrant an update of existing recommendations.16 | Medical eligibility criteria for contraceptive use . Critically appraise the new evidence. Evaluate the new evidence in light of prior evidence. Identify new. 3. guidelines remain current: 1.Part I Figure 1. to meet the needs of the family planning client. . the Selected group to reassess guidelines practice recommendations and other consensus recommendations on how formally. 5. relevant evidence as soon as it becomes available through an ongoing comprehensive bibliographic search. 2009 Male surgical sterilization Ring ECPs COCs Barrier methods IUDs Fertility COCs NET-EN ECPs female sterilization barrier methods natural family planning emergency awareness-based methods A WHOLactational FAMILY PLANNING CORNERSTONE contraception DMPA NOR amenorrhoea Patch Female surgical POPs NET-EN barrier methods sterilization Intrauterine devices CICs lactational amenorrhea natural family Coitus interruptus Copper IUD for planning female sterilization COCs emergency contraception POCs Patch barrier methods lactational amenorrhea Male surgical sterilization Ring ECPs COCs Barrier methods IUDs Fertility awareness-based methods Lactational amenorrhoea Patch Female surgical Second edition. They provide recommendations made by expert working groups based on an appraisal of relevant evidence. Geneva.

related to emerging published evidence on topics covered by the guideline during interim periods between expert Working Group meetings. Flanagan RG. Curtis KM. the guidelines are of a high methodological quality and are guideline has been revised and updated three times. . Medical eligibility criteria for contraceptive use . Since the release of the fourth edition of the new evidence since the last meetings in 1994 and 1995. The GRC approved the WHO on behalf of the larger expert Working Group on matters updated recommendations on 21 April 2010. Am J Prev Med. in March 1994 and May 1995.1 Development of earlier editions of the Medical held at WHO on 1–4 April 2008. Keeping up with evidence: a new system for WHO’s evidence-based family planning guidance. comprising seven external members. evidence-based decision- each revision. subject matter of the meeting. with each September 2009. The Guidelines Review Committee (GRC) was established by the Director-General of WHO in 2007 to ensure that WHO Since the publication of the first edition of the MEC. preparing summaries of published medical and the experts declared conflicts of interest relevant to the epidemiological literature relevant to medical eligibility criteria. a Working Group of multidisciplinary experts making process. guideline meetings. Eighty-six new recommendations were This document builds on a process initiated in 1994 to develop developed and 165 recommendations were revised for the the first edition. preclude them from participating in the deliberations and was established for this edition. including representatives of many agencies asked to declare any conflict of interest. All participants in the consultation were from 18 countries. At the request primarily obtained from systematic reviews of the most recent of the GSG.2.Part I | 17 1. including nine agency representatives. revision. Two expert Working Group meetings from participating in the deliberations and development of were organized by WHO. Rinehart W. Peterson HB. The Working Group reviewed if necessary. A Guideline and GSG did not find these conflicts of interest sufficient to Steering Group (GSG). was based on the postpartum women. or CIRE system)1. which brought together eligibility criteria for contraceptive use 43 participants from 23 countries. Systematic reviews of the evidence were declared a conflict of interest relevant to the subject matter. WHO first convened a technical consultation on literature. Gaffield ML. All members of the expert Working Group eligibility criteria used by different agencies for various were asked to declare any conflict of interest and three of contraceptives. The fourth edition of the MEC was reviewed was assembled to review newly published evidence pertaining by the newly established GRC and was approved on 16 to the topics addressed in the guideline. The teleconference brought together recommendations of an expert Working Group meeting held at members of the GSG and three experts on VTE during the WHO on 21–24 October 2003. which gathered 36 participants postpartum period. recommendations. Moreover. they were presented to the Working Group recommendation formulation because the WHO Secretariat and provided the basis for their decision-making. new evidence is identified through an ongoing comprehensive bibiliographic search (the Continuous The second edition of the MEC was based on the Identification of Research Evidence. including representatives of with evaluating such evidence and issuing interim guidance many agencies and organizations.2 Methods The fourth edition of the MEC was based on the recommendations of an expert Working Group meeting 1. publication of the document followed in 1996. the Working Group used the opportunity to consider inclusion of new medical conditions and new contraceptive To assure that the guidelines remain current between methods. 26 January 2010 via teleconference to review new evidence regarding the risk of venous thromboembolism (VTE) in The third edition of the MEC.28(5):483–90. which brought together 32 new evidence warrants further evaluation. The GSG was formed to advise development of recommendations. In circumstances where at WHO on 8–10 March 2000. 2005. 1 Mohllajee AP. two participants and organizations. With developed through a transparent. recommendations and thus they were not asked to withdraw to review the background classifications and to formulate from this process. This recommendations of an expert Working Group meeting held evidence is synthesized and reviewed. interim guidance has been issued twice. The initial process involved comparing the fourth edition. These conflicts of interest and preparing a draft classification for review by a larger group were determined not to be sufficient to preclude the experts of experts and agencies. the GSG is tasked participants from 17 countries. as appropriate. prepared on topics with newly published evidence since the but they were not asked to withdraw from the process of meeting in 2000. MEC.

which has served as an The meeting involved 75 individuals representing a wide external advisory group to WHO on family planning guidelines range of stakeholders. to be compliant with the group considered whether recommendations in the MEC WHO requirements for guideline development and to gain input pertaining to hormonal contraceptive use among women at from a larger advisory group. and drafting questions submitted completed surveys. professional societies. including individuals from approval for the planning and ultimately the final document a number of implementing agencies.htm . survey available in English. see: www. a second technical consultation (GDG). giving priority to controversial topics and those current revision. The respondents were revision. Assessment. All participants in the see the Acknowledgements at the beginning of this document. the first GDG meeting convened in of interest were determined not to be sufficient to preclude Ferney Voltaire. Recommendations considered to be consistent with the 2 The first edition was published in 2012. clarifying recommendations the format of the guidance. asked to rank the importance of various outcomes pertaining •• convening an additional consultation to define the scope of to topics that had been identified as priority questions for the the revision. for the earlier MEC editions. these results were presented to relating to population. in light of the accumulating evidence. the WHO Secretariat presented brief •• applying the Grading Recommendations. the meeting on 15 February 2012. including topics clinical questions of importance.2. consultation were asked to declare any conflict of interest. Through a consensus-driven process. 13 participants declared an academic conflict of interest 1.2. a Guideline the use of hormonal contraception and HIV acquisition. and At the meeting.18 | Medical eligibility criteria for contraceptive use . and to these alterations included: forward the link for the survey to others in their professional communities familiar with family planning and the MEC during •• creation of groups with varying roles to undertake the the period 2 March – 2 May 2013. Several key aspects of the and WHO regional and country offices.2 Specifically. The GSG. fifth edition broad group of stakeholders with expertise in family planning In preparation for the fifth edition of the document.3 become inconsistent with the updated body of evidence. the CIRE system1 was used to identify from this process. the Evidence Secretariat and the GDG. was part of the larger GDG. Steering Group (GSG). and to give input regarding addressed in interim guidance. These conflicts On 14–15 May 2013. no new evidence had been identified through CIRE were 3 For further information on GRADE. were obtained from the GRC. which was formerly called the expert Working Group was convened by WHO during 31 January – 1 February 2012. as well as the Ministry updating process were adjusted to be in closer alignment with of Health in each of the Member States. They were asked to requirements set forth in the WHO handbook for guideline voluntarily complete an electronic 24-question anonymous development. France. To further inform decision-making with respect to clinical 1. and recommendations for which 2014. The GRC approved the technical statement recommendations from the fourth edition of the MEC for which presenting the conclusions and updated recommendations of new evidence was available. French and Spanish.3 Prioritization of topics for the revision process relevant to the subject matter of the meeting. both and familiarity with the guideline. an Evidence and discussion at a larger meeting convened in March 2014. comparator and the GDG during the meeting to inform the prioritization process. the WHO Secretariat reached out to a for contraceptive use. and a Guideline Development Group progression and transmission.2 Development of the Medical eligibility for criteria questions and priorities. Prior of recommendations and so they were not asked to withdraw to the meeting. summaries of new evidence to the GDG to determine whether Development and Evaluation (GRADE) approach to evidence the existing recommendation remained consistent or had review and recommendation formulation. as well as to suggest other outcomes and for which new evidence had emerged.gradeworkinggroup.Part I Following new findings of epidemiological studies regarding Secretariat including a GRADE methodologist. authored by the GRC Secretariat. For a summary of the members high risk of HIV or women living with HIV should be changed of the WHO Secretariat. outcome (PICO questions) to guide the preparation of systematic reviews. intervention. since 2003. to initiate the revision process them from participating in the deliberations and development for the development of the fifth edition of the MEC. org/index. the second edition in updated body of evidence. Recommendations considered to be possibly inconsistent with The groups responsible for the development of the fifth the updated body of evidence were selected for presentation edition of the MEC included: a WHO Secretariat. More than 250 individuals with a Category 2/3 classification.

2. Assessment. All other existing recommendations from the MEC fourth edition (approximately 2000 recommendations):a •• reaffirmed by the GDG in March 2014. for which the existing recommendation contraceptive methods and/or formulations of methods. Development and Evaluation. during this meeting the GDG was asked to address that were determined to lack clarity by the GRC. was potentially inconsistent with the updated body of based upon their global relevance and availability in multiple evidence. fifth edition: selection of topics for 2014 revision Prioritized topics reviewed by the Guideline Development Group (GDG) using the GRADE process in 2014: 1. that these recommendations may be confusing to users of the document. methods. Medical eligibility criteria for contraceptive use .Part I | 19 determined by the GDG to need no further review during the Thus. with new evidence. approved for 4 years of use. Topics not prioritized for 2014 update. Topics identified as important to the field and/or topics with new. 3. Sino-implant (II) •• progesterone-releasing vaginal ring (PVR) •• ulipristal acetate (UPA) for emergency contraception. Interim guidance issued by WHO since the MEC fourth edition (2 topics): •• CHC use during the postpartum period (guidance updated in 2010) •• hormonal contraceptive use among women at high risk of HIV acquisition and women living with HIV (guidance reaffirmed in 2012). potentially inconsistent evidence identified (6 topics): •• progesterone-only contraceptive (POC) use among breastfeeding women •• combined hormonal contraceptive (CHC) use among breastfeeding women •• CHC use among women with superficial venous disorders •• CHC use by age group •• hormonal contraceptive use among women using antiretroviral therapy •• emergency contraceptive pill (ECP) use among women with obesity (new condition added to ECP recommendations).1 Medical eligibility criteria for contraceptive use. as earlier reviews by the GRC noted were reaffirmed by the GRC and thus were not reviewed. .e. All existing current recommendations which were classified as category recommendations that did not fall into one of these categories “2/3” in the fourth edition. Recommendations reviewed by the GDG for clarity. Participants were also asked to review the two the MEC fourth edition. topics consider whether WHO should include several new conditions. i. by the GDG at the second meeting in March 2014 based on meeting one or more of the following criteria: topics identified Also at this first GDG meeting. Table 1. as required by the Guidelines Review Committee (GRC) (2 topics): •• intrauterine device (IUD) use among women with increased risk of sexually transmitted infections (STIs) (no new evidence identified since 2008 systematic review) •• CHC use among women with known dyslipidaemias. the members were asked to as controversial or of particular importance to the field. or recommendations from the MEC fourth edition Further. newly introduced contraceptive interim guidance documents released since the fourth edition. GRADE: Grading Recommendations. 4. topics with interim guidance issued by WHO since countries. topics were prioritized for review and consideration revision process. a Evidence continuously monitored using CIRE system. New contraceptive methods added to the MEC for the fifth edition (4 methods): •• subcutaneously-administered depot medroxyprogesterone acetate (DMPA) 104 mg •• 2-rod levonorgestrel (LNG)-containing implant with 75 mg LNG/rod. CIRE: Continuous Identification of Research Evidence.

where appropriate. et al.5 Decision-making during the Guideline critical safety outcomes. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Lohr KN. need to be formally reviewed for this revision.20 | Medical eligibility criteria for contraceptive use . . meta-analyses were generally not of the data.4 The systematic reviews may be accessed their disclosed academic conflicts of interest were sufficient in Annex 2. The quality of evidence presented in individual review. The PRISMA Group. These systematic reviews. according to the GRADE approach to evidence performed. reporting on 1. the GDG developed members of the GDG. questions with specified available to all GDG members prior to the consultations. For details of the declared academic interests with experts in the field were also used to identify other see Annex 1. Preventive Services Task Force: a review of the process. Reference lists and direct contact (Dr Sitruk-Ware). Teutsch SM. and final drafts were made electronically questions using the PICO format (i. the GRADE methodologist to assess the quality of the summarized GDG considered these potential harms. contraceptive formulations paying particular attention to the strength and consistency and outcome measures. the benefits of preventing unintended pregnancy. the PubMed and Cochrane databases to preclude them from participating in the deliberations and were searched for studies published in any language in a development of recommendations relevant to ulipristal acetate peer-reviewed journal up to 15 January 2014. of interest using a specific contraceptive method compared with the same population not using the method. assessed the recommendations in the MEC. Members of the GDG and safety risks of using a given method among women with a members of the External Peer Review Group (who did not particular medical condition or characteristic.5 GRADE evidence profiles were then prepared by a arrive at a category designation. 2001. PLoS Med. the WHO Secretariat and the GDG agreed that safety outcomes. In general. Liberati A. neither grey literature nor conference abstracts were included in these reviews.Part I For the topics outlined in Table 1.S. In most cases. PICO questions were also crafted to Development Group meetings also identify relevant indirect evidence that may have included During 9–12 March 2014 and 24–25 September 2014. The remainder participate in the GDG meeting) submitted Declaration of of the existing recommendations were determined to be Interest forms to the WHO Secretariat: 14 individuals declared consistent with the body of published evidence and did not an academic conflict of interest relevant to the MEC guidance. 5 Harris RP.2. including those in press.1.6(6):e1000097. The systematic reviews values that prioritized the availability of a wide range of that resulted from this process were peer-reviewed by selected contraceptive options. Am J Prev Med. as each clinical outcome assessed. Mulrow CD. The written and orally presented systematic reviews PICO questions generally guide the systematic review to focus and GRADE evidence profiles served as the basis for the GDG’s on studies of populations with the condition or characteristic deliberations. Due to The GDG considered the overall quality of the safety evidence. GRADE evidence profiles were well as the other GRADE constructs of values and preferences. found no conflicts of interest sufficient For each of the priority topics listed in Table 1. Tetzlaff J. Current methods of the U. To system. Helfand M. heterogeneity of study designs.20(3 Suppl):21–35. WHO comparator populations without the condition or characteristic convened a series of GDG meetings to review the evidence of interest using the same method. Altman DG. as women vary in their preferences regarding contraceptive selection and in the value they place 4 Moher D. systematic to preclude anyone from participating in the deliberations reviews were conducted in accordance with PRISMA or development of recommendations. comparators and outcomes) to Printed copies of GRADE evidence profiles for each topic were serve as the framework for the systematic reviews and GRADE also given to each GDG member during the March 2014 GDG evidence tables. or reporting on surrogate for the priority topics and. the GRADE evidence evidence and include the range of the estimates of effect for profiles. In order to inform the MEC recommendations. populations. to inform (Dr Glasier) and the progesterone-releasing vaginal ring the systematic reviews.e. 2009. within the range 1–4.4 Evidence identification and synthesis interest and. The WHO Secretariat and the GDG reviewed all declarations of 1. Woolf SH. meeting.1. with the exception of two members (Dr Glasier and Dr Sitruk-Ware). interventions. the quality of evidence pertaining studies within a systematic review was assessed by review to each recommendation was low or very low and only authors using the United States Preventive Services Task Force addressed potential harms related to contraceptive use. studies. revise specific outcomes. therefore. prepared for each PICO question for which evidence was found The GDG endorsed an approach to patient preferences and and clinical outcomes were reported.2. In the case of the two guidelines to answer PICO-formatted questions regarding exceptions.

which will include widespread dissemination through the 6 Madden T.e. Nease RF. accessed 24 March 2015). International Council of Nurses (ICN) and the International . UNFPA. Development and Research Training ahead of print] in Human Reproduction (HRP) within the WHO Department 7 Hooper DJ. Expanding contraceptive partner organizations working in the area of sexual and choice in the developing world: lessons from the Lao People’s Repub- lic and the Republic of Zambia. comprising eight experts who 1–4 scale has been used to categorize medical eligibility for did not participate in the GDG meeting. closely with sexual and reproductive health points of contact lescents’ contraceptive use and discontinuation in developing coun. Ba-Thike K. training institutions this guidance by the WHO Secretariat as appropriate. Darroch JE. UNICEF. the GDG dissemination and evaluation plan will be implemented. the External Peer Review Group. 2012 (https:// Society of Obstetricians and Gynaecologists (FIGO). as well as upholding the majority of the contraceptive use. Comments received contraceptive use. Trevitt JL. considered the potential benefits and risks of contraceptive the availability of a range of contraceptive options is critical method use with respect to each of the medical conditions or because a woman’s contraceptive choices are made at a personal characteristics assessed.Part I | 21 on different beneficial and harmful outcomes. since costs may vary widely throughout different regions. cross-sec. of Reproductive Health and Research (i. The document.18:421–34. particular time and in a particular societal and cultural context. the GDG arrived at new and revised The recommendations in the Medical eligibility criteria for recommendations. Hormonal contraceptive methods for women at high risk of HIV Owing to the focus of this guidance on the safety of specific and living with HIV: 2014 guidance statement was approved by contraceptive methods for women with medical conditions or the WHO Guidelines Review Committee (GRC) on 7 July 2014. in advance of the entire guideline revision. women living with HIV. and based on encouragement from with advantages and disadvantages of specific contraceptive the GDG. Patterns and trends in ado. self-administered.10 A draft version of the entire MEC document was sent to the Since publication of the first edition of the MEC in 1996. the www. compliance and preferenc- es among hormonal contraception users: a global. multifactorial and subject to Owing to the public health importance of recommendations change. governmental and nongovernmental 8 d’Arcangues CM. Croft TN. tional. fifth edition guidance were released during existing recommendations using the categories 1–4. WHO issued its contraceptive eligibility guidance for methods varying according to individual circumstances. Clin Drug Investig. A comprehensive the topics they reviewed in 2014 (see Box 1. opportunity costs were not formally The statement was released on 24 July 2014. Eur J Contracept Reprod Health Care. WHO collaborating centres.pdf. WHO and the World Bank).3 Dissemination and evaluation of the not be defined as “strong” or “weak” according to GRADE Medical eligibility criteria for contraceptive methodology and would instead retain the 1–4 scale reflecting use. and reproductive health projects The WHO Secretariat will work 9 Blanc A. [Epub Programme of Research. The and ministries of health as the basis for determining final version of this document was approved by the GRC on contraceptive eligibility for women with medical conditions 18 March 2015. at the 20th assessed during the formulation of these recommendations International AIDS Conference. reproductive health.35(2):63–71. In addition. professional organizations. and civil society groups engaged in sexual 2013.org/pubs/AIU-2012-estimates.6 7 In addition. UNDP. it was determined that recommendations would 1. contraceptive attributes in women’s contraceptive decision making. or characteristics. Int Perspect Sex Reprod Health. professional organizations. and these choices are complex.8 9 Decision-making for contraceptive methods usually on hormonal contraceptive use for women at risk of HIV and requires making trade-offs among the different methods. WHO Member States. will be organized during the summer and autumn of 2015 ceptive services – estimates for 2012. Through consensus. awareness.30(11):749–63. Peipert JF. women living with HIV or at high risk of acquiring the infection perceptions and interpretations. Say L. 2015. For a global live Facebook Chat on 1 June 2015.1). fifth edition eligibility for contraceptive use. online survey. to avoid confusion and retain consistency.pii: S0002-9378(15)00107–6.guttmacher. the United Nations (UN) agency cosponsors of the Special Am J Obstet Gynecol. in the WHO regional offices to conduct a series of regional tries and comparisons with adult women. Tsui AO. Politi MC. The role of WHO regional and country offices. Adding it up: costs and benefits of contra. events during 2015–2016. 2010. New York (NY): Guttmacher at international conferences convened by the International Institute and United Nations Population Fund (UNFPA). Secura GM. Medical eligibility criteria for contraceptive use . personal characteristics. Attitudes. 2009. special panel sessions 10 Singh S. These categories are well known by health. from these reviewers were addressed and incorporated into care providers. As a result.

and identify areas for further refinement and Population Women of reproductive age (with a specific research gaps in contraceptive eligibility criteria. Recommendations Information on using the recommendations in practice. 91. opportunities to ensure effective use CHCs. combined injectable edition of the MEC and the updated fifth edition is available in contraceptives) without restriction (MEC Category 1). combined contraceptives by age group contraceptive vaginal ring. the correct and consistent use of condoms. Databases PubMed and Cochrane Library •• Due to heterogeneity of study designs. and the evidence for combined hormonal contraceptives Selection criteria for the systematic review (CHCs) and potential for decreased bone mineral density (BMD) among adolescents. revised use combined hormonal contraceptives (combined and confirmed) are presented in Part II. with a specific focus on adolescents? (Indirect dissemination will be actively sought.3 and 2. If there is a risk of STI/HIV. combined contraceptive patch.1). combined injectable contraceptives) (MEC Category 2).4–2. Recommendations for combined hormonal contraceptives. combined contraceptive patch.4 Reviewed recommendations Comparator Non-use of CHCs Outcome Decreased bone mineral density The Guideline Development Group (GDG) determined priority Databases PubMed and Cochrane Library searched topics to be addressed as part of the revision process for the fifth edition (see Table 1. Selection criteria for the systematic review professional organizations and civil society will be fielded to assess the extent and effectiveness of the dissemination. The risk of Intervention CHC use cardiovascular disease increases with age and may also Comparator Non-use of CHCs increase with CHC use. 93–96).Part I Confederation of Midwives (ICM) to update the membership Question 2: Are women who use combined hormonal of these societies about the revised recommendations. •• Women 40 years and older can generally use combined hormonal contraceptive methods (combined oral 1. male or female. oral contraceptives. •• CHCs do not protect against sexually transmitted infections (STIs).6 and Tables 2. contraceptive searched formulations and outcome measures a meta-analysis was not performed. and therefore may not accurately predict current Population Women of reproductive age or future (postmenopausal) fracture risk (1–3). BMD is a surrogate marker Study design Randomized controlled trials.6. cohort studies evaluate the level of implementation of the guidance into and case-control studies national policies. is recommended. Study design Randomized controlled trials. Part II (see section 2. starting on p. focus on adolescents) Intervention CHC use 1. WHO offices and partners. sections 2. An evaluation survey evidence) targeting ministries of health. including HIV. Question 1: Are women who use combined hormonal Remarks contraceptives (CHCs) at increased risk for fracture compared with women who do not use CHCs? (Direct •• In 2014. CHC can be used until menopause. Once contraceptives (CHCs) at increased risk for decreased translations of the document in other official languages of bone mineral density compared with women who do not the UN become available. pp. the GDG focused specifically on the evidence evidence) pertaining to fracture risk among women of all ages.22 | Medical eligibility criteria for contraceptive use .7. In the absence of other adverse Outcome Fracture clinical conditions. A summary of changes between the fourth combined contraceptive vaginal ring. as •• Women from menarche to < 40 years of age can well as recommendations in the fifth edition (new. . cohort for fracture risk that may not be valid for premenopausal studies and case-control studies women.

Quality of the evidence (intervention versus comparator. bone mineral density (indirect): . especially in those choosing very-low-dose formulations (< 30 µg ethinylestradiol-containing combined oral contraceptives) (16–29). Medical eligibility criteria for contraceptive use . with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances. 15). CHC use may decrease BMD in adolescents. perceptions and interpretations. low bone mineral density (indirect): Combined contraceptive patch use versus very low non-use in adolescents. choices are complex. Women’s contraceptive choices are made in a particular time. fracture low risk (direct): COC use versus non-use in adolescents. 5. and may preserve bone mass in those who are perimenopausal (45-54). societal and cultural context. Summary of the evidence Evidence is inconsistent on the question of whether CHC use affects fracture risk (4–15). multifactorial and subject to change. education and counselling to ensure informed choice.Part I | 23 •• Voluntary use of contraception by women is critical for upholding their reproductive rights. comprehensive contraceptive information. All women have the right to evidence-based. although three recent studies show no effect (4. Decision- making for contraceptive methods usually requires the need to make trade-offs among the different methods. outcome) CHC use versus non-use of CHC. CHC use has little to no effect on BMD in premenopausal women (30–44).

24 | Medical eligibility criteria for contraceptive use .3)a CI: confidence interval. two studies forearm fracture.07–1.Part I GRADE table 2 (Question 2): Are women who use combined hormonal contraceptives (CHCs) at increased risk for decreased bone mineral density compared with women who do not use CHCs.29). including the 2 good-quality cohort studies 6 poor) duration of follow-up studies.86–1. with a specific focus on adolescents? (Indirect evidence) Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect participants) Oral combined hormonal contraceptive use vs non-use in adolescent women Bone mass 1 RCT (n=83). including 1 good-quality 7 case-control (1 good.GRADE table 1 (Question 1): Are women who use combined hormonal contraceptives (CHCs) at increased risk for fracture compared with women who do not use CHCs? (Direct evidence) Type and number of studies Outcome Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Oral combined hormonal contraceptive use vs non-use Fracture 3 cohort studies Serious Serious No serious Serious indirectness No duration. 4 studies showed no differencea (n=3242) Patch use vs non-use in adolescent women BMD 1 non-randomized Very serious Cannot determine Very serious Serious indirectness None Very 1 study found no effect of patch on BMD trial (n=10) limitations (1 study) imprecision (intermediate low vs non-use (1 poor) outcome) RCT: randomized controlled trial. 5 fair. 6 fair.05. six studies 15–20mcg EE. a Eight studies evaluated 30–35mcg ethinyl estradiol (EE) formulation (one 30–40mcg EE). outcome) effect. 3 studies studies (n=84 695 3 poor) during adolescence) found a statistically significant but weak cases) association (risk estimate range 1. OR: odds ratio. Low 7 studies showed no association between CHC (n=128 255). . 11 (2 good. variability in non-use. a Six studies evaluated any fracture. two not specified. limitations inconsistency imprecision (no study specifically response effect use and fracture risk. evaluated CHC use observed study (OR 1. 95% CI 0. Serious Serious No serious Serious indirectness 1 study showed Low 9 studies showed oral CHC use associated density (BMD) 1 non-randomized limitations inconsistency imprecision (intermediate duration-response with less BMD gain (or greater loss) than trial (n=84). two studies hip fracture.

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breastfeeding outcomes or infant outcomes. No consistent effects on infant growth or development) illness have been reported (1–6). studies have been inadequately designed to determine whether a risk of either serious or subtle long-term effects exists. cohort studies advantages and disadvantages of specific contraceptive and case-control studies methods varying according to individual circumstances. Question 1: Among breastfeeding women. Study design Randomized controlled trials. however. supplementation) use of condoms is recommended. during lactation. . comprehensive contraceptive outcomes or infant outcomes. •• Voluntary use of contraception by women is critical for Question 2: Among breastfeeding women. the correct and consistent exclusivity. Recommendations for combined hormonal Recommendations contraceptives among breastfeeding women •• Breastfeeding women < 6 weeks postpartum should not use combined hormonal contraceptives (combined oral contraceptives. with Study design Randomized controlled trials. health. combined contraceptive patch. contraceptive formulations and outcome measures. supplementation) women exposed to combined oral contraceptives (COCs) Infant outcomes (growth. does initiation upholding their reproductive rights. Selection criteria for the systematic review •• Breastfeeding women ≥ 6 months postpartum can generally use CHCs (MEC Category 2). Decision- Selection criteria for the systematic review making for contraceptive methods usually requires the need to make trade-offs among the different methods. compared with no information. Population Breastfeeding women perceptions and interpretations. Adverse health outcomes Databases PubMed and Cochrane Library or manifestations of exogenous estrogen in infants exposed searched to CHCs through breast-milk have not been demonstrated. and consistently. combined injectable at < 6 weeks postpartum have negative effects on contraceptives) (MEC Category 4). Comparator No contraception or use of non-hormonal •• Combined hormonal contraceptives (CHCs) do not protect contraception against sexually transmitted infections (STIs). When used correctly Infant outcomes (growth. cohort studies and case-control studies Remarks Population Breastfeeding women •• Due to heterogeneity of study designs. a meta-analysis was Intervention Use of CHCs not performed. Female Databases PubMed and Cochrane Library condoms are effective and safe. Women’s contraceptive choices are made in a evidence) particular time. If there is a risk of STI/HIV. compared •• Breastfeeding women ≥ 6 weeks to < 6 months postpartum with no contraception or non-hormonal contraception? (primarily breastfeeding) generally should not use CHCs (Direct evidence) (MEC Category 3). health. condoms offer one of the most effective development) methods of protection against STIs. societal and cultural context. choices are complex. does initiation of combined hormonal contraceptives (CHCs) combined contraceptive vaginal ring.Part I 2. All women have the of combined hormonal contraceptives (CHCs) at ≥ 6 weeks postpartum have negative effects on breastfeeding right to evidence-based. HIV. education and counselling to ensure informed contraception or non-hormonal contraception? (Direct choice.28 | Medical eligibility criteria for contraceptive use . effects on breastfeeding continuation or exclusivity in exclusivity. including HIV. Intervention Use of CHCs Summary of the evidence Comparator No contraception or non-hormonal contraception Clinical studies demonstrate conflicting results regarding Outcome Breastfeeding outcomes (duration. multifactorial and subject to change. but are not used as widely searched by national programmes as male condoms. including Outcome Breastfeeding outcomes (duration.

Medical eligibility criteria for contraceptive use . CICs: no evidence . breastfeeding and infant outcomes: For COCs compared with non-hormonal or very low non-use. supplementation: For COCs compared with non-hormonal or very low non-use. combined injectable no evidence contraceptives (CICs): ≥ 6 weeks postpartum: (method.Part I | 29 Quality of the evidence < 6 weeks postpartum: (method. breastfeeding duration: For COCs compared with non-hormonal or low non-use. low only pills (POPs). breastfeeding episodes: very low For COCs. breastfeeding duration: very low For COCs. breastfeeding continuation: For COCs compared with non-hormonal or very low non-use. ring. outcome) For COCs compared with progestogen. ring. infant outcomes: For patch. breastfeeding continuation: low For COCs. infant outcomes: low For patch. supplementation: low For COCs. outcome) For COCs.

RR 1.13–0.41). RR 1.17–0.29.3) at 8 weeks. 1 poor-quality study found initiation of mestranol at 2 weeks associated with lower likelihood vs initiation at 6 weeks (RR 0.Part I (1 fair) Infant growth 1 RCT (n=127) Serious Cannot determine Serious No indirectness Not Low EE vs POP (1 RCT): no difference in percent limitations (1 study) imprecision applicable change in weight (P = 0. length (P = 0. 2 non.56).78–1.40. mestranol) and duration vs 95%.6) at 6 months Use of 1 RCT (n=127) Serious Cannot determine Serious No indirectness Not Low EE vs POP (1 RCT): no difference at 8 weeks supplementation limitations (1 study) imprecision applicable (data not provided) 30 | Medical eligibility criteria for contraceptive use . 95% CI 0.88 [95% CI 0. 1 poor-quality study of various COCs found no difference in breastfeeding continuation at 6 weeks.96) or non-use (RR 0.0 (95% CI 0. Very serious Serious No serious Serious indirectness Variability in Very low 1 RCT found EE COC associated with lower continuation randomized limitations inconsistency imprecision (older COC outcomes likelihood of breastfeeding continuation vs studies (n=550) (1 fair-quality formulations with assessed placebo or Cu-IUD at 6 months (84% vs 91% RCT. RR 0.64) .71–1.82–1. does initiation of combined hormonal contraceptives (CHCs) at < 6 weeks postpartum have negative effects on breastfeeding outcomes or infant outcomes.0] vs placebo quality studies) of follow-up and 0. 95% CI 0.1 (95% CI 0. (1 fair) 44% vs 41%.97] vs IUD) but no difference at 12 months (61% vs 59% vs 65%).GRADE table 1 (Question 1): Among breastfeeding women.79–0.79) from weeks 2–8 COCs initiated at < 6 weeks postpartum vs non-hormonal or non-use Breastfeeding 1 RCT. compared with no contraception or non-hormonal contraception? (Direct evidence) Type and number Limitations Other Outcome of studies Inconsistency Imprecision Indirectness Quality Estimate of effect factors (number of participants) Combined oral contraceptives (COCs) vs progestogen-only pills initiated at < 6 weeks postpartum Breastfeeding 1 RCT (n=127) Serious Cannot determine Serious No indirectness Not Low Ethinyl estradiol (EE) vs POP (1 RCT): 64% vs continuation limitations (1 study) imprecision applicable 64%. 2 poor. (1 fair) or head circumference (P = 0.92 [95% CI 0.

RR 2. Very serious Serious No serious Serious indirectness Variability in Very low 1 fair-quality RCT found EE COC associated 3 observational limitations inconsistency imprecision (most studies outcomes with lower infant weight at 6 months (7864 studies (n=100) (1 fair-quality evaluated mestranol assessed vs 8333) and 1 year (9938 vs 10 746) vs RCT.0–5.5 mestranol COC) [95% CI 1. EE: ethinyl estradiol. RR 3. (1 poor) component of COC P = 0. and 2 studies less weight gain with COC) CI: confidence interval.Part I | 31 .5 to 4. RR 2.7–8.0%.4% vs 7. COC) and duration placebo.8]) at day 91. IUD: intrauterine device.01 for quinestrol and mestranol vs no formulations) COC Use of 2 RCTs (n=727) Serious No serious Serious Serious indirectness Variability in Low 1 fair-quality RCT found EE COC associated supplementation limitations inconsistency imprecision (largest study duration of with increased likelihood of supplementation (1 fair.3% vs 3.6 vs 5.4%. 4 poor-quality studies of mestranol quality studies) of follow-up COC reported conflicting results vs placebo or no COC (1 study no difference.3 months. 1 study growth greater with COC. 5 poor.1–5.6 [95% CI 1.8%. COC: combined oral contraceptive. RR: relative risk.1]) at day 8 Infant growth 3 RCTs (n=712). EE or mestranol) vs duration (n=696) limitations (1 study) imprecision (older estrogen no COC (1 study): 2. Medical eligibility criteria for contraceptive use . 1 poor) [n=451] evaluated follow-up vs injectable placebo (19.4 [95% CI 1.4]) or oral placebo (19. POP: progestogen-only pill. Type and number Limitations Other Outcome of studies Inconsistency Imprecision Indirectness Quality Estimate of effect factors (number of participants) Breastfeeding 1 cohort study Very serious Cannot determine No serious Serious indirectness None Very low Various COCs (quinestrol. 1 poor-quality RCT found mestranol COC associated with increased likelihood (12.4% vs 8. controlled trial. RCT: randomized.

1 cohort study found no difference in infant growth through 8 years. 1 study plus 1 study found no difference between mestranol COC and IUD in age at with < 50 supplementation women) Infant growth 2 non. does initiation of combined hormonal contraceptives (CHCs) at > 6 weeks postpartum have negative effects on breastfeeding outcomes or infant outcomes.Part I Breastfeeding 1 cohort study Serious Cannot Very serious No None Very low 1 small study found EE COC associated with more breastfeeding episodes (n=20) limitations determine imprecision indirectness episodes than IUD on 7 of 21 days from postpartum day 42 to (1 fair) (1 study) day 63 with no differences on other days Use of 3 non. 1 cohort study showed no difference between EE COC and IUD from day 42 to 63 COC: combined oral contraceptive. Serious No serious No serious No None Low 2 non-randomized studies found no difference between ethinyl continuation randomized limitations inconsistency imprecision indirectness estradiol (EE) COC vs non-COC (various) in breastfeeding studies (n=339) (2 fair) continuation rates at 6 or 12 months (RR 0. IUD: intrauterine device. (1 fair) (1 study) P < 0. (various) at 3–12 months (differences ranged from 10–25% at study (n=359 1 poor) various time points). but not at 5–6 months and no difference in mean weight at cohort studies 1 poor) 1 year. Serious Serious Serious No None Low 2 fair-quality non-randomized studies found EE COC associated supplementation randomized limitations inconsistency imprecision indirectness with increased likelihood of use of supplementation vs non-COC studies.6 months. 3 (3 fair. 1 non-randomized study study with < 50 found mestranol COC 0.96–0. 1 non-randomized study found no difference in change (n=455 plus 1 in weight at 12–16 or 20–24 weeks.7 vs 4. RR: relative risk. 1 cohort (3 fair.GRADE table 2 (Questions 2): Among breastfeeding women.1 mg with more infant growth than women) 0.075 mg or IUD. compared with no contraception or non-hormonal contraception? (Direct evidence) Type and number of Other Outcome Limitations Inconsistency Imprecision Indirectness Quality Estimate of effect studies (number factors of participants) Combined oral contraceptive (COC) initiated at ≥ 6 weeks postpartum vs non-hormonal or non-use Breastfeeding 2 non. 1 cohort study found no difference.99 in both studies) Duration of 1 cohort study Serious Cannot Serious No None Very low 1 cohort study found no difference between EE COC vs no oral breastfeeding (n=96) limitations determine imprecision indirectness contraceptives in duration of breastfeeding (3. . EE: ethinyl estradiol. Serious Serious Serious No None Low 1 cohort study found EE COC associated with lower infant randomized limitations inconsistency imprecision indirectness growth vs non-COC (various) from 3–4 months (599 vs 708 g) studies.05) 32 | Medical eligibility criteria for contraceptive use .

