CONCISE REVIEW FOR CLINICIANS

Current Issues in Contraception
Mary L. Marnach, MD; Margaret E. Long, MD; and Petra M. Casey, MD

CME Activity
Target Audience: The target audience for Mayo Clinic Proceedings is primarily the educational activity. Safeguards against commercial bias have been
internal medicine physicians and other clinicians who wish to advance their put in place. Faculty also will disclose any off-label and/or investigational
current knowledge of clinical medicine and who wish to stay abreast of ad- use of pharmaceuticals or instruments discussed in their presentation. Dis-
vances in medical research. closure of this information will be published in course materials so that
Statement of Need: General internists and primary care physicians must those participants in the activity may formulate their own judgments
maintain an extensive knowledge base on a wide variety of topics covering regarding the presentation.
all body systems as well as common and uncommon disorders. Mayo Clinic In their editorial and administrative roles, William L. Lanier, Jr, MD, Thomas J.
Proceedings aims to leverage the expertise of its authors to help physicians Beckman, MD, Terry L. Jopke, Kimberly D. Sankey, and Nicki M. Smith, MPA,
understand best practices in diagnosis and management of conditions have control of the content of this program but have no relevant financial
encountered in the clinical setting. relationship(s) with industry.
Accreditation: College of Medicine, Mayo Clinic is accredited by the Accred- Drs Marnach, Long, and Casey receive research support from Merck & Co,
itation Council for Continuing Medical Education to provide continuing med- Inc. Drs Long and Casey are certified Nexplanon trainers who are not paid
ical education for physicians. for training services.
Credit Statement: College of Medicine, Mayo Clinic designates this journal- Method of Participation: In order to claim credit, participants must complete
based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s).TM the following:
Physicians should claim only the credit commensurate with the extent of 1. Read the activity
their participation in the activity. 2. Complete the online CME Test and Evaluation. Participants must achieve
Learning Objectives: On completion of this article, you should be able to a score 80% on the CME Test. One retake is allowed.
(1) describe several contraceptive issues commonly encountered in practice, Participants should locate the link to the activity desired at http://bit.ly/
(2) review best practices relating to these issues, and (3) provide resources Xw8oCd. Upon successful completion of the online test and evaluation,
and guidance for the selection of contraception for women with common you can instantly download and print your certificate of credit.
coexisting medical issues. Estimated Time: The estimated time to complete each article is approxi-
Disclosures: As a provider accredited by ACCME, College of Medicine, mately 1 hour.
Mayo Clinic (Mayo School of Continuous Professional Development) Hardware/Software: PC or MAC with internet access.
must ensure balance, independence, objectivity, and scientific rigor in its Date of Release: 3/1/2013
educational activities. Course Director(s), Planning Committee members, Expiration date: 2/28/2015 (Credit can no longer be offered after it has
Faculty, and all others who are in a position to control the content of passed the expiration date.)
this educational activity are required to disclose all relevant financial rela- Privacy Policy: http://www.mayoclinic.org/global/privacy.html
tionships with any commercial interest related to the subject matter of Questions? Contact dletcsupport@mayo.edu.

Abstract

Contraceptive management in women should take into account patient lifestyle and coexisting medical
issues as well as method safety, efficacy, and noncontraceptive benefits. This review focuses on common
and timely issues related to contraception encountered in clinical practice, including migraine headaches
and associated risk of ischemic stroke, the use of combined hormonal contraception along with citalopram
and escitalopram, contraceptive efficacy and safety in the setting of obesity, contraceptives for treatment of
menorrhagia, the association of intrauterine contraception and decreased risk of cervical cancer, and the
association of venous thromboembolism and combined hormonal contraception. Recent trends sup-
porting the use of long-acting reversible contraception are also reviewed.
ª 2013 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2013;88(3):295-299

