JPOG

JAN/FEB 2012 JUL/aug 2012 Vol. Vol. 38 38 No. No.
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JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
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ISSN 1016-0124 (INDONESIA)
JOURNAL WATCH
PAEDIATRICS
Paediatric Psoriasis Managing Headache in Children

GYNAECOLOGY
Dysmenorrhoea What Are the Benefits and Risks of HRT?

CME ARTICLE
P 3 SK
An Update on Emergency Contraception
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J UL/ AUG 2 0 1 2 Vol. 38 No. 4
Journal Watch
133 Proton pump inhibitors and hip fracture in postmenopausal women Screening for cervical cancer in Europe: Cost-effectiveness of HPV versus cytology screening Screening and cervical cancer mortality Nicotine replacement patches in pregnancy: Negative study 134 Peer-led parenting intervention for disruptive child behaviour Results of modern paediatric burn care
133
135 Chlorhexidine to the umbilical cord in developing countries Moderate or late preterm birth and health outcomes Paediatricians influence parental febrile behaviour 136 Oral amoxicillin for severe early childhood pneumonia in rural Pakistan
136
Editorial Board
Board Director, Paediatrics Professor Pik-To Cheung Associate Professor Department of Paediatrics and Adolescent Medicine The University of Hong Kong Board Director, Obstetrics and Gynaecology Professor Pak-Chung Ho Head, Department of Obstetrics and Gynaecology The University of Hong Kong
Professor Biran Affandi University of Indonesia Dr Karen Kar-Loen Chan The University of Hong Kong Associate Professor Oh Moh Chay KK Womens and Childrens Hospital, Singapore Associate Professor Anette Jacobsen KK Womens and Childrens Hospital, Singapore Professor Rahman Jamal Universiti Kebangsaan Malaysia Dato Dr Ravindran Jegasothy Hospital Kuala Lumpur, Malaysia Associate Professor Kenneth Kwek KK Womens and Childrens Hospital, Singapore Dr Siu-Keung Lam Kwong Wah Hospital, Hong Kong Professor Terence Lao Chinese University of Hong Kong Dr Kwok-Yin Leung The University of Hong Kong
Dr Tak-Yeung Leung Chinese University of Hong Kong Professor Tzou-Yien Lin Chang Gung University, Taiwan Professor Somsak Lolekha Ramathibodi Hospital, Thailand Professor Lucy Chai-See Lum University of Malaya, Malaysia Professor SC Ng National University of Singapore Professor Hextan Yuen-Sheung Ngan The University of Hong Kong Professor Carmencita D Padilla University of the Philippines Manila Professor Seng-Hock Quak National University of Singapore Dr Tatang Kustiman Samsi University of Tarumanagara, Indonesia Professor Perla D Santos Ocampo University of the Philippines Associate Professor Alex Sia KK Womens and Childrens Hospital, Singapore
Dr Raman Subramaniam Fetal Medicine and Gynaecology Centre, Malaysia Professor Walfrido W Sumpaico MCU-DFT Medical Foundation, Philippines Professor Cheng Lim Tan KK Womens and Childrens Hospital, Singapore Associate Professor Kok Hian Tan KK Womens and Childrens Hospital, Singapore Dr Surasak Taneepanichskul Chulalongkorn University, Thailand Professor Eng-Hseon Tay Thomson Womens Cancer Centre, Singapore Professor PC Wong National University of Singapore Dr George SH Yeo KK Womens and Childrens Hospital, Singapore Professor Hui-Kim Yap National University of Singapore Professor Tsu-Fuh Yeh China Medical University, Taiwan
JPOG JUL/AUG 2012 i
J UL/ AUG 2 0 1 2 Vol. 38 No. 4
Review Article
Paediatrics
137 Paediatric Psoriasis Paediatric psoriasis is a common disorder with significant morbidity. New advances in biologic therapy,
as well as recent reviews assessing classification, have led to a greater understanding of the condition of psoriasis. Presented in this review article is an overview of the presentation of psoriasis as well as an up-to-date review of management options. Vyom Sharma, David Orchard
137
Review Article
Gynaecology
147 Dysmenorrhoea Dysmenorrhoea is a medical condition characterized by severe uterine pain during menstruation
manifesting as cyclical lower abdominal pain. Mainstay treatment is generally supportive providing symptomatic relief, and more directive surgical treatment is reserved for specific secondary causes of dysmenorrhoea or for refractory cases. Therefore, patients with primary dysmenorrhoea may simply need reassurance and simple analgesics, while those with secondary dysmenorrhoea require investigation and treatment of the underlying organic problem. An overview of managing this condition is presented in this article. Shilpa Kolhe, Shilpa Deb