Singh R. II. 1972. Leeman L. Hefnawi F. Am J Obstet Gynecol. Combined oral contraceptive use among breastfeeding women: a systematic review. 1969.105(3):324–34. Am J Obstet Gynecol. Bhiraleus P. Effects of oral contraceptives on lactation. V.Part I | 33 References 1. 6. Curtis K. et al.23(1):24–8. . Talaat M. Fertil Steril. Contraception. and experimental studies on lactation. 3. biochemical. Fertil Steril. Abdel Razek S. Effect of hormonal contraceptives during breastfeeding on infant’s milk ingestion and growth. Kapp N. Abdallah M. Medical eligibility criteria for contraceptive use . Kamal I. Clinical. 2. 2013. Younis N. Effect of progestin compared with combined oral contraceptive pills on lactation: a randomized controlled trial. 1970. Bahamondes MV. et al. Modesto W. Tagui A. biochemical. Bahamondes L. Kamal I. Ghoneim M. Koetsawang S. Magalhaes A. Chiemprajert T.119(1):5-13. Clinical effects of steroids on the initiation of lactation. and experimental studies on lactation. 5. Ghoneim M. Ogburn T. Ostrom K.82(1):10–16. Espey E. Hefnawi F. Obstet Gynecol. Clinical. Schrader R. 2010. Pinto e Silva JL. 2012.100(2):445-50. Clinical effects of gestagens on lactation.108(4):655-8. Tilley IB. 4.

combined contraceptive vaginal ring. thromboembolism (VTE) compared with non-postpartum. combined injectable contraceptives) without restriction non-pregnant women? (Indirect evidence) (MEC Category 1). but are not contraceptives) (MEC Category 4). the correct •• Women who are < 21 days postpartum with other and consistent use of condoms is recommended. other risk factors for venous thromboembolism (VTE) •• Due to heterogeneity of study designs. combined injectable HIV. immediately post-caesarean contraceptives among postpartum women delivery. Female condoms are effective and safe. Study design Randomized controlled trials. contraceptive patch. transfusion at delivery. •• Women who are > 42 days postpartum can use CHC Question 2: Among women of reproductive age. evidence) combined contraceptive vaginal ring. does combined hormonal contraceptive (CHC) use increase risk of venous other risk factors for VTE can generally use CHCs (combined thromboembolism (VTE) compared with no CHC use? (Direct oral contraceptives. combined postpartum women have increased risk of venous contraceptive patch. transfusion at delivery. BMI > 30 kg/m2. cohort studies and case-control studies the balance of benefits and harms for CHC use among postpartum women. combined contraceptive patch. postpartum haemorrhage. Comparator Non-use of CHCs immediately post-caesarean delivery. •• CHCs do not protect against sexually transmitted infections combined injectable contraceptives) (MEC Category 3). postpartum with other risk factors for VTE. condoms offer one of the oral contraceptives. Recommendations for combined hormonal postpartum haemorrhage. When risk factors for VTE should not use CHCs (combined used correctly and consistently. The Databases searched PubMed and Cochrane Library GDG also considered that risk of pregnancy during the first 21 days postpartum is very low. combined contraceptive patch. contraceptive generally should not use combined hormonal contraceptives formulations and outcome measures. and Population Women of reproductive age with and without other risk factors for VTE. combined injectable contraceptives) (MEC Population Postpartum women Category 3). combined injectable contraceptives) (MEC Category 2). including combined contraceptive vaginal ring. the risks associated with Comparator Non-postpartum. at different time points postpartum. a meta-analysis was (CHCs) (combined oral contraceptives. For women ≤ 42 days postpartum with other Intervention CHC use risk factors for VTE. •• Women who are 21–42 days postpartum and do not have Question 1: Among postpartum women. BMI > 30 kg/m2. cohort combined contraceptive patch. but increases after that Recommendations time in non-breastfeeding women. such as •• Voluntary use of contraception by women is critical for immobility. and the availability of other contraceptive Outcome VTE methods that are safe for use by postpartum women. All women have the . including HIV.34 | Medical eligibility criteria for contraceptive use . including the risk Intervention Postpartum of VTE in the postpartum period. pre-eclampsia or Outcome VTE smoking. upholding their reproductive rights. (STIs). For women ≤ 42 days used as widely by national programmes as male condoms. do methods (combined oral contraceptives. pre-eclampsia or smoking. If there is a risk of STI/HIV. use of CHCs may pose an additional increased Databases searched PubMed and Cochrane Library risk for VTE. combined contraceptive studies and case-control studies vaginal ring. such as immobility. non-pregnant rapid repeat pregnancy. Women who are 21–42 Selection criteria for the systematic review days postpartum with other risk factors for VTE generally should not use CHC methods (combined oral contraceptives. ovulation before first •• Women who are < 21 days postpartum and do not have menses is common (1). most effective methods of protection against STIs. combined contraceptive vaginal ring. use of CHCs may pose an additional increased risk for VTE. Selection criteria for the systematic review Remarks •• The Guideline Development Group (GDG) considered Study design Randomized controlled trials.Part I 3. combined not performed. the benefits of preventing rapid repeat pregnancy.

outcome) CHC use versus non-CHC use postpartum. Women’s contraceptive choices are made in a particular time. Medical eligibility criteria for contraceptive use . but the numbers needed to harm were lowest in the first 6 weeks postpartum (2). Decision- making for contraceptive methods usually requires the need to make trade-offs among the different methods. declining to near baseline levels by 42 days postpartum (3–7). this risk is most pronounced in the first 3 weeks after delivery. low pregnant.Part I | 35 right to evidence-based. non-postpartum. VTE risk is elevated during pregnancy and the postpartum period. Rates were significantly different only after 13 weeks postpartum. with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances. VTE (indirect): . societal and cultural context. choices are complex. very low VTE (direct): First 6 weeks postpartum versus non. multifactorial and subject to change. comprehensive contraceptive information. Summary of the evidence One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with non-users at all time points postpartum. education and counselling to ensure informed choice. perceptions and interpretations. Quality of the evidence (intervention versus comparator.

limitations inconsistency imprecision indirectness effect in first 6 weeks.2) in thromboembolism (773 017 person.5–13) CI: confidence interval.3–1.2–0.Part I GRADE table 2 (Question 2): Among women of reproductive age.7 (95% CI 0. non-postpartum Venous 4 cohort studies Serious No serious No serious Serious Duration-response Low Any VTE (2 studies): rate ratio 21.6) variability in vs not using highest risk. does combined hormonal contraceptive (CHC) use increase risk of venous thromboembolism (VTE) compared with no CHC use? (Direct evidence) Type and number Outcome of studies (number Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect of participants) CHC use vs non-use in postpartum period Venous 1 cohort study Serious Cannot Serious No indirectness None Very low VTE (1 study): rate ratio 1.6–18) vs 3. 36 | Medical eligibility criteria for contraceptive use . using CHC associated with and 12 (95% CI 7. incidence (VTE) years) (1 fair) (1 study) 4.9 (95% CI 0.5 thromboembolism (n=3 365 650).9–18. do postpartum women have increased risk of venous thromboembolism (VTE) compared with non- postpartum. (CI not available) and 22 (95% CI (VTE) control study (285 (1 good.2 (95% CI 6.5 (95% CI 3. .6) vs 0. 4 fair) (direction (not women first 1–3 weeks 18–27) and OR 84 (95% CI 32–223) cases) consistent.9) per 1000 person-years in weeks 0–6 and 0. non-pregnant women? (Indirect evidence) Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect participants) First 6 weeks postpartum vs non-pregnant.1–3.3 (95% CI 0. 4 of which reported incidence by week and 1 of which reported the proportion of VTE events by week. b Based on 6 studies. limitations determine imprecision weeks 0–6 for CHC use vs non-use.a weeks magnitude) CHC) 0–6 associated with DVT (1 study): incidence ratio 15 higher risk than after (95% CI 13–18) week 7b Pulmonary embolism (1 study): incidence ratio 9.GRADE table 1 (Question 1): Among postpartum women. OR: odds ratio.5) per 1000 person-years in weeks 7–13 CI: confidence interval. a Based on 5 studies.3 (95% CI 0.3–5. 1 case.

Boulet SL. et al. Nielsen AK. Risk of a thrombotic event after the 6-week postpartum period. 6. Nelson-Piercy C. Paidas MJ. Curtis KM. Devereux RB. Medical eligibility criteria for contraceptive use . Fleming KM. 3. 7. Marchbanks PA. Fleming KM. Tata LJ. Petersen JF. Danish nationwide historical cohort 1995–2009. 2014. Risk factors for first venous thromboembolism around pregnancy: a population- based cohort study from the United Kingdom. Grainge MJ.370(14):1307– 15.156(3):366–73. Whiteman MK. Tepper NK. Lokkegaard EC. . 2014. Glasier A.121(19):3953–61. 2013. 2011. 2012. Sultan AA. Jackson E. Blood.117(3):691– 703.123(5):987–96.Part I | 37 References 1. West J. et al. Obstet Gynecol. Jackson E. 2011. Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy. 4. 5. Risk of venous thromboembolism during the postpartum period: a systematic review. Thromb Haemost. 2014. Bergholt T. Postpartum venous thromboembolism: incidence and risk factors. Navi BB. Obstet Gynecol. Gaffield ME. Kamel H. Obstet Gynecol. Fiaschi L. Hovsepian DA. Br J Haematol.112(1):73–8. Tata LJ. Risk of first venous thromboembolism in and around pregnancy: a population-based cohort study. Nelson-Piercy C. Monsour M. Hooper WC. Sultan AA. 2. Elkind MS. Return of ovulation and menses in postpartum nonlactating women: a systematic review. West J. Sriram N.117(3):657–62. N Engl J Med.

studies and case-control studies Population Women with SVT Summary of the evidence Intervention Use of CHCs One study suggested that among women with varicose veins. however. contraceptive evidence) formulations and outcome measures. a meta-analysis was Selection criteria for the systematic review not performed. but are not Comparator Non-use of CHCs used as widely by national programmes as male condoms. generally use combined hormonal contraceptives (combined The subcondition “superficial thrombophlebitis” has been oral contraceptives. All women have the Databases searched PubMed and Cochrane Library right to evidence-based. cohort (STIs). Female condoms are effective and safe. choices are thromboembolism (VTE) compared with non-use of CHCs? complex. statistical significance was not reported and the number of events was small (1). Decision- (Direct evidence) making for contraceptive methods usually requires the need to make trade-offs among the different methods. If there is a risk of STI/HIV.38 | Medical eligibility criteria for contraceptive use . education and counselling to ensure informed Question 2: Among women with superficial venous choice. Study design Randomized controlled trials. The overall name of the •• Women with superficial venous thrombosis (SVT) can condition has been changed to “superficial venous disorders”. combined contraceptive patch. The disease nomenclature has been updated to reflect current combined injectable contraceptives) without restriction recognized standard terminology and more accurately describe (MEC Category 1). changed to “superficial venous thrombosis” (SVT). SVT may be associated Question 1: Among women with varicose veins. the correct studies and case-control studies and consistent use of condoms is recommended. the condition and sub-conditions. does use with an increased risk of venous thromboembolism (VTE). combined contraceptive vaginal ring.Part I 4. with Selection criteria for the systematic review advantages and disadvantages of specific contraceptive methods varying according to individual circumstances. multifactorial and subject to change. including HIV. One Databases searched PubMed and Cochrane Library study demonstrated that among women with SVT. combined contraceptive vaginal ring. comprehensive contraceptive information. Recommendations for combined hormonal Recommendations contraceptives among women with superficial •• Women with varicose veins can use combined hormonal venous disorders contraceptives (combined oral contraceptives. Women’s contraceptive choices are made in a thrombosis (SVT). Comparator Non-use of CHCs the rate of VTE and SVT was higher in oral contraceptive users Outcome VTE compared with non-users. cohort perceptions and interpretations. When Population Women with varicose veins used correctly and consistently. including Intervention Use of CHCs HIV. the risk of VTE was higher in oral contraceptive users compared with non-users (2). of combined hormonal contraceptives (CHCs) increase the risk of venous thromboembolism (VTE) or superficial venous Remarks thrombosis (SVT) compared with non-use of CHCs? (Direct •• Due to heterogeneity of study designs. . societal and cultural context. does use of combined hormonal contraceptives (CHCs) increase the risk of venous particular time. Outcome VTE or SVT •• Voluntary use of contraception by women is critical for upholding their reproductive rights. •• CHCs do not protect against sexually transmitted infections Study design Randomized controlled trials. combined contraceptive patch. combined injectable contraceptives) (MEC Category 2). condoms offer one of the most effective methods of protection against STIs.

Medical eligibility criteria for contraceptive use . very low risk of SVT: Women with superficial venous thrombosis: (intervention versus comparator. outcome) Use of CHCs versus non-use of CHCs. risk very low of VTE: .Part I | 39 Quality of the evidence Women with varicose veins: (intervention versus comparator. very low risk of VTE: Use of CHCs versus non-use of CHCs. outcome) Use of CHCs versus non-use of CHCs.

5–119.5) for no OC use and 43.97 in women with history of thrombosis (96 335 women-years) limitations (1 fair) (1 study) imprecision varicose veins. DVT + PE. a Adjusted for age. OR: odds ratio. does use of combined hormonal contraceptives (CHCs) increase the risk of venous thromboembolism (VTE) or superficial venous thrombosis (SVT) compared with non-use of CHCs? (Direct evidence) Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect participants) Use of oral contraceptives vs non-use in women with varicose veins Deep vein 1 cohort study Serious Cannot determine Serious No indirectness None Very low IRR 5. similar pattern observed for DVT.40 in women with history of venous (96 335 women-years) limitations (1 fair) (1 study) imprecision varicose veins.0 (95% CI 15.0 (95% CI 3. BMI. OC: oral contraceptive.4 for OC use vs non-use with history of SVT (based on OR of 5.1 (95% CI 2. . 2. (VTE) OR 8. does use of combined hormonal contraceptives (CHCs) increase the risk of venous thromboembolism (VTE) compared with non-use of CHCs? (Direct evidence) Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect participants) Use of oral contraceptives vs non-use in women with superficial venous thrombosis Venous 1 case-control study Serious Cannot determine Serious No indirectness None Very low OR 4.8–9.42 in women with no (DVT) history of varicose veins Superficial 1 cohort Serious Cannot determine Serious No indirectness None Very low IRR 1.Part I IRR: incidence rate ratio.3–4.7) for OC use thromboembolism (1445 cases) limitations (1 fair) (1 study) imprecision vs non-use with no history of SVT. and PE.3) OC use.GRADE table 1 (Question 1): Among women with varicose veins. 4. smoking and family history of VTE. GRADE table 2 (Question 2): Among women with superficial venous thrombosis (SVT).45 in women with no thrombosis history of varicose veins (SVT) 40 | Medical eligibility criteria for contraceptive use . reference no SVT history/no OC use)a CI: confidence interval.

. J R Coll Gen Pract. Blood. 1978. Roach RE. Rosendaal FR. Cannegieter SC. 2. The risk of venous thrombosis in individuals with a history of superficial vein thrombosis and acquired venous thrombotic risk factors. Lijfering WM. Medical eligibility criteria for contraceptive use . Oral contraceptives. and varicose veins.122(26):4264–9. Helmerhorst FM. venous thrombosis. Royal College of General Practitioners’ Oral Contraception Study.Part I | 41 References 1. van Hylckama Vlieg A. 2013.28(192):393–9.

as well (Indirect evidence) as decreased levels of high-density lipoprotein (HDL). “known hyperlipidaemias”. cohort (VTE) or pancreatitis compared with no CHC use? (Direct and case-control studies evidence) Population Women of reproductive age with dyslipidaemia Selection criteria for the systematic review Intervention CHC use Study design Randomized controlled trials. •• The GDG noted that the baseline absolute risk for cardiovascular disease among women of reproductive age is very low. combined injectable Question 2: Among women of reproductive age using contraceptives) (MEC Category 2). Recommendations for combined hormonal Question 3: Among women with known dyslipidaemias contraceptives among women with without other known cardiovascular risk factors. Population Women of reproductive age with increase in total cholesterol. decrease in HDL) Intervention CHC use Databases searched PubMed and Cochrane Library Comparator Non-use of CHCs Recommendations Outcome Arterial thrombotic events (e. They also specified that the condition should Outcome ATE or VTE or pancreatitis include only women “without other known cardiovascular Databases searched PubMed and Cochrane Library risk factors” for better clarity. does combined hormonal contraceptive (CHC) use increase risk dyslipidaemias for worsening of lipid abnormalities compared with no CHC use? (Indirect evidence) Question 1: Among women with known dyslipidaemias. Using available cardiovascular risk prediction . combined contraceptive vaginal ring. known cardiovascular risk factors should be changed to “known dyslipidaemias” to better Comparator No known dyslipidaemia describe the spectrum of clinically important lipid abnormalities. Women Selection criteria for the systematic review with known severe genetic lipid disorders at much higher lifetime risk for cardiovascular disease may warrant further Study design Randomized controlled trials. are women with known dyslipidaemias without other known cardiovascular appropriate because of the rarity of the conditions and the risk factors at increased risk for ATE.Part I 5.42 | Medical eligibility criteria for contraceptive use . VTE or pancreatitis known cardiovascular risk factors can generally use combined hormonal contraceptive methods (combined Databases searched PubMed and Cochrane Library oral contraceptives. VTE or pancreatitis high cost of screening. combined contraceptive patch. cohort Comparator Non-use of CHCs and case-control studies Outcome Worsening of lipid abnormalities (e. venous thromboembolism Study design Randomized controlled trials. does combined hormonal contraceptive (CHC) use increase risk of arterial thromboembolism (ATE). compared to women without known dyslipidaemias? low-density lipoprotein (LDL) and triglycerides. are known risk factors for cardiovascular disease.g. myocardial infarction or thrombotic •• Women with known dyslipidaemias without other stroke). Selection criteria for the systematic review without other known cardiovascular risk factors. cohort clinical consideration. Increased levels of total cholesterol. Routine screening is not combined hormonal contraception (CHC). LDL or dyslipidaemia triglycerides.g. and case-control studies Population Women of reproductive age using Remarks CHCs •• The Guideline Development Group (GDG) determined that Intervention Known dyslipidaemia without other the existing condition name.

Decision- fatal myocardial infarction (MI) or stroke. 10-year risks upholding their reproductive rights. it methods varying according to individual circumstances. and while it is well no known dylipidaemia. and indirect evidence from one study identified in our systematic review noted only a slight CHC use versus non-use of very low increased risk for VTE among COC users with the condition CHCs. ATE. Independent of COC use. including HIV. choices are levels greater than 280 mg/dL has < 1% 10-year risk for complex. a meta-analysis was not performed. established that elevated triglyceride levels are associated VTE or pancreatitis (indirect): with acute pancreatitis. risk of lipid approximately 5%. societal and cultural context. All women have the for cardiovascular disease remain low. predict that a choice. very low with triglyceride levels ≥ 1000 mg/dL estimated at use of CHC.9% 10-year advantages and disadvantages of specific contraceptive risk for a non-fatal or fatal first MI or stroke. recent making for contraceptive methods usually requires the guidelines released by the American College of Cardiology need to make trade-offs among the different methods. was concluded that even if combined oral contraceptive perceptions and interpretations. No comparative (direct): data were available to assess the risk of pancreatitis among Know dyslipidaemia versus very low women with known dyslipidaemias. dyslipidaemia (3). including HIV. Further. One retrospective women with severe genetic lipid disorders may warrant cohort study suggested an increased risk for stroke and further clinical consideration given that these women are at VTE among COC users with dyslipidaemia compared to COC much higher lifetime risk for cardiovascular disease. Female condoms are effective and safe. One case-control study suggested an increased risk for MI among COC users with hypercholesterolemia compared to •• Use of combined hormonal contraception (CHC) among non-users without hypercholesterolemia (1). (COC) use increases risk for MI or stroke among women of reproductive age with known dyslipidaemias and no other Summary of the evidence risk factors for cardiovascular disease. education and counselling to ensure informed Society of Cardiology. users without dyslipidaemia (2). Medical eligibility criteria for contraceptive use .Part I | 43 models. published in 2012. comprehensive contraceptive guidelines from the Fifth Joint Task Force of the European information. even among healthy perimenopausal women •• Voluntary use of contraception by women is critical for with high total cholesterol and normal HDL. One prospective cohort •• The GDG determined that risk for arterial thrombotic events study suggested no worsening of lipid abnormalities among was the main safety concern for women with known CHC users with dyslipidaemia compared to non-users with dyslipidaemias without other cardiovascular risk factors. Women’s contraceptive choices are made in a healthy woman aged 45–49 years with total cholesterol particular time. When used correctly and consistently. multifactorial and subject to change. but are not used as widely by national programmes as male condoms. similarly. abnormalities (indirect): •• Due to heterogeneity of study designs. with and the American Heart Association predict a 1. severe hypertriglyceridemia is a very rare condition with a risk for pancreatitis associated CHC use versus non. contraceptive formulations and outcome measures. condoms offer one of the most effective methods of protection against STIs. . the absolute risk for these serious adverse events remains low. The most recent right to evidence-based. there does not appear to be a clear association between dyslipidaemia and risk for VTE among Quality of the evidence women of reproductive age. VTE or pancreatitis compared to users without the condition. ATE. •• CHCs do not protect against sexually transmitted infections (STIs). If there is a risk of STI/HIV. the correct and consistent use of condoms is recommended.

reference no COC use/no hyperlipidaemia CI: confidence interval. 44 | Medical eligibility criteria for contraceptive use .39 (95% CI 1. does combined hormonal contraceptive (CHC) use increase risk of arterial thromboembolism (ATE).6–108.14 per 10 000 woman-years. venous thromboembolism (VTE) or pancreatitis compared with no CHC use? (Direct evidence) Type and number Outcome of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Use of combined oral contraceptives (COCs) vs non-use in women with hyperlipidaemia Myocardial 1 case. are women with known dyslipidaemias without other known cardiovascular risk factors at increased risk for ATE.04–1.8) for no COC use/hyperlipidaemia.85) and pulmonary (1 poor) (not COC use vs embolism (PE) non-use) CI: confidence interval. Very serious Cannot determine Serious No indirectness None Very low OR 7.5) for COC use/ (248 cases) (1 poor) hyperlipidemia and 3. IRR: incidence rate ratio.7 (95% CI 5. VTE or pancreatitis compared to women without known dyslipidaemias? (Indirect evidence) Type and number Outcome of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Women with hyperlipidaemia vs no hyperlipidaemia prescribed combined oral contraceptives Deep vein 1 cohort study Very serious Cannot determine No serious Serious None Very low 8.6–6.3 (95% CI 1. based on infarction control study limitations (1 study) imprecision OR 24. IRR thrombosis (DVT) (n=329 995) limitations (1 study) imprecision indirectness 1.5 for COC use vs no COC use. . OR: odds ratio.51 vs 6.GRADE table 1 (Question 1): Among women with known dyslipidaemias without other known cardiovascular risk factors.Part I GRADE table 2 (Question 2): Among women of reproductive age using combined hormonal contraception (CHC).

Part I | 45 .76 (95% CI 1. Medical eligibility criteria for contraceptive use .76 per 10 000 woman years.14 vs 5. IRR: incidence rate ratio.GRADE table 3 (Question 3): Among women with known dyslipidaemias without other known cardiovascular risk factors. does combined hormonal contraception (CHC) use increase risk of worsening lipid abnormalities compared with no CHC use? (Indirect evidence) Type and number Outcome of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Worsening hyperlipidemia in users of combined oral contraceptives vs non-users Transient ischemic 1 cohort study Very serious Cannot determine No serious Serious indirectness None Very low 10.06) cerebrovascular (1 poor) non-use) accidents CI: confidence interval.51–2. attacks and (n=329 995) limitations (1 study) imprecision (not COC use vs IRR 1.

Tanis BC. 3. Cats VM.Part I References 1. 2001.46 | Medical eligibility criteria for contraceptive use . Lavi I. Rennert G. Grunwald K. et al.183(18):E1319-25.345(25):1787–93. 2. 1992. van den Bosch MA. N Engl J Med. Kemmeren JM. The efficacy and tolerability of norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol): results of an open. Helmerhorst FM. Algra A. 2011. multicenter study of 59.166(6 Pt 2):1963–8. . Runnebaum B. Oral contraceptives and the risk of myocardial infarction. Rabe T. Gronich N. Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study. Am J Obstet Gynecol.701 women. CMAJ.

injectables. There is theoretical concern about the potential exposure of the neonate Study design Randomized controlled trials. and access to services is limited. DMPA/NET-EN may be one of the few types of methods widely available and accessible to breastfeeding Comparator Non-use of POCs women immediately postpartum. Recommendations for progestogen-only 6a. Databases PubMed and Cochrane Library searched . progestogen-only Databases PubMed and Cochrane Library injectables (DMPA and NET-EN). head ≥ 4 weeks postpartum circumference. compared with those not using POCs? (Direct evidence) •• Breastfeeding women who are < 6 weeks postpartum generally should not use progestogen-only injectables Selection criteria for the systematic review (DMPA/NET-EN) (MEC Category 3). Recommendations for use of levonorgestrel- Selection criteria for the systematic review releasing intrauterine devices (LNG-IUDs) Study design Randomized controlled trials. use without restriction the following contraceptive methods: IUDs) initiated up to 6 weeks postpartum have an impact POPs. arm circumference or skin. arm circumference or skin-fold thickness). Question 2: Among breastfeeding women (and their infants). can generally use progestogen-only pills (POPs). infant growth (as measured ≥ 6 weeks to < 6 months postpartum by weight. cohort studies < 48 hours postpartum and case-control studies •• Breastfeeding women who are < 48 hours postpartum can Population Breastfeeding women and their infants generally use LNG-IUDs (MEC Category 2). length. infant •• Breastfeeding women who are 6 weeks to < 6 months health (as measured by illness and mortality). •• Breastfeeding (and non-breastfeeding) women can use an fold thickness). and does the use of progestogen-only contraceptives (POCs) and levonorgestrel (LNG) and etonogestrel (ETG) implants (MEC levonorgestrel-releasing intrauterine devices (LNG-IUDs) have an impact on breastfeeding or infant health outcomes Category 2). Intervention Use of POCs or LNG-IUDs initiated ≤ 6 weeks postpartum ≥ 48 hours to < 4 weeks postpartum Comparator Use of POCs or LNG-IUDs initiated > 6 •• Breastfeeding (and non-breastfeeding) women generally weeks postpartum should not have an LNG-IUD inserted from 48 hours to Outcome Breastfeeding continuation and exclusivity/ < 4 weeks postpartum (MEC Category 3). supplementation.Part I | 47 6. and LNG and ETG implants searched (MEC Category 1). cohort studies to DMPA/NET-EN during the first 6 weeks postpartum. progestogen-only injectables (DMPA and NET-EN). Outcome Breastfeeding continuation and exclusivity/ supplementation. ≥ 6 months postpartum does the use of progestogen-only contraceptives (POCs) •• Breastfeeding women who are ≥ 6 months postpartum can and levonorgestrel-releasing intrauterine devices (LNG. Recommendations for use of progestogen-only contraceptives and levonorgestrel-releasing contraceptives (pills. length. in many settings pregnancy-related morbidity and Population Breastfeeding women and their infants mortality risks are high. infant health (as measured LNG-IUD without restriction at ≥ 4 weeks postpartum (MEC by illness and mortality). Medical eligibility criteria for contraceptive use . on breastfeeding or infant health outcomes compared with and LNG and ETG implants (MEC Category 1). initiation after 6 weeks postpartum? (Direct evidence) 6b. implants) intrauterine devices among breastfeeding women < 6 weeks postpartum •• Breastfeeding women who are < 6 weeks postpartum Question 1: Among breastfeeding women (and their infants). In Intervention Use of POCs or LNG-IUDs such settings. infant development Category 1). infant growth (as measured by weight. head circumference. postpartum can use without restriction the following infant development contraceptive methods: POPs. and case-control studies However.

If there is a risk of STI/HIV. breastfeeding very low choice.Part I Puerperal sepsis relevant outcomes of infant growth. Use of supplementation: very low •• POCs do not protect against sexually transmitted infections (STIs). Available LNG-IUD was associated with decreased breastfeeding data from clinical and observational trials do not suggest duration compared with delayed insertion (5). education and counselling to ensure informed Breastfeeding continuation. comprehensive contraceptive information. breastfeeding low methods/formulations and outcome measures. the theoretical risks of progestogen-only injectables may outweigh the benefits. All women have the Progestogen-containing implants: right to evidence-based. duration: perceptions and interpretations.48 | Medical eligibility criteria for contraceptive use . When Progestogen-only injectables (DMPA/NET-EN): used correctly and consistently. breastfeeding duration. of life may be exposed to higher hormone levels with use of progestogen-only injectables. However. However. 28. as compared to the exposure Quality of the evidence using other methods of progestogen-only contraceptives < 6 weeks postpartum: (POCs). Progestogen-only pills (POPs): •• Due to heterogeneity of study designs. societal and cultural context. 7. as infants in the first 6 weeks breastfeeding outcomes (11. particularly in settings with Breastfeeding outcomes access to a wide variety of contraceptive methods. Decision- making for contraceptive methods usually requires the LNG-IUD: need to make trade-offs among the different methods. including HIV. Infant outcomes Summary of the evidence POPs: Forty-seven articles reporting on 45 different studies were Infant growth: very low identified in the systematic review that investigated the use of POCs in breastfeeding women and reported clinically . with advantages and disadvantages of specific contraceptive Breastfeeding continuation anxd breastfeeding very low methods varying according to individual circumstances. demonstrates no harmful effects on infant growth. 13. and generally Category 4). and use of particular time. multifactorial and subject to change. 16). health or breastfeeding •• Breastfeeding (and non-breastfeeding) women with performance. whether similar effects occur following One randomized trial found that immediate insertion of the progestogen exposure in humans is unclear (1–3). In other studies. Two other an increased risk for either breastfeeding performance randomized controlled trials assessing early versus delayed or infant health outcomes with use of progestogen-only initiation of POCs failed to show a difference in breastfeeding injectables compared to outcomes in studies using other outcomes (4. the Guideline 4 weeks postpartum demonstrated no detrimental effect on Development Group felt that. a meta- duration: analysis was not performed. Women’s contraceptive choices are made in a episodes. the correct and consistent use of condoms is recommended. Breastfeeding continuation: very low •• Voluntary use of contraception by women is critical for upholding their reproductive rights. condoms offer one of the most effective methods of protection against STIs. these studies have been Remarks inadequately designed to determine whether a risk of long- term effects exists. health or development (6. but are not used as widely by national programmes as male condoms. 42). including Breastfeeding duration and use of low supplementation: HIV. choices are supplementation: complex. 45). initiation of LNG-IUD after progestogen-only methods (4–8). Direct evidence demonstrates no effect of puerperal sepsis should not have an LNG-IUD inserted (MEC POCs on breastfeeding performance (4–51). contraceptive Breastfeeding continuation. Female condoms are effective and safe. •• Animal data suggest an effect of progesterone on the developing brain.

Medical eligibility criteria for contraceptive use .Part I | 49 Progestogen-only injectables (DMPA/NET-EN): Progestogen-only injectables (DMPA/NET-EN): Infant growth: low Infant growth: low Progestogen-containing implants: Progestogen-containing implants: Infant growth: low Infant growth: low LNG-IUD: LNG-IUD: Infant growth: very low Infant growth: very low ≥ 6 weeks postpartum: Breastfeeding outcomes POPs: Breastfeeding duration: low Breastfeeding continuation and use of very low supplementation: Progestogen-only injectables (DMPA/NET-EN): Breastfeeding duration: low Breastfeeding continuation and use of very low supplementation: Progestogen-containing implants: Breastfeeding duration and use of low supplementation: Breastfeeding continuation: very low LNG-IUD: Breastfeeding duration and use of very low supplementation: Infant outcomes POPs: Infant growth: low .

76–1. RR 0.3) at 8 weeks.41). length (P = 0. or head circumference (P = 0. RR 0.79) from weeks 2–8 LNG-IUD initiated at < 6 weeks postpartum vs non-hormonal contraception Breastfeeding 1 RCT (n=110) Very serious Cannot determine Serious No indirectness NA Very low LNG-UD (30 mcg/d or 10 mcg/d) vs Cu-IUD (1 RCT): continuation limitations (1 study) imprecision 58% vs 79% at 8 months.Part I 41% vs 44%.05) (1 poor) Infant growth 1 RCT (n=110) Very serious Cannot determine Serious No indirectness NA Very low LNG-IUD (30 mcg/d or 10 mcg/d) vs Cu-IUD (1 RCT): limitations (1 study) imprecision no differences through 12 months (1 poor) .74 (95% CI 0.94 (95% CI 0. RR 0. does the use of progestogen-only contraceptives (POCs) and levonorgestrel-releasing intrauterine devices (IUDs) have an impact on breastfeeding or infant health outcomes compared with those not using POCs? (Direct evidence) Question 2: Among breastfeeding women (and their infants). 50 | Medical eligibility criteria for contraceptive use .57–0.99 (95% CI 0.95) (1 poor) Breastfeeding 1 RCT (n=110) Very serious Cannot determine Serious No indirectness NA Very low LNG-IUD 30 mcg/d vs LNG IUD 10 mcg/d vs Cu-IUD duration limitations (1 study) imprecision (1 RCT): 197 vs 182 vs 208 days (P > 0. does the use of progestogen-only contraceptives (POCs) and levonorgestrel-releasing intrauterine devices (LNG-IUDs) initiated up to 6 weeks postpartum have an impact on breastfeeding or infant health outcomes compared with initiation after 6 weeks postpartum? (Direct evidence) Type and number Factor of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Progestogen-only pill (POP) vs combined oral contraceptive (COC) initiated at < 6 weeks postpartum Breastfeeding 1 RCT (n=127) Serious Cannot determine Serious No indirectness NA Low Norethindrone vs ethinyl estradiol (EE) COC (1 RCT): continuation limitations (1 fair) (1 study) imprecision 64% vs 64%.63–1.4) at 6 months Use of 1 RCT (n=127) Serious Cannot determine Serious No indirectness NA Low Norethindrone vs EE COC (1 RCT): no difference at supplementation limitations (1 fair) (1 study) imprecision 8 weeks (data not provided) Infant growth 1 RCT (n=127) Serious Cannot determine Serious No indirectness NA Low Norethindrone vs EE COC (1 RCT): no difference in limitations (1 fair) (1 study) imprecision percent change in weight (P = 0.56).GRADE table 1 (Question 1): Among breastfeeding women (and their infants).

Serious No serious No serious No indirectness Variability in Low None of 4 studies found various POPs associated continuation randomized limitations (1 fair.inconsistency imprecision interventions with lower likelihood of breastfeeding continuation. inconsistency imprecision or increased duration of breastfeeding vs non- (n=1732) 4 poor) hormonal methods Infant growth 6 cohort Very serious No serious No serious No indirectness None Low None of 5 studies found DMPA or NET-EN associated studies limitations inconsistency imprecision with decreased infant growth. quality cohort and 2 studies found POPs associated with higher likelihood 3 cohort study. 1 study found (n=4403) (5 poor) progestogen-only injectable associated with increased weight gain through 3 months POPs initiated at < 6 weeks postpartum vs non-hormonal Breastfeeding 1 non. in a 3rd study continuation studies limitations (1 fair. (1 study) imprecision interventions weaning occurred later with DMPA or NET-EN (n=617) 2 poor) and outcomesa Use of 5 cohort Very serious No serious No serious No indirectness Variability in Low All 5 studies found DMPA or NET-EN associated with supplementation studies limitations (1 fair. limitations inconsistency imprecision interventions at ≤ 14 hours postpartum (PP) vs placebo in randomized (2 poor) and breastfeeding initiation. inconsistency imprecision interventions similar or lower likelihood of exclusive breastfeeding (n=1370) 4 poor) and outcomesa Duration of 5 cohort Very serious No serious No serious No indirectness None Low All 5 studies found DMPA associated with no difference breastfeeding studies limitations (1 fair. 3 poor. Type and number Factor of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Progestogen-only injectable initiated at < 6 weeks postpartum vs non-hormonal Breastfeeding 3 cohort Very serious Cannot determine Serious No indirectness Variability in Very low No clear differences in 2 studies. outcomesa of breastfeeding continuation studies quality studies) (n=756) Breastfeeding 1 RCT (n=20) Very serious No serious Very serious No indirectness Variability in Very low 1 RCT found no difference between norethisterone initiation and 1 non.Part I | 51 . trial (n=273). 1 non-randomized trial found trial (n=20) outcomesa lynestrenol at 2 days PP associated with initiation of breastfeeding at 3 vs 5 days PP with placebo Medical eligibility criteria for contraceptive use .

inconsistency imprecision interventions of progestogen-containing implants on measures of (n=520) 2 poor) and breastfeeding continuation.Part I 1 non. 1 small.6 months PP) Infant growth 1 RCT (n=20). 1 poor-quality outcomesa study found LNG associated with somewhat later initiation of supplementation (5. outcomesa cohort studies quality studies) (n=1083) Progestogen-containing implants initiated at < 6 weeks postpartum vs non-hormonal Breastfeeding 3 cohort Very serious Serious Serious No indirectness Variability in Very low 3 studies reported conflicting findings regarding effects continuation studies limitations (1 fair. Type and number Factor of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Duration of 2 cohort Very serious No serious Serious No indirectness Variability in Low 2 studies found POPs associated with somewhat breastfeeding studies limitations inconsistency imprecision interventions longer duration of breastfeeding vs non-hormonal (n=572) (2 poor) and comparators outcomesa Use of 2 cohort Very serious Serious No serious No indirectness Variability in Very low 1 fair-quality study found norgestrel associated with supplementation studies limitations (1 fair. non-randomized study randomized quality cohort and found greater increase with lynestrenol than placebo trial (n=20).4 vs 4.inconsistency imprecision interventions growth. 3 studies. the 1 fair-quality study outcomesa found no difference between nomegestrol implant in 2nd month PP vs Cu-IUD Breastfeeding 2 cohort Very serious No serious Serious No indirectness Variability in Very low 2 studies found no differences in breastfeeding episodes studies limitations (1 fair. limitations (2 fair. Serious No serious No serious No indirectness Variability in Very low 4 studies found no difference on measures of infant 52 | Medical eligibility criteria for contraceptive use . inconsistency imprecision interventions frequency (n=392) 1 poor) and outcomesa Duration of 1 cohort study Serious Cannot determine Very serious No indirectness None Very low 1 fair-quality cohort study found no difference between breastfeeding (n=80) limitations (1 fair) (1 study) imprecision etonogestrel (ETG) implant at 28–56 days PP vs Cu-IUD in duration of breastfeeding . 3 poor. poor-quality. inconsistency imprecision interventions more frequent supplementary feeding but no difference (n=1000) 1 poor) and in proportion of women supplementing.

Type and number Factor of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Use of 3 cohort Very serious Serious Serious No indirectness Variability in Very low 2 studies found no difference in use of supplementation studies limitations (1 fair. inconsistency imprecision interventions difference in measures of infant growth. 1 poor-quality study found no difference between progesterone pellets at 30 or 60 days vs Cu-IUD or placebo injection in breastfeeding rates Use of 2 cohort Very serious No serious Serious No indirectness None Very low 2 studies found no differences in use of supplementation studies limitations (1 fair. 1 poor-quality study found LNG outcomesa associated with slower weight gain than Cu-IUD or barrier/no method Multiple progestogen-only methods initiated at < 6 weeks postpartum vs non-hormonal Breastfeeding 1 cohort study Very serious Cannot determine Serious No indirectness None Very low 1 study found no difference between LNG implant or continuation (n=319) limitations (1 study) imprecision POP prior to discharge vs non-hormonal contraception (1 poor) in breastfeeding continuation at 2–6 weeks PP Use of 1 cohort study Very serious Cannot determine Serious No indirectness None Very low 1 study found no difference between LNG implant or supplementation (n=319) limitations (1 study) imprecision POP prior to discharge vs non-hormonal contraception (1 poor) in use of supplementation at 2–6 weeks PP Non-orally available progesterone initiated at < 6 weeks postpartum vs non-hormonal Breastfeeding 2 cohort Very serious Serious Serious No indirectness None Very low 1 fair-quality study found progesterone pellets at continuation studies limitations (1 fair. 1 study found norethindrone (n=430) 2 poor) and associated with increased likelihood of outcomesa supplementation at 3 months Infant growth 6 cohort Serious No serious No serious No indirectness Variability in Low 2 fair-quality and 2 poor-quality studies found no studies limitations (2 fair.Part I | 53 . 1 poor- (n=870) 4 poor) and quality study found LNG associated with more weight assessment of gain than Cu-IUD. inconsistency imprecision 30–35 days PP associated with decreased likelihood (n=1092) 1 poor) of breastfeeding at 6 months (51% vs 58%) and 12 months (11% vs 18%). inconsistency imprecision supplementation (n=1092) 1 poor) Medical eligibility criteria for contraceptive use . inconsistency imprecision interventions supplementation.

inconsistency imprecision (n=1092) 1 poor) LNG-IUD initiated at > 6 weeks postpartum vs non-hormonal Duration of 1 RCT (n=320) Serious Cannot determine Serious No indirectness None Very low LNG-IUD at 6–8 weeks PP vs Cu-IUD (1 RCT): 149 vs breastfeeding limitations (1 fair) (1 study) imprecision 160 days Use of 1 RCT (n=320) Serious Cannot determine Serious No indirectness None Very low LNG-IUD at 6–8 weeks PP vs Cu-IUD (1 RCT): supplementation limitations (1 fair) (1 study) imprecision no difference in exclusive breastfeeding Infant growth 1 RCT (n=320) Serious Cannot determine Serious No indirectness None Very low LNG-IUD at 6–8 weeks PP vs Cu-IUD (1 RCT): 54 | Medical eligibility criteria for contraceptive use . 2 studies reported some findings 2 cohort quality cohort suggesting greater weight gain studies study. 2 poor- (n=1750) quality studies) . Type and number Factor of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Infant growth 2 cohort Very serious No serious Serious No indirectness None Very low 2 studies found no differences in infant growth studies limitations (1 fair. limitations (2 inconsistency imprecision supplementation 1 cohort study poor) (n=212) Infant growth 1 RCT Very serious No serious No serious No indirectness Variability in Low None of 3 studies found decreased infant growth with (n=170).Part I limitations (1 fair) (1 study) imprecision no difference in infant growth Progestogen-only injectable initiated at > 6 weeks postpartum vs non-hormonal Breastfeeding 1 RCT Very serious Cannot determine Serious No indirectness None Very low DMPA at 6 weeks PP vs non-hormonal (1 RCT): continuation (n=170) limitations (1 study) imprecision no difference in rates of discontinuation (1 poor) Duration of 1 cohort study Serious Cannot determine No serious No indirectness None Low DMPA or NET-EN at 6–8 weeks PP vs non-hormonal breastfeeding (n=1538) limitations (1 fair) (1 study) imprecision contraception (1 cohort study): no difference in duration of breastfeeding Use of 1 RCT Very serious No serious Serious No indirectness None Very low 2 studies found no differences in use of supplementation (n=170). limitations (1 fair.inconsistency imprecision outcomesa DMPA or NET-EN.

limitations inconsistency imprecision interventions and 1 non-randomized trial found lower mean age at 1 non. Type and number Factor of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) POP initiated at > 6 weeks postpartum vs non-hormonal Breastfeeding 1 RCT (n=144) Very serious Cannot determine Very serious No indirectness None Very low Norgestrel at 6 weeks PP vs non-hormonal continuation limitations (1 study) imprecision contraception (1 RCT): no difference in discontinuation (1 poor) of breastfeeding Duration of 2 cohort Serious No serious No serious No indirectness Variability in Low 2 studies found no difference in breastfeeding duration breastfeeding studies limitations (2 fair) inconsistency imprecision interventionsa (n=1709) Use of 1 RCT Very serious Serious No serious No indirectness Variability in Very low 1 RCT found no difference in use of supplementation supplementation (n=144). quality cohort and randomized studies. 2 poor. outcomesa studies quality studies) (n=1829) Progestogen-only implant or progestogen-containing IUD initiated at > 6 weeks postpartum vs non-hormonal Breastfeeding 2 cohort Very serious No serious Very serious No indirectness None Very low 2 studies found no difference in breastfeeding rates continuation studies (n=57) limitations inconsistency imprecision (2 poor) Breastfeeding 4 cohort Serious No serious No serious No indirectness Variability in Low 4 studies found no difference in breastfeeding duration duration studies limitations (4 fair) inconsistency imprecision outcomesa (n=2329) Medical eligibility criteria for contraceptive use .Part I | 55 .inconsistency imprecision interventions growth 3 non. limitations (2 fair. (2 poor) and supplementation with lynestrenol vs IUD + placebo randomized outcomesa (11 vs 15 weeks. P not reported) trial (n=120) Infant growth 1 RCT Serious No serious No serious No indirectness Variability in Low 4 studies found no difference in measures of infant (n=144).

inconsistency imprecision interventions growth (n=2386) 2 poor) and outcomesa Multiple progestogen-only methods initiated at > 6 weeks postpartum vs non-hormonal 56 | Medical eligibility criteria for contraceptive use . Type and number Factor of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Use of 3 cohort Serious No serious Serious No indirectness Variability in Low 3 studies found no difference in use of supplementation studies limitations (2 fair. inconsistency imprecision interventions growth (n=988) 1 poor) and outcomesa .Part I Breastfeeding 1 cohort study Very serious Cannot determine Very serious No indirectness None Very low DMPA.38) (1 poor) Infant growth 1 cohort study Very serious Cannot determine Very serious No indirectness None Very low DMPA at 6 weeks PP vs non-hormonal contraception (n=140) limitations (1 study) imprecision (1 cohort study): no difference in weight through (1 poor) 26 weeks PP Non-orally available progesterone initiated at > 6 weeks postpartum vs non-hormonal Breastfeeding 2 cohort Very serious No serious No serious No indirectness Variability in Very low 1 fair-quality study found elcometrine implant continuation studies limitations (1 fair. inconsistency imprecision interventionsa associated with higher breastfeeding rate at 3 and (n=788) 1 poor) 5 months (but not at 9 and 12 months). inconsistency imprecision interventions supplementation (n=549) 1 poor) and outcomesa Infant growth 6 cohort Serious No serious No serious No indirectness Variability in Low 6 studies found no difference in measures of infant studies limitations (4 fair. 1 poor-quality study found no difference between progesterone pellets vs Cu-IUD or placebo at 6 or 13 months PP Breastfeeding 1 cohort study Serious Cannot determine Serious No indirectness None Very low Nesterone implant at 55–60 days PP vs Cu-IUD duration (n=200) limitations (1 fair) (1 study) imprecision (1 cohort study): 273 vs 263 days (NS) Infant growth 3 cohort Serious No serious No serious No indirectness Variabilty in Low 3 studies found no differences in measures of infant studies limitations (2 fair. POP or LNG-IUD vs non-hormonal contraception duration (n=34) limitations (1 study) imprecision (1 cohort study): 183 vs 183 days (P =0.