From the Division of

E
very year in the United States nearly 50% WHAT’S NEW IN COMBINED ESTROGEN-
Gynecology, Department
of pregnancies are unintended, and 43% AND PROGESTIN-CONTAINING HORMONAL of Obstetrics and Gyne-
of these end in termination.1 Therefore, CONTRACEPTION? cology, Mayo Clinic,
the availability of convenient, effective contra- Many women worldwide favor combined Rochester, MN.

ception represents a public health need. The estrogen- and progestin-containing hormon-
Centers for Disease Control and Prevention al contraception (CHC), which includes
(CDC) United States medical eligibility criteria pills, patches, and rings with compliance-
for contraceptive use in women with various dependent failure rates reported as 2% to
medical conditions is based on evaluation of 9% per year.2 In comparison, pregnancy
available data and serves as a useful resource rates associated with intrauterine contracep-
for informing contraceptive counseling and se- tion (IUC), the contraceptive implant (pro-
lection.2 This review focuses on several com- gestin-only subcutaneous implant that lasts
mon issues in contraceptive management. up to 3 years), injections, and sterilization

Mayo Clin Proc. n March 2013;88(3):295-299 n http://dx.doi.org/10.1016/j.mayocp.2013.01.007 295
www.mayoclinicproceedings.org n ª 2013 Mayo Foundation for Medical Education and Research

This OC contains 22 days of various combina. tion (MI) with the use of CHC appears to be extremely rare in healthy women of reproduc- WHY WORRY ABOUT CITALOPRAM (OR tive age. ommend routine screening for thrombogenic orrhagia and has data supporting its use for mutations. Observational studies have shown a 2.6 It provides Cardiovascular risk or myocardial infarc- contraception for up to 5 years. dia- duction in the need for operative intervention phragm. This is con.1016/j. for abnormal uterine bleeding (menorrhagia).doi. CONTRACEPTION. tive methods. torsade de pointes (a form of botic risk and the use of 20. including the copper IUC. norgestimate. and estradiol valerate).and progestin-containing drospirenone should be counseled regarding po- hormonal contraceptives. an FDA with lower mean blood loss and improved he. Alternative contraceptive methods should be ened hormone-free intervals resulting in shorter. an electrocar- pounds (third-generation progestins. nonhormonal contracep- reduction of up to 90% and consequent re. ESCITALOPRAM) AND CHC? Danish women aged 15 to 49 years who Citalopram has been associated with a prolonged were using CHC were followed up for 15 years QTc interval that may trigger a life-threatening to evaluate the association of arterial throm- arrhythmia.13 Additionally. In the largest cohort study to date. and gestodene) or months.mayoclinicproceedings.org/10.7 A recent estradiol OCs.4 n n 296 Mayo Clin Proc.88(3):295-299 http://dx. which “step up” (VTE) (absolute risk.4 When using OCs in