147
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PUBLISHER: Journal of Paediatrics, Obstetric & Gynaecology (JPOG) is published 6 times a year by UBM Medica, a division of United Business Media. CIRCULATION: JPOG is a controlled circulation for medical practitioners in South East Asia. It is also available on subscription to members of allied professions. SUBSCRIPTION: The price per annum is US$42 (surface mail, students US$21) and US$48 (overseas airmail, students US$24); back issues US$8 per copy. EDITORIAL MATTER published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of UBM Medica. Although great care has been taken in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. COPYRIGHT: 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, in any language, without written consent of copyright owner. Permission to reprint must be obtained from the publisher. ADVERTISEMENTS are subject to editorial acceptance and have no influence on editorial content or presentation. UBM Medica does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature. Philippine edition: Entered as second-class mail at the Makati Central Post Office under Permit No. PS-326-01 NCR, dated 9 Feb 2001. Printed by Fortune Printing International Ltd, 3rd Floor, Chung On Industrial Building, 28 Lee Chung Street, Chai Wan, Hong Kong.
JPOG JUL/AUG 2012 ii
formula yang disempurnakan memberikan dukungan nutrisi pada periode kejar tumbuh untuk bayi prematur atau berat lahir rendah.
SGM BBLR dengan
ASI adalah nutrisi terbaik bagi Ananda. Namun jika terdapat indikasi medis dan dalam kondisi spesifik (prematur / berat badan lahir rendah), SGM BBLR dengan formula yang disempurnakan hadir memberikan solusi untuk Ananda berkebutuhan khusus agar tetap tumbuh kembang optimal.
Tinggi energi mendukung periode kejar tumbuh. Mendukung perkembangan otak yang pesat. Mendukung pembentukan sel darah merah yang diperlukan untuk perkembangan otak, fungsi otot maupun fungsi jantung. Mendukung periode kejar tumbuh. 12 Asam Amino Esensial, termasuk Arginin yang tidak dapat disintesis oleh bayi prematur.1
Karena Anda Mengerti yang Terbaik untuk Ananda

Informasi Penting : ASI adalah makanan terbaik untuk bayi. ASI menyediakan nutrisi terbaik serta memberikan perlindungan terhadap penyakit. ASI sebaiknya diberikan secara eksklusif selama 6 bulan pertama kehidupan bayi dan dianjurkan sampai anak berusia 2 tahun dengan pemberian makanan tambahan yang sesuai. Susu formula dapat diberikan atas rekomendasi dokter / bidan, hanya bila ibu tidak bisa memberikan ASI. Sebelum memutuskan untuk menggunakan susu formula, seorang ibu hendaknya diperingatkan tentang implikasi sosial maupun ekonomi dari keputusannya. Ikuti petunjuk penyiapan dengan baik. Cara menyiapkan susu formula yang tidak benar bisa membuat bayi sakit. Peganglah bayi anda dan jangan pernah meninggalkan bayi sendirian pada saat minum susu botol.
1
Wu, G.; et al. (August 2004.Journal of Nutritional Biochemistry 15 (8): 332-451)
J UL/ AUG 2 0 1 2 Vol. 38 No. 4
Review Article
Gynaecology
157 What Are the Benefits and Risks of HRT? Opinions concerning the benefits and risks of hormone replacement therapy (HRT) have varied over the
past decade. Maintaining and regularly updating ones knowledge about HRT is paramount so that accurate information can be given to patients. Elizabeth Farrell
157
Review Article
Paediatrics
164 Managing Headache in Children Headache is a common symptom in children. Recurrent or persistent headache is most commonly due to
migraine (with and without aura), tension headache, or chronic daily headache. This article will focus on the clinical management of headache in children including migraine. M A McShane, S J Hughes
Continuing Medical Education
P 3 SK
169 An Update on Emergency Contraception
169
The use of emergency contraception plays an important role in preventing unplanned pregnancies and the need for termination of pregnancies in these circumstances. This article provides an update on the development of emergency contraception, and examines the methods and safety of emergency contraception as well as the barriers to their use. Hang-Wun Raymond Li, Sue Seen-Tsing Lo, Ernest Hung-Yu Ng, Pak-Chung Ho
The Journal of Paediatrics, Obstetrics and Gynaecology contains articles under licence from UBM Media LLC. The articles appearing on pages 4953, and pages 6780 are reprinted with permission of Consultant for Pediatricians. Copyright 2011 UBM Media LLC. All rights reserved.