1 cohort study (n=35) RCTs. Cu-IUD: copper-bearing intrauterine device.06) Use of 3 RCTs Serious Serious No serious No indirectness Variability in Very low Inconsistent effects on use of supplementation among supplementation (n=205) and limitations inconsistency imprecision interventions 7 studies 4 cohort (3 fair-quality and studies RCTs. 1 RCT study) found no difference in rate of lactation failure Breastfeeding 1 RCT (n=96) Serious Not applicable 1 Very serious No indirectness None Very low Immediate LNG-IUD vs 6–8 weeks PP (1 RCT): 5 vs duration limitations (1 fair) study) imprecision 8. POP: progestogen-only pill. NA: not applicable. LNG-IUD: levonorgestrel intrauterine device. P = 0. a Refers to variability in the progestogen evaluated.02). 1 poor. EE: ethinyl estradiol.and outcomesa (n=660) 3 poor-quality cohort studies) Infant growth 1 RCT (n=40) Very serious No serious Serious No indirectness Variability in Low 4 studies found no differences in measures of infant and 3 cohort limitations (1 fair. Medical eligibility criteria for contraceptive use . NS: not significant.5 weeks (P=0.Part I | 57 . timing of initiation of POC. outcome measures assessed. COC: combined oral contraceptive. RR: relative risk. RCT: randomized controlled trial. and/or timing of outcome assessment. Type and number Factor of studies Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Earlier vs later initiation of progestogen-only methods Breastfeeding 2 RCTs Serious No serious Serious No indirectness Variabilty in Low 1 RCT found immediate LNG-IUD associated with continuation (n=165) and limitations inconsistency imprecision interventions lower breastfeeding rate at 6 months vs initiation at 1 cohort study (2 fair-quality and 6–8 weeks PP (6% vs 24%. outcomesa found norethindrone implant at 6 days PP associated quality cohort with lower rate at 8 months (57% vs 67%). and (n=543) 3 poor-quality outcomesa cohort studies) CI: confidence interval. PP: postpartum. 1 fair.inconsistency imprecision interventions growth studies quality RCT.

Provera during pregnancy or lactation. Effect of hormonal 23. Int J Gynaecol Obstet. Some effects of depo-medroxyprogesterone acetate (DMPA): observations in the nursing infant 18. Effects of contraceptives during breastfeeding on infant’s milk progestogen-only contraceptives on breast-feeding and ingestion and growth. Infant growth. Krupa FG. Effect of 1971. 1976. Clinical. II. Salem HS. on the serum levels of immunoglobulins of 1994. Shaaban MM. Progestin-only contraception 1. Br Med J. Pfau JL. Adv Contracept. 9. on lactation. Singh R. Ostrom K. Wagner CK. 2011. Fernandez ID. Reyes MV. NORPLANT. C osta ML. Jones KP. Obstet Gynecol. Pardthaisong T. Munoz G. J Hum Lact. BJOG. A ffandi B. Murphy PA. 11. 2008. 1999. infant growth. Contraception. Modesto W. Quintana SM. 1992. 2006. 1986. Hefnawi F. el-Mahgoub S. A. A bdulla KA. Leeman L. . et al.74(2):203–5. Sigurdardottir K. Z anartu J. Shoukry M. Gonzalez GB. Bahamondes MV. Silva de S· MF. Espey E.16(4):339–50. 7. agner CK. 1977. 2012. Prihartono J. during lactation. Gottfredsdottir H. 24. uniplant. progesterone receptor immunoreactivity in the fetal and Contraception. Fisher SG. 2012. Creinin MD. Fertil Steril. Zepeda A. Gibson implant during the immediate postpartum period: a pilot M. et al. Lactogenesis after early postpartum use of study. 4. Howard CR. Contraception. Lubis F.504(1):42– 14. Joyce DN.105(3):324–34.85(4):374–80. of nomegestrol acetate subdermal contraceptive implant. Peliowsky H. Research Training in Human Reproduction. Safety of the etonogestrel-releasing 16. neonatal rat forebrain. Karmadibrata S. el-Saeed M.45(4):313–24. 22.28(1):45. Cecatti JG. development: a gap between bench and bedside? Schrader R. and experimental studies Contraception. 12. a long-acting contraceptive progestogen on lactation.149(6):2743–9. Brito MB.100(2):445-50. Pinto e Silva JL.47(2):174–6. Rehder PM. Aguilera E.87(6):836– an intrauterine contraceptive device in lactating women. el-Ganzoury B. Postplacental or delayed levonorgestrel intrauterine 17. 19. Lawrence RA. B jarnadottir RI.27(3):340–59. Ferriani RA. Ternullo SR. Abol-Oyoun el SM. Tothill AU. Abdou I.Part I References 13. Development and of early postpartum use of the contraceptive implants. Dahlberg K. Sousa MH. 2011. 8. A bdel-Aleem H. Vieira CS. Determinants M of exclusive breastfeeding in a cohort of primiparous 20. The use 54. Campino C. K arim M. Int J Gynaecol Obstet.84(5):499–504 .32(3):261–6. Makhlouf A. Obstet Gynecol. 1996. 2012. The many faces of progesterone: a role in W vaginal rings do not affect maternal bone turnover and adult and developing male brain. Kamal I. Shaaban MM. 10. P rogestogen-only contraceptives during lactation: I. B ahamondes L.80(6):519–26. et al. B aheiraei A. M cEwan JA. Lopez JM.50(1):35-53. Reeves MF. the contraceptive implant: a randomized controlled trial. et al. Am J Obstet Gynecol. growth and development of children exposed to Depo- 1982. Chen BA. 43.14(10):2499–505. Injected progestogen and lactation. Schwarz EB.58 | Medical eligibility criteria for contraceptive use . J Comp Neurol. Dewey KG. 21. Ogburn T. Effect of Norplant on mothers and infants in the postpartum period. 5. Younis N. 3.54(5):281–6. periurban peruvian mothers. Stoddard G. 2001. 2013. Magalhaes A. Clinical effects of gestagens on lactation. Comparative study of the effects postpartum depot medroxyprogesterone on early of a progestogen-only pill containing desogestrel and breastfeeding cessation. biochemical.119(1):5-13. D iaz S. Norplant((R)) implants and progesterone 2. Yazlle ME. Fikri F. Talaat M. uadros PS. Effect of progestin compared with combined Endocrinology. Contraception. Early experience in contraception with a new progestogen. Distribution of Q prevents bone loss in postpartum breastfeeding women.20(1):43–8.108(11):1174–80. Front Neuroendocrinol. 1969. 6. Tagui device insertion and breast-feeding duration. atias SL. Ammar R. Contraception. The long-term and in the long-term user. 56. Hum Reprod. et al. Obstet Gynecol. 2007.2(4):371–80. density during lactation and after weaning.1(5742):200–3. Contraception. Ardsetani N. B rownell EA. Costa-Paiva L. Progesterone receptors and neural 15. 2009. the mothers and their breastfed infants. The effect of immediate Geirsson RT. 1985. Nommsen-Rivers LA. Dieben TO. World Health Organization Task force for Epidemiological Research on Reproductive Health. Wagner CK. Gray R.117(5):1114–21. Effect Special Programme of Research. 2001. 2013. Samil Contraception. oral contraceptive pills on lactation: a randomized controlled trial. Elwan SI. Turok DK. Contraception. Hawkins DF. RS. G urtcheff SE. Tilley IB. Ghazizadeh S. Yenchit C. Ghoneim M.

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changes in weight. Recommendations for safety of depot Question 2: Among healthy women or among a general medroxyprogesterone acetate delivered population of women of reproductive age. ectopic pregnancy or method discontinuation due to Recommendations a medical condition) or outcomes related to Age: medical conditions (i. contraceptive efficacy. Population Women of reproductive age using DMPA-SC Intervention Presence of medical condition or specific HIV: characteristics •• Women living with HIV who have asymptomatic or mild Comparator No medical condition or specific clinical disease (WHO stage 1 or 2) can use DMPA without characteristic restriction (MEC Category 1). B. blood pressure. changes in bone DMPA (MEC Category 2). .65 subcutaneously mL) delivered subcutaneously (DMPA-SC) have an increased risk for serious adverse events or other relevant Question 1: What is the safety of depot medroxyprogesterone outcomes compared with those who use DMPA delivered acetate (104 mg/0.65 mL) delivered subcutaneously intramuscularly (DMPA-IM)? (Indirect evidence) (DMPA-SC) for women with medical conditions or other Selection criteria for the systematic review specific characteristics established within the World Health Organization’s eligibility criteria for contraceptive use? (Direct evidence) Study design Randomized controlled trials. Medical eligibility criteria for contraceptive use . cohort studies and case-control studies •• Women with endometriosis can use DMPA without restriction (MEC Category 1). Outcome Serious adverse events (i. Selection criteria for the systematic review Endometriosis: Study design Randomized controlled trials. changes in •• Women living with HIV who have severe or advanced HIV weight. Selection criteria for the systematic review Population Healthy women or general population of reproductive-age women Study design Randomized controlled trials.e. cohort studies and case-control studies Intervention Use of DMPA-SC Population Women of reproductive age with medical Comparator Users of DMPA-IM conditions or other specific characteristics Outcome Serious adverse events or outcomes relevant Intervention Use of DMPA-SC to medical conditions (i. •• Young women (menarche to < 18 years) can generally use contraceptive efficacy. mineral density) •• Women between the ages of 18 and 45 years can use Databases PubMed and Cochrane Library DMPA without restriction (MEC Category 1) searched •• Women > 45 years old can generally use DMPA (MEC Category 2). do those who use depot medroxyprogesterone acetate (104 mg/0. Databases PubMed and Cochrane Library searched Obesity: •• Women with a body mass index (BMI) ≥ 30 kg/m2 can use DMPA without restriction (MEC Category 1).e. cohort studies and case-control studies A. changes in clinical disease (WHO stage 3 or 4) can use DMPA without bone mineral density) restriction (MEC Category 1).e.Part I | 61 7. changes in weight. Comparator Users of DMPA-intramuscular (DMPA-IM). vaginal bleeding) for endometriosis included non-comparative Databases PubMed and Cochrane Library prospective data searched Outcome Serious adverse events (i.e.

7–12). If there is a risk of STI/ HIV. with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances. but are not used as widely by national DMPA-SC and HIV: very low programmes as male condoms. complex.62 | Medical eligibility criteria for contraceptive use . weight change. bleeding patterns and other adverse effects. effects on serum estradiol levels and high suggests a similar safety profile. change to the existing recommendations for DMPA was warranted with inclusion of DMPA-SC as a new method. effects have been reported among healthy reproductive age •• DMPA-SC does not protect against sexually transmitted users (1. All women have the DMPA-SC versus DMPA. When used correctly and consistently. including HIV. and decreases in BMD.Part I •• Young women (menarche to < 18 years) with a BMI ≥ 30 DMPA-SC for six months experienced minimal weight gain kg/m2 can generally use DMPA (MEC Category 2). including HIV. serious adverse events were rare •• There is evidence for differential weight gain among and DMPA-SC improved pain symptoms associated with the normal-weight and obese adolescents who use DMPA. from three Phase 3 contraceptive trials and four reports from a small prospective cohort study reported similar contraceptive Remarks efficacy. the correct and consistent use of condoms is Quality of the evidence recommended. condoms offer one of the most effective methods of DMPA-SC and age: very low protection against STIs. contraceptive very low right to evidence-based. Two prospective. bleeding patterns and experience of other adverse not performed. education and counselling to ensure informed DMPA-SC versus DMPA. Evidence density among adolescents. Limited evidence from three Phase 3 contraceptive trials reported no consistent differences in weight change or bleeding patterns according to age. Female condoms are DMPA-SC and endometriosis: very low effective and safe. DMPA-IM and DMPA-SC appear to be therapeutically •• The body of evidence evaluating use of DMPA-SC and equivalent. 3. Due to heterogeneity of contraceptive efficacy (1). infections (STIs). a meta-analysis was change. In addition. similar effects on weight study designs and outcome measures. Women’s contraceptive choices are made in a (indirect): particular time. condition (4. changes in very low. non-comparative studies demonstrated that women with endometriosis treated with . the two formulations demonstrate similar DMPA-IM among healthy women of reproductive age pharmacokinetics. multifactorial and subject to change. 13). adolescents aged < 18 years were not included in any studies (1–3). including variations in a number of biomarkers. comprehensive contraceptive efficacy (indirect): information. NET-EN is MEC Category 2 due to evidence that experiences of serious adverse events were rare and regarding potential effects of NET-EN on bone mineral occurred at similar rates as in users of DMPA-IM (6). women living with HIV tolerated injection of DMPA-SC and However. among •• The Guideline Development Group determined that no obese and non-obese DMPA-SC users (1. weight gain very low choice. Summary of the evidence A randomized trial evaluating changes in bone mineral density (BMD) among adult DMPA-SC and IM users demonstrated no differences at two years of follow-up (1). 5). societal and cultural context. Decision- bleeding pattern (indirect): making for contraceptive methods usually requires the need to make trade-offs among the different methods. DMPA-SC and obesity: very low •• Voluntary use of contraception by women is critical for upholding their reproductive rights. A randomized cross-over study reported that but not those using norethisterone enanthate (NET-EN). choices are DMPA-SC versus DMPA. perceptions and interpretations. 3.

GRADE table 1 (Question 1): What is the safety of depot medroxyprogesterone acetate (104 mg/0.Part I | 63 .65 mL) delivered subcutaneously (DMPA-SC) for women with medical conditions or other specific characteristics established within the World Health Organization’s eligibility criteria for contraceptive use? (Direct evidence) Type and number of studies Outcome Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) DMPA-SC use in women in different BMI categories Contraceptive 1 RCT and Serious limitations No serious No serious No indirectness None Very low No pregnancies in women in all BMI efficacy 1 cohort from an (2 fair) inconsistency imprecision categories RCT (n=2321) Weight gain 2 non-randomized Serious limitations No serious No serious No indirectness None Very low No differences in weight gain across studies (n=2336) (1 fair-quality and inconsistency imprecision BMI categories 1 poor) Changes 1 study with Serious limitations Cannot determine No serious No indirectness None Very low No differences in bleeding patterns in bleeding pooled data (1 fair) (1 study) imprecision across BMI categories patterns from 3 studies (n=2321) Change in bone 1 cohort study Very serious Cannot determine Very serious No indirectness None Very low No differences in BMD changes mineral density (n=15) limitations (1 poor) (1 study) imprecision across BMI categories DMPA-SC use in women in different age groups Weight gain 1 study with Serious limitations Cannot determine No serious No indirectness None Very low No differences in weight gain across pooled data (1 fair) (1 study) imprecision age categories from 3 studies (n=2321) Changes 1 study with Serious limitations Cannot determine No serious No indirectness None Very low No differences in bleeding patterns in bleeding pooled data (1 fair) (1 study) imprecision across age categories patterns from 3 studies (n=2321) Medical eligibility criteria for contraceptive use .

enrolled women aged 18–35 years DMPA-SC in women with endometriosis Weight gain 2 uncontrolled Very serious No serious Serious No indirectness No comparison Very low Weight gain 0.90–1.70–0. RCT: randomized controlled trial.35 kg at women without 18 months endometriosis 64 | Medical eligibility criteria for contraceptive use .95 kg at studies (n=289) limitations (1 fair) inconsistency imprecision group of 6 months and 0. DMPA: depot medroxyprogesterone acetate. .Part I Change in 2 uncontrolled Very serious No serious Serious No indirectness No comparison Very low Increase in amenorrhoea 20% at bleeding studies (n=289) limitations (1 fair) inconsistency imprecision group of 3 months and 24% at 6 months in pattern women without 1 study.1% with both efficacy (1 fair) (1 study) imprecision DMPA-SC and DMPA-IM Change in 1 RCT (n=357) Serious limitations Cannot determine Serious No indirectness None Very low No differences in menstrual bleeding (1 fair) (1 study) imprecision irregularity. Type and number of studies Outcome Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Changes in 1 RCT (n=534) No serious Cannot determine Serious No indirectness BMD changes Very low Smaller decrease in median BMD bone mineral limitations (1 good) (1 study) imprecision not reported by with DMPA-SC vs DMPA-IM density age category. BMI: body mass index. heavier bleeding pattern BMD: bone mass density. IM: intramuscular. SC: subcutaneous. 1 study reported 35 bleeding endometriosis or spotting days in 1st 90 days and 24 in 2nd 90 days DMPA-SC vs DMPA-IM in women with HIV Contraceptive 1 RCT (n=357) Serious limitations Cannot determine Serious No indirectness None Very low Pregnancy rate 1.

Medical eligibility criteria for contraceptive use . IM: intramuscular.5 kg with DMPA- data from 3 studies limitations (1 fair) (1 study) imprecision SC vs 5.Part I | 65 . SC: subcutaneous. RCT: randomized controlled trial.GRADE table 2 (Question 2): Among healthy women or among a general population of women of reproductive age. do those who use depot medroxyprogesterone acetate (104 mg/0.8 kg with DMPA-IM at 36 (n=2321) months Change in 1 RCT (n=534) No serious Cannot determine Serious No indirectness None Very low No differences in rates of bleeding limitations (1 study) imprecision intermenstrual bleeding or pattern (1 good) amenorrhoea between DMPA-SC vs DMPA-IM DMPA: depot medroxyprogesterone acetate.65 mL) delivered subcutaneously (DMPA-SC) have an increased risk for serious adverse events or other relevant outcomes compared with those who use DMPA delivered intramuscularly (DMPA-IM)? (Indirect evidence) Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect participants) DMPA-SC vs DMPA-IM use in healthy women Contraceptive 1 RCT (n=534) No serious Cannot determine Serious No indirectness None Very low Low rates of pregnancy with DMPA-SC efficacy limitations (1 study) imprecision and DMPA-IM (1 good) Weight gain 1 study with pooled Serious Cannot determine Serious No indirectness None Very low Median weight gain 4.

Segall-Gutierrez P. Mishell DR. Fertil Steril.74(3):234–8. Darney PD. Stanczyk FZ.80(1):7–17. Bode FR. Schlaff WD. 2010. Jr. Nakigozi GF. ovulation suppression and return to ovulation following a lower dose subcutaneous formulation of Depo-Provera. . Contraception. Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. 10.65 mL. Xiang AH. 70. et al. Taylor D. Crosignani PG. 13. 2009. Speroff L.89(5):385-95. and extremely obese women. Changes in weight with depot medroxyprogesterone acetate subcutaneous injection 104 mg/0. 4. Bode FR. Ray A.Part I References 12. 6. Du J. 8.66 | Medical eligibility criteria for contraceptive use . Arias RD. Tilley I. Johnson JV. Jain J. et al. A pilot study examining short-term 1. changes in bone mineral density among class 3 obese Subcutaneous DMPA vs. Ross D. Contraceptive efficacy and safety of DMPA-SC. 2007. Stanczyk FZ. Ray A. obese. Lopez C.81(6):487–95.86(6):739–45. Ross D. mineral density. Mondo G. Dutton C. Watanabe RM. 2006. Jain J. Preference for Sayana® Press versus intramuscular Depo-Provera among HIV-positive women in Rakai. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Follicular development and ovulation in extremely obese women receiving depomedroxyprogesterone acetate subcutaneously. Wajszczuk C.85(2):314–25. Badger GJ. Contraception. Bergqvist A. intramuscular DMPA: a 2-year users of depot-medroxyprogesterone acetate. Jr. et al. Bergqvist A. 2006. Carson SA. Liu X.70(1):11–8. Nakawooya H. Mizraji K. Contraception. 3. 5. Nicosia A. 2014.87(6):1267– acetate subcutaneous injection 104 mg. Luciano A. Goldstein J. Westhoff C. 2006. Fertil Steril.18(3):199–205. Effect of subcutaneous depo-medroxyprogesterone acetate (DMPA-SC) on serum androgen markers in normal-weight.21(1):248–56. 2012. Contraception. Brucker C. Kaunitz AM. Contraception. Agarwal R. Stanzcyk F. Liu X. Cushman M. Contraception. Makumbi F. Azen S. 2013. Ray A. Polis CB. 9.70(4):269–75. Deterioration in cardiometabolic risk markers in obese women during depot medroxyprogesterone acetate use.85(1):36–41. Milsom I. Changes of depomedroxyprogesterone acetate on coagulation in bleeding patterns with depot medroxyprogesterone parameter: a pilot study. Contraception. Luciano A. 2004. 2004. Ross D. 7. Gray RH. Contraception. Jakimiuk AJ. Pharmacokinetics. 11. Ross D. Segall-Gutierrez P. Ge M. 2007. Uganda: a randomized crossover trial. Jain JK. Eur J randomized study of contraceptive efficacy and bone Contracept Reprod Health Care. Segall-Gutierrez P.75(4):261–7. 2012. Hum Reprod. Segall-Gutierrez P. Effect 2. Hernandez G. Contraception. Mishell DR. Kaunitz AM. Trigo E. Ge M. Niu C. Wolter KD. Jain JK.

e. 143–158). studies were identified that looked at safety of the implant among healthy women compared to those who do not use the SI (II). either use of no contraceptive method copper-bearing IUDs. pregnancy or method discontinuation due to blood pressure.e. withdrawal. ectopic users of other implants (Norplant.e. pregnancy or method discontinuation due to Implanon/Nexplanon) a medical condition) or outcomes related to Outcome Serious adverse events (i. ectopic medical conditions (i. In addition. quality profile and daily release rates. a meta-analysis was not performed. Jadelle. cohort studies reproductive-age women and case-control studies Intervention Use of Sino-implant (II) Population Women with medical conditions or other specific characteristics Comparator Users of non-hormonal contraceptive methods (i. Implanon/Nexplanon) IUDs. do those who use Sino-implant (II) have an increased risk for serious adverse events or other relevant outcomes compared with those who Question 1: What is the safety of the contraceptive implant do not use Sino-implant (II)? (Indirect evidence) Sino-implant (II) for women with medical conditions established within the World Health Organization’s eligibility Selection criteria for the systematic review criteria for contraceptive use? (Direct evidence) Study design Randomized controlled trials. Due to heterogeneity of study designs and outcome measures. changes in weight. Question 2: Among healthy women or among a general implant (II) population of women of reproductive age. Medical eligibility criteria for contraceptive use .) or Outcome Serious adverse events (i. etc. If there is a risk of STI/HIV. withdrawal.e. vaginal bleeding) a medical condition) or outcomes related to Databases PubMed and Cochrane Library medical conditions (i.) or users of other implants barrier methods. including HIV. tubal ligation/ or use of a non-hormonal method such as vasectomy.Part I | 67 8. •• The Sino-implant (II) does not protect against sexually transmitted infections (STIs). vaginal bleeding) Databases PubMed and Cochrane Library Recommendations searched •• Recommendations for Sino-implant (II) will be the same recommendations as for other levonorgestrel implants (see p. Given this. Remarks •• Although there was no direct evidence regarding Sino- implant (II) among women with medical conditions. the panel decided to make the same recommendations for SI (II) as the other LNG implants. etc. either use of no contraceptive Intervention Use of Sino-implant (II) method or use of a non-hormonal method Comparator Non-use of a hormonal contraceptive such as barrier methods. copper-bearing (Norplant.e.e. . When used correctly and consistently. Recommendations for safety of Sino. Jadelle. the correct and consistent use of condoms is recommended. tubal ligation/vasectomy. the safety data from studies of other levonorgestrel (LNG) implants among women with medical conditions is used due to the similarity of SI (II) and other LNG implants in hormone formulation. cohort studies Selection criteria for the systematic review and case-control studies Population Healthy women or general population of Study design Randomized controlled trials. (i. searched blood pressure. changes in weight.

 8). Women’s contraceptive choices are made in a Healthy women or general population of reproductive age particular time. 4–6). (intervention versus comparator. Similar effects on selected markers of disease in healthy women were seen for healthy women using SI (II) compared to women using SI (I) or Norplant. while another RCT failed to find this association and also reported no association between duration of use. bone mineral density (7). comprehensive contraceptive implant (II). outcome) •• Voluntary use of contraception by women is critical for upholding their reproductive rights. weight (1. One RCT found an increased pregnancy rate among women weighing 70 kg or over using SI (II) (9). but are not used as widely by national characteristics: programmes as male condoms. Decision- making for contraceptive methods usually requires the need to make trade-offs among the different methods. multifactorial and subject to change. weight and pregnancy (3). 6). These three articles reported on four randomized controlled trials (RCTs) and found no difference between users of SI (II) and users of SI (I) or Norplant with respect to incidence of serious adverse events. Female condoms are Women with medical conditions or other specific effective and safe. education and counselling to ensure informed choice. outcome) complex. All women have the Sino-implant (II) versus non-use of Sino.Part I condoms offer one of the most effective methods of Quality of the evidence protection against STIs. Other adverse events: very low When looking at the studies on healthy women. When investigating serious adverse events in healthy women using SI (II). . The studies suggest that SI (II) is not harmful and may be beneficial for women with menorrhagia. Two studies provided limited evidence regarding menorrhagia (1. These markers of disease were liver function (3). with Sino-impant (II) versus non-use of Sino-implant (II). societal and cultural context. blood pressure (1. three articles were identified (1–3). various advantages and disadvantages of specific contraceptive outcomes (indirect): methods varying according to individual circumstances. Weight gain: moderate Summary of the evidence Blood loss: low Bone mineral density: very low No studies were identified that provided direct evidence on Blood pressure: low the use of the Sino-implant (II) among women with medical conditions in the MEC that included a comparison group. evidence Pregnancy: very low from four studies comparing SI (II) users with users of other LNG-containing implants demonstrates that SI (II) has a similar safety profile with no significant differences in serious adverse events such as ectopic pregnancy or discontinuation due to medical problems (1–3). ovarian cysts and benign myomas (6). no evidence right to evidence-based. serious adverse events (direct): information. including HIV. Ectopic pregnancy: low perceptions and interpretations.68 | Medical eligibility criteria for contraceptive use . choices are women: (intervention versus comparator.

1 very 3 studies.and 1 poor.Part I | 69 . Serious limitations No serious No serious No indirectness None Moderate No difference between SI (II) and 1 cohort study (n=617) (2 fair. 1 poor) inconsistency imprecision haemoglobin levels with SI (II) vs haemoglobin SI (I) or Norplant Bone mineral 1 cross-sectional study Very serious Cannot determine Very serious Serious None Very low No difference between SI (II).GRADE table 1 (Question 2): Among healthy women or among a general population of women of reproductive age. less weight gain with poor-quality cohort SI (II) than control (no method or study) non-hormonal) in 1 study Blood loss.inconsistency imprecision measures increased BP with SI (II). SI (I) density (BMD) (n=166) limitations (1 poor) (1 study) imprecision indirectness and Norplant in BMD after ≥ 3 years (intermediate outcome) Blood pressure 1 RCT (n=2297). 1 cohort study found poor-quality cohort pressure higher BP with control (no method study) effects or non-hormonal) than SI (II) Other adverse 2 RCTs (n=22 672) Serious limitations No serious No serious No indirectness Variability in Very low No difference between SI (II) and events (2 fair) inconsistency imprecision outcomes SI (I) or Norplant in various adverse measured events or reasons for removal Medical eligibility criteria for contraceptive use . SI (I). or quality RCT.inconsistency imprecision SI (I) or Norplant in weight gain in quality RCT. 1 very of blood Norplant. Very serious No serious No serious No indirectness Variability in Low 1 RCT found very few cases of (BP) 1 cohort study (n=617) limitations (1 fair. do those who use Sino-implant (II) have an increased risk for serious adverse events or other relevant outcomes compared with those who do not use Sino-implant (II)? (Indirect evidence) Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect participants) Sino-implant (II) vs Sino-implant (I) or Norplant in healthy women Ectopic 4 RCTs (24 972) Serious limitations No serious Serious No indirectness None Low Very few ectopic pregnancies and pregnancy (4 fair) inconsistency imprecision no clear difference in risk in 4 RCTs of SI (II) vs SI (I) or Norplant Weight gain 3 RCTs (n=4443). 2 RCTs (n=389) Serious limitations No serious Serious No indirectness None Low No clear difference in blood loss or change in (1 fair.

70 | Medical eligibility criteria for contraceptive use . RCT: randomized controlled trial. BP: blood pressure. 1 RCT found no association between weight and risk of pregnancy BMD: bone mineral density. Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect participants) Effects of weight on contraceptive efficacy in women using Sino-implant (II) Pregnancy 2 RCTs (n=10 940) Serious limitations Serious Serious No indirectness None Very low 1 RCT found higher pregnancy rate (2 fair) inconsistency imprecision in women ≥ 70 kg than women < 60 kg (P not reported). SI (II): Sino-implant (II).Part I . SI (I): Sino-implant (I).

II with Norplant. Mao J.15:101–7. 2. Qi L. Ren L. Wang Z. A multicentre study of CLa Implant and Sino-implant: expanded application (two-year follow-up).20:92–7. Gong Q. Chinese J Fam Plann. . The safety of Sino-implant II – 3 years clinical observation. 1998. J Reproduc Contracep. et al. et al. A multicenter comparative clinical study of two types of Sino-implant. Wang G. Chai Y. 8. Meng F. Fan H. 3. Fan H.79:87–95. 6. 1998. 1997. Li W.7(2):12–16. Xue L.8:101–10. 9. Chinese J Fam Plann. Ye L. The effects of long-acting contraceptive implants on bones of reproductive women. Meng F. Liu K. Li Y. Reprod Contracept. Chen X. 4. Guan Y. Han L. Zhao J. Guan F. J Reprod Contracept.Part I | 71 References 1. Zhang G. Multicenter clinical study of two Sino-subdermal implants. et al. Liu X. The effects of three types of long-acting subcutaneous implants on menstrual blood loss. Ni F. 1998. Fan H. 2002. Han L. I and No. Wu M. Xing Q. Li Y. Chen B. Effect of three types of subdermal implants on female body weight. Han L. Chinese J Fam Plann. Gao E. Hong Y. Yang D. Jin Y. 2000. J Reprod Med. Xie Z. Bian C. et al. et al. Gong Q. et al. Sun L. 2004. Jiang J. Shen H. Yang D. Li Y. 1998.6:539– 42. Chinese J Fam Plann. Yang Z. et al. 2002. Mei F. Yu L. A comparative study on the acceptability of China-made subdermal implants. Fan H. Fang K. Tan J. Medical eligibility criteria for contraceptive use . 7.79:282–6.5:210–1. A multicenter comparative clinical study of Sino- Levonorgestrel-Releasing Implants – No. Guan Y. Liu J.6:250–3. Chinese J Fam Plann. 5.

Breastfeeding is not recommended for who do not use these forms of emergency contraception? one week after taking UPA since it is excreted in breast- (Direct evidence) milk. angina pectoris. St John’s effects) wort/Hypericum perforatum) can use COCs. nevirapine.g. primidone. •• Women who are breastfeeding can use COCs or LNG ulipristal acetate (UPA) or combined oral contraceptive regimens for ECPs without restriction (MEC Category 1). oxcarbazepine. emergency contraceptive pill (ECP) condition of obesity and the new method. LNG or without restriction (MEC Category 1). Outcome Any adverse events or pregnancy Databases PubMed and Cochrane Library searched . Recurrent ECP use is an ulipristal acetate (UPA) or combined oral contraceptive (COC) indication that the woman requires further counselling regimens for emergency contraceptive pills (ECPs). or other thromboembolic conditions. LNG or UPA for Study design Randomized controlled trials. efavirenz. LNG or UPA for ECPs without restriction including pharmacokinetic studies (MEC Category 1). Recommendations for use of emergency Recommendations contraceptive pills. including adding the •• For pregnant women. •• There are no restrictions for use of COCs. for ECPs (MEC Category 2). •• There are no restrictions on repeated ECP use for COCs. 3 or 4 for use of combined hormonal contraceptives (CHCs) or progestogen-only contraceptives Selection criteria for the systematic review (POCs). past ectopic pregnancy. Question 1: Among women with certain characteristics or medical conditions. are on other contraceptive options. the course of her pregnancy.72 | Medical eligibility criteria for contraceptive use . rifampicin. ECPs may be less UPA) effective among women with BMI ≥ 30 kg/m2 than among Intervention Obesity women with BMI < 25 kg/m2. fosphenytoine. LNG or UPA for Databases PubMed and Cochrane Library ECPs without restriction (MEC Category 1). eligibility criteria (MEC) update (pregnancy. Although this method is not indicated ulipristal acetate for a woman with a known or suspected pregnancy. cohort studies ECPs in cases of rape (MEC Category 1). severe liver disease. or the fetus if ECPs are accidentally used. there is no known harm to the woman. rifabutin. LNG or UPA) generally use COCs. conditions outlined in the Medical including ischaemic heart disease. LNG or UPA (MEC Category 1). can generally use breastfeeding. Selection criteria for the systematic review •• Women who have experienced past ectopic pregnancies Study design Primary research articles in all languages. phenobarbital. carbamazepine. can Intervention Use of hormonal ECPs (COCs. LNG or UPA for ECPs Population Women using hormonal ECPs (COCs. Outcome Any adverse events (did not include side. Comparator Non-use of hormonal ECPs •• Women using CYP3A4 inducers (e. are those who use levonorgestrel (LNG). •• Women with severe liver disease. (COC) regimens for emergency contraceptive pills (ECPs) Women who are breastfeeding can generally use UPA at increased risk for adverse events compared with those (MEC Category 2). repeated [ECP] use and rape). phenytoin. cerebrovascular attack. there are no Comparator Non-obesity safety concerns. Question 2: Among women who use levonorgestrel (LNG). COCs. LNG or UPA for ECPs (MEC Category 2). and case-control studies •• Women who are obese can use COCs. history of severe cardiovascular •• Women with migraines can generally use COCs. LNG or UPA complications. CYP3A4 inducers. Frequently repeated ECP those with obesity at increased risk for adverse events or use may be harmful for women with conditions classified pregnancy compared with those who do not have obesity? (Direct evidence) as Category 2. Strong CYP3A4 searched inducers may reduce the effectiveness of ECPs. LNG or UPA for ECPs (MEC Category 2). can use COCs. including jaundice. Despite this. migraine.Part I 9. use is not applicable. Breast-milk should be expressed and discarded during that time (1). Population Women with characteristics or medical •• Women with history of severe cardiovascular disease.

Female condoms are effective and safe. though this •• Due to heterogeneity of study designs and outcome increase was not significant in one of the studies (8. education and counselling to ensure informed Currently pregnant women choice. condoms offer one of the Breastfeeding women most effective methods of protection against STIs. migraine or severe liver breastfeeding women (3–4). No studies were identified •• The duration of use of ECPs is less than the duration of that examined UPA. therefore. Poor pregnancy the use of ECPs in cases of rape. very low upholding their reproductive rights. •• ECPs do not protect against sexually transmitted infections Quality of the evidence (STIs). 9). There are no restrictions for outcomes among breastfeeding women (2. adverse pregnancy outcomes: making for contraceptive methods usually requires the GRADE methodology was not used to assess quality of need to make trade-offs among the different methods. Medical eligibility criteria for contraceptive use . Decision. choices are LNG-ECP use versus non-use of LNG-ECP. One cohort study and have less clinical impact for women with history of severe one randomized controlled trial analysed outcomes among cardiovascular complications. One pharmacokinetic study appear elsewhere in the MEC and there was no evidence demonstrates that LNG does pass to breast-milk but is found suggesting safety concerns for ECP use among women with in minimal quantities (6). All women have the infant growth/behaviour: right to evidence-based. after use of UPA compared with non-obese women. •• The GDG decided to change the term “history of severe A small pharmacokinetic study found that concomitant cardiovascular complications” to “history of severe efavirenz use decreased LNG levels in women taking LNG-ECP cardiovascular disease” to be more consistent with (0. Women using LNG-.Part I | 73 Remarks Summary of the evidence •• Ulipristal acetate (UPA) was added as a new method to the Four direct studies examined LNG-ECP use among pregnant MEC.75 mg) by 56% compared with LNG-ECP alone (7). comprehensive contraceptive information. including HIV. There is limited evidence from one study that suggests obese •• According to labelling information.or COC-ECP use among women with regular use of COCs or POPs and thus would be expected to medical conditions or characteristics. This condition does not to LNG and those unexposed. the correct Women with certain characteristics or medical conditions: and consistent use of condoms is recommended. 5). rifampicin markedly women with BMI ≥ 30 kg/m2 experience an increased risk of decreases UPA levels by 90% or more. very low used as widely by national programmes as male condoms. measures. which may decrease pregnancy after use of LNG compared with women with BMI its efficacy (1). with evidence for studies that did not report clinical outcomes. Evidence from two studies suggests that obese use of other CYP3A4 inducers as well as LNG and COCs. and two cohort studies analysed disease (including jaundice). but are not LNG-ECP use versus non-use of LNG-ECP. or breastfeeding women (2–5). Breastfeeding remove the condition “angina pectoris” from the MEC outcomes do not seem to differ between women exposed recommendations for ECPs. outcome) used correctly and consistently. a meta-analysis was not performed. Theoretical concerns. UPA. perceptions and interpretations. angina pectoris.or COC-ECPs: (intervention versus comparator: outome) Obesity versus non-obesity. breastfeeding outcomes: •• Voluntary use of contraception by women is critical for LNG-ECP use versus non-use of LNG-ECP. terminology used elsewhere in the MEC. Women’s contraceptive choices are made in a particular time. extend to < 25 kg/m2 (8). societal and cultural context. advantages and disadvantages of specific contraceptive including pharmacokinetic studies. If there is a risk of STI/HIV. multifactorial and subject to change. women may also experience an increased risk of pregnancy which have similar metabolic pathways to UPA. methods varying according to individual circumstances. including HIV. risk of pregnancy: moderate . When (intervention versus comparator. outcomes appear rare among pregnant women who used ECPs •• The Guideline Development Group (GDG) decided to during conception cycle or early in pregnancy. very low complex.

ectopic pregnancy. 1 RCT (1 poor-quality cohort. imprecision milk volume in 2 studies. (n=1158) 1 fair-quality RCT). resumption of subjective self-report menstruation or pattern of breastfeeding in 1 study Infant growth 1 cohort study Very serious limitations No inconsistency No serious No indirectness Very low No differences in infant 74 | Medical eligibility criteria for contraceptive use . or other pregnancy complications Neonatal or fetal 2 cohort studies Very serious limitations No inconsistency Serious No indirectness Very low No differences in rates of outcomes (n=780) (1 poor. outcomes poorly defined LNG-ECP during pregnancy vs no LNG-ECP Pregnancy 2 cohort studies Very serious limitations No inconsistency Serious No indirectness Very low No differences in risk of outcomes (n=780) (1 poor. 1 fair) imprecision birth defects or fetal growth . some no difference in duration outcomes based on of lactation. 1 RCT (1 poor-quality cohort.GRADE tables 1 (Question 1): Among women with certain characteristics or medical conditions. imprecision growth or behaviour (n=1158) 1 fair-quality RCT). ulipristal acetate (UPA) or combined oral contraceptive (COC) regimens for emergency contraceptive pills (ECPs) at increased risk for adverse events compared with those who do not use these forms of emergency contraception? (Direct evidence) Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Quality Estimate of effect participants) LNG-ECP during breastfeeding vs no LNG-ECP Breastfeeding 1 cohort study Serious limitations No inconsistency No serious No indirectness Very low No differences in breast- outcomes (n=143). are those who use levonorgestrel (LNG). 1 fair) imprecision spontaneous abortion or still birth.Part I and behaviour (n=143).