THROMBOEMBOLISM. cervical cap. 20 mg or higher along with CHC. and 2 days of (DMPA). which contain 21 identically dosed ODDS RATIOS pills per package. and varied oral history of each patient should be obtained. the levonorgestrel intrauterine system has The World Health Organization does not rec- received FDA approval for treatment of men. and specifically OCs.007 www. 3500 women) in users of CHC compared with port the thickening endometrium. AND a continuous or extended fashion.to 40-mg ethinyl polymorphic ventricular tachycardia). 4 days progesterone acetate contraceptive injection of estradiol valerate alone. increased risk of venous thromboembolism cycle breakthrough bleeding. Advisory Committee has concluded that the ben- moglobin/hematocrit and ferritin levels has efits of CHC likely outweigh the risks in most received US Food and Drug Administration women. the relative risk of MI was 1. are recommended. drospire. MAYO CLINIC PROCEEDINGS are lower (<1%) and do not require regular Mayo Clinic consensus statement recom- attention.2 dysmenorrhea and endometriosis. Further. tem.org .5. depot medroxy- tions of estradiol valerate and dienogest. A new 28-day OC associated users of similar OCs. cysts as well as extended and continuous contra- ceptives associated with 4 or no scheduled men. novel com. VENOUS strual intervals per year. March 2013.2013. condoms. Breakthrough women who do not use CHC.to 3-fold increased risk over OCs TREATING ABNORMAL UTERINE BLEEDING containing levonorgestrel).01. the progestin drospirenone have a greater risk of VTE (1. approximately 1 event per the progestin dose each week in order to sup. or sterilization. diogram and review of the personal and family none.11 Nonetheless. do not considerably increase the risk of Because of reported menstrual blood loss VTE. and levonorgestrel intrauterine sys- hormone-free pills. discussed with patients taking citalopram or lighter monthly flow and lower risk of ovarian escitalopram plus CHC.5 The progestin-only contraceptive methods. tives containing third-generation progestogens strual intervals generally resolves within a few (desogestrel. monophasic CARDIOVASCULAR RISK: BEYOND formulations. higher in users of the contraceptive patch vs strual bleeding.mayocp. this risk may be have long been used off label to treat heavy men.8 contraceptive (OC) regimens including short. women using Combined estrogen.9 Oral contracep- bleeding associated with fewer scheduled men.10 Although the abso- WITH CONTRACEPTION lute risk of VTE remains low.to 7-fold trasted with triphasic formulations used for late.3 mended the following: before prescribing citalo- Recent trends in CHC have included lower pram at 40 mg or higher or escitalopram at estrogen doses (as low as 10 mg/d). including the progestin-only pill. tential increased risk.12 (FDA) approval for treatment of menorrhagia. provide alternatives for women at risk for VTE.