Review Articles
Comprehensive reviews providing the latest clinical information on all aspects of the management of medical conditions affecting children and women.
Case Studies
Interesting cases seen in general practice and their management.
The Cover: Managing Headache in Children 2012 UBM Medica
Pictorial Medicine
Vignettes of illustrated cases with clinical photographs.
For more information, please refer to the Instructions for Authors on our website www.jpog.com, or contact: The Editor UBM Medica Asia Pte Ltd, No 3 Lim Teck Kim Road, Genting Centre, Singapore 088934 Tel: (65) 6223 3788 Fax: (65) 6221 4788 E-mail: enquiry@jpog.com
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JPOG JUL/AUG 2012 iii
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PPI use by postmenopausal women increas-
GYNAECOLOGY
Proton pump inhibitors and hip fracture in postmenopausal women
es the risk of hip fracture among smokers but not among non-smokers.
Khalili H et al. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. BMJ 2012; 344 (Feb. 25): 15 (e372).
Screening for cervical cancer in Europe: Cost-effectiveness of HPV versus cytology screening
Human papillomavirus (HPV) testing for cervical cancer screening is more sensitive but less specific than cytological screening. Cost-effectiveness analyses have given varying results partly because key factors vary between countries. A microsimulation model has been used to compared the costeffectiveness of > 1,500 screening policies in five European scenarios. The model was validated using Dutch data, and costs were derived from studies in the Netherlands. The model showed that HPV testing was usually preferable. Primary cytological It has been suggested that regular use of a proton pump inhibitor (PPI) may increase the risk of hip fracture. Data from the US Nurses Health Study have confirmed the association in postmenopausal women. A total of 79,899 postmenopausal women in the study provided biennial information on PPI use and other risk factors from 2000 to 2008. During follow-up, there were 893 hip fractures. The rate of hip fracture was 2.02 events per 1,000 personyears among PPI users and 1.51 events per 1,000 person-years among non-users. After adjustment for age, women who used a PPI for at least 2 years had a 35% increase in risk, the risk increasing with longer use. Among smokers, the use of PPIs increased the risk of hip fracture by 51%, but there was no significant increase in risk with PPIs in nonsmoking women. There is uncertainty about whether screening for cervical cancer reduces cervical cancer mortality or simply increases the time from diagnosis to death (lead time). A study in Sweden has shown that Smoking in pregnancy can cause miscarriage, plascreening might be preferred when the cost of cytology was low and when HPV was highly prevalent and testing for HPV costly. HPV screening is often preferable to cytological screening in cervical cancer screening programmes in Europe.
De Kok IMCM et al. Primary screening for human papillomavirus compared with cytology screening for cervical cancer in European settings: cost effectiveness analysis based on a Dutch microsimulation model. BMJ 2012; 344 (March 1): 17 (e670).
screening improves prognosis. The study included all 1,230 women who had a diagnosis of invasive cervical cancer between 1999 and 2001 in Sweden. For women aged 2365 years, the cure rate was 92% for cancers detected by smear test screening and 66% for cancers detected because of symptoms, a significant difference. The rate of cure was also significantly higher among women screened at recommended intervals than among women overdue for screening. Smear test screening for cervical cancer increases cure rates, and the effect is independent of lead-time bias.
Andrae B et al. Screening and cervical cancer cure: population based cohort study. BMJ 2012; 344 (March 24): 18 (e900); Arbyn M et al. Effect of screening on deaths from cervical cancer in Sweden. Ibid: 11(e804) (editorial).