3) for UPA-ECPb BMI: body mass index.0) for UPA- 2 meta-analyses analyses evaluated in ECPa that included from clinical the other) 2 studies each.0–9.6 (95% CI 2.1 (95% CI 0. a Estimates adjusted for conception probability. further intercourse. clinical trials limitations inconsistency imprecision observed 2 studies): OR 3. trials with Overweight vs normal or underweight 1 study included methodological (n=2976. OR: odds ratio. and hours since unprotected intercourse (up to 120 hours) not statistically significant in univariate anal- yses. age.4 (95% CI 2.4) for LNG-ECP (analysed in secondary analysis (not and OR 2.97 (95% CI 0. b Estimate adjusted for further acts of unprotected intercourse.8) for UPA-ECPa. (n=2173.0) for any ECP.5) for any (n=4690) (2 studies with in 1 meta. race.9) for LNG-ECP and 0.89–7. ever being pregnant. Medical eligibility criteria for contraceptive use .6 (95% CI 0. ulipristal acetate (UPA) or combined oral contraceptive (COC) regimens for emergency contraceptive pills (ECPs). CI: confidence interval. age. time from unprotected intercourse to treatment.75– in both analyses) limitations) 3.27–2. 2 studies): OR 2.Part I | 75 . 2 studies): OR 1.1 (95% CI 1.0–6. are those with obesity at increased risk for adverse events or pregnancy compared with those who do not have obesity? (Direct evidence) Type and number of Outcome Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect studies (number of participants) Obese (BMI ≥ 30 kg/m2) vs overweight (25–30 kg/m2) vs normal or underweight (< 25 kg/m2) Pregnancy 3 cohorts from Serious No serious No serious No indirectness Dose-effect Moderate Obese vs normal or underweight (n=2701. ECP. 2.GRADE table 2 (Question 2): Among women who use levonorgestrel (LNG). smoking.86–4.0–4. OR 4. and pregnancy history.5 (95% CI 0.

Hum Reprod. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. 2. Kwara A. 2013. Yogev Y. Kiser JJ. Gilad O. Zhang L. Moreau C. levonorgestrel (Plan B). Straface G.2012:1–4. Shaaban OM. Reyes V.5 mg for emergency contraception. Kames MA. Scherrer B.24(7):1605-11. Chen J. 5. Cavaliere AF. Gainer E. 2007.uk/hcp/abbreviated- prescribing-information-uk. Caruso A.84(2):296–9. Levonorgestrel used for emergency contraception during lactation-a prospective observational cohort study on maternal and infant safety. Carducci B. Lillo S. Mathe H. 3. De Santis M. 2009. ellaOne® ulipristal acetate. Levonorgestrel pharmacokinetics in plasma and milk of lactating women who take 1. Cu-Uvin S. 4. Fertil Steril.26(3):219–21. Klinger G. Caviedes R. Infect Dis Obstet Gynecol. Pharmacokinetic interactions between the hormonal emergency contraception. 2011. Contraception.co. Nour SA. 9. Ren F. Mawhinney S. 2012.ellaone. Results from pooled Phase III studies of ulipristal acetate for emergency contraception. Pregnancy outcome after levonorgestrel-only emergency contraception failure: a prospective cohort study. 2013. and Efavirenz. Contraception. J Matern Fetal Neonatal Med. Abbreviated prescribing information (UK).Part I References 1. et al. . Polakow-Farkash S. Cheng L. Yu W.86(6):673–80. 2013 (http://www. Contraception. Emergency contraceptive pills as a backup for lactational amenorrhea method (LAM) of contraception: a randomized controlled trial. Carten ML. 2012. Stahl B. Forcelledo Ml. 8. Levy D. Wang Y. Failure of the emergency contraceptive levonorgestrel and the risk of adverse effects in pregnancy and on fetal development: an observational cohort study. Trussell J. 6. Glasier A. Hum Reprod. Massai R. et al. Yones EM. London: HRA Pharma UK & Ireland Ltd.76 | Medical eligibility criteria for contraceptive use . 7. Hassen SG. Blithe D. accessed 23 October 2014).87(3):363–9. Merlob P.84(4):363–7. 2005.22(6):1578–84. Cameron ST.

Study design Randomized controlled trials. does intrauterine device (IUD) insertion increase risk for pelvic inflammatory disease (PID) the GRADE process. Risk of STIs varies by individual behaviour and local STI prevalence. This was addressed by the Guideline compared with women with an increased risk of STIs that do Development Group (GDG). Using an algorithm to classify STI risk status among IUD users. cohort studies •• IUDs do not protect against STIs. with generally should not have an IUD inserted until appropriate advantages and disadvantages of specific contraceptive testing and treatment occur (MEC Category 3). Intervention Initiation of copper-bearing IUD (Cu-IUD) or condoms offer one of the most effective methods of levonorgestrel-releasing IUD (LNG-IUD) protection against STIs. increased risk of STIs. while many women at increased risk of STIs can one study reported that 11% of women at high risk of STI generally have an IUD inserted. but are not used as widely by national programmes as male condoms. IUD insertion methods varying according to individual circumstances. Current algorithms for determining Summary of the evidence increased risk of STIs have poor predictive value. When used correctly and consistently. All women have the searched right to evidence-based. education and counselling to ensure informed Recommendations choice. may further increase the risk of PID among women at perceptions and interpretations. Decision- LNG-IUD initiation (MEC Category 2). Quality of the evidence For STI and IUD: No new evidence . not have an IUD inserted until appropriate testing and the incidence of PID after IUD insertion was low (2.Part I | 77 10. Outcome PID •• Voluntary use of contraception by women is critical for Databases PubMed and Cochrane Library upholding their reproductive rights. especially for women at increased risk of STIs. •• Women at increased risk of STIs can generally continue use of either Cu-IUD or LNG-IUD (MEC Category 2). Medical eligibility criteria for contraceptive use . However. If there is a and case-control studies risk of STI/HIV. choices are infections (STIs) can generally undergo either Cu-IUD or complex. the correct and consistent use of condoms Population Women at increased risk of STIs is recommended. some women at increased experienced IUD-related complications compared with 5% of risk (very high individual likelihood) of STIs should generally those not classified as high risk (1). cohort of women considered to be at high risk based on high background rates of STIs in the general population (2). The GDG highlighted the universal recommendation for dual Selection criteria for the systematic review protection with condoms. including HIV. multifactorial and subject to change. Therefore. as no new evidence was identified to update this Question 1: Among women with an increased risk of sexually recommendation.2%) in a treatment occur. Women’s contraceptive choices are made in a •• Many women with increased risk of sexually transmitted particular time. there was no evidence to take through transmitted infections (STIs). Female condoms are Comparator Non-initiation of Cu-IUD or LNG-IUD effective and safe. Some women at making for contraceptive methods usually requires the increased risk (very high individual likelihood) of STIs need to make trade-offs among the different methods. societal and cultural context. comprehensive contraceptive information. including HIV. Recommendations for intrauterine Remarks devices among women with increased risk for •• The Guideline Review Committee advised that this sexually transmitted infections recommendation be revised to clarify the Category 2/3 recommendation in the MEC fourth edition. who decided that the best not undergo IUD insertion? course of action was to revise the clarification. In another small study. although limited evidence suggests that this risk is low.

Adawadkar S. Use of sexually transmitted disease risk assessment algorithms for selection of intrauterine device candidates. Ivey S. J Womens Health.59(2):97–106. Contraception. Weiner M DH. Cropsey KL. . Long-term. Sinei SK. 1999. 2. Sekadde-Kigondu C. Matthews C. reversible contraception use among high- risk women treated in a university-based gynecology clinic: comparison between IUD and depo-provera. orrison CS.19(2):349–53. Campbel S.Part I References 1.78 | Medical eligibility criteria for contraceptive use . 2010. Miller WC.

including HIV. nor the timing Recommendations of supplementary food introduction (6) significantly differed among PVR users compared with users of non-hormonal or •• Women who breastfeed and are ≥ 4 weeks postpartum. multifactorial and subject to change. societal and cultural context.) health. use of PVR versus non-PVR measures. education and counselling to ensure informed breastfeeding performance. contraceptive methods. with Study Design Randomized controlled trials. 5). comprehensive contraceptive only contraceptive (POC) methods.g. copper-bearing the progesterone-releasing vaginal ring (PVR) on maternal IUDs. progestogen-only contraceptives (POCs) during 12 months of can use without restrictions the progesterone-releasing observation. vaginal ring (PVR) (MEC Category 1). the number of breastfeeding episodes (2. a meta-analysis was not performed. development. infant growth or infant health? choice. Female condoms are progesterone-releasing vaginal ring effective and safe. the proportion of women fully breastfeeding (2). breastfeeding performance. there is no known harm to the woman. A woman who uses the PVR must be actively breastfeeding (e. either use of no contraceptive method or use of a non- Seven prospective cohort studies examined the effect of using hormonal method such as condoms or other barrier methods. Decision- Selection criteria for the systematic review making for contraceptive methods usually requires the need to make trade-offs among the different methods. including HIV. compared with non-use of progestogen. Intervention PVR Summary of the evidence Comparator Non-use of a POC method (i. but are not used as widely by national programmes as male condoms. Recommendations for use of protection against STIs. contraceptive. One study reported no significant •• If the progesterone-releasing vaginal ring (PVR) is difference in infant health (5). 4. breastfeeding performance (e. various outcomes: •• The PVR does not protect against sexually transmitted Pregnancy: low infections (STIs). right to evidence-based. etc. infant health longer (1–7). 4. If there is a risk of STI/ HIV. Infant weight: low condoms offer one of the most effective methods of . at least four No statistically significant differences in infant weight gain breastfeeding episodes per day) to maintain the efficacy of were observed among PVR users compared with women using the method. Population Breastfeeding women perceptions and interpretations. pregnancy Of the six studies that evaluated various measures of breastfeeding performance. When used correctly and consistently. Quality of the evidence •• Due to heterogeneity of study designs and outcome Among breastfeeding women. (growth. or the fetus.g. cohort studies advantages and disadvantages of specific contraceptive and case-control studies methods varying according to individual circumstances.Part I | 79 11. information. tubal ligation/vasectomy.e. All women have the vaginal ring (PVR). 7). infant health and infant growth. withdrawal. the course of her pregnancy. supplementation). neither duration of lactation Databases PubMed and Cochrane Library searched (1. •• Voluntary use of contraception by women is critical for Question 1: Among breastfeeding women and their infants. the correct and consistent use of condoms is Breastfeeding outcomes: low recommended. choices are complex. 6) and similar patterns of infant weight gain were observed in another study that compared Remarks PVR and IUD users (5). does the use of the progesterone-releasing contraceptive upholding their reproductive rights. Women’s contraceptive choices are made in a (Direct evidence) particular time. Medical eligibility criteria for contraceptive use . affect maternal health. accidentally used during pregnancy. compared with other hormonal and non-hormonal Outcome Maternal adverse events. non-hormonal or POCs (3. during the first year postpartum or continuation. or adverse health events). duration of lactation.

Norplant or progesterone-only pill (POP) Pregnancy 7 cohort studies Serious No serious No serious No indirectness None Low Few pregnancies and similar pregnancy rates (n=3397) limitations inconsistency imprecision in breastfeeding women using PVR vs IUD (6 (5 fair. 2 poor) Breastfeeding 2 cohort studies Serious No serious No serious No directness None Low No differences between PVR and IUD (2 studies) episodes (n=2083) limitations inconsistency imprecision (2 fair) Continuation of use 5 cohort studies Serious No serious No serious No indirectness None Low 4 studies found PVR associated with lower (n=2722) limitations inconsistency imprecision continuation/higher discontinuation vs IUD. 2 poor) Infant weight gain 7 cohort studies Serious No serious No serious No indirectness None Low No difference between ring vs IUD (7 studies). 2 poor) . infant growth and infant health? (Direct evidence) Type and number of Other Outcome Limitations Inconsistency Imprecision Indirectness Quality Estimate of effect studies (number factors of participants) Progesterone-releasing vaginal ring (PVR) vs intrauterine device (IUD). or POP (1 study) Use of 4 cohort studies Serious No serious No serious No indirectness None Low No difference between PVR and IUD (3 studies). (3 fair. or POP (1 study) (5 fair. or POP (1 study) in (3 fair. 1 poor) proportion fully breastfeeding. or POP (1 study) (2 fair. affect maternal health.Part I associated with fewer supplementation episodes and days than IUD at all follow-up periods (P < 0. duration (n=1117) limitations inconsistency imprecision Norplant (2 studies). Norplant (2 studies). does the use of the progesterone-releasing contraceptive vaginal ring (PVR). (n=3397) limitations inconsistency imprecision Norplant (2 studies). 2 poor) studies). breastfeeding performance. or POP (1 study) (1 fair. 1 study found ring 80 | Medical eligibility criteria for contraceptive use . compared with non-use of progestogen-only contraceptive (POC) methods. supplementation (n=1129) limitations inconsistency imprecision Norplant (2 studies). Norplant (1 study).001) Breastfeeding 4 cohort studies Serious No serious No serious No indirectness None Low No difference between PVR and IUD (4 studies).GRADE table 1 (Question 1): Among breastfeeding women and their infants. 2 poor) 1 study found PVR associated with higher continuation/lower discontinuation Bleeding episodes 3 cohort studies Very serious No serious No serious No indirectness None Low No clear differences between PVR vs IUD (n=2279) limitations inconsistency imprecision (3 studies).

1991. Contraception. IX. et al.57:371–9. 1997. 1998. Norplant® implants. Sayed EH. Miranda P.55:225- 32. et al. progestin-only pills. Reyes MV. Fertility regulation in nursing women. 7.14:2499–505. .56:223–32. Contraceptives for lactationg women: A comparative trial of a progesterone-releasing vaginal ring and the copper T380A IUD. Shao WQ. Norplant® implants and progesterone vaginal rings do not affect maternal bone turnover and density during lactation and after weaning. duration of lactation. Peralta O. Herreros C. Contraception. Sivin I. Miranda P.40:705-10. Miranda P. Miranda P. Shaaban MM. J Steriod Biochem Mol Biol.Part I | 81 References 1. The comparative trial of TCu 380A IUD and progesterone- releasing vaginal ring used by lactating women. Gonzalez GB. 1997. 4. J Hu. Contraception. et al. Progeseterone plasma levels and contraceptive efficacy of a progesterone-releasing vaginal ring. Campino C. Maturana X. Chen JH. Zepeda A. Juez G. Casado ME. Diaz S. Reyes MV. 1999. et al. 3. Jackanicz TM. Zepeda A. Diaz S. Shaaban M. Contraception. 5. et al. Contraception. Lopez JM. Diaz S. 6. 1999.60:9–14. 1985. Casado ME. Valdes P. Lavin P. et al.32:603–22. Hum Reprod. and bleeding patterns during use of progesterone vaginal rings. Medical eligibility criteria for contraceptive use . Fertility regulation in nursing women: VIII. J Cong. Contraception with progestogens and progesterone during lactation. Diaz S. Massai R. Zepeda A. and copper T380-A intrauterine devices. Croxatto HB. infant growth. MH Zou. Contraceptive performance. Wu SC. Preregistration study on the safety and contraceptive efficacy of a progesterone-releasing vaginal ring in Chilean nursing women. 2.

or indirectly by measurement of genital HIV shedding or plasma viral load in women as a proxy for infectivity). with incident HIV patches. method (i.) Outcomes Risk of HIV disease progression (as indicated Question 1: Does the use of a particular method of hormonal by HIV viral load. implants. copper-bearing IUDs. and women living with HIV using antiretroviral therapy Selection criteria for the systematic review Background Study design Randomized trials and cohort studies Population Women of reproductive age living with HIV Owing to the public health importance of recommendations Intervention Use of a hormonal contraceptive method on hormonal contraceptive use for women at risk of HIV and (injectables.) for infectivity in women) Outcome Incident. Recommendations for use of hormonal Question 2: Does the use of various hormonal contraceptive contraception among women at high risk of methods accelerate HIV disease progression in women living with HIV? HIV.Part I 12. either use of no method or use of a non- hormonal method such as condoms or other barrier methods. copper-bearing on 7 July 2014 (1). etc. IUDs. progression to contraception directly increase the risk of HIV acquisition in AIDS. or a composite women? outcome of progression to AIDS.e. rings or LNG-IUDs) Comparator Non-use of hormonal contraceptive methods (i. laboratory-confirmed HIV infection Population Women of reproductive age living with HIV in women Intervention Use of a hormonal contraceptive method (injectables. . the following recommendations were patches. Selection criteria for the systematic review Question 3: Does the use of various hormonal contraceptive Study design Randomized controlled trials and methods increase the risk of female-to-male HIV sexual observational cohort studies transmission? Population Women of reproductive age at risk of HIV infection Selection criteria for the systematic review Intervention Use of a hormonal contraceptive method Study designs (a) Randomized trials and cohort studies (injectables. ART initiation. tubal ligation/vasectomy. withdrawal. tubal ligation/vasectomy.e. etc. assessing proxy measures ligation/vasectomy. either use of no contraceptive (b) randomized controlled trials. rings or LNG-IUDs) issued ahead of this fifth edition of the MEC in the document Comparator Non-use of hormonal contraceptive methods entitled Hormonal contraceptive methods for women at high (i. ART initiation or death). implants.82 | Medical eligibility criteria for contraceptive use . studies. etc. women living with HIV. death. women living with HIV. oral contraceptives. withdrawal. tubal indirect evidence. rings or LNG-IUDs) infection rates in male sexual partners as an Comparator Non-use of a hormonal contraceptive outcome variable).e. (reporting direct evidence. copper-bearing IUDs. either use of no method or use of a non- risk of HIV and living with HIV: 2014 guidance statement. cohort method or use of a non-hormonal method such as condoms or other barrier methods. cross-sectional studies (reporting withdrawal. CD4 count. implants. patches.) Outcomes Risk of HIV transmission to male partners (measured either directly by HIV seroconversion among previously HIV-negative male partners. oral contraceptives. oral contraceptives. which hormonal method such as condoms or other was approved by the WHO Guidelines Review Committee (GRC) barrier methods.

one study among sex workers in Kenya did (12). infections (STIs). ovulation. Seven injectables (DMPA and NET-EN). while one did (11). Recommendations among women at high risk of HIV in women using a non-hormonal contraceptive method infection: (i. it was agreed that the showed a significant increase in risk (5. ARV pharmacokinetics. withdrawal) or no contraceptive method •• Women at high risk of acquiring HIV can use the following (2–27). ovarian activity. including male and female condoms. ARV effectiveness (HIV disease progression. progestogen-only implants. between use of COCs and HIV acquisition (3. assessed non-specified injectables.Part I | 83 Question 4: Are there any possible interactions between at high risk of HIV acquisition considering POIs should hormonal contraceptive methods and antiretroviral (ARV) also be informed about and have access to HIV preventive medications? measures. if a DMPA-specific result This must be considered when adapting guidelines to local was unavailable. 11. At the meeting in 2014. POIs. 7). and other measures to prevent and therapy (ART) reduce their risk of HIV infection and sexually transmitted Comparator Hormonal contraception and no ART. Selection criteria for the systematic review •• Women at high risk of acquiring HIV can generally use LNG-releasing IUDs (LNG-IUDs) (MEC Category 2). non. contraceptive patches Eight studies assessed the use of COCs and were considered and rings. as at limitations” (28). Study design Clinical trials. a significant increase in risk using one statistical model but Given the importance of this issue. bleeding). Some studies suggest that women Five studies assessed the use of NET-EN injectables and were using POI contraception may be at increased risk of HIV considered to be “informative but with important limitations” acquisition. 12). 9. and adverse effects of either the hormonal contraceptive or the Twenty-two prospective observational studies have assessed ARV medication. Medical eligibility criteria for contraceptive use . WHO expert groups continue to actively monitor studies were considered to be “informative but with important any emerging evidence. depend upon the local context. CD4 count). CICs. 13). progestogen-only to be “informative but with important limitations” (28). only injectables (POIs) should be informed that available studies on the association between POI contraception and Progestogen-only contraceptives HIV acquisition have important methodological limitations hindering interpretation. breakthrough against STIs/HIV. including COCs. outcomes over time •• Hormonal contraceptives. condoms. Outcome Contraceptive hormone pharmacokinetics. maternal mortality and HIV prevalence. 8–10. The results were mixed: three of the studies the 2012 technical consultation. 5-11). or. combined Combined hormonal contraceptives injectable contraceptives (CICs). these contexts. regardless of which form of contraception comparative studies examining changes in they choose. progestogen-only pills (POPs). Nine studies assessed DMPA. Summary of the evidence (Question 1: HIV acquisition) viral load. (28). POPs. and five showed no significant increase increase their risk of HIV acquisition. women at high risk of this association was not statistically significant using another HIV infection should be informed that POIs may or may not statistical model (6. and levonorgestrel (LNG) of these studies found no statistically significant association and etonogestrel (ETG) implants (MEC Category 1). other studies have not found this association.e. case series and pharmacokinetic studies Remarks Population Women of reproductive age •• It is critically important that women and couples at risk of HIV infection be informed about and have access to male Intervention Hormonal contraception and antiretroviral and female condoms. one showed epidemiological data did not warrant a change to the MEC. hormonal contraceptive methods without restriction: combined oral contraceptive pills (COCs). 13). and LNG-IUDs do not protect contraceptive effectiveness (pregnancy. although •• Women at high risk of HIV who are using progestogen. Women and couples in risk (3. 8. including rates of injectable contraceptive use. Cu-IUD. Four of them reported no statistically significant The public health impact of any such association would association with HIV acquisition (3. . observational studies. the risk of HIV acquisition among women using a method of hormonal contraception versus the risk of HIV acquisition 12a.

as measured by their reproductive rights and continues to be an important CD4 count < 200 cells/mm3. five suggested no association •• Voluntary use of contraception by women living with HIV between use of progestogen-only injectable (POI) who wish to prevent pregnancy is critical for upholding contraceptives and progression of HIV. Female condoms are effective and safe. however. Two prospective observational studies directly assessed the •• Women living with asymptomatic or mild HIV clinical effects of different hormonal contraceptive methods on female- disease (WHO stage 1 or 2) can generally use the LNG-IUD to-male HIV transmission by measuring seroconversions (MEC Category 2). is critical whether various hormonal contraceptive methods affect for prevention of HIV transmission to non-infected sexual plasma HIV viral load have found no effect (38–53). including HIV. 12b. one of which was classified requires the need to make trade-offs among the different as “unlikely to inform the primary question” (4. etonogestrel (ETG) implants (MEC Category 1). Neither of methods.84 | Medical eligibility criteria for contraceptive use . 21). this study. with advantages and disadvantages of specific these studies reported a statistically significant increased risk contraceptive methods varying according to individual of HIV acquisition. Consistent had mixed results. education and counselling to oral contraceptive (OC) users (COCs and POPs) when compared ensure informed choice. or mortality (29– oral contraceptive pills (COCs). to follow-up and method-switching among groups. progestogen-only injectables COC users when compared with users of copper-bearing IUDs (DMPA and NET-EN). perceptions and interpretations. circumstances. a composite outcome of declining CD4 count or death among progestogen-only pills (POPs). Quality of the evidence (Question 1: HIV acquisition) Summary of the evidence (Question 2: disease progression. Out of six available studies. Question 3: female-to-male transmission) For progestogen-only injectables (DMPA and low NET-EN) and COCs: Two systematic reviews investigating Questions 2 and 3 informed the contraceptive eligibility recommendations for For implants: very low women living with asymptomatic or mild HIV clinical disease (WHO stage 1 or 2). combined injectable 35). initiation of ART. One study found no difference in ART Decision-making for contraceptive methods usually . as measured by contraceptive methods without restriction: combined CD4 count < 200 cells/mm3. Recommendations among women living with asymptomatic or mild HIV clinical disease Combined hormonal contraceptives (CHCs) (WHO stage 1 or 2): •• Women living with asymptomatic or mild HIV clinical Out of eight available studies. All (31–35). partners.Part I Two studies assessed implants. in male partners of women known to be using hormonal •• Because there may be interactions between certain contraceptives. male or female. point estimate for COCs (5). seven suggested no association disease (WHO stage 1 or 2) can use the following hormonal between use of COCs and progression of HIV. interpretation (36. societal and cultural context. multifactorial and subject to change. and levonorgestrel (LNG) and (Cu-IUDs) (36. 72). The majority of indirect studies measuring and correct use of condoms. Studies indirectly assessing the effect of various hormonal Remarks contraceptive methods on female-to-male HIV transmission by •• Hormonal contraceptives do not protect against sexually measuring genital viral shedding as a proxy for infectivity have transmitted infections (STIs). 28). contraceptive patches and rings. limiting its choices are complex. 37). methods of hormonal contraception and certain but not statistically significant. (see p. or mortality strategy for reducing vertical HIV transmission. 37). antiretroviral medications (ARVs). One randomized trial found an increased risk of a women have the right to evidence-based. but are not used as widely Progestogen-only contraceptives (POCs) by national programmes as male condoms. and for protection against other STIs. comprehensive composite outcome of declining CD4 count or death among contraceptive information. but confidence intervals were wide (4. had significant loss are made in a particular time. Women’s contraceptive choices with users of Cu-IUDs. One of these studies reported an elevated. initiation of ART. refer to the The other study also did not find a statistically significant recommendations on ART medication interactions association for COCs (4). One randomized controlled trial found an increased risk of contraceptives (CICs).

association between POI contraception and female-to-male •• Because there may be interactions between certain transmission of HIV (5). and correct use of condoms. HIV clinical disease need not have their IUD removed (MEC to-male HIV transmission by measuring seroconversions Category 2 for continuation). 72). combined injectable informed the contraceptive eligibility recommendations for contraceptives (CICs). societal and cultural context. Consistent plasma HIV viral load have found no effect (38–53). perceptions and interpretations. . The majority of indirect studies measuring •• Hormonal contraceptives do not protect against sexually whether various hormonal contraceptive methods affect transmitted infections (STIs). progestogen-only (WHO stage 3 or 4). including HIV. collection method. and for protection against other STIs. with advantages and disadvantages of specific undergo a GRADE assessment. women have the right to evidence-based. Recommendations among women living with severe or advanced HIV clinical disease (WHO stage 3 or 4) Summary of the evidence (Question 2: disease •• Women living with severe or advanced HIV clinical disease progression. male or female. Medical eligibility criteria for contraceptive use . LNG-IUD users with severe or in male partners of women known to be using hormonal advanced HIV clinical disease should be closely monitored contraceptives. studies providing indirect requires the need to make trade-offs among the different evidence assessing proxy measures of transmission did not methods. but are not used as widely Disease progression – progestogen-only low by national programmes as male condoms. However. refer to the and female-to-male HIV transmission (4). and levonorgestrel (LNG) All of the identified studies excluded women with severe and etonogestrel (ETG) implants (MEC Category 1). education and counselling to ensure informed choice. is critical for prevention of HIV transmission to non-infected sexual Quality of the evidence partners. Question 3: female-to-male transmission) (WHO stage 3 or 4) can use the following hormonal contraceptive methods without restriction: combined Two systematic reviews investigating Questions 2 and 3 oral contraceptive pills (COCs).Part I | 85 initiation or CD4 count between users and non-users of the LNG-IUD (MEC Category 3 for initiation) until their illness LNG-IUD (54). injectables (DMPA and NET-EN). One study reported a statistically significant for pelvic infection. multifactorial and subject to change. women who already have Two prospective observational studies directly assessed the an LNG-IUD inserted and who develop severe or advanced effects of different hormonal contraceptive methods on female. while another study did not find a methods of hormonal contraception and certain statistically significant association between use of DMPA antiretroviral medications (ARVs). injectables (DMPA and NET-EN) and OCs (COCs and POPs): •• Voluntary use of contraception by women living with HIV who wish to prevent pregnancy is critical for upholding Disease progression – LNG-IUD: very low their reproductive rights and continues to be an important Disease transmission (direct evidence) – very low strategy for reducing vertical HIV transmission. All progestogen-only injectables (DMPA and NET. RNA versus DNA. although some participants experienced (WHO stage 3 or 4) should generally not initiate use of the progression to severe or advanced disease during the trials. the best way to measure genital HIV shedding (with respect to choices are complex. Women’s contraceptive choices Note: As there remains considerable uncertainty regarding are made in a particular time. women living with severe or advanced HIV clinical disease preogestogen-only pills (POPs). The findings of recommendations on ART medication interactions studies indirectly assessing the effect of various hormonal (see p. and cell-associated versus Decision-making for contraceptive methods usually cell/free measures of DNA and RNA). 12c. Female condoms are effective and safe. contraceptive methods varying according to individual circumstances. contraceptive methods on female-to-male HIV transmission by measuring genital viral shedding as a proxy for infectivity Remarks have been mixed. contraceptive patches and rings. has improved to asymptomatic or mild HIV clinical disease (WHO stage 1 or 2). comprehensive EN) and OCs (COCs and POPs): contraceptive information. or advanced HIV clinical disease (WHO stage 3 or 4) •• Women living with severe or advanced HIV clinical disease from enrolment.

POPs. The other study also did not find a progestogen-only injectables (DMPA and NET- statistically significant association for OCs (4). implants (MEC Category 1). to-male HIV transmission by measuring seroconversions in •• Women using the newer non-nucleoside/nucleotide reverse male partners of women with known hormonal contraceptive transcriptase inhibitors (NNRTIs). use status. injectables (DMPA and NET-EN) and OCs (COCs to-male HIV transmission by measuring seroconversions and POPs): in male partners of women known to be using hormonal contraceptives. NET-EN and implants (MEC Category 2). POPs. initiation of ART. or mortality studies measuring whether various hormonal contraceptive (29–35). while the other study •• Women using protease inhibitors (e. NET-EN. female-to-male transmission of HIV (5). However. limiting its interpretation (36. contraceptive patches and rings. and cell-associated versus had mixed results. seven suggest no association HIV transmission by measuring genital viral shedding as a between use of COCs and progression of HIV. CICs. etravirine and rilpivirine. One of these studies reported an elevated. had significant loss to follow-up and method. progestogen-only injectables (DMPA and study. 37). The majority of indirect studies measuring cell/free measures of DNA and RNA).86 | Medical eligibility criteria for contraceptive use . or mortality (31–35). RNA versus DNA. point estimate for oral Disease transmission (direct evidence) – very low contraceptives (OCs) (5). COC users when compared with users of copper-bearing IUDs (Cu-IUDs) (36. Disease progression – LNG-IUD: very low but not statistically significant. Recommendations among women living with HIV using antiretroviral therapy (ART) Out of six available studies. as measured by CD4 count transcriptase inhibitor (NRTI) can use all hormonal < 200 cells/mm3. CICs. including LNG-IUD 12d. One of these studies reported a statistically can use all hormonal contraceptive methods without significant association between injectable contraception and restriction (MEC Category 1). Quality of the evidence Two prospective observational studies directly assessed the Disease progression – progestogen-only low effects of different hormonal contraceptive methods on female. this only pills (POPs). progestogen- and POP) users when compared with Cu-IUD users. can generally use COCs. of DMPA and female-to-male HIV transmission (4). 37). contraceptive patches and rings. Progestogen-only contraceptives (POCs). and levonorgestrel (LNG) and etonogestrel (ETG) switching among groups. studies providing indirect whether various hormonal contraceptive methods affect evidence assessing proxy measures of transmission did not plasma HIV viral load have found no effect (38–53). women using Two prospective observational studies directly assessed the efavirenz or nevirapine can use DMPA without restriction effects of different hormonal contraceptive methods on female. five suggested no association between use of progestogen-only injectable contraceptives •• Women taking any nucleoside/nucleotide reverse and progression of HIV. outcome of declining CD4 count or death among OC (COC combined injectable contraceptives (CICs). and can use DMPA without restriction (MEC Category 1). One randomized trial found an increased risk of a methods affect plasma HIV viral load have found no effect composite outcome of declining CD4 count or death among (38–53). patches. ritonavir and did not find a statistically significant association between use ARVs boosted with ritonavir) can generally use COCs. The majority of indirect by CD4 count < 200 cells/mm3. EN) and OCs (COCs and POPs): Studies indirectly assessing the effect of various hormonal Note: As there remains considerable uncertainty regarding contraceptive methods on female-to-male HIV transmission by the best way to measure genital HIV shedding (with respect to measuring genital viral shedding as a proxy for infectivity have collection method. and LNG and ETG implants (MEC Category 2).Part I Combined hormonal contraceptives (CHCs) The findings of studies indirectly assessing the effect of various hormonal contraceptive methods on female-to-male Out of eight available studies. (MEC Category 1). as measured proxy for infectivity have been mixed.g. . initiation of ART. NET-EN). undergo a GRADE assessment. One study found no difference in ART initiation or CD4 count •• Women using ART containing either efavirenz or nevirapine between users and non-users of the LNG-IUD (54). One contraceptive methods without restriction: combined oral randomized trial found an increased risk of a composite contraceptive pills (COCs). rings. however.

co-administration resulted in higher progestin for prevention of HIV transmission to non-infected sexual levels (68). comprehensive contraceptive information. 56. contraception alone: Decision-making for contraceptive methods usually requires the need to make trade-offs among the different Efavirenz-containing ART versus other ART in very low methods. with advantages and disadvantages of specific women using hormonal contraception: contraceptive methods varying according to individual ART + hormonal contraception versus ART alone: low circumstances. All with COCs (55. One study found higher progestin levels with partners. In women using and correct use of condoms. Based primarily on condoms are effective and safe. Etravirine and rilpivirine do not interact with asymptomatic or mild HIV clinical disease. •• Voluntary use of contraception by women living with HIV who wish to prevent pregnancy is critical for upholding Integrase inhibitors their reproductive rights and continues to be an important The integrase inhibitor raltegravir does not appear to interact strategy for reducing vertical HIV transmission. Female concurrent PI use in users of POPs (69). including one large study. societal and cultural context. Women living significant decreases in contraceptive hormone levels in with severe or advanced HIV clinical disease (WHO stage 3 women using COCs. 56). provided that their HIV clinical disease containing ART. 64). For efavirenz- (MEC Category 2). is critical the patch. the effectiveness of DMPA users with severe or advanced HIV clinical disease should is likely not affected by NNRTIs. male or female. be closely monitored for pelvic infection.Part I | 87 •• Women using the integrase inhibitor raltegravir can use all Non-nucleoside reverse transcriptase inhibitors (NNRTIs) hormonal contraceptive methods without restriction (MEC Category 1). LNG-IUD primarily on pharmacokinetic data. education and counselling to Quality of the evidence ensure informed choice. . Three clinical studies. One retrospective chart review of women using who already have an LNG-IUD inserted and who develop efavirenz-containing ART showed increased contraceptive severe or advanced HIV clinical disease need not have their failure rates for women using LNG implants (65). and vice versa (66. and vice versa (66. Hormonal contraception + ART versus hormonal very low choices are complex. Women’s contraceptive choices are made in a particular time. women have the right to evidence-based. multifactorial and subject to change. 71). perceptions and interpretations. and for protection against other STIs. women COCs (63. 70. a pharmacokinetic study showed consistent is asymptomatic or mild (WHO stage 1 or 2). 67). •• Women living with HIV and using ARVs should discuss the potential impact of certain ARVs on contraceptive efficacy with their health-care provider. but are not used as widely pharmacokinetic data. affected by PIs. 62). found use of nevirapine-containing ART did not increase ovulation or •• Women using ARV medication can generally use LNG-IUDs pregnancy rates in women using COCs (57–60). Consistent levels with ritonavir and ritonavir-boosted PIs. Protease inhibitors (PIs) Remarks •• Hormonal contraceptives do not protect against sexually Pharmacokinetic data suggest decreases in COC progestin transmitted infections (STIs). and a small clinical study showed higher or 4) generally should not initiate use of the LNG-IUD (MEC ovulation rates in women taking efavirenz-containing ART and Category 3 for initiation) until their illness has improved to COCs (57. Based IUD removed (MEC Category 2 for continuation). the effectiveness of DMPA is likely not by national programmes as male condoms. Summary of the evidence (Question 4: hormonal contraception–ART interactions) Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) NRTIs do not appear to have significant risk of interactions with hormonal contraceptive methods (55. However. 67). Medical eligibility criteria for contraceptive use . 61. including HIV.

09–4. . Cox model analysis results were used when different statistical methods were presented. with statistically significant effects in 4 studies.78.66.92).46–2.94–2.78).75) 88 | Medical eligibility criteria for contraceptive use .3–2.46–1.: (i) no adjust- ment for any measure of condom use. effects are based on adjusted risk estimates.46 and 0. IRR: incidence rate ratio. An explanation of the quality assessment for each study included in this table is described in the systematic review by Polis et al.87. 95% CI 0. 2 studies no clear effect (NET-EN and DMPA reported separately with no clear association and opposite effects for each type of hormonal contraceptive) DMPA: HR range 0. NET-EN: norethisterone enanthate.50) (3). 5 studies no effect (HR range 0.87–2.5–5. 95% CI 0.7) (n=1272) limitations determine imprecision (1 study) CI: confidence interval.0).0 in 6 studies: 4 studies increased risk (HR range 1. 1 study trend towards increased risk (HR 1. with statistically significant effects in 1 study. 2013) stratified estimates for COC (HR 0.. with statistically significant effects in 1 study. no study had all three major flaws – i. 1 study no effect (HR 0.0).6 (95% CI 0.49–1. 1 study no effect (HR 0. (n=27 585) limitationsa inconsistency imprecision moderate 95% CI 1. 2014 (28).12) and POP (HR 0..0 in 9 studies: 6 studies increased risk (HR range 1.60–1. (ii) unclear measurement of exposure to hormonal contraception.GRADE table 1 (Question 1): Does the use of a particular method of hormonal contraception directly increase the risk of HIV acquisition in women? Type and number of Overall Outcome Limitations Inconsistency Imprecision Indirectness Estimate of effect studies (number quality of participants) Injectable contraceptive use vs non-use HIV acquisition 9 cohort studiesa Serious Serious No serious No indirectness Low Injectables overall: hazard ratio (HR) or incidence rate ratio (IRR) range (n=28 219) limitationsa inconsistency imprecision 0.0–2. while all of these studies had important limitations or risk of bias.8 in 8 studies: 1 study increased risk (HR 1. 2 studies trend towards decreased effect (HRs 0.8.5). DMPA: depot medroxyprogesterone acetate.1–2.53–1.5. a Restricted to studies classified as “considered informative with important limitations”.Part I NET-EN: HR range 0. Note: For all the studies summarized for this question. HR: hazard ratio.94.55–5. 95% CI 0.99)b Implant use vs non-use HIV acquisition 1 cohort study Serious Cannot Serious Very low HR 1. (iii) inter-survey interval (time between study visits) < 6 months – and therefore were given an overall quality rating of “low” rather than “very low”. 95% CI 0.3–2. b One study (McCoy et al.66–1. 1 study trend towards decreased risk (IRR 0.86–0.e.5 in 5 studies: 4 studies increased risk (HR range 1.2) Oral contraceptive use vs non-use HIV acquisition 8 cohort studiesa Serious Serious No serious No indirectness Low to HR or IRR range 0.91. 95% CI 0.1). 95% CI 0.8).

3) for to CD4 count (1 fair) OC and 1. < 200 cells/mm3 CD4 count progression or initiation of ART Injectable contraceptive use vs non-use Mortality 5 cohort studies Serious Serious No serious No indirectness Low HR range 0.6 (95% CI 1.4 (95% CI 0. 1 poor) Progression to 4 cohort studies Serious No serious No serious No indirectness Low.1 (95% CI 0.1) for DMPA Progression 1 RCT (n=599) Serious Cannot determine Serious No indirectness Low HR 1.4) < 200 cells/mm3 (1 fair) for OC and 1.5 (95% CI 0. progression 4 cohort studies Serious No serious No serious No indirectness Low.5 (95% CI 1.38–3. 0.0 in 3 studies (no estimate showed AIDS or initiation of (n=6308) limitations inconsistency imprecision moderate statistically significant effect).0–2.0 to 2.7–3.72 (95% CI 0.91 (95% CI 0.8 (95% CI 1. HR 1.4 (95% CI 0. HR range 0.5) for DMPA for mortality.53–0.3).4 in 5 studies (no estimate (n=7136) limitations inconsistency imprecision showed statistically significant effect) (1 good. 1 study reported HR antiretroviral therapy (1 good. 3 fair.36) for ART initiation and HR (ART) 1 poor) 0. estimate not of ART (2 good. 1 study reported to AIDS or initiation (n=6851) limitations inconsistency imprecision moderate HR of 0.Part I | 89 .41–1.3–2.63–3.0). absolute risk increase limitations (1 study) imprecision 0.3–2. HR range 0.17) for progression to CD4 count < 200 cells/mm3 Mortality.82 (95% CI 0.72–1 in 4 studies.7/100 woman-years.0) (1 fair) for OC and 1.8 (95% CI 1.98–2.3). HR 1. HR 1.6/100 woman-years.6) for DMPA for CD4 count progression or initiation of ART Mortality or 1 RCT (n=599) Serious Cannot determine Serious No indirectness Low HR 1. absolute risk increase progression limitations (1 study) imprecision 4. absolute risk increase to CD4 count limitations (1 study) imprecision 3.88/100 woman-years.61–1.1–2.57–1.7–1. 2 fair) statistically significant in other studies Medical eligibility criteria for contraceptive use .98).GRADE table 2 (Question 2): Does the use of various hormonal contraceptive methods accelerate HIV disease progression in women living with HIV? Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Quality Estimate of effect participants) Hormonal contraception (oral or injectable) vs copper-bearing intrauterine device (Cu-IUD) Mortality 1 RCT (n=599) Serious Cannot determine Serious No indirectness Low HR 1.6 (95% CI 1. 2 fair.