and 82% of adolescent pregnancies are CONTRACEPTION FOR WOMEN WITH unplanned.19 Long-acting for women of any age who have migraine with reversible contraception is safe in most women. given their choice of birth control methods. for postprocedural cramping. 42% are sexually active. CHC use also confers a 2. Prior approach is an excellent option for women who expulsion is not a contraindication to another have completed childbearing.2013.17 ficulty. Mayo Clin Proc. The contraindications to IUC use are Combined estrogen. aura or focal neurologic symptoms. n March 2013.3 per 1000 participants graines in the absence and presence of aura is compared with 34.20 contraceptive efficacy. they typically improve 5 days of last intercourse.to 3-fold to 20-fold lower pregnancy rate was reported increased risk of ischemic stroke compared with in LARC users. pregnancy rates women without migraine. Types and dosages of progestins do not 10 years.2 Progestogen-only and nonhormonal orrhea) is recommended for women younger contraceptives are preferred methods of contra. especially with extended retained for primary contraception for up to cycles.14 No excess risk was seen for arterial Women with a BMI of more than 30 kg/m2 thrombosis (MI or thrombotic stroke) with who need emergency contraception (EC) are any of the progestin-only methods. In this instance. anti-inflammatory drugs (NSAIDs) are helpful line contraception by the CDC because of con.6 per 1000 participants in graine.19 more in some monthly and extended-cycle formula. including nulliparas. IUC placement. Long-acting reversible increased risk of ischemic stroke as compared contraception was the choice in 75% of women with migraine without aura. tionally. Recent data from the Contraceptive CHOICE Project was reassuring. Data quantifying among 15.org . Sexually trans- cerns about increasing VTE risk in obese mitted infection screening (chlamydia and gon- women. ring (nonelong-acting in women without migraines. Furthermore. than 9000 women aged 14 to 45 years were tions.3 per 1000 participants na- difficult to interpret given differing CHC formu. in all women is the copper IUC placed within tion.2 Of women aged 15 to 19 years.01. to 3-fold independent risk of ischemic stroke including OCs. and abortion rates in the project partic- lations. (58% choosing IUCs and 17% implants).to 19-year-old women in the ischemic stroke risk in CHC users with mi. This device may be with continued use. Permanent tors. CHOICE study were 6. A 22 rience migraine without aura have a 2.mayoclinicproceedings.5 per 1000 participants the benefits in women older than 35 with mi. IUC.88. Women who expe. patch.and progestin-containing few.to 8-fold plant (LARC) at no cost. The American College of Obstetri- ELEVATED BODY MASS INDEX cians and Gynecologists endorses LARC as Much attention has been focused on obesity and a first-line option for adolescents.18 An extremely efficacious EC occasionally more so at initiation of the medica.3 The IUC expulsion rate is 3% to 5% in sterilization using a transcervical hysteroscopic all users and 5% to 22% in adolescents. or im- aura is further associated with a 6.15 However.4 to 7. better served by administration of ulipristal ac- etate rather than levonorgestrel EC because of THE MIGRAINE CONUNDRUM the much lower pregnancy rates associated Headaches are common in women using CHCs.CURRENT ISSUES IN CONTRACEPTION to 1. with ulipristal.16 The risks of CHC usually outweigh ipants were 4. without dif- divided by the height in meters squared).org/10.2 Alternatives to CHC are recommended similarly aged nonparticipants. Withdrawal of about 20 mg of estradiol triggers migraines.15 Migraine with reversible contraception [LARC]). supporting TREND TOWARD LONG-ACTING the use of low-dose estradiol-only pills (10 mg) REVERSIBLE CONTRACEPTION during part of the traditional placebo interval In the Contraceptive CHOICE study.3 In- implant and IUC regardless of body mass index trauterine contraceptives can be inserted in (BMI) (calculated as the weight in kilograms most women.88(3):295-299 n http://dx.007 297 www.mayocp. affect headache risk.2. Oral nonsteroidal hormonal contraception is deemed second.doi. INTRAUTERINE CONTRACEPTION TODAY with a cumulative 3-year pregnancy rate of only Current IUC has not been associated with pelvic 1 in 100 woman-years for the contraceptive inflammatory infection or tubal infertility.1016/j. compared with 19. than 24 years and older women with risk fac- ception for women who are obese. as noted in the Table.