Screening and cervical cancer mortality
OBSTETRICS
Nicotine replacement patches in pregnancy: Negative study
JPOG JUL/AUG 2012 133
replacement for smoking cessation during pregnancy. Ibid: 846847 (editorial).
and improved life support systems have meant that the prognosis for burns patients has improved in recent decades. Data from a single modern paedi-
PAEDIATRICS
Peer-led parenting intervention for disruptive child behaviour
Parents in socioeconomically disadvantaged groups may have difficulty obtaining appropriate advice and management for children with disruptive behaviour problems. Researchers in London, England, have shown that a peer-led parenting intervention may be effective. cental abruption, preterm birth, low birth weight, and neonatal morbidity and mortality. Behavioural support for smoking cessation is effective in pregnancy, but the value of nicotine replacement therapy is uncertain. A trial in England has failed to show benefit from nicotine replacement patches in pregnancy. A total of 1,050 women smokers (five or more cigarettes a day) were randomized at seven hospitals to nicotine replacement patches or placebo patches for 8 weeks, beginning at 1224 weeks gestation. All subjects received behavioural cessation support. The rate of abstinence from the quit date until delivery (validated by measurements of exhaled carbon monoxide or salivary cotinine) was 9.4% (nicotine replacement) vs 7.6% (placebo), a non-significant difference. Compliance, however, was poor, with only 7.2% of the replacement group and 2.8% of the placebo group continuing with the patches for more than a month. The rates of adverse pregnancy and birth outcomes were similar in the two groups. The addition of nicotine replacement
Day C et al. Evaluation of a peer led parenting intervention for disruptive behaviour problems in children: community based randomised controlled trial. BMJ 2012; 344 (March 24): 17 (e1107); Stewart-Brown S. Peer led parenting support programmes. Ibid: 10 (e1160) (editorial).
atric burns unit in Texas have correlated burn area and prognosis.
The study included 116 families, mostly from black and ethnic minority groups, and 116 index children with disruptive behavioural problems. Randomization was to intervention or waiting list controls. The intervention consisted of an 8-week peerled parenting programme based on principles of social learning theory and delivered by trained peer facilitators in a manualized group format at schools and childrens centres. Using the parent-reported intensity subscale of the Eyberg child behaviour inventory, improvement in child disruptive behaviour and positive parenting practices was significantly greater in the intervention group compared with the control group. All respondents described their satisfaction with the intervention as a great deal or quite a lot. The drop-out rate was 8.5%. The intervention was successful. Between 1998 and 2008, a total of 952 children were treated for burns involving between 30% and > 90% of total body surface area (TBSA). Mean age was 7.3 years and 66% were boys. Overall, mortality was 13% (3% with 3039% burns rising to 55% with > 90% burns). Multi-organ failure developed in 16% of patients, 6% with 3039% TBSA involvement and 45% with >90% TBSA involved, and 9% developed sepsis (2% to 26%). Mortality increased rapidly with 62% or greater TBSA involvement. It is suggested that children with more than 60% TBSA burns should be transferred immediately to a specialist burns unit.
patches to behavioural cessation support was not beneficial, but compliance was poor.
Coleman T et al. A randomized trial of nicotine-replacement therapy patches in pregnancy. NEJM 2012; 366: 808818; Oncken C. Nicotine
Results of modern paediatric burn care

New drug treatments, new grafting techniques,
Kraft R et al. Burn size and survival probability in paediatric patients in modern burn care: a prospective observational cohort study. Lancet 2012; 379: 10131021; Tompkins RG. Survival of children with burn injuries. Ibid: 983984 (comment).
Peer Reviewed
Journal Watch
Chlorhexidine to the umbilical cord in developing countries

About half of all neonatal deaths around the world are caused by infections, and the umbilicus is regarded as a major point of entry for infective organisms, especially in the rural areas of developing countries where hygiene is often poor. Data from Nepal have suggested that the application of chlorhexidine to the umbilical cord after birth could reduce umbilical infection and neonatal mortality. Now, two studies reported in one issue of the Lancet, one in rural Bangladesh and one in rural Pakistan, have confirmed the benefits of cord cleansing with chlorhexidine.