CI: confidence interval.91 limitations (1 study) imprecision (1 poor) ART: antiretroviral therapy. DMPA: depot medroxyprogesterone acetate.28–1.96 (95% CI 0.61 (95% CI 0. Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Quality Estimate of effect participants) Oral contraceptive use vs non-use Mortality 6 cohort studies Serious No serious No serious No indirectness Low. RCT: randomized controlled trial. HR range 0. 2< 200 cells/mm3studies reported no events 2 poor) Progression to AIDS 5 cohort studies Serious No serious No serious No indirectness Low HR range 0. reported HR 0. .3 in 4 studies (no estimate or initiation of ART (n=6078) limitations inconsistency imprecision showed statistically significant effect)a. 2 fair. 2 fair) Levonorgestrel IUD vs no hormonal contraception Initiation of ART 1 study (n=40) Very serious Cannot determine Very serious No indirectness Very low 43% vs 45%. P = 0.25–1.0 in 4 studies (no estimate to AIDS or initiation (n=6059) limitations inconsistency imprecision moderate showed statistically significant effect)a of ART (2 good.84–1. 1 study (1 good.Part I Mortality. HR: hazard ratio. progression 4 cohort studies Serious No serious No serious No indirectness Low.52–1.79) for progression to CD4 count < 200 cells/mm3 90 | Medical eligibility criteria for contraceptive use . HR range 0.45) for ART 2 poor) initiation and HR 0.65–1. (1 good. (2013) on risk with DMPA and OC separately (29). a Includes data from Heffron et al.1 in 4 studies (no estimate (n=6864) limitations inconsistency imprecision moderate showed statistically significant difference)a. OC: oral contraceptives. 3 fair.

0 (95% CI 1. absolute increase about 1 transmission/100 person-years (5).49–13)c CI: confidence interval. a Combined estimate from Heffron et al.1–3.5 (95% CI transmission (2 fair)b inconsistency imprecision 0.Part I | 91 .70)c Oral hormonal contraceptive use vs non-use HIV 2 cohort studies (n=2635) Serious limitations No serious Very serious No indirectness Very low HR 2.49) for injectable and 2.4). HR: hazard ratio.18–2. Medical eligibility criteria for contraceptive use .5) when adjusted for viral load.6) and 0.57 (95% CI transmission (2 fair)b inconsistency imprecision 0.30–6. (2012) not rated but limitations noted in assessment of condom use and potential for residual confounding (5).75–5.1 (95% CI 0. (2012) for injectable or oral hormonal contraceptive use vs non-use: HR 2. Heffron et al. (2013) rated fair-quality (4). b Lutalo et al.1–3.8) and 2.0 (95% CI 1.19–1.40 (95% CI 0.GRADE table 3 (Question 3): Does the use of various hormonal contraceptive methods increase the risk of female-to-male HIV sexual transmission? Type and number of Outcome studies (number of Limitations Inconsistency Imprecision Indirectness Quality Estimate of effecta participants) Injectable hormonal contraceptive use vs non-use HIV 2 cohort studies (n=2635) Serious limitations Serious Very serious No indirectness Very low HR 2. c HR 1.11 (95% CI 0.

COC: combined oral contraceptive. IRR: incidence rate ratio. 1 cohort study found lower study (n=4531) trial.97 [95% CI 1. 1 study reported 1 failure with EFV vs 7 with NVP in women using various hormonal contraceptives.Part I injectables) Efavirenz (EFV) vs other ART in women using hormonal contraception Pregnancy 2 cohort studies Serious limitations Unclear Serious No indirectness Denominators Very low 1 study found 12. pregnancy rate prior to initiation of ART vs quality cohort after initiation in women on various hormonal study) contraceptives.10 [95% CI 0.89–10. 1 poor) inconsistency imprecision in hormonal measures of ART treatment failure in 3 studies contraception. but estimates were imprecise (IRR 3. and 1 study ART regimens.00] for COC and 1.GRADE table 4 (Question 4): Are there any possible interactions between hormonal contraceptive methods and ARV medications? Type and number of studies Outcome Limitations Inconsistency Imprecision Indirectness Other factors Quality Estimate of effect (number of participants) Hormonal contraception + antiretroviral therapy (ART) vs hormonal contraception alone Pregnancy 1 non.21] vs 5.28–3. of both) and measures of ART effectiveness CI: confidence interval.55–6.01] for 92 | Medical eligibility criteria for contraceptive use . 1 poor. 1 study of COCs.4% pregnancy rate with (n=1197) (2 fair) imprecision not provided in EFV vs 0% with nevirapine (NVP) or loopinavir 1 study (LPV)/ritonavir (RTV) in women using LNG implant. DMPA: depot medroxyprogesterone acetate. but denominators were unclear ART + hormonal contraception vs ART alone ART 3 cohort studies Serious limitations No serious Serious No indirectness Variability Low No effect of hormonal contraception on effectiveness (n=679) (2 fair.63–1. (1 study of DMPA.94] vs 1.11 [95% CI 1. . Note: Table includes evidence from comparative studies reporting clinical outcomes.38 [95% CI 2. 1 cohort non-randomized contraception + COC vs no ART. Serious limitations No serious No serious No indirectness Variability Very low 1 non-randomized trial found no difference randomized trial (1 good-quality inconsistency imprecision in hormonal in pregnancy rate with nevirapine-based ART (n=336).

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et al. J Infect Dis. Polis CB. Landay A. Determinants of HIV Chintu N. AIDS.Part I 26. 2001. Masese L. . Kissinger PJ. Carter RJ. Steyn and HIV-1 disease progression among postpartum PS. Rinaldi A. et al. AIDS. Contraception. Were use in a cohort of Louisiana women. Effect of hormonal contraceptive use 27. Jalalian-Lechak Z.181(5):1598–606. Watts DH. Levy J.gov/pmc/articles/PMC1758227/ 42. Survival and progression of HIV in cervical and vaginal secretions. Phillips SJ. progression among women in Uganda and Zimbabwe. early HIV-1 infection. Acquir Immune Defic Syndr. et al.202(10):1538–42. Stringer EM. 1996. Matongo I. Mugo N. Kreiss JK.e1–8. Donnell D. Association between 33. et al. Plummer workers in Thailand. Mbori-Ngacha D. et al. Richardson BA. 2009. Lavreys L. Morrison CS. Hormonal contraceptive use and HIV disease human immunodeficiency virus DNA. Antiretroviral adherence 31. 41. Weiss H. Limpakarnjanarat K. Kenya. Gitau R. et al. Celum C. Pregnancy. Thammapornpilap P. 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Mildvan D. Depo-medroxyprogesterone in women on 56. Garner D. Combined oral contraceptives Nalugoda F. Lehtovirta P. PloS One. Overbaugh J. Stuart GS.28(5):791–3. Baeten JM. and Efavirenz. Ristola M. 67. in contrast to Bahamondes L. Le Goff J. Corbett A.55(4):473–82. Welch MJ. Stevens M. Hoetelmans RM. Gray RH. Watts H. Lack of effect of tenofovir antiretroviral therapy: effective contraception and lack disoproxil fumarate on pharmacokinetics of hormonal of clinically significant interactions. Weiss HA. et al. et al. Delany-Moretlwe S. Landolt NK. Iacobone D.80(1):44–52. et al. Clax PA. Mandaliya K. Zara F. et al. 2002. 2007. Mandaliya K.2012:137192. Kiwanuka N. infected women in Dakar. Aho I. J Acquir Immune Defic Syndr. Peeters M. contraceptives. Cohn SE. 50.6(3):e17480.77(3):190–3. Phanuphak N. J Acquir Immune Defic Syndr. 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The effect of efavirenz on the pharmacokinetics transmitted HIV-1 population. et al. Kumwenda W. Contraception. Molife L. Vandermeulen K. Hays M. Persson A. and other risk factors for shedding does not reduce oral contraceptive effectiveness. combined oral contraceptives. Cu-Uvin cervicovaginal shedding of human immunodeficiency S. Woodfall B. 2011. intracellular pharmacokinetics of zidovudine. Preidis GA. Pharmacokinetic interaction between with protease inhibitors in HIV-1-infected women: nevirapine and ethinyl estradiol/norethindrone when pharmacokinetic results of ACTG trial A5188. Thevanayagam L. Contraceptive efficacy of oral 58. Hutman HW. Rusizoka 2014.20(14):1833–41. Eley T. Spinillo A. Segal Y. Richardson BA. Perry SH. Kigozi G. DeVange DM. Carten ML. Antivir 52. 2006. Aweeka F. 2013.62(5):534–9. Mulanga-Kabeya C. living with HIV in a resource-limited setting in sub- Bardeguez A. Scholler-Gyure M.350(9082):922–7. Ahluwalia J. Motsa N. et al. Moses A. 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Atrio J. Moreau AR. Jr. Br J Clin Pharmacol. .96 | Medical eligibility criteria for contraceptive use .Part I 69.65(1):72–7. accessed on 18 July 2014).org/ data/NewsItem/103_CROI_2013. et al.hiv-druginteractions. Borland J.71(4):616–20. Anderson MS. Effect of protease inhibitors on steady-state pharmacokinetics of oral norethindrone contraception in HIV-infected women. Dolutegravir has no effect on the pharmacokinetics of methadone or oral contraceptives with norgestimate and ethinyl estradiol. Jin B. 3–6 March 2013 (http://www. Chen S. J Acquir Immune Defic Syndr. Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women. Stanczyk FZ. Atlanta (GA): 20th Conference on Retroviruses and Opportunistic Infections. Kovacs A. et al. Peppercorn A. Song I.pdf. Cherala G. Kost JT. Mishell DR. 2014. 2011. 71. 70. Mark S. Wajima T. Bieberdorf FA. Hanley WD. Neely M.

Part II | 97 Part II Using the recommendations . Medical eligibility criteria for contraceptive use .

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women and children but also as a human right.htm. which includes taking into account clients’ matters relating to the reproductive system and to its functions sexual and reproductive health care needs and considering all and processes”1. lactational amenorrhoea method. care. family planning the number and spacing and timing of their services by providing policy-makers. These evidence.3 A rights-based as: “a state of complete physical. mental and social well. . and not merely the absence of disease or infirmity. The Programme of Action also states that appropriate eligibility criteria when helping clients choose and the purpose of sexual health “is the enhancement of life use a family planning method safely.who. These (e. 1995).177/20.html. The goal of the document and individuals to decide freely and responsibly is to improve access to. http://www. These rights rest (MEC) provides guidance regarding which clients can use on the recognition of the basic right of all couples contraceptive methods safely. accessed 24 April popin/icpd/conference/offeng/poa. 95 (A/CONF. decision-makers children and to have the information and means to and the scientific community with recommendations that do so. 1994: para. and not merely counselling and care related to reproduction and sexually transmitted diseases”. age). of the recommendations allows for consideration of multiple International and regional human rights treaties. include the guarantee that states should ensure timely and affordable access to good quality sexual and reproductive 2. accessed 24 April 2015).g. including family planning services and information.171/13. protection and fulfilment Recognizing the importance of agreements made at the ICPD of human rights contribute to positive health outcomes. respects dignity. coitus by states in 2001. is based recommendations do not indicate a “best” method that recognized not only as a key intervention for improving the should be used in a particular medical context.int/iris/bitstre ed Nations. and quality of. Geneva: Population and Development (Cairo. target 5b calls for universal access to interruptus.2 on the medical eligibility criteria for the use of specific contraceptive methods. United Nations. 7. hypertension) or relevant characteristics to access to contraceptive information and services. male and female reproductive health by 2015. Unit. 2014 (http://apps. and personal relations. privacy and The Programme of Action of the International Conference on confidentiality. un. Methods covered by this guidance include all hormonal contraceptives. 2015).pdf. 1995: para. and other international conferences and summits. In: Report of the Fourth World Conference on Women (Beijing. approach to the provision of contraceptives assumes a holistic being. and is sensitive to individuals’ needs and Population and Development (ICPD) defines reproductive health perspectives in a client–provider partnership.g.2 (A/CONF. national methods that could be used safely by people with certain constitutions and laws provide guarantees specifically relating health conditions (e. Among the Millennium Development Goals (MDGs) agreed barrier methods. and emergency contraception. 4–15 September. In: Report of the International Conference on mation and services: guidance and recommendations. confidentiality and informed in the following way: choice.un. autonomy. 5–13 September 1994). and the right to attain the highest standard can be used for developing or revising national guidelines of sexual and reproductive health.1 Reproductive and sexual health care as a human health information and services. the Beijing The provision of contraceptive information and services Declaration and Platform for Action defines reproductive rights that respect individual privacy. right which should be delivered in a way that ensures fully informed decision-making. along with a wide range of safe contraceptive 2 Beijing Declaration and Platform for Action.1.1 Background Reproductive rights embrace certain human rights that are already recognized in national laws. in all view of clients. international human rights documents and other The Medical eligibility criteria for contraceptive use relevant consensus documents. Medical eligibility criteria for contraceptive use .org/ am/10665/102539/1/9789241506748_eng.org/documents/ga/conf177/aconf177–20en.Part II | 99 2. fertility awareness-based methods. World Health Organization. rather. intrauterine devices. http://www. review health of men. accessed 17 April 2015). 1 Programme of Action of the International Conference on Population 3 Ensuring human rights in the provision of contraceptive infor- and Development. Reproductive and sexual health sterilization. including contraception. Evidence shows that the respect.

cervical caps). RamaRao S. The impact of quality of care on contraceptive use: equipped and accessible facilities must be available. to be maintained and held in stock (e. but are eligible to use various contraceptive methods. preference – must also be taken into account. and social. Int Fam Plann Perspect. Decisions these should not be seen as eligibility requirements for about what methods to use should also take into account specific contraceptive methods. and these vary according to individual insertion. 7 Sanogo D. appropriately trained personnel in adequately 4 Koenig MA. and supplies for infection-prevention link between quality of care and contraceptive use. Factors to provider (i. •• Adequate and appropriate equipment and supplies need zania. voluntary choice of a contraceptive method. This information should at least include: 2. . Kessy FL. Such procedures and choice should be strongly encouraged if the human and material The following service-delivery criteria are universally relevant resources are available to carry them out. fitting and/or removal by a trained health-care circumstances. Lacuest M. J Biosoc Sci. anaemia and sexually transmitted infections (STIs).4 5 6 7 include the characteristics of the potential user. J Reprod Health. M’bow B. however. quality of care and access to facilities on contraceptive use in Tan. Diop CB. her choices are made at a particular time. it provides health care. •• Service providers should be provided with guidelines. the adverse effects profile of different products. 2007. Information should be presented using language and multifactorial and subject to change. economic and cultural factors. of different methods. choices are complex. informed choices for themselves. IUDs. client Improving quality of care and use of contraceptives in Senegal. Delivery of care in accordance with the client’s human and cost. in a particular societal and cultural context. contraceptive 6 RamaRao S.100 | Medical eligibility criteria for contraceptive use . make trade-offs among the advantages and disadvantages •• In order to offer methods that require surgical approaches. Instead. While this document primarily addresses medical eligibility –– how it works. The development of international norms for medical eligibility This document does not provide recommendations about criteria and practice recommendations for contraceptive use which specific product or brand to use after selecting a is only one aspect of improving the quality of reproductive particular type of contraceptive method.2 Contraceptive choice –– the relative effectiveness of the method. point of view. behavioural and other non-medical criteria – particularly client –– common side-effects. From a woman’s –– information on STI protection. increase people’s satisfaction and continued use of consider when choosing a particular contraceptive method contraception. These procedures include clinical judgment and user preferences.Part II methods. The impact of demand factors. Decision-making formats that can be easily understood and accessed by the regarding contraceptive methods usually requires the need to client.e. implants. diaphragms. and the promotion of Issues of service quality and access that affect method use breastfeeding and cessation of smoking. Pangolibay B. treatment and follow-up procedures that reflect or medically relevant physiological or personal characteristics high standards of public health and clinical practice. 2003.7:57–73. Costello M. N’diaye P. procedures). Baltimore appropriate infection-prevention procedures must be (MD): Johns Hopkins University. considerations of social. the screening and treatment of cervical cancer. Many family planning programmes have included guidance for whether women with specific medical conditions screening. and evidence from longitudinal data from rural Bangladesh. Women’s choices.1. sterilization. make an informed. reproductive rights is fundamental to quality of care. 2003. the baseline risk of disease. 2003. To provide –– health risks and benefits of the method.29(2):76–83. Afr cards or other screening tools. perceptions and interpretations. criteria for contraceptive use. Johnes H.g. contraceptive choices to clients in a way that respects and –– signs and symptoms that would necessitate a return to fulfils their human rights necessitates enabling clients to make the clinic. –– information on return to fertility after discontinuing are often taken away from them or limited by direct or indirect method use. –– correct usage of the method.39:1–26. 5 Arends-Kuenning M. availability and patient preferences. followed. Jones H. but they should not to the initiation and follow-up of all contraceptive method use: be seen as prerequisites for the acceptance and use of family planning methods since they are not necessary to establish •• Clients should be given adequate information to help them eligibility for the use or continuation of a particular method. The commodities.

in turn.1 compares 2. Most men and women tend to be more effective users as Contraceptive choice is in part dependent on the effectiveness they become more experienced with a method. •• Schistosomiasis with fibrosis of the liver or of > 20 years’ duration •• Severe (decompensated) cirrhosis •• Endometrial or ovarian cancer •• Sickle cell disease •• Epilepsy •• STI b •• High blood pressure (systolic > 160 mm Hg or •• Stroke diastolic > 100 mm Hg)a •• Systemic lupus erythematosus (SLE) •• HIV (WHO stages 1–4)b •• Thrombogenic mutations •• Ischaemic heart disease •• Tuberculosis a Throughout this document.1.g. but also on how consistently and correctly it is used. These conditions are noted in Box 2.0/10.g condoms and pills) have a wide range of effectiveness. Box 2. is dependent for some methods not effectively (consistently and correctly) the method will be used.Part II | 101 2.1333 (e. income. which. because and/or incorrect use).1.3 Effectiveness of method (e. b Dual protection is strongly recommended for protection against HIV/AIDS and other STIs when a risk of STI/HIV transmission exists.1. . Consistent and correct usage can both of their relatively higher typical-use failure rates. only on the protection afforded by the method itself. or with nephropathy/ hepatocellular carcinoma of the liver (HCA) retinopathy/neuropathy or other vascular disease. However.7 kPa).4 Conditions that expose a woman to increased the percentage of women experiencing an unintended risk as a result of unintended pregnancy pregnancy during the first year of contraceptive method use when the method is used perfectly (consistently and correctly) Women with conditions that may make unintended pregnancy and when it is used typically (assuming occasional non-use an unacceptable health risk should be advised that. 120/80 mm Hg = 16. Methods methods of contraception may not be the most appropriate that depend on consistent and correct usage by clients choice for them. Table 2. and culture. of the contraceptive method in preventing unplanned programmatic aspects also have a profound effect on how pregnancy. of barrier methods for contraception and behaviour-based desire to prevent or delay pregnancy. Medical eligibility criteria for contraceptive use . This can be achieved through the simultaneous use of condoms with other methods. sole use vary greatly with client characteristics such as age. or the consistent and correct use of condoms alone.1 Conditions that expose a woman to increased health risk as a result of unintended pregnancy •• Breast cancer •• Malignant gestational trophoblastic disease •• Complicated valvular heart disease •• Malignant liver tumours (hepatoma) and •• Diabetes: insulin-dependent. blood pressure measurements are given in mm Hg. To convert to kPa. multiply by 0.

Contraceptive efficacy.05 0. United States % of women experiencing an unintended % of women continuing pregnancy within the first year of use use at one year3 Method Typical use1 Perfect use2 (1) (2) (3) (4) No method4 85 85 – Spermicides 5 28 18 42 Fertility awareness-based methods 24 – 47 Standard Days Method®6 – 5 – TwoDay Method®6 – 4 – Ovulation Method6 – 3 – Sympto-thermal method – 0.102 | Medical eligibility criteria for contraceptive use .10 Source: Trussell J.3 67 NuvaRing ® 9 0. 2011. . In: Hatcher RA. Cates W.2 80 Implanon ® 0.10 100 Emergency contraceptives: Emergency contraceptive pills or insertion of a copper-bearing intrauterine device after unprotected intercourse substantially reduces the risk of pregnancy.9 Lactational amenorrhea method: LAM is a highly effective.Part II Table 2. Kowal D.6 78 Mirena® (LNG) 0.8 0.5 100 Male sterilization 0. New York (NY): Ardent Media.2 0.05 84 Female sterilization 0.5 0.4 – Withdrawal 22 4 46 Sponge – – 36 Parous women 24 20 – Nulliparous women 12 9 – Condom7 Female 21 5 41 Male 18 2 43 Diaphragm 8 12 6 57 Combined pill and progestin-only pill 9 0. Policar M.3 67 Evra patch 9 0. Trussell J. editors. Nelson AL.2 56 Intrauterine devices Paragard® (copper T) 0.3 67 Depo-Provera 6 0.1 Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception and the percentage continuing use at the end of the first year. Contraceptive technology: twentieth revised edition. temporary method of contraception.15 0.

See the text for the derivation of estimates for the other methods (Trussell. bottle feeds are introduced. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. creams. about 89% become pregnant within one year. The United States Food and Drug Administration has in addition declared the following 19 brands of oral contraceptives to be safe and effective for emergency contraception: Ogestrel® (one dose is two white pills). . Cryselle®. 2 Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly). ella® and Next Choice One Dose® are the only dedicated products specifically marketed for emergency contraception in the United States at the time of writing. the male condom. estimates for fertility-awareness-based methods. and Lybrel® (one dose is six yellow pills). Nordette® (one dose is four light-orange pills). The label for Plan B One-Step (one dose is one white pill) says to take the pill within 72 hours after unprotected intercourse. to maintain effective protection against pregnancy. the frequency or duration of breastfeeds is reduced. 9 Plan B One-Step®. or Quasence® (one dose is four white pills). 6 The Ovulation Method and TwoDay Method® are based on evaluation of cervical mucus. another method of contraception must be used as soon as menstruation re- sumes. Among such populations. Estimates of the probability of pregnancy during the first year of typical use for spermicides and the diaphragm are taken from the 1995 National Survey of Family Growth corrected for underreporting of abortion. Research has shown that all of the brands listed here are effective when used within 120 hours after unprotected sex.Part II | 103 Notes: 1 Among typical couples who initiate use of a method (not necessarily for the first time). Portia®. The sympto-thermal method is a double-check method based on evaluation of cervical mucus to determine the first fertile day and evaluation of cervical mucus and temperature to determine the last fertile day. or the baby reaches 6 months of age. Low-Ogestrel®. withdrawal. the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. Seasonale® or Trivora® (one dose is four pink pills). the percentage who experience an accidental preg- nancy during the first year if they do not stop use for any other reason. Seasonique® (one dose is four light-blue-green pills). Enpresse® (one dose is four orange pills). gels. 3 Among couples attempting to avoid pregnancy. 4 The percentages becoming pregnant in columns 2 and 3 are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. See the text for the derivation of the estimate for each method (Trussell. 7 Without spermicides. The label for Next Choice One Dose (one dose is one peach pill) says to take one pill within 72 hours after unprotected intercourse. 2011). Lessina® (one dose is five pink pills). Aviane® or LoSeasonique® (one dose is five orange pills). the pill and Depo-Provera are taken from the 1995 and 2002 National Survey of Family Growth corrected for underreporting of abortion. Lo/Ovral®. 2011). 8 With spermicidal cream or jelly. 5 Foams. Lutera® or Sronyx® (one dose is five white pills). Levora®. Jolessa®. Medical eligibility criteria for contraceptive use . the percentage who continue to use a method for one year. 10 However. The Standard Days Method® avoids intercourse on cycle days 8–19. vaginal suppositories and vaginal film.

5 Return to fertility preparation of guidelines for delivery of contraceptive services. the first column family planning programme managers and the scientific indicates the conditions (each in a separate row).104 | Medical eligibility criteria for contraceptive use . as described in section 2. continuation of use. These may include high prevalence provides space for any necessary clarifications or presentation rates of STIs and HIV in the geographic area. Male and female sterilization should be regarded will vary.3. including HIV. permanent infertility.g. Women and men seeking contraceptive eligibility. cultural and behavioural context of each client characteristic (e. regardless of the duration likely that the application of these categories at country level of their use. condoms offer one of the most are noted in the columns of the tables for each contraceptive effective methods of protection against STIs. including HIV. transmission and strongly recommend dual protection to all persons at significant risk. the problems of exposure to STIs. In this regard. The median delay in return provided.1.6 STIs and contraception: dual protection contraceptive methods included in the guidance with each condition. In particular. including HIV. contraceptive provision to assure quality of care in services. Several community. these differences used correctly and consistently. It aims to provide guidance to national family conditions are subdivided to differentiate between varying planning and reproductive health programmes in the degrees of the condition.8 it is important that health-care appropriate approach. each contraceptive (provided in section 2. either through the simultaneous use Initiation and continuation of condoms with other methods or through the consistent and The medical eligibility criteria for the initiation and continuation correct use of condoms alone for prevention of both pregnancy of all contraceptive methods are used in the evaluation of and STIs. Each condition was defined as representing either In addition to the imperative of international norms for a known pre-existing medical/pathological condition (e. A family planning provider may want to providers offer information on safer sexual practices to prevent consult an expert in the underlying condition. sterilization are regarded as irreversible (or permanent). When continuation of a contraceptive method differ. with the at country and programme levels in a manner that reflects the exception of depot medroxyprogesterone acetate (DMPA) and diversity of situations and settings in which contraceptives are norethisterone enanthate (NET-EN). and/or individual risk behaviour such as multiple partners without using condoms.1.Part II 2. of evidence regarding the classification . When a risk of HIV and health importance. Where I and C are Female condoms are effective and safe. the category is the same for initiation and widely by national programmes as male condoms. While it is unlikely that the classification of categories to fertility with these methods is 10 and 6 months. hypertension) or a medically relevant individual the social. The second column classifies the condition for initiation and/or continuation into one of the four MEC categories. No other methods result in consideration. must also be considered. All other methods are reversible. C = continuation). but are not used as not denoted. Client history will often be the most other STI transmission exists.g. respectively. diabetes. experience of various types of providers and the resources and all individuals and couples considering these methods available at the service-delivery point will have to be taken into should be counselled accordingly. only male and female reference.2 How to use this document As shown in Table 2. It is not meant to serve as the actual guidelines but rather as a Among contraceptive methods.2 in a simplified template of the tables for The present document is intended for use by policy-makers. The third column 8 This can be context specific. it is very from the date of the last injection.7). the level of clinical knowledge and as permanent methods (no possibility of future childbearing). deserve special consideration It is expected that national and institutional health-care and because of the equal importance of preventing pregnancy service-delivery environments will decide the most suitable and preventing transmission of infections among sexually means for screening for conditions according to their public active clients of reproductive age. 2. Where medical eligibility for initiation and should be encouraged and facilitated where appropriate. usually with prompt The guidance in this document is intended for interpretation return to fertility upon method discontinuation. The assessment of continuation criteria is clinically advice must always be reminded of the importance of condom relevant whenever a woman develops the condition while she use for preventing the transmission of STI/HIV and such use is using the method. age. method (I = initiation. history of pregnancy). in this document would change during this process. Recommendations are presented in tables according to the 2.

Where resources for clinical judgment are limited. provision of a method to a woman with a condition community-based services. these are described at the beginning of the relevant sections. 2. for such a woman.3). For a method/condition classified as Category 3.2 Template of contraceptive method tables Type of contraceptive Condition Category Clarifications/evidence I = initiation C = continuation Condition Condition classified as Category 1. Medical eligibility criteria for contraceptive use .3 Using the categories in practice use of that method is not usually recommended unless other more appropriate methods are not available or acceptable. the four-category classification classified as Category 3 requires careful clinical judgement framework can be simplified into two categories. method (see Table 2. With this and access to clinical services. but careful follow-up may be required. a classification of Category 1 or 2 indicate that severity of the condition and the availability. practicality and a woman can use a method. such as in However. Classification of a Careful follow-up will be required. Medical eligibility criteria (MEC) categories for contraceptive use Category 1 A condition for which there is no restriction for the use of the contraceptive method Category 2 A condition where the advantages of using the method generally outweigh the theoretical or proven risks Category 3 A condition where the theoretical or proven risks usually outweigh the advantages of using the method Category 4 A condition which represents an unacceptable health risk if the contraceptive method is used Table 2. the simplification. and a classification of Category 3 acceptability of alternative methods should be taken into or 4 indicate that a woman is not medically eligible to use the account.3 Interpretation and application of the categories in practice With limited resources for clinical Category With good resources for clinical judgement judgement 1 Use method in any circumstances Yes (Use the method) 2 Generally use the method 3 Use of method not usually recommended unless other more appropriate methods are not available or not acceptable No (Do not use the method) 4 Method not to be used . 3 or 4 Clarifications and evidence regarding the classification Different categories are used for fertility awareness- based (FAB) methods and surgical sterilization. Categories 1 and 4 are self-explanatory.Part II | 105 2. method/condition as Category 2 indicates the method can generally be used. Table 2.

however. decision that is. medical decisions must be based upon will need to determine how far and by what means it may be informed choice.106 | Medical eligibility criteria for contraceptive use . found a family and retain their fertility methods (Article 23)9. in such of space. The promotion of different conceptive methods. and to look closely at the with disabilities. the nature of the disability and the specifics of but are not related to use of the method. •• referral and follow-up for contraceptive use as appropriate. require decisions regarding of the particular contraceptive method should be distinguished appropriate contraception considering the preferences of the from practices that may be appropriate for good health care individual. It is expected that national and institutional have difficulty remembering to take daily medications. Geneva: World Health Organiza- tion. individuals with intellectual or mental health disabilities who delivery system. Health-care professionals often fail to offer sexual •• provider training and skills and reproductive health services to people with disabilities. For health-care and service-delivery environments will decide the women who have difficulty with menstrual hygiene. ties. the impact most suitable means for screening for conditions according to of the contraceptive method on menstrual cycles should also their public health importance. because of concerns about an criteria need to be considered in light of the country context. or it may require or a individual. Client history will often be the be considered. net/a61r106. people with disabilities must have access. Resolution adopted by the United Nations General Assembly.4 Programmatic implications 2.1 People with disabilities applying the medical eligibility criteria in this document to programmes: According to United Nations Convention on the Rights of •• informed choice Persons with Disabilities (CRPD). an appropriate method for women with impaired circulation or immobile extremities. http://www. This may involve upgrading both staff and more challenging to discern the will and preferences of the facilities where feasible and affordable. accessed 24 April 2015). based on adequate sexual and reproductive possible to extend their services to the more peripheral levels health education.10 Provision of contraceptive services to people Service-delivery practices that are essential for the safe use with disabilities may.un-documents. increased risk of DVT.5 Clients with special needs The following issues need to be addressed when 2. some barrier methods may be difficult to use obstacle to the provision of a contraceptive method. often as those well acquainted with prevailing health conditions. 2006 (A/RES/61/106. most appropriate approach. These improvements must be made within the context of users’ informed choices and medical 9 United Nations Convention on the Rights of Persons with Disabili- safety. and other methods will be preferable for so as to be applicable to providers at all levels of the service.int/disabilities/world_report/2011/ report/en/. the recommendations on medical eligibility thrombogenic mutations. accessed 9 April 2015). even in the absence of known As a next step. behaviours and cultures. to all forms of •• elements of quality of care sexual and reproductive health care (Article 25) as part of the •• essential screening procedures for administering the general right to marry. 10 World report on disability 2011.Part II 2. When the nature of the disability makes it of the health system. and redeployment consistent with Article 12 of the CRPD. to the greatest extent possible. consistent with the will and preference of that individual. contraceptives should only be provided in a manner modest addition of equipment and supplies.5. United Nations.who. It will also be necessary to address misperceptions cases a process of supported decision-making should be sometimes held by providers and users about the risks and instituted in which individuals who are trusted by the individual side-effects of particular methods.htm. but as for those with limited manual dexterity. Countries In all instances. Specifically. based on the common misconception that they are not sexually active. COCs may not be complementary to it. on an equal basis with others. . personal ombudsman and other support needs and perspectives of women and men in the context of persons jointly participate with the individual in reaching a informed choice. 2011 (http://www. A family planning provider may want to consult an expert in the underlying condition. good health-care practices unrelated to safe contraception should be considered neither as a prerequisite nor as an For example. Given the history of Adaptation is not always an easy task and is best done by involuntary sterilization of persons with disabilities.

increased to protect their sexual and reproductive health. new contraceptive methods included in this fifth edition. There is an acceptance and increased prevalence of contraceptive use. Appropriate sexual and reproductive health services. cardiovascular disorders) that may limit the use of some changes to the labelling of certain conditions (in order to be methods in older women do not generally affect young people. adolescents are also at increased risk for STIs. Political and cultural factors may affect adolescents’ ability to access contraceptive information and services. clients also apply to young people. same methods of contraception as adults. While adolescents may choose to use any one of the contraceptive methods available in their communities. these concerns must be balanced against the edition of the MEC. have a right to privacy and confidentiality in health matters.6). and details for the since these conditions are rare in this age group. Adolescents. or that health workers may be judgmental. where contraceptive services are available. including contraception. For example. Expanding the number of method contraceptive information and services that are necessary choices offered can lead to improved satisfaction. .g. Social and behavioural issues should be key considerations in the choice of contraceptive methods by adolescents. These changes include: changes to MEC that many of the same eligibility criteria that apply to older categories between the earlier editions and the fifth edition. (e. have also been shown to be less especially important to ensure that decisions about sterilization tolerant of side-effects and therefore have high discontinuation are only made with the full. Even if adolescents are able to obtain contraceptive services. uncoerced and informed consent of rates. urgent need to implement programmes that both meet the Proper education and counselling – both before and at the contraceptive needs of adolescents and remove barriers to time of method selection – can help adolescents address their services. policy or practice. including HIV. All adolescents. either alone or with support. In general. and must have Every effort should be made to prevent the costs of services access to a variety of contraceptive choices. Method choice may also be influenced by factors such the individual. adolescents are eligible to use all the particular needs and make informed and voluntary decisions.4–2.g.5. While some concerns have been expressed about 2. sexually 2. consistent with current clinical practice). Adolescents in many countries lack adequate access to space or limit pregnancy. For instance.6 Summary of changes within the MEC fifth edition the use of certain contraceptive methods by adolescents (e. Medical eligibility criteria for contraceptive use . compared with the fourth edition (see advantages of preventing unintended pregnancy. including reproductive health care. Age alone does and/or methods from limiting the options available. the use of progestogen-only injectables by those below The following tables highlight changes within the fifth 18 years). 11 Ibid. should be available and accessible to all adolescents without necessarily requiring parental or guardian authorization by law. in some cases. For example. not constitute a medical reason for denying any method to adolescents.2 Adolescents active adolescents who are unmarried have very different needs from those who are married and want to postpone. they may not do so because of fear that their confidentiality will not be respected. regardless of marital status. adolescents (in particular unmarried ones) may not be able to obtain them because of restrictive laws and policies. in some settings.Part II | 107 a technique for menstrual management in institutions. However.11 it is married or unmarried. some conditions recommendations for new conditions issued in the fifth edition. using methods that do not require a daily regimen may be more convenient. as sporadic patterns of intercourse and the need to conceal sexual activity and contraceptive use. It is clear Tables 2.

108 | Medical eligibility criteria for contraceptive use . immediately after delivery of the placenta BF=2 b) ≥ 48 hours to < 4 weeks 3 3 c) ≥ 4 weeks 1 1 d) Puerperal sepsis 4 4 Superficial venous disorders a) Varicose veins 1 1 1 1 1 1 1 b) Superficial venous thrombosis 2a 2a 1 1 1 1 1 Known dyslipidaemias without other 2a 2a 2a 2a 2a 1a 2a known cardiovascular risk factors STIs I C I C a) Current purulent cervicitis or 1 1 1 1 1 4 2a 4 2a chlamydial infection or gonorrhoea b) Other STIs (excluding HIV and 1 1 1 1 1 2 2 2 2 hepatitis) c) Vaginitis (including Trichomonas 1 1 1 1 1 2 2 2 2 vaginalis and bacterial vaginosis) d) Increased risk of STIs 1 1 1 1 1 2/3a 2 2/3a 2 .Part II Table 2. including after caesarean section) a) < 48 hours including insertion 1 not BF=1.4 Summary of changes from the fourth edition to the fifth edition of the MEC (changes are highlighted in bold) Condition COC/P/ CIC POP DMPA LNG/ ETG Cu-IUD LNG-IUD CVR implants NET-EN Breastfeeding a) < 6 weeks postpartum 4 4 2a 3a 2a b) ≥ 6 weeks to < 6 months 3 3 1 1 1 (primarily breastfeeding) c) ≥ 6 months postpartum 2 2 1 1 1 Postpartum (non-breastfeeding women) a) < 21 days 1 1 1 (i) without other risk factors for VTE 3a 3a (ii) with other risk factors for VTE 4a 4a b) ≥ 21 days to 42 days 1 1 1 (i) without other risk factors for VTE 2a 2a (ii) with other risk factors for VTE 3a 3a c) ≥ 42 days 1 1 1 1 1 Postpartum (breastfeeding or non-breastfeeding women.

NET-EN: norethisterone enanthate injectable contraceptive. LNG: levonorgestrel. ETG: etonogestrel. 2a 2/3a 2a 2/3a 2a 2 = NET-ENa d) Integrase inhibitors Raltegravir (RAL) 1 1 1 1 1 2/3a 2a 2/3a 2a BMI: body mass index. 2a 2/3a 2a 2/3a 2a 2 = NET-ENa Ritonavir (RTV) 2a 2a 2a 1 = DMPA. CIC: combined injectable contraceptives. Medical eligibility criteria for contraceptive use .Part II | 109 Condition COC/P/ CIC POP DMPA LNG/ ETG Cu-IUD LNG-IUD CVR implants NET-EN HIV/AIDS I C I C High risk of HIV 1 1 1 1a 1 2 2 2 2 Asymptomatic or mild HIV clinical 1a 1a 1a 1a 1a 2 2 2 2 disease (WHO stage 1 or 2) Severe or advanced HIV clinical 1a 1a 1a 1a 1a 3 2a 3 2a disease (WHO stage 3 or 4) Antiretroviral therapy a) Nucleoside reverse transcriptase inhibitors (NRTIs) I C I C Abacavir (ABC) 1 1 1 1 1 2/3a 2a 2/3a 2a Tenofovir (TDF) 1 1 1 1 1 2/3a 2a 2/3a 2a Zidovudine (AZT) 1 1 1 1 1 2/3a 2a 2/3a 2a Lamivudine (3TC) 1 1 1 1 1 2/3a 2a 2/3a 2a Didanosine (DDI) 1 1 1 1 1 2/3a 2a 2/3a 2a Emtricitabine (FTC) 1 1 1 1 1 2/3a 2a 2/3a 2a Stavudine (D4T) 1 1 1 1 1 2/3a 2a 2/3a 2a b) Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Efavirenz (EFV) 2a 2a 2a 1 = DMPA. DMPA: depomedroxyprogesterone acetate (intramuscular and sub-cutaneous) injectable. Cu-IUD: copper-bearing IUD. a Please consult the relevant table for each contraceptive method in section 2.7 for a clarification to this classification. VTE: venous thromboembolism. COC: combined oral contraceptives. LNG-IUD: levonorgestrel-releasing intrauterine device. . 2a 2/3a 2a 2/3a 2a 2 = NET-ENa Ritonavir-boosted darunavir (DRV/r) 2a 2a 2a 1 = DMPA. 2a 2/3a 2a 2/3a 2a 2 = NET-ENa Ritonavir-boosted lopinavir (LPV/r) 2a 2a 2a 1 = DMPA. CVR: combined contraceptive vaginal ring. POP: progestogen-only pills. 2a 2/3a 2a 2/3a 2a 2 = NET-ENa Rilpivirine (RPV) 1 1 1 1 1 2/3a 2a 2/3a 2a c) Protease inhibitors (PIs) Ritonavir-boosted atazanavir (ATV/r) 2a 2a 2a 1 = DMPA. 2a 2/3a 2a 2/3a 2a 2 = NET-ENa Etravirine (ETR) 1 1 1 1 1 2/3a 2a 2/3a 2a Nevirapine (NVP) 2a 2a 2a 1 = DMPA. STI: sexually transmitted infection. P: combined patch.