progestin-only pills. Short-term doxycycline. Long-acting sists. MD. reversible contraception may be the ideal first copy should be considered for evaluation.mary@mayo. Spiekerman AM.edu). 2010: adapted from the World Health Organization Medical Eligibility Criteria for Contraceptive THE NEWEST LARC Use. Mayo Clinic.3 If heavy bleeding per. http:// offers high contraceptive efficacy for up to 3 www. adenocarci- noma. Abbreviations and Acronyms: BMI = body mass index.1016/j. or estradiol have been used for treat- Current endometrial or cervical cancer ment of prolonged bleeding.000 women showed that the risk of cervical Correspondence: Address to Mary L. proper placement CHC.org/10. Absolute Contraindications to periods in 11 international trials included infre- Intrauterine Device Insertion quent bleeding in 34% of the reference periods.2 There are many excellent contraceptive choices today for women across their reproductive life- span. MAYO CLINIC PROCEEDINGS with the implant assessed in 90-day reference TABLE. 2011. returning to that of nonusers after 10 years. Obstet Gynecol.cdc. strual intervals per year with CHC. ACOG with CHC. Marnach.3 Bleeding patterns of the pituitary-ovarian axis in oral contraceptive regimens with n n 298 Mayo Clin Proc.org . thus serving as a long-term alter.mayoclinicproceedings. NSAIDs. Unintended pregnancy in the United between OCs and cervical cancer. 121: Long-acting reversible contraception: has a neutral effect on bone density as well as implants and intrauterine devices.90 at 5 or more years). or compliance issues.doi. option for most women. EC = emergency contraception. 2011. including those with higher BMI. Current pregnancy frequent bleeding in 7%. American College of Obstetricians and Gynecologists. Contraception. Willis SA. The single-rod etonogestrel subdermal implant Centers for Disease Control and Prevention website.24 about 14. Sulak PJ. 200 First St SW. OC = oral contraceptive. It Practice Bulletin No. (relative risk. medical eligibil- ETONOGESTREL SUBDERMAL IMPLANT: ity criteria for contraceptive use.007 www. concurrent citalopram IUC AND DECREASED RISK OF CERVICAL or escitalopram use.23 In a recent Intrauterine device in the uterus Acute pelvic inflammatory disease or Mayo Clinic study.88(3):295-299 http://dx. migraine.gov/mmwr/pdf/rr/rr59e0528.8% of the partic- intrauterine infection in the past 3 mo ipants discontinued the implant because of Distorted endometrial cavity preventing bleeding. Accessed Decem- ber 28. on lactation. Centers for Disease Control and Prevention. Morb Mortal Wkly Rep. Finer LB. highly efficacious first 3 to 6 months after IUC placement may be LARC methods as well as fewer scheduled men- treated with NSAIDs. contraception. 2012. NSAID = nonsteroidal anti- inflammatory drug. U.118(1): 184-196. 84(5):478-485. Roches- ter. LARC = long-acting reversible contraception. IUC = intrauterine esis may be cellular immunity triggered by contraception. for a protective cofactor in cervical carcinogen. MN 55905 (marnach. 4.2013. 2010. VTE = venous risk of cervical cancer in OC users. 2006.and progestin-containing hormonal papillomavirus detection among women with. The possible mechanism contraceptive injection. Pooled thromboembolism data from 24 studies involving more than 16. It remains REFERENCES unclear whether there is a causal relationship 1. 1. March 2013.59:1-88. or DMPA. Kuehl TJ. years with a lower dose of progestin than that 3. DMPA = depot medroxyprogesterone acetate out cervical cancer. Con- CANCER traceptive management may be informed by the In a pooled analysis of 26 studies. Zolna MR.25 Ongoing elevated human chorionic gonadotropin level with trophoblastic disease CONCLUSION Data from the Centers for Disease Control and Prevention. FDA = Food and Drug Administration. prolonged bleeding in Unexplained vaginal bleeding 18%. 4th ed [early release]. ciation was noted between IUC use and human CDC = Centers for Disease Control and Prevention.22 The risk decreased after OC use ceased. IUC has been CDC United States medical eligibility criteria reported to have an association with lower rates for contraceptive use document. and adenosquamous cancers.21 This data contrasts with an increased MI = myocardial infarction. Divi- cancer increases with increasing duration of use sion of Gynecology. pelvic ultrasonography or office hysteros.S.mayocp.01. IUC. CHC = combined estrogen. States: incidence and disparities. Greater inhibition native for prior DMPA users.pdf. 2.2 of cervical squamous cell cancers. Women have indicated preference for Mild cramping and irregular bleeding in the nonecompliance-dependent. and amenorrhea in 22%.21 No asso.