Neonatal mortality was 22.5 per 1,000 live births (SC), 26.6 per 1,000 (MC), and 28.3 per 1,000 (DC), a significant reduction with SC, but not with MC, compared with DC. The rate of severe cord infection (redness and pus) was 3.3 per 1,000 (SC), 1.2 per 1,000 (MC), and 4.2 per 1,000 (DC), a significant reduction with MC, but not with SC, compared with DC. These researchers conclude that cord cleansing with chlorhexidine is effective, but the optimum frequency of application is to be established. In rural Pakistan, the study included 187 population clusters and 9,741 neonates. Randomization was to one of four options for infants delivered by traditional birth attendants (TBAs): supply of 4% chlorhexidine solution to be applied to the cord by the TBA at birth and then daily by family members for up to 14 days, and supply of soap for handwashing; supply of chlorhexidine only; supply of soap for handwashing only; or promotion of dry cord care. Chlorhexidine cleansing was associated with a significant 42% reduction in risk of omphalitis compared with dry cord care, but handwashing had no significant effect. Similarly, chlorhexidine was associated with a significant 38% reduction in neonatal mortality, but there was no reduction with handwashing. These researchers conclude that cord cleansing with chlorhexidine is effective and that the provision of chlorhexidine in birth kits might reduce neonatal mortality.
El Arifeen S et al. The effect of cord cleansing with chlorhexidine on neonatal mortality in rural Bangladesh: a community-based, clusterrandomised trial. Lancet 2012; 379: 10221028: Soofi S et al. Topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural district of Pakistan: a community-based, cluster-randomised trial. Ibid: 10291036; Osrin D, Hill ZE. Chlorhexidine cord cleansing to reduce neonatal mortality. Ibid: 984986 (comment).
representative prospective cohort study including 18,818 infants born in 20002002 and still living in the UK at the age of 9 months. Health outcomes in relation to gestational age at birth were assessed at ages 3 and 5 years and included growth, hospital admissions, longstanding illness, wheezing, use of prescribed drugs, and parental rating of childrens health. In general, there was an inverse relationship between gestational age at birth and frequency of adverse health outcomes. The greatest number of such outcomes was among children born at moderate or late preterm (3236 weeks) or at early term (3738 weeks). Birth at 3236 weeks accounted for 5.7% of children with three or more hospital admissions at ages 9 months to 5 years. Birth before 32 weeks accounted for 3.8% of such children and birth at 3738 weeks for 7.2%. For a limiting longstanding illness, the corresponding population attributable fractions were 5.4% for birth at 3236 weeks, 2.7% for birth before 32 weeks, and 5.4% for birth at 3738 weeks.
In Bangladesh, a cluster randomized trial included 133 clusters (29,760 neonates) with randomization to one of three options: a single application of chlorhexidine to the cord soon after birth (single cleansing, SC); daily application for 7 days (multiple cleansing, MC); or dry cord care (DC). The UK Millennium cohort study is a nationally
Moderate or late preterm birth and health outcomes
Modestly preterm birth and early term birth contribute more to the burden of adverse health outcomes than does very preterm birth.
Bryle EM et al. Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study. BMJ 2012; 344 (March 17): 17 (e896).
Home treatment with oral amoxicillin was at least as effective as current WHO policy for severe pneumonia.
Soofi S et al. Effectiveness of community case management of severe pneumonia with oral amoxicillin in children aged 259 months in Matiari district, rural Pakistan: a cluster-randomised controlled trial. Lancet 2012; 379: 729737; Black RE, El Arifeen S. Communitybased treatment of severe childhood pneumonia. Ibid: 692694 (comment).