110 | Medical eligibility criteria for contraceptive use . efavirenz. carbamazepine. St John’s wort/Hypericum perforatum) Repeated ECP use 1a 1a 1a Rape 1 1 1 COC: combined oral contraceptives.6 Progesterone-releasing vaginal ring (PVR) (changes are highlighted in bold) Condition Category Pregnancy NA Breastfeeding and ≥ 4 weeks postpartum 1 . or other thromboembolic conditions) Migraine 2 2 2 Severe liver disease (including jaundice) 2 2 2 CYP3A4 inducers (e. rifabutin.5 Emergency contraceptive pills (ECPs) (changes are highlighted in bold) Emergency contraceptive pills (ECPs) (changes are highlighted in bold) Condition COC LNG UPA Pregnancy NAa NAa NAa Breastfeeding 1 1 2a Past ectopic pregnancy 1 1 1 Obesity 1a 1a 1a History of severe cardiovascular disease (ischaemic heart 2 2 2 disease. phenytoin. rifampicin. oxcarbazepine. a Please consult the relevant table for each contraceptive method in section 2. cerebrovascular attack. 1a 1a 1a phenobarbital.g. LNG: levonorgestrel.Part II Table 2. UPA: ulipristal acetate. fosphenytoin.7 for a clarification to this classification. Table 2. CYP3A4: cytochrome P450 3A4 enzyme. primidone. nevirapine.

best judgement. however. Limited information is available on the safety of these methods Limited data do not suggest that the small absolute risk for among women with specific medical conditions. norethisterone and norgestimate are associated with the lowest The combined contraceptive patch (P) and combined vaginal risk (20). are considered here: hormone formulations (43–60). arterial events associated with COC use varies according to the epidemiological data on the long-term effects of P and CVR use type of progestogen (5. the Guideline Development Group COMBINED ORAL CONTRACEPTIVES (COCs) (GDG) concluded that the evidence available for COCs applies to CICs in many but not all instances. CHCs Medical eligibility criteria for contraceptive use . In fact. thromboembolism (VTE) compared to non-use. therefore. the combined contraceptive patch (P) and the formulations in healthy women (61–75).1 Combined hormonal contraceptives (CHCs) Pending further evidence. best judgement. Cyclofem = medroxyprogesterone acetate 25 mg plus P users. 60). . 49. ring (CVR) are relatively new contraceptive methods. were not available for the GDG to review. As CICs are administered by grade squamous intraepithelial lesions found that use of the injection. however. has a shorter According to available evidence.7 Tables use. 20–34). Moreover. Venous thrombosis is rare among women of reproductive age. this is not the case with injectables. ischaemic heart disease). Reports of transient. 61). for severe pathologies progestogen. and CVR. The assigned categories should. the GDG concluded that the evidence However. and limited evidence on women with low- comparison with COCs (40–42). the CVR provides a duration of effect and is more rapidly metabolized than the comparable safety and pharmacokinetic profile and has similar synthetic estrogens used in other contraceptive formulations effects on ovarian function to COCs with similar hormone such as COCs. Evidence from use combined contraceptive vaginal ring (CVR). haemostasis and no infection related to use during three cycles of follow-up and coagulation. exposure associated with use of COCs and progestogen-only be considered a preliminary. These differences in obese women (BMI ≥ 30 kg/m2) found that weight gain for imply that the type and magnitude of estrogen-related side. Limited evidence suggests the 2. less than 25% of users experienced these estradiol cypionate 5 mg events (45. therefore. which All COCs are associated with an increased risk for venous will be re-evaluated as new data become available. The absolute differences. the P provides a comparable COMBINED INJECTABLE CONTRACEPTIVES (CICs) safety and pharmacokinetic profile to COCs with similar Two CIC formulations. short-term breast discomfort and skin-site reactions were greater among 1. are very small. women in this category was not different between CVR users effects associated with CICs may be different from those and COC users (76). and available for COCs applies to the combined contraceptive P there are few epidemiological data on their long-term effects.g. Mesigyna = norethisterone enanthate 50 mg plus effectiveness of the P may decline for women weighing 90 kg estradiol valerate 5 mg or more (58. CICs are a relatively new contraceptive method. Therefore. estradiol plus a progestogen (35–39). irrespective of their progestogen content. the first-pass metabolism by the liver is avoided. vaginal ring did not worsen the condition (64). 2. Estradiol is less potent. while the effect of the hormonal categories as COCs.Part II .7. Pending further evidence. 6. for which the effect continues for some time after the last injection. According to available evidence. 50. Most of the available studies received support from the manufacturers of these Recommendations in this guidance are the same for all COC methods. The assigned categories should. which will be pills (POPs) can be reduced immediately by discontinuing their re-evaluated as new data become available. formulations. A number of studies have found differences in risk for VTE associated COMBINED CONTRACEPTIVE PATCH (P) AND COMBINED with COCs containing different types of progestogens (1–19). the The recommendations in this guidance refer to low-dose GDG assigned categories for CICs somewhere between the COCs containing ≤ 35 mcg ethinyl estradiol combined with a categories for COCs and POPs.COMBINED HORMONAL CONTRACEPTIVES | 111 2. the classification of conditions was the same as for COCs. 56–58. CICs contain the naturally occurring estrogen. However. and therefore the P and CVR should have the same There is also the concern that. (e. Limited evidence from use in women post experienced by COC/P/CVR users. be considered a preliminary. lipid metabolism and liver function in post-abortion (77). thereby minimizing estradiol’s effect on the liver. short-term studies of medical and surgical abortion found no serious adverse events CICs have shown little effect on blood pressure. CONTRACEPTIVE VAGINAL RING (CVR) Current evidence suggests that COCs containing levonorgestrel.

CVR or CICs is not required. 93–102. BMD is a surrogate marker for fracture risk that may not be valid for premenopausal women. and may preserve bone mass in those who are perimenopausal (103. including HIV. When used correctly and consistently. a) Menarche to < 40 years 1 1 1 1 although 3 recent studies show no effect b) > 40 years 2 2 2 2 (90–92). especially in those choosing very low dose formulations (< 30 µg ethinyl estradiol-containing COCs) (91. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition.112 | Medical eligibility criteria for contraceptive use . P. AGE †* Evidence: Evidence about whether CHC use affects fracture risk is inconsistent (78–89). 106–109). including HIV. There is no known harm to the woman. and which. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. 110–117). PARITY a) Nulliparous 1 1 1 1 b) Parous 1 1 1 1 . P. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY PREGNANCY NA NA NA NA NA = not applicable Clarification: Use of COCs. 93–105). 104. CHC use has little to no effect on BMD in premenopausal women (90. or the fetus if COCs. therefore. CHC use may decrease bone mineral density (BMD) in adolescents.COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). CVR or CICs are accidentally used during pregnancy. may not accurately predict current or future (postmenopausal) fracture risk (118–120). but are not used as widely by national programmes as male condoms.Part II . the correct and consistent use of condoms is recommended. If there is a risk of STI/HIV. Female condoms are effective and safe. the course of her pregnancy. condoms offer one of the most effective methods of protection against STIs.

If there is a risk of STI/HIV. postpartum haemorrhage. use of CHCs may pose an i) without other risk factors for VTE 2 2 2 2 additional increased risk for VTE. c) > 42 days 1 1 1 1 . this risk is most pronounced in the first 3 weeks after delivery. but are not used as widely by national programmes as male condoms. CHCs Medical eligibility criteria for contraceptive use . VTE risk is elevated during pregnancy and the postpartum period. ii) with other risk factors for VTE 3 3 3 3 Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with non-users at all time points postpartum. the correct and consistent use of condoms is recommended. including HIV. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive BREASTFEEDING † Evidence: Clinical studies demonstrate conflicting results regarding effects on a) < 6 weeks postpartum 4 4 4 4 breastfeeding continuation or exclusivity in b) > 6 weeks to < 6 months 3 3 3 3 women exposed to COCs during lactation. but the numbers needed to harm were lowest in the first 6 weeks postpartum (132). pre- b) > 21 days to 42 days eclampsia or smoking. transfusion at delivery. use of CHCs is generally not recommended prior to 6 months postpartum in women who are breastfeeding. immediately post-caesarean delivery. ii) with other risk factors for VTE 4 4 4 4 BMI > 30 kg/m2. POSTPARTUM (IN NON-BREASTFEEDING WOMEN) † Although the risk of venous thromboembolism (VTE) is the same in breastfeeding and non-breastfeeding women.Part II . 3 3 3 3 such as immobility. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. a) < 21 days Clarification: For women up to 6 weeks i) without other risk factors for VTE postpartum with other risk factors for VTE. No postpartum (primarily breastfeeding) consistent effects on infant growth or illness have been reported (121–126). When used correctly and consistently. Female condoms are effective and safe. declining to near baseline levels by 42 days postpartum (127-131). Adverse health c) > 6 months postpartum 2 2 2 2 outcomes or manifestations of exogenous estrogen in infants exposed to combined contraceptives through breast-milk have not been demonstrated. including HIV. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. however. studies have been inadequately designed to determine whether a risk of either serious or subtle long-term effects exists. Rates were significantly different only after 13 weeks postpartum. condoms offer one of the most effective methods of protection against STIs.COMBINED HORMONAL CONTRACEPTIVES | 113 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs).

Female condoms are effective and safe. 142–151). PAST ECTOPIC PREGNANCY* 1 1 1 1 HISTORY OF PELVIC SURGERY 1 1 1 1 SMOKING Evidence: COC users who smoked were at a) Age < 35 years 2 2 2 2 increased risk of cardiovascular diseases. 31. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. When used correctly and consistently. a) First trimester 1 1 1 1 b) Second trimester 1 1 1 1 Evidence: Women who started taking COCs immediately after first-trimester medical or c) Immediate post-septic abortion 1 1 1 1 surgical abortion did not experience more side- effects or adverse vaginal bleeding outcomes or clinically significant changes in coagulation parameters compared with women who used a placebo. P. the correct and consistent use of condoms is recommended. or delayed COC initiation (134–141). a non-hormonal contraceptive method. CVR or CICs may be started immediately post-abortion. . C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. condoms offer one of the most effective methods of protection against STIs. an IUD. Studies also i) < 15 cigarettes/day 3 3 3 2 showed an increased risk of MI with increasing ii) > 15 cigarettes/day 4 4 4 3 number of cigarettes smoked per day (30. especially myocardial infarction (MI). including HIV. but are not used as widely by national programmes as male condoms. compared b) Age > 35 years with those who did not smoke. If there is a risk of STI/HIV. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive POST-ABORTION Clarification: COCs.Part II . including HIV. Limited evidence on women using the CVR immediately after first-trimester medical or surgical abortion indicated no serious adverse events and no infection related to CVR use during 3 cycles of follow-up post-abortion (77).COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs).114 | Medical eligibility criteria for contraceptive use .

However. CHCs Medical eligibility criteria for contraceptive use . 167. . In such settings. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive OBESITY Evidence: Obese women who use COCs are more likely to experience VTE than obese a) > 30 kg/m2 BMI 2 2 2 2 women who do not use COCs. Limited evidence suggests that obese women who use COCs do not have a higher risk of acute MI or stroke than obese non-users (146. 171). but are not used as widely by national programmes as male condoms.Part II . P. P. A similar weight gain during 3 months was noted in both the COC group and the CVR group across all BMI categories (76). Female condoms are effective and safe.COMBINED HORMONAL CONTRACEPTIVES | 115 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). 151–156). CVR or CICs simply because their blood pressure cannot be measured. The absolute risk b) Menarche to < 18 years and 2 2 2 2 of VTE in healthy women of reproductive age > 30 kg/m2 BMI is small. The effectiveness of the patch decreased among women who weighed > 90 kg in 1 study (172). pregnancy-related morbidity and mortality risks are high. No association was found between pregnancy risk and BMI among P users (161. women should not be denied use of COCs. 171). condoms offer one of the most effective methods of protection against STIs. In many of these settings. evidence suggests that contraceptive effectiveness is maintained among obese CHC users (157–172). 147. Overall. however. blood pressure measurements are unavailable. When used correctly and consistently. among women with very high BMI using COC. evidence is inconsistent (161. BLOOD PRESSURE MEASUREMENT NA NA NA NA NA = not applicable UNAVAILABLE Clarification: It is desirable to have blood pressure measurements taken before initiation of COC. CVR or CICs may be among the few methods widely available. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. including HIV. in some settings. the correct and consistent use of condoms is recommended. 167. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. Limited evidence suggests obese women are no more likely to gain weight after 3 cycles of using CVR or COCs than overweight or normal-weight women. P. and COCs. including HIV. CVR or CIC use. If there is a risk of STI/HIV.

144. smoking. 33. 32. 33. b) Adequately controlled 3 3 3 3 Clarification: Women adequately treated for hypertension. 150. P.Part II . COC (properly taken measurements) users were at increased risk of stroke. 142.116 | Medical eligibility criteria for contraceptive use . the risk of cardiovascular disease may increase substantially. Discontinuation of COCs in women ii) systolic ≥ 160 or diastolic 4 4 4 4 with hypertension may improve blood pressure ≥ 100 mm Hg control (186). including HIV. HYPERTENSION For all categories of hypertension. Although there are no data. c) Elevated blood pressure levels Evidence: Among women with hypertension. P. When multiple risk factors do exist. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive. a) History of hypertension. 174). 151. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive CARDIOVASCULAR DISEASE MULTIPLE RISK FACTORS FOR 3/4 3/4 3/4 3/4 Clarification: When a woman has multiple ARTERIAL CARDIOVASCULAR major risk factors. CVR or CIC users. but are not used as widely by national programmes as male condoms. including HIV. COC. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. the correct and consistent use of condoms is recommended. 26. CVR or CICs may hypertension and known increase her risk to an unacceptable level. 90–99 mm Hg 173–185). Female condoms are effective and safe. dyslipidaemias) However. and peripheral arterial disease compared with i) systolic 140–159 or diastolic 3 3 3 3 non-users (14. diabetes. disease. classifications are based on the assumption that no other risk factors for cardiovascular disease exist. If there is a risk of STI/HIV. When used correctly and consistently. as soon as evaluated (including hypertension in feasible. where blood pressure hypertension are at reduced risk of acute MI CAN be evaluated and stroke as compared with untreated women. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. a simple addition of categories for multiple risk factors is not intended. P. CVR or CIC users with adequately controlled and monitored hypertension should be at reduced risk of acute MI and stroke compared with untreated hypertensive COC. condoms offer one of the most effective methods of protection against STIs. pregnancy) Evidence: Women who did not have a blood pressure check before initiation of COC use had an increased risk of acute MI and stroke (26. older age. a combination of 2 risk factors assigned a Category 2 may not necessarily warrant a higher category.g. for example. 31. 173. use of COCs.COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). d) Vascular disease 4 4 4 4 . any of which alone would DISEASE substantially increase the risk of cardiovascular (e. acute MI. where 3 3 3 3 Clarification: Evaluation of cause and level blood pressure CANNOT be of hypertension is recommended.

protein S. including HIV.g. compared with COC measurable and normal) users who did not have a history of high blood pressure during pregnancy.COMBINED HORMONAL CONTRACEPTIVES | 117 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). prothrombin conditions and the high cost of screening. condoms offer one of the most effective methods of protection against STIs. 33. but are not used as widely by national programmes as male condoms. . factor V Leiden. When used correctly and consistently. including HIV. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive HISTORY OF HIGH BLOOD PRESSURE 2 2 2 2 Evidence: Women using COCs who had a history DURING PREGNANCY of high blood pressure in pregnancy had an (where current blood pressure is increased risk of MI and VTE. protein C. COC users had a 2. The absolute risks of acute MI and VTE in this population remained small (32. the correct and consistent use of condoms is recommended. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. 187–192). DEEP VEIN THROMBOSIS (DVT)/ PULMONARY EMBOLISM (PE)* a) History of DVT/PE 4 4 4 4 b) Acute DVT/PE 4 4 4 4 c) DVT/PE and established on 4 4 4 4 anticoagulant therapy d) Family history 2 2 2 2 (first-degree relatives) e) Major surgery i) with prolonged immobilization 4 4 4 4 ii) without prolonged 2 2 2 2 immobilization f) Minor surgery without 1 1 1 1 immobilization KNOWN THROMBOGENIC 4 4 4 4 Clarification: Routine screening is not MUTATIONS appropriate because of the rarity of the (e.to 20-fold higher risk of thrombosis than non-users (3. 174. 151. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. Female condoms are effective and safe. CHCs Medical eligibility criteria for contraceptive use . 155. mutation. 176. and antithrombin deficiencies) Evidence: Among women with thrombogenic mutations.Part II . If there is a risk of STI/HIV. 193–214).

the correct and consistent use of condoms is recommended. Female condoms are effective and safe.118 | Medical eligibility criteria for contraceptive use . b) Superficial venous thrombosis 2 2 2 2 Clarification: SVT may be associated with an (SVT) increased risk of VTE. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.Part II . CURRENT AND HISTORY OF 4 4 4 4 ISCHAEMIC HEART DISEASE STROKE 4 4 4 4 (history of cerebrovascular accident) . When used correctly and consistently. including HIV. however. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive SUPERFICIAL VENOUS DISORDERS † a) Varicose veins 1 1 1 1 Evidence: One study suggested that among women with varicose veins. If there is a risk of STI/HIV. statistical significance was not reported and the number of events was small (215).COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). but are not used as widely by national programmes as male condoms. condoms offer one of the most effective methods of protection against STIs. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. the risk of VTE was higher in oral contraceptive users compared with non- users (216). Evidence: One study demonstrated that among women with SVT. the rate of VTE and superficial venous thrombosis (SVT) was higher in oral contraceptive users compared with non- users. including HIV.

the correct and consistent use of condoms is recommended. 1 study suggested an increased risk for VTE and for stroke among COC users with dyslipidaemia compared to COC users without dyslipidaemia (22). Evidence: Limited evidence on use of CHCs among women with dyslipidaemia and risk of cardiovascular outcomes provided inconsistent results. CHCs Medical eligibility criteria for contraceptive use . are known risk factors for cardiovascular disease. risk of atrial fibrillation. Increased levels of total cholesterol. If there is a risk of STI/HIV.Part II .COMBINED HORMONAL CONTRACEPTIVES | 119 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). as well as a decreased level of high-density lipoprotein (HDL). history of subacute bacterial endocarditis) . VALVULAR HEART DISEASE* a) Uncomplicated 2 2 2 2 b) Complicated (pulmonary 4 4 4 4 hypertension. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. No evidence of risk for pancreatitis was identified. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive KNOWN DYSLIPIDAEMIAS WITHOUT 2 2 2 2 Clarification: Routine screening is not OTHER KNOWN CARDIOVASCULAR appropriate because of the rarity of the condition RISK FACTORS † and the high cost of screening. and 1 study suggested no worsening of lipid abnormalities among CHC users with dyslipidaemia compared to non-users with dyslipidaemia (218). Women with known severe genetic lipid disorders are at much higher lifetime risk for cardiovascular disease and may warrant further clinical consideration. low-density lipoprotein (LDL) and triglycerides. Female condoms are effective and safe. One study suggested an increased risk for MI among COC users with hypercholesterolaemia compared to non-users without hypercholesterolaemia (217). but are not used as widely by national programmes as male condoms. When used correctly and consistently. including HIV. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. including HIV. condoms offer one of the most effective methods of protection against STIs.

stroke and venous thromboembolism (VTE). Female condoms are effective and safe. Certain anticonvulsants lower COC effectiveness. including HIV. classifications are based on the assumption that no other risk factors for cardiovascular disease are present. on drug interactions. b) Severe thrombocytopenia 2 2 2 2 c) Immunosuppressive treatment 2 2 2 2 d) None of the above 2 2 2 2 NEUROLOGIC CONDITIONS HEADACHES* I C I C I C I C Clarification: Classification depends on accurate diagnosis of those severe headaches that are a) Non-migrainous (mild or severe) 1 2 1 2 1 2 1 2 migrainous and those that are not. Classification is for women i) without aura without any other risk factors for stroke. 181. these classifications must be modified in the presence of such risk factors. including hormonal contraceptives (219–236). C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. EPILEPSY 1 1 1 1 Clarification: If a woman is taking anticonvulsants. When used correctly and consistently. Risk age < 35 years 2 3 2 3 2 3 2 3 of stroke increases with age. Available evidence indicates that many women with SLE can be considered good candidates for most contraceptive methods. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive RHEUMATIC DISEASES SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) People with SLE are at increased risk of ischaemic heart disease. Women with a history of migraine who use COCs are about 2–4 times as likely to have an ischaemic stroke as non-users with a history of migraine (142.COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). refer to the last section of this table. . CVR or CIC use is similar to COC use in this regard remains unclear. including HIV. a) Positive (or unknown) 4 4 4 4 Evidence: Antiphospholipid antibodies are antiphospholipid antibodies associated with a higher risk for both arterial and venous thrombosis (237–239). Any new b) Migraine headaches or marked changes in headaches should be evaluated. The extent to which P. If there is a risk of STI/HIV. but are not used as widely by national programmes as male condoms. hypertension and smoking. age > 35 years 3 4 3 4 3 4 3 4 ii) with aura.Part II . CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. 182.120 | Medical eligibility criteria for contraceptive use . at any age 4 4 4 4 4 4 4 4 Evidence: Among women with migraine. For all categories of SLE. 154. women who also had aura had a higher risk of stroke than those without aura (240–242). condoms offer one of the most effective methods of protection against STIs. the correct and consistent use of condoms is recommended. Categories assigned to such conditions in the Medical eligibility criteria for contraceptive use should be the same for women with SLE who present with these conditions. 240–246).

including HIV. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. No data on bipolar disorder or postpartum depression were available. CHCs Medical eligibility criteria for contraceptive use . UNEXPLAINED VAGINAL BLEEDING* (suspicious for serious condition) a) Before evaluation 2 2 2 2 Clarification: If pregnancy or an underlying pathological condition (such as pelvic malignancy) is suspected. Women with menorrhagia did not report worsening of the condition or any adverse events related to COC use (257). When used correctly and consistently. it must be evaluated and the category adjusted after evaluation.Part II . the correct and consistent use of condoms is recommended. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. Evidence: COC use did not increase depressive symptoms in women with depression compared to baseline or to non-users with depression (247–256). Evidence: A Cochrane Collaboration review identified 1 randomized controlled trial evaluating the effectiveness of COC use compared with naproxen and danazol in treating menorrhagic women. REPRODUCTIVE TRACT INFECTIONS AND DISORDERS VAGINAL BLEEDING PATTERNS* a) Irregular pattern without heavy 1 1 1 1 bleeding b) Heavy or prolonged bleeding 1 1 1 1 Clarification: Unusually heavy bleeding should (includes regular and irregular raise the suspicion of a serious underlying patterns) condition. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive DEPRESSIVE DISORDERS DEPRESSIVE DISORDERS 1 1 1 1 Clarification: The classification is based on data for women with selected depressive disorders. including HIV. Female condoms are effective and safe.COMBINED HORMONAL CONTRACEPTIVES | 121 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). condoms offer one of the most effective methods of protection against STIs. If there is a risk of STI/HIV. . There is a potential for drug interactions between certain antidepressant medications and hormonal contraceptives. but are not used as widely by national programmes as male condoms.

122 | Medical eligibility criteria for contraceptive use . BENIGN OVARIAN TUMOURS 1 1 1 1 (INCLUDING CYSTS) SEVERE DYSMENORRHOEA 1 1 1 1 Evidence: There was no increased risk of side-effects with COC use among women with dysmenorrhoea compared with women not using COCs. the correct and consistent use of condoms is recommended. including HIV. condoms offer one of the most effective methods of protection against STIs. Women with endometriosis did not report worsening of the condition or any adverse events related to COC use (258). long-term COC use (≥ 5 years) may increase the risk of carcinoma in situ and invasive carcinoma (64. and some COC users experienced β-hCG levels a more rapid regression in human chorionic b) Persistently elevated β-hCG levels 1 1 1 1 gonadotropin (hCG) levels. 270). Limited evidence suggests that use of COCs during chemotherapeutic treatment does not significantly affect the regression or treatment of post-molar trophoblastic disease compared with women who used a non-hormonal contraceptive method or depot medroxyprogesterone acetate (DMPA) during chemotherapeutic treatment (269). C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. including HIV. Female condoms are effective and safe. Some COC users had a reduction in pain and bleeding (259. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). . When used correctly and consistently. 260). Limited evidence on women with low-grade squamous intraepithelial lesions found use of the vaginal ring did not worsen the condition (64).Part II . compared with non- or malignant disease users (261–268). further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive ENDOMETRIOSIS 1 1 1 1 Evidence: A Cochrane review identified 1 randomized controlled trial evaluating the effectiveness of COC use compared with a gonadotropin-releasing hormone (GnRH) analogue in treating the symptoms of endometriosis. CERVICAL ECTROPION* 1 1 1 1 CERVICAL INTRAEPITHELIAL 2 2 2 2 Evidence: Among women with persistent NEOPLASIA (CIN) human papillomavirus (HPV) infection. GESTATIONAL TROPHOBLASTIC Evidence: Following molar pregnancy evacuation. DISEASE the balance of evidence found COC use did not increase the risk of post-molar trophoblastic a) Decreasing or undetectable 1 1 1 1 disease. but are not used as widely by national programmes as male condoms. If there is a risk of STI/HIV.

the correct and consistent use of condoms is recommended.COMBINED HORMONAL CONTRACEPTIVES | 123 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs).Part II . including HIV. including HIV. Female condoms are effective and safe. When used correctly and consistently. b) Benign breast disease 1 1 1 1 c) Family history of cancer 1 1 1 1 Evidence: Women with breast cancer susceptibility genes (such as BRCA1 and BRCA2) have a higher baseline risk of breast cancer than women without these genes. If there is a risk of STI/HIV. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive CERVICAL CANCER* 2 2 2 2 (AWAITING TREATMENT) BREAST DISEASE* a) Undiagnosed mass 2 2 2 2 Clarification: Evaluation should be pursued as early as possible. Current evidence. d) Breast cancer i) current 4 4 4 4 ii) past and no evidence of current 3 3 3 3 disease for 5 years ENDOMETRIAL CANCER* 1 1 1 1 OVARIAN CANCER* 1 1 1 1 UTERINE FIBROIDS* a) Without distortion of the uterine 1 1 1 1 cavity b) With distortion of the uterine 1 1 1 1 cavity . condoms offer one of the most effective methods of protection against STIs. but are not used as widely by national programmes as male condoms. CHCs Medical eligibility criteria for contraceptive use . CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. 271–293). however. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. The baseline risk of breast cancer is also higher among women with a family history of breast cancer than among those who do not have such a history. does not suggest that the increased risk of breast cancer among women with either a family history of breast cancer or breast cancer susceptibility genes is modified by the use of combined oral contraceptives (175.

Seven of these studies found no statistically significant association between use of COCs and HIV acquisition (371–378). but are not used as widely by national programmes as male condoms. although 1 study among sex workers in Kenya did (379).124 | Medical eligibility criteria for contraceptive use . there is either evidence of no association between COC use and STI acquisition or too limited evidence to draw any conclusions (289–369). . CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. If there is a risk of STI/HIV. HIV/AIDS † High risk of HIV 1 1 1 1 Evidence: Eight studies assessed the use of COCs and were considered to be “informative but with important limitations” (370). For other STIs. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition.Part II . including HIV. Female condoms are effective and safe.COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). condoms offer one of the most effective methods of protection against STIs. the correct and consistent use of condoms is recommended. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive PELVIC INFLAMMATORY DISEASE (PID)* a) Past PID (assuming no current risk factors for STIs) i) with subsequent pregnancy 1 1 1 1 ii) without subsequent pregnancy 1 1 1 1 b) PID – current 1 1 1 1 STIs a) Current purulent cervicitis or 1 1 1 1 chlamydial infection or gonorrhoea b) Other STIs (excluding HIV and 1 1 1 1 hepatitis) c) Vaginitis (including Trichomonas 1 1 1 1 vaginalis and bacterial vaginosis) d) Increased risk of STIs 1 1 1 1 Evidence: Evidence suggests that there may be an increased risk of chlamydial cervicitis among COC users at high risk of STIs. including HIV. When used correctly and consistently.

the correct and consistent use of condoms is recommended. including HIV. 7 suggested no association between use of COCs and progression of HIV. 388).Part II . One of these studies reported an elevated. but are not used as widely by national programmes as male condoms. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. Evidence for asymptomatic or mild HIV disease (WHO stage 1 or 2) and severe or advanced HIV disease (WHO stage 3 or 4): Out of 8 available studies. including HIV. . initiation of antiretroviral therapy (ART). One randomized controlled trial found an increased risk of a composite outcome of declining CD4 count or death among COC users when compared with users of copper-bearing IUDs (387. point estimate for COCs (378). Female condoms are effective and safe. as measured by CD4 count < 200 cells/mm3. but not statistically significant. or mortality (380–386). If there is a risk of STI/HIV. CHCs Medical eligibility criteria for contraceptive use . condoms offer one of the most effective methods of protection against STIs. Two prospective observational studies directly assessed the effects of different hormonal contraceptive methods on female-to-male HIV transmission by measuring seroconversions in male partners of women known to be using hormonal contraceptives. 390–404). on drug interactions. refer to the last section of this table. The majority of indirect studies measuring whether various hormonal contraceptive methods affect plasma HIV viral load have found no effect (381. Studies indirectly assessing the effect of various hormonal contraceptive methods on female-to-male HIV transmission by measuring genital viral shedding as a proxy for infectivity have had mixed results. The other study also did not find a statistically significant association for COCs (389).COMBINED HORMONAL CONTRACEPTIVES | 125 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive Asymptomatic or mild HIV clinical 1 1 1 1 Clarification for asymptomatic or mild HIV disease (WHO stage 1 or 2) disease (WHO stage 1 or 2) and severe or advanced HIV disease (WHO stage 3 or 4): Severe or advanced HIV clinical 1 1 1 1 Because there may be drug interactions between disease (WHO stage 3 or 4) hormonal contraceptives and ARV therapy. When used correctly and consistently. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.

C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. d) Other vascular disease or diabetes 3/4 3/4 3/4 3/4 Clarification: The category should be assessed of > 20 years’ duration according to the severity of the condition.COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs).or non- i) non-insulin dependent insulin-dependent diabetes.Part II . MALARIA 1 1 1 1 ENDOCRINE CONDITIONS DIABETES a) History of gestational disease 1 1 1 1 Evidence: The development of non-insulin- dependent diabetes in women with a history of gestational diabetes is not increased by the use of COCs (412–419).126 | Medical eligibility criteria for contraceptive use . lipid levels appear to be unaffected by COC use (420–422). CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. If there is a risk of STI/HIV. COC use had no adverse effects on liver function (405–411). further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive OTHER INFECTIONS SCHISTOSOMIASIS a) Uncomplicated 1 1 1 1 Evidence: Among women with uncomplicated schistosomiasis.g. Likewise. COC use had limited 2 2 2 2 effect on daily insulin requirements and no effect ii) insulin dependent 2 2 2 2 on long-term diabetes control (e. Female condoms are effective and safe. and most changes remained within normal values (419. Rifampicin is likely to decrease COC effectiveness. condoms offer one of the most effective methods of protection against STIs. The extent to which P or CVR use is similar to COC use in this regard remains unclear. on drug interactions. c) Nephropathy/retinopathy/ 3/4 3/4 3/4 3/4 Clarification: The category should be assessed neuropathy according to the severity of the condition. but are not used as widely by national programmes as male condoms. . b) Non-vascular disease Evidence: Among women with insulin. Changes in lipid profile and haemostatic markers were limited. 422–430). including HIV. b) Fibrosis of the liver 1 1 1 1 (if severe. b) Pelvic 1 1 1 1 refer to the last section of this table. the correct and consistent use of condoms is recommended. When used correctly and consistently. haemoglobin A1c levels) or progression to retinopathy. including HIV. see cirrhosis) TUBERCULOSIS a) Non-pelvic 1 1 1 1 Clarification: If a woman is taking rifampicin.

If there is a risk of STI/HIV. but are not used as widely by national programmes as male condoms. 432). Female condoms are effective and safe. When used correctly and consistently.COMBINED HORMONAL CONTRACEPTIVES | 127 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). CIRRHOSIS a) Mild (compensated) 1 1 1 1 b) Severe (decompensated) 4 4 4 3 . CHCs Medical eligibility criteria for contraceptive use . the correct and consistent use of condoms is recommended. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. 434). C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. 433. Evidence is limited for COC use during active hepatitis (435. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive THYROID DISORDERS a) Simple goitre 1 1 1 1 b) Hyperthyroid 1 1 1 1 c) Hypothyroid 1 1 1 1 GASTROINTESTINAL CONDITIONS GALL BLADDER DISEASE* a) Symptomatic i) treated by cholecystectomy 2 2 2 2 ii) medically treated 3 3 3 2 iii) current 3 3 3 2 b) Asymptomatic 2 2 2 2 HISTORY OF CHOLESTASIS* a) Pregnancy related 2 2 2 2 b) Past-COC related 3 3 3 2 VIRAL HEPATITIS I C I C I C I C a) Acute or flare 3/4 2 3/4 2 3/4 2 3 2 Clarification: The category should be assessed according to the severity of the condition. b) Carrier 1 1 1 1 1 1 1 1 Evidence: Data suggest that in women with chronic hepatitis. including HIV. including HIV.Part II . nor does it increase the risk of hepatocellular carcinoma (431. COC use does not appear to trigger liver failure or severe dysfunction (408. For women who are carriers. COC use does not increase c) Chronic 1 1 1 1 1 1 1 1 the rate or severity of cirrhotic fibrosis. condoms offer one of the most effective methods of protection against STIs. 436).

If there is a risk of STI/HIV. 441). C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. including HIV. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive LIVER TUMOURS* a) Benign i) focal nodular hyperplasia 2 2 2 2 Evidence: There is limited.COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). but are not used as widely by national programmes as male condoms. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. ii) hepatocellular adenoma 4 4 4 3 b) Malignant (hepatoma) 4 4 4 3/4 ANAEMIAS THALASSAEMIA* 1 1 1 1 SICKLE CELL DISEASE 2 2 2 2 IRON-DEFICIENCY ANAEMIA* 1 1 1 1 DRUG INTERACTIONS ANTIRETROVIRAL THERAPY (ART) † a) Nucleoside reverse transcriptase Evidence: NRTIs do not appear to have inhibitors (NRTIs) significant risk of interactions with hormonal contraceptive methods (440. the correct and consistent use of condoms is recommended.Part II . When used correctly and consistently. Female condoms are effective and safe. including HIV. direct evidence that hormonal contraceptive use does not influence either progression or regression of liver lesions among women with focal nodular hyperplasia (437–439). Abacavir (ABC) 1 1 1 1 Tenofovir (TDF) 1 1 1 1 Zidovudine (AZT) 1 1 1 1 Lamivudine (3TC) 1 1 1 1 Didanosine (DDI) 1 1 1 1 Emtricitabine (FTC) 1 1 1 1 Stavudine (D4T) 1 1 1 1 . condoms offer one of the most effective methods of protection against STIs.128 | Medical eligibility criteria for contraceptive use .

Part II . Etravirine and rilpivirine do not interact with COCs (448. Raltegravir (RAL) 1 1 1 1 455). CHCs Medical eligibility criteria for contraceptive use . 454. Evidence: Three clinical studies. These interactions may reduce the effectiveness of the hormonal contraceptive. including 1 large study. c) Protease inhibitors (PIs) Ritonavir-boosted atazanavir 2 2 2 2 (ATV/r) Ritonavir-boosted lopinavir (LPV/r) 2 2 2 2 Ritonavir-boosted darunavir 2 2 2 2 (DRV/r) Ritonavir (RTV) 2 2 2 2 d) Integrase inhibitors Evidence: The integrase inhibitor raltegravir does not appear to interact with COCs (440. a pharmacokinetic study showed consistent significant decreases in contraceptive hormone levels in women taking COCs. Pharmacokinetic data suggest Etravirine (ETR) 1 1 1 1 potential drug interactions between some antiretroviral drugs (particularly some NNRTIs Nevirapine (NVP) 2 2 2 2 and ritonavir-boosted PIs) and some hormonal Rilpivirine (RPV) 1 1 1 1 contraceptives. found use of nevirapine-containing ART did not increase ovulation or pregnancy rates in women taking COCs (442–445). including HIV. . but are not used as widely by national programmes as male condoms. including HIV. the correct and consistent use of condoms is recommended. For efavirenz- containing ART. Female condoms are effective and safe. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive b) Non-nucleoside reverse Clarification: Antiretroviral drugs have the transcriptase inhibitors (NNRTIs) potential to either decrease or increase the levels Efavirenz (EFV) of steroid hormones in women using hormonal 2 2 2 2 contraceptives. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition.COMBINED HORMONAL CONTRACEPTIVES | 129 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). and a small clinical study showed higher ovulation rates in women taking efavirenz-containing ART and COCs (445–447). 449). 441. When used correctly and consistently. condoms offer one of the most effective methods of protection against STIs. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. If there is a risk of STI/HIV.

Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs.130 | Medical eligibility criteria for contraceptive use . including HIV. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. since. Evidence: Use of certain anticonvulsants may decrease the effectiveness of COCs (456–459).Part II . a preparation containing a minimum of 30 µg of ethinyl estradiol (EE) should be used. P or CVR is not barbiturates. the moderate effect of the combined contraceptive is unlikely to be apparent. b) Antifungals 1 1 1 1 Evidence: Studies of antifungal agents have shown no clinically significant pharmacokinetic interactions with COCs (504–513) or CVR (514). . topiramate. the correct and consistent use of condoms is recommended. When used correctly and consistently. or CVR (503). Female condoms are effective and safe. P (502). further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive ANTICONVULSANT THERAPY a) Certain anticonvulsants 3 3 3 2 Clarification: Although the interaction of certain (phenytoin. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.COMBINED HORMONAL CONTRACEPTIVES COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). b) Lamotrigine 3 3 3 3 Clarification: The recommendation for lamotrigine does not apply when lamotrigine is already being taken with other drugs that strongly inhibit (such as sodium valproate) or induce (such as carbamazepine) its metabolism. When a COC is chosen. condoms offer one of the most effective methods of protection against STIs. Evidence: Pharmacokinetic studies show levels of lamotrigine decrease significantly during COC use and increase significantly during the pill-free interval (460–464). including HIV. Some women who used both COCs and lamotrigine experienced increased seizure activity in 1 trial (464). harmful to women. If there is a risk of STI/HIV. in these cases. primidone. ANTIMICROBIAL THERAPY a) Broad-spectrum antibiotics 1 1 1 1 Evidence: Most broad-spectrum antibiotics do not affect the contraceptive effectiveness of COCs (465–501). but are not used as widely by national programmes as male condoms. anticonvulsants with COCs. it is likely to reduce the oxcarbazepine) effectiveness of COCs. P or CVR. c) Antiparasitics 1 1 1 1 Evidence: Studies of antiparasitic agents have shown no clinically significant pharmacokinetic interactions with COCs (411. carbamazepine. 515–519).

it is likely to reduce the effectiveness of COCs. Evidence: The balance of the evidence suggests that rifampicin reduces the effectiveness of COCs (520–535). 535). 522. C = continuation COC P CVR CIC † recommendations reviewed for the COC = combined oral contraceptive MEC 5th edition. but effects on metabolism of COCs are less than with rifampicin. including HIV. CVR or CICs is not harmful to women. Female condoms are effective and safe. and small studies have not shown evidence of ovulation (363. If there is a risk of STI/HIV. further details after this P = combined contraceptive patch table CVR = combined contraceptive vaginal ring * additional comments after this table CIC = combined injectable contraceptive d) Rifampicin or rifabutin therapy 3 3 3 2 Clarification: Although the interaction of rifampicin or rifabutin therapy with COCs. but are not used as widely by national programmes as male condoms. condoms offer one of the most effective methods of protection against STIs. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.Part II . . Data on rifabutin are limited. When a COC is chosen. Use of other contraceptives should be encouraged for women who are long-term users of either of these drugs. P. CVR or CICs.COMBINED HORMONAL CONTRACEPTIVES | 131 COMBINED HORMONAL CONTRACEPTIVES (CHCs) CHCs do not protect against sexually transmitted infections (STIs). When used correctly and consistently. including HIV. a preparation containing a minimum of 30 µg EE should be used. the correct and consistent use of condoms is recommended. CHCs Medical eligibility criteria for contraceptive use . P.