7. cervical cancer: a pooled analysis of 26 epidemiological studies.120(6):1291-1297. Contraception. Vasilakis C. et al. Secura GM. Vaccarella S. The ef- SafetyAlertsforHumanMedicalProducts/ucm299605. Hernandez RK. Bleeding related to venous thromboembolism in users of progestogens alone [let. contraception and risk of venous thromboembolism: national 19. data from randomized trials of ulipristal acetate and levonorges- 9. Implanon users. Preventing un- follow-up study.CURRENT ISSUES IN CONTRACEPTION a shortened hormone-free interval. US Food and Drug Administration epidemiological studies. 2012.125(9):859-868. Materials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/ 22.117(4):777-787. 2011. 2012.007 299 www. Long ME. QTc Contraceptive failure rates of etonogestrel subdermal implants interval prolongation. Committee opinion no. Marintcheva-Petrova M. et al. 17. use. fda. Machlitt A. Intrauterine device Health Drugs and the Drug Safety and Risk Management Advi. Skovlund CW.509 women without cervical cancer from 24 higher risk for blood clots. Zhao Q.org/10. Hormonal trel. 2009. Jensen A. NDA 21-180 Ortho Evra. Svendsen AL. 2011. 2012. Effective other hormonally related headaches. 2011. del Mar Melero-Montes M. Curr Neurol Neurosci Rep. ACOG Practice Bulletin No. N Engl J Med.org . at risk of pregnancy despite using emergency contraception? 2012. 20. Obstet Gynecol. Curr Pain Headache Rep. and torsade de pointes: how should in overweight and obese women.74(2): 15. et al. Obstet Gynecol. A randomized controlled Thrombotic stroke and myocardial infarction with hormonal trial of treatment options for troublesome uterine bleeding in contraception.pdf.24(8):1852-1861. Shuster LT. 1999. Blithe D. et al. Lancet. 16. Madden T. Richelson E. intended pregnancies by providing no-cost contraception.120(4):983-988. Risk of idiopathic 24. cept Reprod Health Care. website. and dienogest: a randomized controlled trial. Weisberg E. Xu H.366(24):2257-2266. Jensen JT. Faubion SS. Vieweg WV. Allsworth JE. Joint Meeting of the Advisory Committee for Reproductive 21. Marnach ML. Contraception. Keiding N.doi. 539: Ad- States claims data.mayoclinicproceedings. http://www. Risk of non-fatal venous thromboem. Hickey M. Løkkegaard E. Løkkegaard E. tion. 13. et al. December 28. Appleby P. Hasnain M. and migraine: clinical considerations. Palmer D. et al. 2011. US Food and Drug Administration. Peipert JF. International Collaboration of Epidemiological Studies of Cervi- UCM282634. 10. Secura GM.13(suppl 1):13-28. BMJ. Cervical cancer and hormonal contraceptives: collaborative 12. 2012.gov/Safety/MedWatch/SafetyInformation/ 23. Hormonal manip- 100-103. Wade JA. Howland RH.01. 2012.354(9190):1610-1611. 2012. 2012. treatment of heavy menstrual bleeding with estradiol valerate 2011.12(11):1023-1031. olescents and long-acting reversible contraception: implants and 11. Accessed cal Cancer. 21-26. The American College of Ob- containing levonorgestrel: case-control study using United stetricians and Gynecologists. 2008. 2007. n March 2013.573 women with cervical drospirenone: label changedproducts may be associated with cancer and 35.84(4):363-367. Parke S. 2012. Faubion SS. Cameron ST.fda. Sheeler RD. cervical infection with human papillomavirus.gov/downloads/AdvisoryCommittees/CommitteesMeeting Lancet Oncol. Birth control pills containing reanalysis of individual data for 16. etonogestrel subdermal implant in a US population. Agger C. Lancet. 2006. Korver T. and risk of sory Committee. Updated fects of Implanon on menstrual bleeding patterns. Mansour D. Castellsagué X. Obstet Gynecol. bolism in women using oral contraceptives containing drospir. Lidegaard Ø. Hum Reprod. Mayo Clin Proc.342:d2151.115(1):206-218. Jick H. Beral V. 2012.mayocp. monal contraceptives. 2011. Eur J Contra- April 10. BMJ. Diaz M.1016/j.2013. Lidegaard Ø. Considerations on 18. ulation strategies in the management of menstrual migraine and 5. Sood R.88(3):295-299 n http://dx.339:b2890. Shuster LT.htm. Casey PM. Peipert JF.87(11):1042-1045. 6. 2010. 110: Noncontraceptive uses of hor. Obstet Gynecol. Fraser IS. Committee on Adolescent Health Care Long-Acting Reversible enone compared with women using oral contraceptives Contraception Working Group. Casey PM. Hormonal contraception 2011.370(9599):1609-1621. Mellinger U. Bury JE. Jick SS. http://www. 2009. Berrington de González A.16(5):461-466. Madden T. US Food and Drug Administration. Citalopram. Obstet Gynecol. Contracep- ter]. 25. Casey PM.11(2):131-138. Glasier A. 8. Ackerman MJ. Accessed December 28. Fraser IS.120(1): we apply the recent FDA ruling? Am J Med. 14. Background Document for intrauterine devices. Mayo Clin Proc. Can we identify women safety concerns about citalopram prescribing. Published December 9.83(5):426-430.