childs illness and may be a driving factor in fever phobia. Parents of children aged 06 were given an 18-question multiple choice questionnaire on fever management including the definition of fever based on body temperature, best place to take temperature, potential side effects of fever, drugs used for treatment, and drug administration techniques. The
Oral amoxicillin for severe early childhood pneumonia in rural Pakistan

In 2008, pneumonia accounted for 18% of all deaths in children under the age of 5 years. Almost half of all deaths in young children occur in Pakistan, India, China, Nigeria, and the Democratic Republic of the Congo. Delayed treatment is responsible for many child pneumonia deaths, and in 2004, the World Health Organization (WHO) and United Nations Childrens Fund recommended antibiotic treatment at home given by trained health workers, instead of hospital referral, for non-severe pneumonia in rural areas. Meta-analyses have confirmed the effectiveness of this policy. Now, a trial in rural Pakistan has shown that the policy is effective for children with severe pneumonia. A cluster randomized trial in rural Sindh province, Pakistan, included 4,410 children aged 259 months with WHO-defined severe pneumonia. The children were screened by lady health workers. Those with severe pneumonia were prescribed oral amoxicillin syrup (45 mg/kg twice daily) for 5 days at home (intervention clusters), or given a single dose of oral co-trimoxazole and referred to the nearest health facility for intravenous antibiotic treatment (control clusters). The children were followed up at 2, 3, 6, and 14 days. Treatment failure by day 6 occurred in 8% (intervention) and 13% (control), a non-significant difference. There were three deaths, two in the intervention group and one in the control group.
questionnaire was based on previous similar sur-
Paediatricians influence parental febrile behavior
veys and recent guidelines from the UK and Italy on fever management. Paediatricians were given a similar but terminologically different questionnaire. The majority of parents (67.8%) said that their paediatrician was their primary source of information on fever and fever management. All parents believed that fever could cause harmful effects like delirium, dehydration, or coma. If left untreated, 89.9% believed that fever could cause brain damage or seizures. The study highlighted a number of wrong behaviours. In similar ratios, paediatricians and parents said that they use sponging or ice packs to reduce fever (78.5% vs 77.8%; P = 0.867), and that they alternated ibuprofen and acetaminophen to treat fever (27% vs 21.4%; P = 0.953), despite guideline recommendations. Of concern, 1.4% of paediatricians and 1.2% of parents said that they use acetylsalicylic acid or steroids as a secondchoice therapy to antipyretic drugs (P = 0.937). Oral antipyretic administration was correctly preferred by 73.1% of paediatricians and 48.7% of parents ( P < 0.0001), compared with rectal administration. The similarities between many of the attitudes and practices related to fever demonstrate
Fever phobia describes an attitude of unreasonable fear that parents may have surrounding fever and treatment for fever in their children. A survey of 388 parents and 480 physicians from Italy showed that physician attitudes towards febrile children can inform how parents handle their
the degree to which parents follow their paediatricians lead. Educational programmes aimed at paediatricians could help modify parental behaviours as well.
Chiappini E et al. Parental and medical knowledge and management of fever in Italian pre-school children. BMC Pediatr 2012; 12(1): 97.
PA EDIA TRICS
Peer Reviewed
Imaging Paediatric Imaging Paediatric Brain Tumours Brain Tumours Paediatric Psoriasis
Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology
Paediatric Psoriasis
Vyom Sharma, MBBS; David Orchard, MBBS, FACD
Tang Phua Vyom Hwee,Sharma, MBBS, FRCR, Diagnostic Radiology MBBS; MMed David Orchard, MBBS, FACD
INTRODUCTION
Psoriasis is a chronic inflammatory disease characterized by well-demarcated erythematous plaques that demonstrate a characteristic silvery scaling. About 3040% of adult cases begin by age 15. Early diagnosis and treatment can arrest progression to disfiguring states that requires extensive treatment, as well as minimize the psychosocial burden imposed by this illness. This article covers an approach to classification, provides some popular regimes treatment, and provides an up-to-date review of management options.
PATHOGENESIS AND AETIOLOGY

The aetiology of psoriasis is multifactorial. There is over- and under-expression of certain proteins in psoriatic lesions. The effects of these expressions are threefold: abnormal keratinocyte differentiation, hyperproliferation of the keratinocyte, and inflammatory infiltration. These actions are mediated by activated T cells and dendritic cells that are present in psoriatic plaques. These cells release pro-inflammatory cytokines which trigger a cascade of cytokines that lead to keratinocyte proliferation, neovascularization, and vasodilation. Much of psoriasis is believed to be mediated by tumor necrosis factor (TNF) a, a pro-inflammatory cytokine, of which increased levels are found in active plaques. Its role in active psoriasis is strongly suggested by increase in TNF levels after therapy and increased levels in psoriatic plaques.