CHCs can be used until menopause. including ectopic gestation. CHC use may Awaiting treatment: Women may use COCs. Additionally. and summaries of the evidence supporting the recommendation(s).12 12 Available at: http://ihs-classification. women with general.COMBINED HORMONAL CONTRACEPTIVES RECOMMENDATIONS REVIEWED FOR FIFTH EDITION VAGINAL BLEEDING PATTERNS These recommendations were reviewed according to WHO Irregular menstrual bleeding patterns are common among requirements for guideline development. In further increase the risk of arterial thrombosis. 2nd edition. Intervention. Comparator. P or CVR. treatment of this condition renders a woman sterile. In general. preparation of the Medical eligibility criteria for contraceptive use. For more CICs. there is no need for restriction of CHC use. AGE women may use CHCs. Cervical ectropion is not a risk factor for cervical cancer. as part of the healthy women. which guided the preparation of worsened in the short term by use of CHCs. COC use reduces the risk of developing endometrial cancer.org/en/02_klassifikation . treatment of this condition renders a woman sterile. treatment of this condition renders a woman sterile.132 | Medical eligibility criteria for contraceptive use . Age ≥ 40 years: The risk of cardiovascular disease increases with age and may also increase with combined hormonal BREAST DISEASE contraceptive (CHC) use. are available in Part I. and the prognosis of women with current or recent breast PAST ECTOPIC PREGNANCY cancer may worsen with CHC use.Part II . GRADE evidence profiles. P or CVR. Breast cancer: Breast cancer is a hormonally sensitive tumour. complicated valvular heart disease are at greatest risk. Family history of DVT/PE (first-degree relatives): Some conditions which increase the risk of DVT/PE are heritable. The Population. are described in greater detail in Part I CERVICAL ECTROPION of this document. DEEP VEIN THROMBOSIS/PULMONARY EMBOLISM Awaiting treatment: Women may use COCs. see: Headache Classification Subcommittee of the International Headache Society. P and CVR are not expected to either. 2004. CHCs provide protection against pregnancy in general.24(Suppl 1):1–150. fifth edition. OVARIAN CANCER VALVULAR HEART DISEASE COC use reduces the risk of developing ovarian cancer. In general. In the absence of other adverse clinical conditions. UNEXPLAINED VAGINAL BLEEDING Outcome (PICO) questions developed by the Guideline Development Group (GDG) and the databases searched There are no conditions that cause vaginal bleeding that will be to retrieve the evidence. and other supplementary remarks from the GDG regarding the recommendations. and Aura is a specific focal neurologic symptom. the overall GRADE assessment of the quality of the evidence. UTERINE FIBROIDS HEADACHES COCs do not appear to cause growth of uterine fibroids. Among women with valvular heart disease. The risk of future ectopic pregnancy is increased in these ENDOMETRIAL CANCER women. systematic reviews. CICs. Cephalalgia. information on this and other diagnostic criteria. The International Classification of Headache Disorders. CERVICAL CANCER (AWAITING TREATMENT) ADDITONAL COMMENTS There is some theoretical concern that CHC use may affect prognosis of the existing disease. While awaiting treatment. CICs.

There is also concern that COCs. THALASSAEMIA There is anecdotal evidence from countries where thalassaemia is prevalent that COC use does not worsen the condition. IRON-DEFICIENCY ANAEMIA CHC use may decrease menstrual blood loss. GALL BLADDER DISEASE COCs. but do not protect against HIV or lower genital tract STIs. and have no first-pass effect on the liver. P or CVR may worsen existing gall bladder disease. LIVER TUMOURS There is no evidence regarding hormonal contraceptive use among women with hepatocellular adenoma. P or CVR may cause a small increased risk of gall bladder disease.Part II . Unlike COCs. CHCs Medical eligibility criteria for contraceptive use . CICs have been shown to have minimal effect on liver function in healthy women. COC use in healthy women is associated with development and growth of hepatocellular adenoma.COMBINED HORMONAL CONTRACEPTIVES | 133 PELVIC INFLAMMATORY DISEASE (PID) COCs may reduce the risk of PID among women with STIs. P or CVR reduce the risk of PID among women with STIs is unknown but they do not protect against HIV or lower genital tract STIs. HISTORY OF CHOLESTASIS Pregnancy-related: History of pregnancy-related cholestasis may predict an increased risk of developing COC-related cholestasis. Past-COC-related: History of COC-related cholestasis predicts an increased risk with subsequent COC use. CICs. . Whether CICs. CICs.

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Pregnancy and use of oral amoxicillin or doxycycline in two randomized trials. Back DJ. 1981. 523.154 | Medical eligibility criteria for contraceptive use . Gupta KC. Evaluation ethinyloestradiol in man. Devenport MH. 2004. Hazari K. 512. Migasana disturbance in simultaneous use of itraconazole and oral S. Gupta K.77(supplement 2):s3–s12.110:300. Adverse effects of the contraceptives. Crook D. A study of interaction of a low-dose Leufkens HGM.65:428–38.34:167–70. Suwannarach C. concomitant use of itraconazole and oral contraceptives. Skee D. 527. 522. Sinofsky FE. Ginsberg A. NuvaRing.27:851–9. MacIver M. Ali MY. La Nouvelle presse médicale. Verhoeven CH. CJ. Hilbert J. bleeding during concomitant use of oral contraceptives and itraconazole. van Puijenbroek EP. 32. users and non-users of oral contraceptives. Acta Endocrinol (Copenh). 1989. Messig M. Carlstrom K. Med J Zambia. Crawford FE.59:553–7. Am J Obstet Gynecol. a new tirazole antifungal drug]. Signalling possible drug-drug interactions combination oral contraceptive with anti-tubercular in a spontaneous reporting system: delay of withdrawal drugs. Grimmer SF. Back DJ. Revue TO. 2002. Meyboom RH. Wong FA. Bolt HM. Eur J Clin Pharmacol. Coresh J. Dogterom P. Tanthayaphinant O. mefloquine: due to primary liver damage with secondary thyroid involvement? BMC Public 506. German). 504. Failure of oral contraceptive with rifampicin. et al. Croft AM. Contraception. Contraception.15:193–7. Wynn V. Zacur HA. Br J Clin Pharmacol. Therapia Hungarica (English edition). Clin contaceptives reduces the biotransformation of proguanil Pharmacokinet. Br J Clin 1979.142:146–9 the clinical course of malaria infection and on the (in Dutch). Kovacs I. 1999. Examination of the on the pharmacokinetics and pharmacodynamics of a potential interaction between ketoconazole (Nizoral) and combination oral contraceptive. 505. Sauerbrey N. 1998. Absence of pharmacokinetic interactions of the combined 516. Tillement JP.21:135–43. 1980. Metabolic Orme ML. 2005. 1998.66:763–7. Effets contrariants de la rifampicine sur les contraceptifs oraux: a propos de 514. Cho T. and française des maladies respiratoires. Rao AP. Pharmacol. 515. Br J Clin Pharmacol. Bull World Health Organ. Breckenridge AM. 1980. 1991. et al. low hormone content (Rigevidon. Breckenridge AM. Gynecol Obstet Invest. The contraceptive vaginal ring. Joshi JV. Lastdrager drugs primaquine and chloroquine. Ned Tijdschr Geneeskd.31:179–81. Hall JM. Looareesuwan S. Mulders TM.2:6. N Z Med J. pharmacokinetics of mefloquine in Thai women.44:429–38. The effect of rifampicin on effects of low-dose fluconazole in healthy female norethisterone pharmacokinetics. contraceptive use on the pharmacokinetics of quinine. anteovin). The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral 518. Kaewvichit S. 39304 with oral contraceptives in normal health women. Egberts ACG. [Letter: Sleeping pills]. 1986. Bunnag D.2:174–82 (in antimycotic co-medication. McGready R. 1997. 1973. Orme ML. Seaton E. . Hirsch A. 520. Joshi UM. Thomsen T. Oranratnachai A. Back DJ. 1986. van Puijenbroek EP. Abrams LS. 1988. 525. Pharmocokinetic overview of Ortho Evra/Evra. 1991. Kappus H. Rieth H. van den Heuvel MW. McDaniel PA. 1975. between fluconazole and an oral contraceptive in healthy Contraception. Stepniewska K. Pharmacokinetics of oral contraceptive steroids following the administration of the antimalarial 507. [Interaction studies with Health. Eur J Clin Pharmacol. Somos P. Hirsch A. Disturbance of withdrawal bledding during 1984. Obstet Gynecol. 513. Fertil Steril.47:689–93.85:189–97. Crawford FE.21:617–29.32:91–7. Herxheimer A. [Pill cycle 517. 524. et al.2:2957 (in French). Pasquale SA. 2003.69:129– French). Meyboom RHB. et al. Lunell NO. Hamori M. Clin Pharmacol Ther. DICP. Effect of oral contraceptive steroids on contraceptives]. Lack of effect of oral 2002. The effects of rifampicin and rifabutin 510. van den Heuvel MW. Park BK. 2001. of the possible interaction of the antifungal triazole SCH 1977. Vinks MH.

534. LeBel M. 535. Deutsche medizinische Wochenschrift.25:255–62 (in German).4:115–6 (in French). 1973. JAMA. Praxis der Pneumologie vereinigt mit Der Tuberkulosearzt. Skolnick JL. 532. Clin Pharmacol Ther. J Clin Pharmacol. Muller F.Part II . [the simultaneous use of rifampicin and other antitubercular agents with oral contraceptives]. Reimers D. 529.49:s31–s8. Stoler BS. Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database. Breuer H. Chaline G. Masson E. 1988. Szoka PR. Paquet F. Muglioni JF. [Letter: Oral contraception and rifampicin]. and pregnancy.28:270–2 (in German). Wessels P. Effects of rifabutin and rifampicin on the pharmacokinetics of ethinylestradiol and norethindrone. 531. Colborn D. oral contraceptives. . Edgren RA. Anderson WH. Katz DB. Kropp R.236:1382.98:1521–3 (in German).47:671–4. 1974. 1971. Reimers D.COMBINED HORMONAL CONTRACEPTIVES | 155 528. Praxis der Pneumologie vereinigt mit Der Tuberkulosearzt. Jezek A. La Nouvelle presse médicale. 1975. et al. 1998. Fertil Steril. Piguet B. 1990.38:1042–50. Allard S. [Effects of rifampicin on the menstrual cycle and on oestrogen excretion in patients taking oral contraceptives]. Guilbert E. [Rifampicin and oral contraceptives (author’s transl)]. Meyer B. 1976. Nocke-Finke L. 530. Rifampicin. CHCs Medical eligibility criteria for contraceptive use . 533. Maree J. A model to detect interactions between roxithromycin and oral contraceptives.

The GDG assigned the same recommendations for Sino- implant (II) as for the other LNG implants. therefore. reversible contraception. a. Both consist of a single-rod endometriosis and HIV among DMPA-SC users appear implant containing 68 mg of ETG. Jadelle® and Sino-implant (II)®. Sino-implant (II) ® is a 2-rod implant. . 5. each rod containing 75 mg 1. DMPA-IM = 150 mg of DMPA given intramuscularly of LNG 2. obesity. considered here are the following: PROGESTOGEN-ONLY INJECTABLES (POIs) 1.2 Progestogen-only contraceptives (POCs) PROGESTOGEN-ONLY IMPLANTS PROGESTOGEN-ONLY PILLS (POPs) Progestogen-only implants are a type of long-acting. The various types of implants that are POPs contain only a progestogen and no estrogen. There are three formulations considered here: b. Further. Implanon® and Nexplanon®. Jadelle® is a 2-rod implant. DMPA-SC = 104 mg of DMPA given subcutaneously c. Norplant® is a 6-rod implant. Pending further evidence.7. with no significant assigned recommendations should be considered a preliminary differences in serious adverse events. DMPA-SC and DMPA-IM appear to be therapeutically No studies were identified that provided direct evidence on equivalent. consistent with existing recommendations for DMPA-IM (1–12). that Sino-implant (II) has a similar safety and pharmacokinetic DMPA-SC should have the same categories as DMPA-IM.156 | Medical eligibility criteria for contraceptive use . These injectables include depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN). safety data from studies of other LNG implants among women with medical conditions were used due to the similarity of Sino-implant (II) and other LNG implants in hormone formulation. 11). such as ectopic best judgement.PROGESTOGEN-ONLY CONTRACEPTIVES 2. with similar safety profiles when used by healthy the use of the Sino-implant (II) among women with medical women (3. the Guideline conditions in the MEC and included a comparison group. Etonogestrel (ETG): The ETG-containing implants are Identified evidence for the conditions of age. Development Group (GDG) concluded that the evidence Evidence from three studies of healthy women demonstrate available for DMPA-IM applies to DMPA-SC and. Levonorgestrel (LNG): The LNG-containing implants are Norplant®. quality profile and daily release rates.Part II . each rod containing 75 mg of LNG 3. NET-EN = 200 mg of NET-EN given intramuscularly 2. the profile to that of other LNG implants. Therefore. (13–15). which will be re-evaluated as new data pregnancy or discontinuation due to medical problems become available. each rod containing 36 mg of LNG (no longer in production).

AGE Evidence: Most studies have found that women lose bone mineral density (BMD) during DMPA use. including HIV. but are not used as widely by national programmes as male condoms. There is no known harm to the woman. Studies generally find no effect of POCs other than DMPA on BMD (5. including HIV. 12. although 1 large study suggests that women who choose c) > 45 years 1 2 1 DMPA may be at higher risk for fracture even prior to initiation of the method (16). Female condoms are effective and safe. Medical eligibility criteria for contraceptive use . 16–60). the relationship between DMPA use during pregnancy and its effects on the fetus remains unclear.PROGESTOGEN-ONLY CONTRACEPTIVES | 157 POCs PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). or the fetus if POCs are accidentally used during pregnancy. When used correctly and consistently. condoms offer one of the most effective methods of protection against STIs. It is unclear whether adult women with long durations of DMPA use can regain BMD to baseline levels before entering menopause and whether adolescents can reach peak bone mass after discontinuation of DMPA. C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition.Part II . the correct and consistent use of condoms is recommended. but a) Menarche to < 18 years 1 2 1 recover BMD after discontinuation. However. The relationship between these changes in BMD during the reproductive years and future fracture risk is unknown. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. the course of her pregnancy. PARITY a) Nulliparous 1 1 1 b) Parous 1 1 1 . Limited evidence b) 18 to 45 years 1 1 1 shows a weak association with fracture. further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY PREGNANCY NA NA NA NA = not applicable Clarification: Use of POCs is not required. If there is a risk of STI/HIV.

PROGESTOGEN-ONLY CONTRACEPTIVES PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) BREASTFEEDING † Clarification: There is theoretical concern about the potential exposure of the neonate to DMPA/NET-EN a) < 6 weeks postpartum 2 3 2 during the first 6 weeks postpartum. PAST ECTOPIC PREGNANCY* 2 1 1 HISTORY OF PELVIC SURGERY 1 1 1 SMOKING a) Age < 35 years 1 1 1 b) Age > 35 years i) < 15 cigarettes/day 1 1 1 ii) > 15 cigarettes/day 1 1 1 . If there is a risk of STI/HIV. 76. however. When used correctly and consistently. including HIV. a) First trimester 1 1 1 b) Second trimester 1 1 1 Evidence: Limited evidence suggests that there are no adverse side-effects when an LNG implant or NET-EN c) Immediate post-septic abortion 1 1 1 are initiated after first-trimester abortion (113–116). Animal data suggest an effect of progesterone on the developing brain. Female condoms are effective and safe. including HIV. health or development (74. In many settings. condoms offer one of the most effective methods of protection against STIs. DMPA/NET-EN may be among the few methods widely available and accessible to c) > 6 months postpartum 1 1 1 breastfeeding women immediately postpartum. b) > 6 weeks to < 6 months 1 1 1 however. these studies have been inadequately designed to determine whether a risk of long-term effects exists. and access to services is limited. pregnancy-related morbidity and mortality postpartum (primarily risks are high. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. In breastfeeding) such settings. whether similar effects occur following progestogen exposure in humans is unclear (110–112). Evidence: Direct evidence demonstrates no harmful effect of POCs on breastfeeding performance (61– 109) and generally demonstrates no harmful effects on infant growth. C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. but are not used as widely by national programmes as male condoms.158 | Medical eligibility criteria for contraceptive use . POSTPARTUM (NON- BREASTFEEDING WOMEN) a) < 21 days 1 1 1 b) > 21 days 1 1 1 POST-ABORTION Clarification: POCs may be started immediately post- abortion.Part II . 99). 89. the correct and consistent use of condoms is recommended.

In many of these settings. Data on other POC methods and other adverse outcomes are limited (10. the correct and consistent use of condoms is recommended. in some settings blood pressure measurements are unavailable. When used correctly and consistently. ARTERIAL CARDIOVASCULAR the risk of cardiovascular disease may increase DISEASE substantially. there is generally no association between baseline weight and weight gain among DMPA users compared with non-users. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. However. condoms offer one of the most effective methods of protection against STIs. thrombosis. If there is a risk of STI/HIV. The dyslipidaemias) effects of DMPA and NET-EN may persist for some time after discontinuation. Evidence is mixed for adolescent DMPA users. although this increase is substantially less diabetes. further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) OBESITY Clarification: There is evidence for differential weight gain among normal-weight and obese adolescents a) > 30 kg/m2 BMI 1 1 1 who use DMPA. with some studies observing greater weight gain among obese compared with normal-weight users. BLOOD PRESSURE MEASUREMENT NA NA NA NA = not applicable UNAVAILABLE Clarification: It is desirable to have blood pressure measurements taken before initiation of POC use. NET-EN is Category 2 due to evidence > 30 kg/m2 BMI regarding potential effects of NET-EN on BMD among adolescents (see row: Age). b) Menarche to < 18 years and 1 2 1 However. pregnancy-related morbidity and mortality risks are high. but are not used as widely by national programmes as male condoms. CARDIOVASCULAR DISEASE MULTIPLE RISK FACTORS FOR 2 3 2 Clarification: When multiple major risk factors exist. women should not be denied use of POCs simply because their blood pressure cannot be measured. including HIV. . In such settings. hypertension and known than with combined oral contraceptives (COCs). Some POCs may increase the risk of (such as older age. but not among those using NET-EN.PROGESTOGEN-ONLY CONTRACEPTIVES | 159 POCs PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). Methodological differences across studies may account for the differences in findings. C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. smoking. Medical eligibility criteria for contraceptive use . Female condoms are effective and safe. including HIV. and POCs are among the few methods widely available. 117– 133).Part II . but other studies showing no association. Evidence: Among adult women.

those who used POPs or progestogen-only injectables (POIs) had a small i) systolic 140–159 or diastolic 1 2 1 increased risk of cardiovascular events compared with 90–99 mm Hg women who did not use these methods (134). When multiple risk factors do exist. where 2 2 2 Clarification: It is desirable to have blood pressure blood pressure CANNOT be measurements taken before initiation of POC evaluated (including hypertension in use. b) Adequately controlled 1 2 1 Clarification: Women adequately treated for hypertension. In many of these settings. pregnancy-related morbidity and mortality risks are high. If there is a risk of STI/HIV. Female condoms are effective and safe. the correct and consistent use of condoms is recommended. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive. POC users with adequately controlled and monitored hypertension should be at reduced risk of acute MI and stroke compared with untreated hypertensive POC users. and POCs are among the few types of methods widely available. where blood pressure hypertension are at reduced risk of acute myocardial CAN be evaluated infarction (MI) and stroke as compared with untreated women. Although there are no data. women should not be denied the use of POCs simply because their blood pressure cannot be measured.PROGESTOGEN-ONLY CONTRACEPTIVES PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.Part II . ii) systolic ≥ 160 or diastolic 2 3 2 ≥ 100 mm Hg d) Vascular disease 2 3 2 HISTORY OF HIGH BLOOD 1 1 1 PRESSURE DURING PREGNANCY (where current blood pressure is measurable and normal) . the risk of cardiovascular disease may increase substantially. C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. including HIV. but are not used as widely by national programmes as male condoms.160 | Medical eligibility criteria for contraceptive use . However. When used correctly and consistently. further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) HYPERTENSION* For all categories of hypertension. classifications are based on the assumption that no other risk factors for cardiovascular disease exist. In such settings. c) Elevated blood pressure levels Evidence: Limited evidence suggests that among (properly taken measurements) women with hypertension. condoms offer one of the most effective methods of protection against STIs. a) History of hypertension. including HIV. in some settings blood pressure pregnancy) measurements are unavailable.

g. Limited evidence indicates that intramuscular injections of DMPA in women on chronic anticoagulation therapy does not pose a significant risk of haematoma at the injection site or increase the risk of heavy or irregular vaginal bleeding (137. C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. protein C. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. any small increased risk is substantially less than that with COCs (134–136). protein S. any small increased risk is substantially less than that with COCs (134–136). the correct and consistent use of condoms is recommended. factor V Leiden. including HIV.Part II . Female condoms are effective and safe. Although evidence on the risk of venous thrombosis with the use of POCs is inconsistent in otherwise healthy women. further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) DEEP VEIN THROMBOSIS (DVT)/ PULMONARY EMBOLISM (PE)* a) History of DVT/PE 2 2 2 b) Acute DVT/PE 3 3 3 Evidence: There is no direct evidence on the use of POCs among women with DVT/PE on anticoagulant therapy. because of the rarity of the conditions and the high prothrombin mutation. If there is a risk of STI/HIV.PROGESTOGEN-ONLY CONTRACEPTIVES | 161 POCs PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). c) DVT/PE and established on 2 2 2 Evidence: There is no direct evidence on the use of anticoagulant therapy POCs among women with DVT/PE on anticoagulant therapy. Medical eligibility criteria for contraceptive use . including HIV. Although evidence on the risk of venous thrombosis with the use of POCs is inconsistent in otherwise healthy women. When used correctly and consistently. but are not used as widely by national programmes as male condoms. and antithrombin deficiencies) . d) Family history (first-degree 1 1 1 relatives) e) Major surgery i) with prolonged immobilization 2 2 2 ii) without prolonged 1 1 1 immobilization f) Minor surgery without 1 1 1 immobilization KNOWN THROMBOGENIC 2 2 2 Clarification: Routine screening is not appropriate MUTATIONS (e. cost of screening. condoms offer one of the most effective methods of protection against STIs. 138).

162 | Medical eligibility criteria for contraceptive use - Part II - PROGESTOGEN-ONLY CONTRACEPTIVES

PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)

POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and
consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective
methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national
programmes as male condoms.
CONDITION CATEGORY CLARIFICATIONS/EVIDENCE
I = initiation, C = continuation
POP DMPA/ LNG/ETG
NET-EN
† recommendations reviewed for the POP = progestogen-only pill
MEC 5th edition, further details after LNG/ETG = levonorgestrel and etonogestrel (implants)
this table DMPA = depot medroxyprogesterone acetate (injectable)
* additional comments after this table NET-EN = norethisterone enanthate (injectable)

SUPERFICIAL VENOUS DISORDERS
a) Varicose veins 1 1 1
b) Superficial venous thrombosis 1 1 1
CURRENT AND HISTORY OF I C I C
ISCHAEMIC HEART DISEASE*
2 3 3 2 3
STROKE* (HISTORY OF I C I C
CEREBROVASCULAR ACCIDENT)
2 3 3 2 3
KNOWN DYSLIPIDAEMIAS WITHOUT 2 2 2 Clarification: Routine screening is not appropriate
OTHER KNOWN CARDIOVASCULAR because of the rarity of the condition and the high
RISK FACTORS cost of screening.
VALVULAR HEART DISEASE
a) Uncomplicated 1 1 1
b) Complicated (pulmonary 1 1 1
hypertension, risk of atrial
fibrillation, history of subacute
bacterial endocarditis)

RHEUMATIC DISEASES

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)*
People with SLE are at increased risk of ischaemic heart disease, stroke and venous thromboembolism. Categories assigned to
such conditions in the Medical eligibility criteria for contraceptive use should be the same for women with SLE who present with
these conditions. For all categories of SLE, classifications are based on the assumption that no other risk factors for cardiovascular
disease are present; these classifications must be modified in the presence of such risk factors. Available evidence indicates that
many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives
(139–156).
I C
a) Positive (or unknown) 3 3 3 3 Evidence: Antiphospholipid antibodies are associated
antiphospholipid antibodies with a higher risk for both arterial and venous
thrombosis (157–159).
b) Severe thrombocytopenia 2 3 2 2
c) Immunosuppressive treatment 2 2 2 2
d) None of the above 2 2 2 2

Medical eligibility criteria for contraceptive use - Part II - PROGESTOGEN-ONLY CONTRACEPTIVES | 163

POCs
PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)

POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and
consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective
methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national
programmes as male condoms.
CONDITION CATEGORY CLARIFICATIONS/EVIDENCE
I = initiation, C = continuation
POP DMPA/ LNG/ETG
NET-EN
† recommendations reviewed for the POP = progestogen-only pill
MEC 5th edition, further details after LNG/ETG = levonorgestrel and etonogestrel (implants)
this table DMPA = depot medroxyprogesterone acetate (injectable)
* additional comments after this table NET-EN = norethisterone enanthate (injectable)

NEUROLOGIC CONDITIONS

HEADACHES* I C I C I C
a) Non-migrainous (mild or severe) 1 1 1 1 1 1 Clarification: Classification depends on accurate
diagnosis of those severe headaches that are
b) Migraine
migrainous and those that are not. Any new
i) without aura headaches or marked changes in headaches should
be evaluated. Classification is for women without any
age < 35 years 1 2 2 2 2 2 other risk factors for stroke. Risk of stroke increases
age > 35 years 1 2 2 2 2 2 with age, hypertension and smoking.

ii) with aura, at any age 2 3 2 3 2 3
EPILEPSY 1 1 1 Clarification: If a woman is taking anticonvulsants,
refer to the last section of this table, on drug
interactions. Certain anticonvulsants lower POC
effectiveness.

DEPRESSIVE DISORDERS

DEPRESSIVE DISORDERS 1 1 1 Clarification: The classification is based on data for
women with selected depressive disorders. No data
on bipolar disorder or postpartum depression were
available. There is a potential for drug interactions
between certain antidepressant medications and
hormonal contraceptives.

Evidence: POC use did not increase depressive
symptoms in women with depression compared with
baseline (160–163).

REPRODUCTIVE TRACT INFECTIONS AND DISORDERS

VAGINAL BLEEDING PATTERNS*
a) Irregular pattern without heavy 2 2 2
bleeding
b) Heavy or prolonged bleeding 2 2 2 Clarification: Unusually heavy bleeding should raise
(includes regular and irregular the suspicion of a serious underlying condition.
patterns)

164 | Medical eligibility criteria for contraceptive use - Part II - PROGESTOGEN-ONLY CONTRACEPTIVES

PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)

POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and
consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective
methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national
programmes as male condoms.
CONDITION CATEGORY CLARIFICATIONS/EVIDENCE
I = initiation, C = continuation
POP DMPA/ LNG/ETG
NET-EN
† recommendations reviewed for the POP = progestogen-only pill
MEC 5th edition, further details after LNG/ETG = levonorgestrel and etonogestrel (implants)
this table DMPA = depot medroxyprogesterone acetate (injectable)
* additional comments after this table NET-EN = norethisterone enanthate (injectable)

UNEXPLAINED VAGINAL BLEEDING* Clarification: If pregnancy or an underlying
(suspicious for serious condition) pathological condition (such as pelvic malignancy)
is suspected, it must be evaluated and the category
Before evaluation 2 3 3
adjusted after evaluation.
ENDOMETRIOSIS 1 1 1
BENIGN OVARIAN TUMOURS 1 1 1
(including cysts)
SEVERE DYSMENORRHOEA 1 1 1
GESTATIONAL TROPHOBLASTIC
DISEASE
a) Decreasing or undetectable 1 1 1
β-hCG levels
b) Persistently elevated β-hCG 1 1 1
levels or malignant disease
CERVICAL ECTROPION 1 1 1
CERVICAL INTRAEPITHELIAL 1 2 2 Evidence: Among women with persistent human
NEOPLASIA (CIN) papillomavirus (HPV) infection, long-term DMPA use
(≥ 5 years) may increase the risk of carcinoma in situ
and invasive carcinoma (164).
CERVICAL CANCER* 1 2 2
(awaiting treatment)
BREAST DISEASE*
a) Undiagnosed mass 2 2 2 Clarification: Evaluation should be pursued as early as
possible.
b) Benign breast disease 1 1 1
c) Family history of cancer 1 1 1
d) Breast cancer
i) current 4 4 4
ii) past and no evidence of current 3 3 3
disease for 5 years
ENDOMETRIAL CANCER* 1 1 1
OVARIAN CANCER* 1 1 1

Medical eligibility criteria for contraceptive use - Part II - PROGESTOGEN-ONLY CONTRACEPTIVES | 165

POCs
PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)

POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and
consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective
methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national
programmes as male condoms.
CONDITION CATEGORY CLARIFICATIONS/EVIDENCE
I = initiation, C = continuation
POP DMPA/ LNG/ETG
NET-EN
† recommendations reviewed for the POP = progestogen-only pill
MEC 5th edition, further details after LNG/ETG = levonorgestrel and etonogestrel (implants)
this table DMPA = depot medroxyprogesterone acetate (injectable)
* additional comments after this table NET-EN = norethisterone enanthate (injectable)

UTERINE FIBROIDS*
a) Without distortion of the uterine 1 1 1
cavity
b) With distortion of the uterine 1 1 1
cavity
PELVIC INFLAMMATORY DISEASE
(PID)*
a) Past PID (assuming no current
risk factors for STIs)
i) with subsequent pregnancy 1 1 1
ii) without subsequent pregnancy 1 1 1
b) PID – current 1 1 1
STIs
a) Current purulent cervicitis or 1 1 1
chlamydial infection or gonorrhoea
b) Other STIs (excluding HIV and 1 1 1
hepatitis)
c) Vaginitis (including Trichomonas 1 1 1
vaginalis and bacterial vaginosis)
d) Increased risk of STIs 1 1 1 Evidence: Evidence suggests that there may be an
increased risk of chlamydial cervicitis among DMPA
users at high risk of STIs. For other STIs, there is
either evidence of no association between DMPA use
and STI acquisition or too limited evidence to draw
any conclusions. There is no evidence for other POCs
(165–172).

166 | Medical eligibility criteria for contraceptive use - Part II - PROGESTOGEN-ONLY CONTRACEPTIVES

PROGESTOGEN-ONLY CONTRACEPTIVES (POCs)

POCs do not protect against sexually transmitted infections (STIs), including HIV. If there is a risk of STI/HIV, the correct and
consistent use of condoms is recommended. When used correctly and consistently, condoms offer one of the most effective
methods of protection against STIs, including HIV. Female condoms are effective and safe, but are not used as widely by national
programmes as male condoms.
CONDITION CATEGORY CLARIFICATIONS/EVIDENCE
I = initiation, C = continuation
POP DMPA/ LNG/ETG
NET-EN
† recommendations reviewed for the POP = progestogen-only pill
MEC 5th edition, further details after LNG/ETG = levonorgestrel and etonogestrel (implants)
this table DMPA = depot medroxyprogesterone acetate (injectable)
* additional comments after this table NET-EN = norethisterone enanthate (injectable)

HIV/AIDS

HIGH RISK OF HIV 1 1 1 See below for Clarification/Evidence

Clarification for high risk of HIV:
Women at high risk of HIV who are using progestogen-only injectables (POIs) should be informed that available studies on the
association between POI contraception and HIV acquisition have important methodological limitations hindering interpretation.
Some studies suggest that women using POI contraception may be at increased risk of HIV acquisition; other studies have not
found this association. The public health impact of any such association would depend upon the local context, including rates of
injectable contraceptive use, maternal mortality and HIV prevalence. This must be considered when adapting guidelines to local
contexts. WHO expert groups continue to actively monitor any emerging evidence. At the meeting in 2014, as at the 2012 technical
consultation, it was agreed that the epidemiological data did not warrant a change to the MEC. Given the importance of this issue,
women at high risk of HIV infection should be informed that POIs may or may not increase their risk of HIV acquisition. Women
and couples at high risk of HIV acquisition considering POIs should also be informed about and have access to HIV preventive
measures, including male and female condoms.

Evidence for high risk of HIV:
Five studies assessed the use of NET-EN injectables and were considered to be “informative but with important limitations” (28).
Four of them reported no statistically significant association with HIV acquisition (3, 8, 9, 13), while one did (11).
Nine studies assessed DMPA, or, if a DMPA-specific result was unavailable, assessed non-specified injectables; these studies
were considered to be “informative but with important limitations” (28). The results were mixed: three of the studies showed a
significant increase in risk (5, 11, 12), one showed a significant increase in risk using one statistical model but this association
was not statistically significant using another statistical model (6, 7), and five showed no significant increase in risk (3, 8–10, 13).
Two studies assessed implants, one of which was classified as “unlikely to inform the primary question” (4, 28). Neither of these
studies reported a statistically significant increased risk of HIV acquisition, but confidence intervals were wide (4, 21).

including HIV. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.PROGESTOGEN-ONLY CONTRACEPTIVES | 167 POCs PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs).Part II . 193–207). SEVERE OR ADVANCED HIV 1 1 1 CLINICAL DISEASE Evidence for asymptomatic or mild HIV clinical (WHO STAGE 3 OR 4) disease (WHO stage 1 or 2) and severe or advanced HIV clinical disease (WHO stage 3 or 4): Out of 6 available studies. 191). 5 suggest no association between use of POIs and progression of HIV. condoms offer one of the most effective methods of protection against STIs. refer to the last section of this table. however. One study reported a statistically significant association between use of POIs and female-to-male transmission of HIV (180). but are not used as widely by national programmes as male condoms. Female condoms are effective and safe. further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) ASYMPTOMATIC OR MILD HIV 1 1 1 Clarification for asymptomatic or mild HIV clinical CLINICAL DISEASE disease (WHO stage 1 or 2) and severe or advanced (WHO STAGE 1 OR 2) HIV clinical disease (WHO stage 3 or 4): Because there may be drug interactions between hormonal contraceptives and ARV therapy. The findings of studies indirectly assessing the effects of various hormonal contraceptive methods on female-to-male HIV transmission by measuring genital viral shedding as a proxy for infectivity have been mixed. One study found no difference in ART initiation or CD4 count between users and non-users of the LNG-IUD (192). had significant loss to follow-up and method switching among groups. When used correctly and consistently. this study. the correct and consistent use of condoms is recommended. . Two prospective observational studies directly assessed the effects of different hormonal contraceptive methods on female-to-male HIV transmission by measuring seroconversions in male partners of women living with HIV and known to be using hormonal contraceptives. Most of indirect studies measuring whether various hormonal contraceptive methods affect plasma HIV viral load have found no effect (189. as measured by CD4 count < 200 cells/mm3. If there is a risk of STI/HIV. One randomized trial found an increased risk of a composite outcome of declining CD4 count or death among oral contraceptive users (COCs and POPs) when compared with users of copper-bearing IUDs. while another study did not find a statistically significant association between use of DMPA and female-to-male HIV transmission (184). C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. on drug interactions. limiting its interpretation (188. or mortality (186–190). including HIV. Medical eligibility criteria for contraceptive use . initiation of antiretroviral therapy (ART).

condoms offer one of the most effective methods of protection against STIs. ii) insulin dependent 2 2 2 LNG implant) suggests that these methods have little effect on short-term or long-term diabetes control (e. on drug interactions.or non-insulin- i) non-insulin dependent dependent diabetes.168 | Medical eligibility criteria for contraceptive use . the correct and consistent use of condoms is recommended. b) Non-vascular disease Evidence: Among women with insulin. Female condoms are effective and safe.g. haemostatic markers or lipid profile (215–218). DMPA injectable. If there is a risk of STI/HIV. Rifampicin is likely to decrease the effectiveness of some POCs. including HIV. HbA1c levels). There is only limited and inconsistent evidence regarding the development of non-insulin-dependent diabetes among users of POCs with a history of gestational diabetes (211–214). C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. see cirrhosis) TUBERCULOSIS a) Non-pelvic 1 1 1 Clarification: If a woman is taking rifampicin. b) Fibrosis of the liver 1 1 1 (if severe. 210). limited evidence showed that DMPA use had no adverse effects on liver function (208). When used correctly and consistently.Part II . MALARIA 1 1 1 ENDOCRINE CONDITIONS DIABETES* a) History of gestational disease 1 1 1 Evidence: POCs had no adverse effects on serum lipid levels in women with a history of gestational diabetes in 2 small studies (209. c) Nephropathy/retinopathy/ 2 3 2 neuropathy d) Other vascular disease or 2 3 2 diabetes of > 20 years’ duration . limited evidence on the use of 2 2 2 progestogen-only methods (POPs. refer b) Pelvic 1 1 1 to the last section of this table. including HIV.PROGESTOGEN-ONLY CONTRACEPTIVES PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. but are not used as widely by national programmes as male condoms. further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) OTHER INFECTIONS SCHISTOSOMIASIS a) Uncomplicated 1 1 1 Evidence: Among women with uncomplicated schistosomiasis.

the correct and consistent use of condoms is recommended. but are not used as widely by national programmes as male condoms. Medical eligibility criteria for contraceptive use . ii) hepatocellular adenoma 3 3 3 b) Malignant (hepatoma) 3 3 3 . When used correctly and consistently. Female condoms are effective and safe. C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. including HIV.Part II . including HIV. condoms offer one of the most effective methods of protection against STIs. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. direct evidence that hormonal contraceptive use does not influence either progression or regression of liver lesions among women with focal nodular hyperplasia (219–221). further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) THYROID DISORDERS a) Simple goitre 1 1 1 b) Hyperthyroid 1 1 1 c) Hypothyroid 1 1 1 GASTROINTESTINAL CONDITIONS GALL BLADDER DISEASE a) Symptomatic i) treated by cholecystectomy 2 2 2 ii) medically treated 2 2 2 iii) current 2 2 2 b) Asymptomatic 2 2 2 HISTORY OF CHOLESTASIS* a) Pregnancy-related 1 1 1 b) Past-COC related 2 2 2 VIRAL HEPATITIS a) Acute or flare 1 1 1 b) Carrier 1 1 1 c) Chronic 1 1 1 CIRRHOSIS a) Mild (compensated) 1 1 1 b) Severe (decompensated) 3 3 3 LIVER TUMOURS* a) Benign i) focal nodular hyperplasia 2 2 2 Evidence: There is limited.PROGESTOGEN-ONLY CONTRACEPTIVES | 169 POCs PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). If there is a risk of STI/HIV.

231). and vice versa (233.Part II . 2 DMPA=1 2 Pharmacokinetic data suggest potential drug NET-EN=2 interactions between some antiretroviral drugs Etravirine (ETR) 1 1 1 (particularly some NNRTIs and ritonavir-boosted PIs) and some hormonal contraceptives. C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. If there is a risk of STI/HIV. the correct and consistent use of condoms is recommended. including HIV.170 | Medical eligibility criteria for contraceptive use . Based primarily on pharmacokinetic data. condoms offer one of the most effective methods of protection against STIs. further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) ANAEMIAS THALASSAEMIA 1 1 1 SICKLE CELL DISEASE 1 1 1 Evidence: Among women with sickle cell disease. IRON-DEFICIENCY ANAEMIA* 1 1 1 DRUG INTERACTIONS ANTIRETROVIRAL THERAPY (ART) a) Nucleoside reverse transcriptase Evidence: NRTIs do not appear to have significant risk inhibitors (NRTIs) of interactions with hormonal contraceptive methods Abacavir (ABC) 1 1 1 (230. Female condoms are effective and safe. including HIV.PROGESTOGEN-ONLY CONTRACEPTIVES PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. Tenofovir (TDF) 1 1 1 Zidovudine (AZT) 1 1 1 Lamivudine (3TC) 1 1 1 Didanosine (DDI) 1 1 1 Emtricitabine (FTC) 1 1 1 Stavudine (D4T) 1 1 1 b) Non-nucleoside reverse Clarification: Antiretroviral drugs have the potential transcriptase inhibitors (NNRTIs) to either decrease or increase the levels of steroid Efavirenz (EFV) hormones in women using hormonal contraceptives. When used correctly and consistently. but are not used as widely by national programmes as male condoms. These interactions Nevirapine (NVP) 2 DMPA=1 2 may reduce the effectiveness of the hormonal NET-EN=2 contraceptive. 234). . POC use did not have adverse effects on haematological parameters and. Rilpivirine (RPV) 1 1 1 Evidence: One retrospective chart review of women using efavirenz-containing ART showed increased contraceptive failure rates for women using LNG implants (232). in some studies. the effectiveness of DMPA is likely not affected by NNRTIs. was beneficial with respect to clinical symptoms (222–229).

NET-EN=2 anticonvulsants with POPs. carbamazepine.Part II . ANTICONVULSANT THERAPY a) Certain anticonvulsants 3 DMPA=1 2 Clarification: Although the interaction of certain (phenytoin. 240). Female condoms are effective and safe. Based primarily on pharmacokinetic data. C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) c) Protease inhibitors (PIs) Clarification: Antiretroviral drugs have the potential Ritonavir-boosted atazanavir to either decrease or increase the levels of steroid 2 DMPA=1 2 (ATV/r) hormones in women using hormonal contraceptives. When used correctly and consistently. implants is not harmful to women. NET-EN and LNG/ETG barbiturates. . One study found higher progestogen levels with concurrent PI use in users of POPs (238). co- administration resulted in higher progestogen levels (237). including HIV. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. the correct and consistent use of condoms is recommended. topiramate. In women using the combined patch. d) Integrase inhibitors Evidence: The integrase inhibitor raltegravir does not appear to interact with norelgestromin-containing Raltegravir (RAL) 1 1 COCs (239. Evidence: Use of certain anticonvulsants may decrease the effectiveness of POCs (241–243). Use of DMPA is Category 1 because its effectiveness is not decreased by the use of certain anticonvulsants. and vice versa (233. 236). If there is a risk of STI/HIV. Whether increasing the hormone dose of POPs alleviates this concern remains unclear. the effectiveness of DMPA is likely not affected by PIs. 234). NET-EN=2 Pharmacokinetic data suggest potential drug Ritonavir-boosted lopinavir (LPV/r) 2 DMPA=1 2 interactions between some antiretroviral drugs NET-EN=2 (particularly some NNRTIs and ritonavir-boosted PIs) and some hormonal contraceptives. Medical eligibility criteria for contraceptive use . but are not used as widely by national programmes as male condoms. NET-EN and LNG/ETG implants.PROGESTOGEN-ONLY CONTRACEPTIVES | 171 POCs PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). it is likely to reduce oxcarbazepine) the effectiveness of POPs. b) Lamotrigine 1 1 1 Evidence: No drug interactions have been reported among women with epilepsy taking lamotrigine and using POCs (244). condoms offer one of the most effective methods of protection against STIs. These interactions may reduce the effectiveness of the hormonal Ritonavir-boosted darunavir 2 DMPA=1 2 contraceptive. including HIV. primidone. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. (DRV/r) NET-EN=2 Ritonavir (RTV) 2 DMPA=1 2 Evidence: Pharmacokinetic data suggest decreases NET-EN=2 in progestogen levels when COCs are used in combination with ritonavir and ritonavir-boosted PIs (235.

the correct and consistent use of condoms is recommended.Part II . it is likely to reduce the effectiveness of POPs. C = continuation POP DMPA/ LNG/ETG NET-EN † recommendations reviewed for the POP = progestogen-only pill MEC 5th edition. including HIV. If there is a risk of STI/HIV. NET-EN and LNG/ETG implants.172 | Medical eligibility criteria for contraceptive use . further details after LNG/ETG = levonorgestrel and etonogestrel (implants) this table DMPA = depot medroxyprogesterone acetate (injectable) * additional comments after this table NET-EN = norethisterone enanthate (injectable) ANTIMICROBIAL THERAPY a) Broad-spectrum antibiotics 1 1 1 b) Antifungals 1 1 1 c) Antiparasitics 1 1 1 d) Rifampicin or rifabutin therapy 3 DMPA=1 2 Clarification: Although the interaction of rifampicin or NET-EN=2 rifabutin with POPs. When used correctly and consistently. condoms offer one of the most effective methods of protection against STIs. NET-EN and LNG/ETG implants is not harmful to women.PROGESTOGEN-ONLY CONTRACEPTIVES PROGESTOGEN-ONLY CONTRACEPTIVES (POCs) POCs do not protect against sexually transmitted infections (STIs). Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. including HIV. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. . Female condoms are effective and safe. Whether increasing the hormone dose of POPs alleviates this concern remains unclear. Use of DMPA is Category 1 because its effectiveness is not decreased by the use of rifampicin or rifabutin. but are not used as widely by national programmes as male condoms.

given the increased or and other supplementary remarks from the GDG regarding the erratic bleeding that may be seen on initiation of DMPA and its recommendations. The effects of DMPA Outcome (PICO) questions developed by the Guideline and NET-EN may persist for some time after discontinuation. However. which suggests a low risk of ectopic pregnancy. are described in greater detail in Part I of this document. irreversibility for 11–13 weeks after administration. The International Classification of Headache Disorders. with regard to POPs or LNG/ETG implants. the Severe thrombocytopenia increases the risk of bleeding. The effects of DMPA and NET-EN. but these Women on anticoagulation therapy who have a history of patterns may persist longer. The effects of DMPA and NET-EN may persist for some time after discontinuation. GRADE evidence profiles. LNG users to develop amenorrhoea. 13 Available at: http://ihs-classification. PAST ECTOPIC PREGNANCY HEADACHES POPs have a higher absolute rate of ectopic pregnancy Aura is a specific focal neurologic symptom. particularly among users of DMPA and symptoms of underlying pathology. there is little concern about these effects use. ETG users are more likely than haemorrhagic ovarian cysts may benefit from DMPA use. which guided the preparation of SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) systematic reviews.org/en/02_klassifikation .Part II . with regard to POPs or LNG/ETG implants. Medical eligibility criteria for contraceptive use . healthy women. fifth edition. The effects of DMPA and NET-EN may Irregular menstrual bleeding patterns are common among persist for some time after discontinuation. DMPA may persist for some time after discontinuation. CURRENT AND HISTORY OF ISCHAEMIC HEART DISEASE UNEXPLAINED VAGINAL BLEEDING There is concern regarding hypo-estrogenic effects and POCs may cause irregular bleeding patterns. Intervention. However. For more compared with other POCs. Additionally.13 HYPERTENSION There is concern that severe headaches may increase with Vascular disease: There is concern regarding hypo-estrogenic use of NET-EN. Cephalalgia. as part of the reduced HDL levels. which may mask reduced HDL levels. POCs overall GRADE assessment of the quality of the evidence. information on this and other diagnostic criteria. Society. severe thrombocytopenia. there is little concern about these effects NET-EN may persist for some time after discontinuation. However. are available in Part I. The effects of NET-EN and effects and reduced high-density lipoprotein (HDL) levels. but still less than using no method. may be useful in the treatment of menorrhagia in women with summaries of the evidence supporting the recommendation(s). Development Group (GDG) and the databases searched to retrieve the evidence.PROGESTOGEN-ONLY CONTRACEPTIVES | 173 RECOMMENDATIONS REVIEWED FOR FIFTH EDITION STROKE POCs These recommendations were reviewed according to WHO There is concern regarding hypo-estrogenic effects and requirements for guideline development.24(Suppl 1):1–150. particularly among users of DMPA and preparation of the Medical eligibility criteria for contraceptive NET-EN. particularly among users of DMPA and NET-EN. Implant use may induce irregular bleeding patterns. However. there is little concern about these effects with regard to POPs VAGINAL BLEEDING PATTERNS or LNG/ETG implants. initiation of this method in women with severe thrombocytopenia should ADDITIONAL COMMENTS be done with caution. The Population. 2nd edition. 2004. POC use frequently induces an irregular DEEP VEIN THROMBOSIS/PULMONARY EMBOLISM bleeding pattern. Comparator. see: Headache The 75 µg desogestrel-containing pill inhibits ovulation in most Classification Subcommittee of the International Headache cycles. especially during the first 3–6 months. DMPA and implants.

PELVIC INFLAMMATORY DISEASE (PID) Whether POCs.PROGESTOGEN-ONLY CONTRACEPTIVES CERVICAL CANCER (AWAITING TREATMENT) Given that COC use in healthy women is associated with development and growth of hepatocellular adenoma. .174 | Medical eligibility criteria for contraceptive use . women may use POCs. although this increase is substantially less than with COCs. Breast cancer: Breast cancer is a hormonally sensitive tumour. treatment of this condition renders a woman sterile. effects. treatment of this condition renders a woman sterile. a history of COC-related cholestasis may predict subsequent cholestasis with POC use. DIABETES Nephropathy/retinopathy/neuropathy. and the prognosis of women with current or recent breast cancer may worsen with POC use. HISTORY OF CHOLESTASIS Theoretically. However. In general. but they do not protect against HIV or lower genital tract STIs. The effects of DMPA and NET-EN may persist for some time after discontinuation. or diabetes of > 20 years’ duration: There is concern regarding hypo-estrogenic effects and reduced HDL levels. UTERINE FIBROIDS POCs do not appear to cause growth of uterine fibroids. IRON-DEFICIENCY ANAEMIA BREAST DISEASE Changes in the menstrual pattern associated with POC use have little effect on haemoglobin levels. ENDOMETRIAL CANCER While awaiting treatment.Part II . other vascular disease. women may use POCs. women may use POCs. this has not been documented. LIVER TUMOURS There is no evidence regarding hormonal contraceptive use among women with hepatocellular adenoma. reduce the risk of PID among women with STIs is unknown. particularly among users of DMPA and NET-EN. While awaiting treatment. like COCs. In general. OVARIAN CANCER While awaiting treatment. In general. Some POCs may increase the risk of thrombosis. treatment of this condition renders a woman sterile. it is not There is some theoretical concern that POC use may affect known whether other hormonal contraceptives have similar prognosis of the existing disease.

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Bieberdorf 227. Maison P. Effects of Depo-Provera or Microgynon on the painful with protease inhibitors in HIV-1-infected women: crises of sickle cell anemia patients. et al. Motsa N. Oral contraceptive use and focal depot medroxyprogesterone acetate and combination nodular hyperplasia of the liver. et al. Atrio J. 2001. The effect of megestrol acetate on sickling. Rahmouni A. et al. 228.PROGESTOGEN-ONLY CONTRACEPTIVES 217. 1999. 1982.2:229–31. Immune Defic Syndr. Contraception. de Castillo Z. 1993. et al. 230. Ladipo OA. Chen S. Pelletier G. Mark S. March B. intracellular pharmacokinetics of zidovudine.56:313–6. Mathieu D. 2011. Adadevoh BK. Skouby SO. sickle cell patients using subdermal implant containing Clin Ther. Odlind V.71(4):616–20. Norplant use by women with norgestimate plasma pharmacokinetics following oral sickle cell disease. FA. Yoong WC. Nascimento ML. Gastroenterol Clin Biol. Tuck SM. Vogler MA. Rocher L. 234. Aweeka FT. contraceptives in diabetic womne: metabolic effects of AIDS. 2010. et al.41:85–7. A cross-over study disoproxil fumarate on pharmacokinetics of hormonal on seum and high density lipoprotein (HDL) lipids and contraceptives. Belghiti antiretroviral therapy: effective contraception and lack J. Thevanayagam L. Isaacs WA. Amaral E. Stek A. Depo-medroxyprogesterone in women on 219. Felicione E. pharmacokinetics: a randomized. fixed-sequence crossover trial in healthy women. Watts DH. 2006. J Acquir 1997.64:433–8. Park JG. Dolutegravir has no effect on the pharmacokinetics of methadone or oral contraceptives 229. Tuck SM. Mishell DR. 1993. Coutinho E. Am J Med Sci. Guerrero F. 3–6 March 2013. Hanley WD.33(10):1503–14. Olsson SE. et al. 1986. Clax profiles. Mwanyumba A. cell disease. Hays M. nomegesterol acetate (Uniplant). Oral for drug interactions leading to unintended pregnancies.33:257–61. living with HIV in a resource-limited setting: concerns 218. Sekar VJ. Radberg T. Pharmacotherapy. diabetes control during progestogen and combined 232. Kearney BP. Fertil Steril. et al. Hitti J. Ojengbede OA. Molsted-Petersen L. Segal Y.81(2):222–7. 2014. Cherqui Bahamondes L. Br J Haematol.13(4):563–9. Guzman SS. Rosenkranz SL. Jr.28(5):791–3. Erlinger S.14:61–5. 236. Ladipo OA. Li J.Part II . Kasserra C. AIDS. Kobeiter H. Hormonal contraceptive use M. 1998.104:868–70. Karlsson K. 2001. et al. The impact of levonorgestrel during phenytoin treatment in a woman sex and contraceptive therapy on the plasma and with Norplant implants. Barbosa IC.306:1735–7. Kamemoto L. De Pauw 221. 2008. 2000. Kovacs Medroxyprogesterone acetate and homozygous sickle- A. Clin Pharmacol Ther. Atlanta (GA): 20th in oral contraceptive pill users with sickle cell anaemia. Song I. 239. antiretroviral therapy. Clin Pharmacol Ther. Athayde C. . with low-dose ritonavir in healthy women. PA. Coombs RW. Howard RJ. Lopes R. Pharmacokinetic interactions between D. Perry SH. Peppercorn A.265:367–70. Austin and transdermal hormones when co-administered KL. Cohn SE. Fertil Steril. Br J Clin Pharmacol. Espino M. Neely M. Conference on Retroviruses and Opportunistic Infections. Vilgrain V. 2014. Pharmacokinetic interaction among women with liver tumors: a systematic review. Cherala G. Horm Metab Res. Lack of effect of tenofovir contraception in diabetic women. between ethinyl estradiol. de Abood M. Jin B. Osotimehin BO. Carbohydrate metabolism in group. 2011. Stanczyk FZ. Defic Syndr. Borland J.80(4):387–90. Yardumian A. contraception in HIV-infected women. O’Mara E. Serjeant GR. Contraceptives. Nascimento ML. Zafrani ES. Anderson MS. Contraception. A retrospective study of 44 cases]. Enhanced metabolism of Bardeguez A.25(11):1008–10. 222.184 | Medical eligibility criteria for contraceptive use . Vangeneugden T. Int J Gynaecol Obstet. Skryten A. Mehta N. Viscola MA. BMJ. 1986. Watts H. pharmacokinetic results of ACTG trial A5188. Kost JT. Nanda K.46:858–64. 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Janni W. Shane-McWhorter L. Failure of Implanon POCs contraception in a patient taking carbamazepine for epilepsia. Helde G. 244. Friese K. 243. Epilepsia. Pharmacotherapy. Osborn C.PROGESTOGEN-ONLY CONTRACEPTIVES | 185 242. Arch Gynecol Obstet. Medical eligibility criteria for contraceptive use .Part II . Ethinyl estradiol. 1998. 2006. not progestogens. Schindlbeck C.273(4):255–6. 2005. reduces lamotrigine serum concentrations. MacFarlane LL. Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy. Brodtkorb E.46(9):1414–7. Reimers A. Cerven JD. .18:1360–4.

BREASTFEEDING 1 1 2 Clarification: Breastfeeding is not recommended for 1 week after taking UPA since it is excreted in breast-milk. If there is a risk of STI/HIV. but are not used as widely by national programmes as male condoms. there is no known harm to the woman. Female condoms are effective and safe. Breast-milk should be expressed and discarded during that time (1).EMERGENCY CONTRACEPTIVE PILLS 2. or other thromboembolic conditions) MIGRAINE* 2 2 2 SEVERE LIVER DISEASE* 2 2 2 (INCLUDING JAUNDICE) . CONDITION CATEGORY CLARIFICATIONS/EVIDENCE COC LNG UPA † † recommendations reviewed for the MEC COC = combined oral contraceptive 5th edition. Evidence: There is limited evidence from 1 study that suggests obese women with BMI ≥ 30 kg/m2 experience an increased risk of pregnancy after use of LNG compared with women with BMI < 25 kg/m2 (2). Two studies suggest obese women may also experience an increased risk of pregnancy after use of UPA compared with non-obese women. further details after this table LNG = levonorgestrel contraceptive * additional comments after this table UPA = ulipristal acetate PREGNANCY NA NA NA NA = not applicable Clarification: Although this method is not indicated for a woman with a known or suspected pregnancy. or the fetus if ECPs are accidentally used. cerebrovascular attack. PAST ECTOPIC PREGNANCY 1 1 1 OBESITY † 1 1 1 Clarification: ECPs may be less effective among women with BMI ≥ 30 kg/m2 than among women with BMI < 25 kg/m2.186 | Medical eligibility criteria for contraceptive use . When used correctly and consistently. there are no safety concerns. the correct and consistent use of condoms is recommended.Part II . including HIV.3 Emergency contraceptive pills (ECPs) EMERGENCY CONTRACEPTIVE PILLS (ECPs) ECPs do not protect against sexually transmitted infections (STIs). Despite this. including HIV. the course of her pregnancy. 3). condoms offer one of the most effective methods of protection against STIs. though this increase was not significant in 1 study (2. HISTORY OF SEVERE CARDIOVASCULAR 2 2 2 DISEASE* (ischaemic heart disease.7.

oxcarbazepine.g.Part II . Evidence: According to labelling information.75 mg) by 56% compared with LNG ECP alone (5). rifabutin. A small pharmacokinetic study found that concomitant efavirenz use decreased LNG levels in women taking LNG ECP (0. Theoretical concerns therefore extend to use of other CYP3A4 inducers as well as to COC and LNG ECPs. CHCs Medical eligibility criteria for contraceptive use . but are not used as widely by national programmes as male condoms. rifampicin. including HIV. including HIV. the correct and consistent use of condoms is recommended. ECPs CONDITION CATEGORY CLARIFICATIONS/EVIDENCE COC LNG UPA † † recommendations reviewed for the MEC COC = combined oral contraceptive 5th edition. 4). which have similar metabolic pathways to UPA. RAPE* 1 1 1 . When used correctly and consistently. phenobarbital.EMERGENCY CONTRACEPTIVE PILLS | 187 POCs EMERGENCY CONTRACEPTIVE PILLS (ECPs) ECPs do not protect against sexually transmitted infections (STIs). condoms offer one of the most effective methods of protection against STIs. efavirenz. primidone. phenytoin. REPEATED ECP USE 1 1 1 Clarification: Repeated ECP use is an indication that the woman requires further counselling on other contraceptive options. Female condoms are effective and safe. further details after this table LNG = levonorgestrel contraceptive * additional comments after this table UPA = ulipristal acetate CYP3A4 INDUCERS † 1 1 1 Clarification: Strong CYP3A4 inducers may (e. fosphenytoin. rifampicin markedly decreases UPA levels St John’s wort/hypericum perforatum) by 90% or more which may decrease its efficacy (1. If there is a risk of STI/HIV. nevirapine. reduce the effectiveness of ECPs. carbamazepine. 3 or 4 for combined hormonal contraception (CHC) or POC use. Frequently repeated ECP use may be harmful for women with conditions classified as Category 2.

outcome (PICO) questions developed by the Guideline 2.EMERGENCY CONTRACEPTIVE PILLS RECOMMENDATIONS REVIEWED FOR FIFTH EDITION References These recommendations were reviewed according to WHO 1. studies of ulipristal acetate for emergency contraception. et al. are described in greater detail in Part I Contraception. GRADE evidence profiles. which guided the preparation of randomized trials of ulipristal acetate and levonorgestrel. migraine. London: HRA Pharma UK & Ireland preparation of the Medical eligibility criteria for contraceptive Ltd. tablet. Results from pooled Phase III overall GRADE assessment of the quality of the evidence.uk/hcp/abbreviated- prescribing-information-uk. Cu-Uvin History of severe cardiovascular disease. Full prescribing information: ELLA (ulipristal acetate) recommendations. comparator. 5. intervention. as part of the information (UK). Kiser JJ.2012:137192. Charleston (SC): Afaxys.. Cameron ST. Carten ML. Inc. Blithe D.ellaone. Infect Dis Obstet Gynecol. summaries of the evidence supporting the recommendation(s).188 | Medical eligibility criteria for contraceptive use . Rape There are no restrictions for the use of ECPs in cases of rape.co. the 3. and S. Trussell J. The duration of use of ECPs is less than that of regular use of COCs or POPs and thus would be expected to have a lower risk for adverse health outcomes. . Abbreviated prescribing requirements for guideline development.gov/drugsatfda_docs/ ADDITIONAL COMMENTS label/2014/022474s004lbl.86(6):673–80. updated June 2014 (http://www.Part II . 2012. Pharmacokinetic interactions between the hormonal severe liver disease (including jaundice) emergency contraception.pdf.84(4):363–7. and other supplementary remarks from the GDG regarding the 4. fifth edition. use. Mathe H. Scherrer B. accessed 9 March 2015).accessdata. and Efavirenz. are available in Part I. Kwara A. Development Group (GDG) and the databases searched Levy D. levonorgestrel (Plan B). ellaOne® ulipristal acetate. 2011. Glasier A. systematic reviews. Additionally. Contraception. The population. accessed 23 October 2014). Moreau C. of this document. 2013 (http://www.fda. Can we identify women at risk of pregnancy despite using emergency contraception? Data from to retrieve the evidence. Mawhinney S. 2012.

If there is a risk of STI/HIV. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.INTRAUTERINE DEVICES | 189 2. Heavy bleeding or removals for bleeding do not seem to be associated with age. the correct and consistent use of condoms is recommended. Female condoms are effective and safe. a) Menarche to < 20 years 2 2 b) > 20 years 1 1 PARITY Evidence: Risks of pregnancy. including HIV. 7–10). Medical eligibility criteria for contraceptive use . perforation and expulsion are low among all IUD users. Young women using Cu-IUDs may have an increased risk of expulsion compared with older Cu-IUD users (1–15). further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) this table * additional comments after this table PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY PREGNANCY 4 4 Clarification: The IUD is not indicated during pregnancy and should not be used because of the risk of serious pelvic infection and septic spontaneous abortion. C = continuation Cu-IUD LNG-IUD IUDs † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition. condoms offer one of the most effective methods of protection against STIs. Data do not suggest an increased delay in return to fertility for nulliparous IUD users (1. including HIV. and differences by parity may not be clinically meaningful.4 Intrauterine devices (IUDs) INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). infection and perforation are low among IUD users of any age.Part II . a) Nulliparous 2 2 b) Parous 1 1 . When used correctly and consistently.7. AGE Evidence: Risks of pregnancy. 3. but are not used as widely by national programmes as male condoms. infection.

condoms offer one of the most effective methods of protection against STIs. the correct and consistent use of condoms is recommended. including HIV. i) breastfeeding 1 2 ii) non-breastfeeding 1 1 b) ≥ 48 hours to < 4 weeks 3 3 c) ≥ 4 weeks 1 1 d) Puerperal sepsis 4 4 . but are not used as widely by national programmes as male condoms. In other studies. Two other randomized controlled trials assessing early vs delayed initiation of progestogen-only contraceptives failed to show a difference in breastfeeding outcomes (31. including caesarean section) a) < 48 hours Evidence: Immediate postpartum Cu-IUD insertion.Part II . Female condoms are effective and safe. C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition.INTRAUTERINE DEVICES INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). 32). including insertion immediately particularly when insertion occurs immediately after delivery of the placenta after delivery of the placenta. is associated with lower expulsion rates than delayed postpartum insertion. When used correctly and consistently. including HIV. post-placental placement at the time of caesarean section has lower expulsion rates than post-placental vaginal insertions. Insertion complications of perforation and infection are not increased by IUD placement at any time during the postpartum period (16–29).190 | Medical eligibility criteria for contraceptive use . Additionally. further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) this table * additional comments after this table POSTPARTUM † (breastfeeding or non-breastfeeding women. If there is a risk of STI/HIV. One randomized controlled trial found that immediate insertion of the LNG-IUD was associated with decreased breastfeeding duration compared with delayed insertion (30). initiation of LNG-IUD at 4 weeks postpartum or later demonstrated no detrimental effect on breastfeeding outcomes (33–35). CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.

but are not used as widely by national programmes as male condoms. condoms offer one of the most effective methods of protection against STIs. Expulsion was greater when an IUD was inserted following a second- trimester abortion vs a first-trimester abortion. Medical eligibility criteria for contraceptive use .Part II . Women should not be denied use of IUDs simply because their blood pressure cannot be measured. including HIV. When used correctly and consistently. Evidence: There was no difference in risk of complications for immediate vs delayed insertion of an IUD after abortion. including HIV.INTRAUTERINE DEVICES | 191 INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). it is not materially related to safe and effective IUD use. the correct and consistent use of condoms is recommended. b) Second trimester 2 2 c) Immediate post-septic abortion 4 4 PAST ECTOPIC PREGNANCY* 1 1 HISTORY OF PELVIC SURGERY 1 1 (see postpartum. further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) IUDs this table * additional comments after this table POST-ABORTION* a) First trimester 1 1 Clarification: IUDs can be inserted immediately after first-trimester. . C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition. There were no differences in safety or expulsions for post-abortion insertion of an LNG-IUD compared with a Cu-IUD (36–48). CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. spontaneous or induced abortion. If there is a risk of STI/HIV. including caesarean section) SMOKING a) Age < 35 years 1 1 b) Age ≥ 35 years i) < 15 cigarettes/day 1 1 ii) ≥ 15 cigarettes/day 1 1 OBESITY a) ≥ 30 kg/m2 BMI 1 1 b) Menarche to < 18 years and 1 1 ≥ 30 kg/m2 BMI BLOOD PRESSURE MEASUREMENT NA NA NA = not applicable UNAVAILABLE Clarification: While a blood pressure measurement may be appropriate for good preventive health care. Female condoms are effective and safe.

A single reading of blood pressure level is not sufficient to classify a woman as hypertensive. If there is a risk of STI/HIV. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. diabetes.INTRAUTERINE DEVICES INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). the correct and consistent use of condoms is recommended. including HIV. smoking. including HIV. further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) this table * additional comments after this table CARDIOVASCULAR DISEASE MULTIPLE RISK FACTORS FOR 1 2 ARTERIAL CARDIOVASCULAR DISEASE (such as older age. When used correctly and consistently. a) History of hypertension. classifications are based on the assumption that no other risk factors for cardiovascular disease exist. where 1 2 blood pressure CANNOT be evaluated (including hypertension in pregnancy) b) Adequately controlled 1 1 hypertension. the risk of cardiovascular disease may increase substantially.Part II . C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition. but are not used as widely by national programmes as male condoms. hypertension and known dyslipidaemias) HYPERTENSION* For all categories of hypertension.192 | Medical eligibility criteria for contraceptive use . When multiple risk factors do exist. where blood pressure CAN be evaluated c) Elevated blood pressure levels (properly taken measurements) i) systolic 140–159 or diastolic 1 1 90–99 mm Hg ii) systolic ≥ 160 or diastolic 1 2 ≥ 100 mm Hg d) Vascular disease 1 2 HISTORY OF HIGH BLOOD 1 1 PRESSURE DURING PREGNANCY (where current blood pressure is measurable and normal) . condoms offer one of the most effective methods of protection against STIs. Female condoms are effective and safe.

further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) IUDs this table * additional comments after this table DEEP VEIN THROMBOSIS (DVT)/ PULMONARY EMBOLISM (PE)* a) History of DVT/PE 1 2 b) Acute DVT/PE 1 3 Evidence: Although evidence on the risk of venous thrombosis with the use of progestogen-only contraceptives (POCs) is inconsistent. and antithrombin deficiencies) SUPERFICIAL VENOUS DISORDERS a) Varicose veins 1 1 b) Superficial venous thrombosis 1 1 . Female condoms are effective and safe. any small increased risk is substantially less than that with COCs (49–51). but are not used as widely by national programmes as male condoms. When used correctly and consistently. including HIV. mutation. any small increased risk is substantially less than that with combined oral contraceptives (COCs) (49–51). protein S. the correct and consistent use of condoms is recommended. including HIV. If there is a risk of STI/HIV.Part II . protein C.g. prothrombin cost of screening. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. Medical eligibility criteria for contraceptive use . c) DVT/PE and established on 1 2 Evidence: Although evidence on the risk of venous anticoagulant therapy thrombosis with the use of POCs is inconsistent. factor V Leiden. d) Family history (first-degree 1 1 relatives) e) Major surgery i) with prolonged immobilization 1 2 ii) without prolonged 1 1 immobilization f) Minor surgery without 1 1 immobilization KNOWN THROMBOGENIC 1 2 Clarification: Routine screening is not appropriate MUTATIONS because of the rarity of the conditions and the high (e. Limited evidence indicates that insertion of the LNG-IUD does not pose major bleeding risks in women on chronic anticoagulant therapy (52–54).INTRAUTERINE DEVICES | 193 INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). condoms offer one of the most effective methods of protection against STIs. C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition.

further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) this table * additional comments after this table CURRENT AND HISTORY OF 1 I C ISCHAEMIC HEART DISEASE* 2 3 STROKE* 1 2 (history of cerebrovascular accident) KNOWN DYSLIPIDAEMIAS WITHOUT 1 2 Clarification: Routine screening is not appropriate OTHER KNOWN CARDIOVASCULAR because of the rarity of the condition and the high RISK FACTORS cost of screening. The category should be assessed according to the severity of the thrombocytopenia and its clinical manifestations.Part II . stroke and venous thromboembolism. a) Positive (or unknown) I C Evidence: Antiphospholipid antibodies are antiphospholipid antibodies associated with a higher risk for both arterial and 1 1 3 venous thrombosis (72. risk of atrial endocarditis are advised for insertion. consultation with a specialist and certain pretreatments may be warranted. Evidence: The LNG-IUD may be a useful treatment for menorrhagia in women with severe thrombocytopenia (54). . including HIV. Female condoms are effective and safe. history of subacute bacterial endocarditis) RHEUMATIC DISEASES SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) People with SLE are at increased risk of ischaemic heart disease. C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition. fibrillation. Categories assigned to such conditions in the Medical eligibility criteria for contraceptive use should be the same for women with SLE who present with these conditions.194 | Medical eligibility criteria for contraceptive use . If there is a risk of STI/HIV. classifications are based on the assumption that no other risk factors for cardiovascular disease are present. b) Severe thrombocytopenia 3 2 2 Clarification: Severe thrombocytopenia increases the risk of bleeding. In women with very severe thrombocytopenia who are at risk for spontaneous bleeding. When used correctly and consistently.INTRAUTERINE DEVICES INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). these classifications must be modified in the presence of such risk factors. 73). Available evidence indicates that many women with SLE can be considered good candidates for most contraceptive methods. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. VALVULAR HEART DISEASE a) Uncomplicated 1 1 b) Complicated (pulmonary 2 2 Clarification: Prophylactic antibiotics to prevent hypertension. the correct and consistent use of condoms is recommended. but are not used as widely by national programmes as male condoms. condoms offer one of the most effective methods of protection against STIs. For all categories of SLE. including hormonal contraceptives (54–71). including HIV.

including HIV. Evidence: Evidence from studies examining the treatment effects of the LNG-IUD among women with heavy or prolonged bleeding reported no increase in adverse effects and found the LNG-IUD to be beneficial in the treatment of menorrhagia (74–81). further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) IUDs this table * additional comments after this table c) Immunosuppressive treatment 2 1 2 d) None of the above 1 1 2 NEUROLOGIC CONDITIONS HEADACHES* I C Clarification: Any new headaches or marked changes in headaches should be evaluated. but are not used as widely by national programmes as male condoms. the correct and consistent use of condoms is recommended. including HIV.Part II . REPRODUCTIVE TRACT INFECTIONS AND DISORDERS VAGINAL BLEEDING PATTERNS I C a) Irregular pattern without heavy 1 1 1 bleeding b) Heavy or prolonged bleeding 2 1 2 Clarification: Unusually heavy bleeding should (includes regular and irregular raise the suspicion of a serious underlying patterns) condition. at any age 1 2 3 EPILEPSY 1 1 DEPRESSIVE DISORDERS DEPRESSIVE DISORDERS 1 1 Clarification: The classification is based on data for women with selected depressive disorders. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation.INTRAUTERINE DEVICES | 195 INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). Female condoms are effective and safe. . Medical eligibility criteria for contraceptive use . No data on bipolar disorder or postpartum depression were available. C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition. If there is a risk of STI/HIV. There is a potential for drug interactions between certain antidepressant medications and hormonal contraceptives. When used correctly and consistently. a) Non-migrainous (mild or severe) 1 1 1 b) Migraine i) without aura age < 35 years 1 2 2 age > 35 years 1 2 2 ii) with aura. condoms offer one of the most effective methods of protection against STIs.

When used correctly and consistently. C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition. pelvic pain and dyspareunia (82–86).INTRAUTERINE DEVICES INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). the correct and consistent use of condoms is recommended. including HIV.196 | Medical eligibility criteria for contraceptive use .Part II . CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. but are not used as widely by national programmes as male condoms. Female condoms are effective and safe. further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) this table * additional comments after this table UNEXPLAINED VAGINAL BLEEDING Clarification: If pregnancy or an underlying (suspicious for serious condition) I C I C pathological condition (such as pelvic malignancy) is suspected. including HIV. BENIGN OVARIAN TUMOURS 1 1 (including cysts) SEVERE DYSMENORRHOEA* 2 1 GESTATIONAL C TROPHOBLASTIC Evidence: Limited evidence suggests that women DISEASE using an IUD following uterine evacuation for a molar pregnancy are not at increased risk of a) Decreasing or undetectable 3 3 developing post-molar trophoblastic disease when β-hCG levels compared to women using other methods of b) Persistently elevated β-hCG 4 4 contraception (87–90). There is no need to remove the IUD before evaluation. levels or malignant disease CERVICAL ECTROPION 1 1 CERVICAL INTRAEPITHELIAL 1 2 NEOPLASIA (CIN)* CERVICAL CANCER* I C I C (awaiting treatment) 4 2 4 2 BREAST DISEASE* a) Undiagnosed mass 1 2 b) Benign breast disease 1 1 c) Family history of cancer 1 1 d) Breast cancer i) current 1 4 ii) past and no evidence of 1 3 current disease for 5 years ENDOMETRIAL CANCER* I C I C 4 2 4 2 . If there is a risk of STI/HIV. condoms offer one of the most effective methods of protection against STIs. ENDOMETRIOSIS 2 1 Evidence: LNG-IUD use among women with endometriosis decreased dysmenorrhoea. it must be evaluated and the Before evaluation 4 2 4 2 category adjusted after evaluation.

including HIV.INTRAUTERINE DEVICES | 197 INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). the correct and consistent use of condoms is recommended. condoms offer one of the most effective methods of protection against STIs. C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition. Continued use of an IUD depends on the woman’s informed choice and her current risk factors for STIs and PID. there were no adverse health events with LNG-IUD use. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. There is usually no need for removal of the IUD if the client wishes to continue its use (see WHO publication Selected practice recommendations for contraceptive use)1. further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) IUDs this table * additional comments after this table I C I C OVARIAN CANCER* 3 2 3 2 UTERINE FIBROIDS* Evidence: Among women with fibroids. b) With distortion of the uterine 4 4 cavity ANATOMICAL ABNORMALITIES* a) Distorted uterine cavity (any 4 4 congenital or acquired uterine abnormality distorting the uterine cavity in a manner that is incompatible with IUD insertion b) Other abnormalities (including 2 2 cervical stenosis or cervical lacerations) not distorting the uterine cavity or interfering with IUD insertion PELVIC INFLAMMATORY DISEASE (PID)* a) Past PID (assuming no current risk factors for STIs) I C I C i) with subsequent pregnancy 1 1 1 1 ii) without subsequent pregnancy 2 2 2 2 b) PID – current 4 2 4 2 Clarification for continuation: Treat the PID using appropriate antibiotics. Female condoms are effective and safe. Evidence: Among IUD users treated for PID. Medical eligibility criteria for contraceptive use . and a) Without distortion of the uterine 1 1 there was a decrease in symptoms and size of cavity fibroids for some women (91–97).Part II . but are not used as widely by national programmes as male condoms. including HIV. . If there is a risk of STI/HIV. When used correctly and consistently. there was no difference in clinical course if the IUD was removed or left in place (98–100).

Risk of STIs varies by individual behaviour and local STI prevalence. but are not used as widely by national programmes as male condoms. the incidence of PID after IUD insertion was low (2. Among women who have an IUD inserted. including HIV. Continued use of an IUD depends on the woman’s informed choice and her current risk factors for STIs and PID. Evidence: Using an algorithm to classify STI risk status among IUD users. Current algorithms for determining increased risk of STIs have poor predictive value. If there is a risk of STI/HIV. while many women at increased risk of STIs can generally have an IUD inserted. When used correctly and consistently. Therefore.INTRAUTERINE DEVICES INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). the absolute risk of subsequent PID was low among women with STI at the time of insertion but greater than among women with no STI at the time of IUD insertion (101–108). C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition. Evidence: There is no evidence regarding whether IUD insertion among women with STIs increases the risk of PID compared with no IUD insertion. including HIV. the correct and consistent use of condoms is recommended. some women at increased risk (very high individual likelihood) of STIs should generally not have an IUD inserted until appropriate testing and treatment occur. There is usually no need for removal of the IUD if the client wishes to continue its use.2%) in a cohort of women considered to be high-risk based on high background rates of STIs in the general population (109). 1 study reported that 11% of high-STI-risk women experienced IUD- related complications compared with 5% of those not classified as high risk (104). although limited evidence suggests that this risk is low. In another small study.Part II . CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. .198 | Medical eligibility criteria for contraceptive use . b) Other STIs (excluding HIV and 2 2 2 2 hepatitis) c) Vaginitis (including Trichomonas 2 2 2 2 vaginalis and bacterial vaginosis) d) Increased risk of STIs 2/3 2 2/3 2 Clarification: IUD insertion may further increase the risk of PID among women at increased risk of STIs. condoms offer one of the most effective methods of protection against STIs. Female condoms are effective and safe. further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) this table * additional comments after this table STIs † I C I C a) Current purulent cervicitis or 4 2 4 2 Clarification for continuation: Treat the STI using chlamydial infection or gonorrhoea appropriate antibiotics.

limited evidence CLINICAL DISEASE shows no increased risk of overall complications (WHO STAGE 1 OR 2) or infectious complications when comparing women living with HIV to women not living with HIV. further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) IUDs this table * additional comments after this table HIV/AIDS † HIGH RISK OF HIV I C I C Evidence: Among women at risk for HIV. Medical eligibility criteria for contraceptive use . Female condoms are effective and safe. ASYMPTOMATIC OR MILD HIV 2 2 2 2 Evidence: Among IUD users. including HIV. C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition. but are not used as widely by national programmes as male condoms. Cu- IUD use did not increase risk of HIV acquisition 2 2 2 2 (110–120). condoms offer one of the most effective methods of protection against STIs.INTRAUTERINE DEVICES | 199 INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). see 1 1 cirrhosis) TUBERCULOSIS* I C I C a) Non-pelvic 1 1 1 1 a) Pelvic 4 3 4 3 MALARIA 1 1 . One study found no difference in initiation of antiretroviral therapy (ART) or CD4 count between users and non-users of the LNG-IUD (129). CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. IUD use among women living with HIV was not associated with increased risk of sexual transmission from female to male partners (121– 128). including HIV. Furthermore. the correct and consistent use of condoms is recommended. Evidence: One study found no difference in ART initiation or CD4 count between users and non- users of the LNG-IUD (129). OTHER INFECTIONS SCHISTOSOMIASIS a) Uncomplicated 1 1 b) Fibrosis of the liver (if severe. SEVERE OR ADVANCED HIV 3 2 3 2 Clarification for continuation: IUD users with CLINICAL DISEASE severe or advanced HIV clinical disease should be (WHO STAGE 3 OR 4) closely monitored for pelvic infection. If there is a risk of STI/HIV. When used correctly and consistently.Part II . IUD use did not adversely affect progression of HIV when compared to hormonal contraceptive use among women living with HIV.

g.INTRAUTERINE DEVICES INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). ii) insulin-dependent 1 2 c) Nephropathy/retinopathy/ 1 2 neuropathy d) Other vascular disease or 1 2 diabetes of > 20 years’ duration THYROID DISORDERS a) Simple goitre 1 1 b) Hyperthyroid 1 1 c) Hypothyroid 1 1 GASTROINTESTINAL CONDITIONS GALL BLADDER DISEASE a) Symptomatic i) treated by cholecystectomy 1 2 ii) medically treated 1 2 iii) current 1 2 b) Asymptomatic 1 2 HISTORY OF CHOLESTASIS* a) Pregnancy-related 1 1 b) Past-COC related 1 2 . further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) this table * additional comments after this table ENDOCRINE CONDITIONS DIABETES a) History of gestational disease 1 1 b) Non-vascular disease i) non-insulin-dependent 1 2 Evidence: Limited evidence on the use of the LNG- IUD among women with insulin. If there is a risk of STI/HIV. C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition.or non-insulin- dependent diabetes suggests that these methods have little effect on short-term or long-term diabetes control (e. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. the correct and consistent use of condoms is recommended. When used correctly and consistently. but are not used as widely by national programmes as male condoms. HbA1c levels). including HIV. haemostatic markers or lipid profile (130. Female condoms are effective and safe.200 | Medical eligibility criteria for contraceptive use .Part II . condoms offer one of the most effective methods of protection against STIs. including HIV. 131).

C = continuation Cu-IUD LNG-IUD † recommendations reviewed for the Cu-IUD = copper-bearing IUD MEC 5th edition.Part II . but are not used as widely by national programmes as male condoms.INTRAUTERINE DEVICES | 201 INTRAUTERINE DEVICES (IUDs) IUDs do not protect against sexually transmitted infections (STIs). Medical eligibility criteria for contraceptive use . Lamivudine (3TC) 2/3 2 2/3 2 Didanosine (DDI) 2/3 2 2/3 2 Emtricitabine (FTC) 2/3 2 2/3 2 Stavudine (D4T) 2/3 2 2/3 2 . the correct and consistent use of condoms is recommended. condoms offer one of the most effective methods of protection against STIs. When used correctly and consistently. Female condoms are effective and safe. If there is a risk of STI/HIV. severe or a) Nucleoside reverse transcriptase advanced HIV clinical disease (WHO stage 3 inhibitors (NRTIs) I C I C or 4) as a condition is classified as Category 3 Abacavir (ABC) 2/3 2 2/3 2 for initiation and Category 2 for continuation. However. CONDITION CATEGORY CLARIFICATIONS/EVIDENCE I = initiation. including HIV. including HIV. further details after LNG-IUD = levonorgestrel-releasing IUD (20 µg/24 hours) IUDs this table * additional comments after this table VIRAL HEPATITIS a) Acute or flare 1 1 b) Carrier