JPOG JULY/AUG 2012 137
PAEDIATRIC S PAEDIATRICS
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Figure 1. Typical well-demarcated, salmon-pink patches with silvery scale.
Genetic influences are suggested by studies which state positive family history in first-degree relatives somewhere between 10% and 73%; however, more recent studies suggest figures of approximately 70%. Major gene for psoriasis susceptibility is thought mainly to be located on chromosome 6, the site of HLA class I (associated with early onset disease) and II (late onset disease) antigens which are thought to produce differing subtypes of the disease. However, environmental factors are believed to play a significant role in the development of the condition, suggested by twin studies demonstrating disparity in concordance, with only 35% of monozygotic twins demonstrating psoriasis. A highly relevant environmental factor is streptococcal infection, which has an established association with guttate-type psoriasis. It is postulated that streptococcal antigen activate lymphocytes which induces mitotic activity. However, certain individuals with the Cw*0602 allele are four times more likely to develop guttate psoriasis. Other noted associations are of an increased incidence of psoriasis seen in sufferers of Kawasaki disease, Crohns disease, ulcerative colitis and bone marrow transplantation, all supporting the im-
Figure 2. Psoriasis in the concha of the ear.
Figure 3. Napkin psoriasis.
munological basis for disease.
EPIDEMIOLOGY
One-third of adults with psoriasis report onset in childhood. Ethnic variation is not clear, with some studies quoting incidence highest in Caucasian, followed by black and then Asian populations. Other studies, however, noted no variance except in the Inuit race, postulating the role of omega-3 fatty acids in the prevention of psoriasis. Classically, some authors have observed female preponderance by 2:1; however, the larger
PA EDIA TRICS
PA ED IATRICS Peer Reviewed
studies showed approximately equal gender distribution. Age distribution in the paediatric population is unclear. The inclusion of psoriatic diaper rash drastically increases incidence of psoriasis in children under 2, the most common pattern of presentation in children of that age group. If excluded, however, studies show identical distribution amongst all age groups.
In babies, the napkin area is frequently involved (Figure 3). Psoriasis in this distribution will generally have no scale and the diagnosis is made on the salmon-pink colour of the erythema and the welldemarcated borders of the plaques. Itch is variable but mostly not a significant symptom. Differential diagnosis includes other papulosquamous disorders of childhood, including: atopic dermatitis, discoid eczema (nummular dermatitis), tinea corporis, lichen planus, drug reactions, pityriasis rosea, pityriasis rubra pilaris. Discoid (nummular) eczema (Figure 4a) tends to be more pruritic, is less well defined with more intensity towards the centre, and can be oozing. Tinea corporis (Figure 4b) tends to have a more active edge, and there will often be a history of gradual expansion. Pityriasis rosea (Figure 4c) may have a herald patch and have the oval lesions lining along the ribs, and the scale is described as trailing rather than leading the outer annulus. These diagnoses can be excluded with biopsy if there are difficulties with clinical diagnosis. If psoriasis is extremely aggressive, it may
DIAGNOSIS
Psoriasis primarily is diagnosed clinically and classified on the basis of morphology. It presents mostly as well-demarcated erythematous lesions with fine or coarse silvery scaling (Figure 1). The predominant areas affected are the knees, elbows, buttocks, and scalp although these areas are not as typically involved in the paediatric population as compared with adults. Certain sites when involved are highly suggestive of psoriasis and include the umbilicus (Figure 1), the concha of the ear (Figure 2), and the natal cleft. Isolated facial involvement can occur and is more common in the paediatric population than in adults. Intertriginous areas are also commonly affected in children possibly presenting as vulvitis, balanitis, and perianal itching.
Figure 4. Differential diagnosis. a. Discoid eczema. b. Tinea corporis. c. Pityriasis rosea.
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Figure 5. Pustular psoriasis requires hospitalization.
large studies. In the largest study of 1,262 cases in Australia, it composed 4050% of all cases. The thickness of the plaques and degree of scaling can be highly variable from patient to patient although is usually consistent from plaque to plaque on a given patient.
take on the form of pustular psoriasis (Figure 5). In this setting, there is frequently lethargy, fever, elevated white cell count, and elevated liver transaminases. The pustules are sterile, and children mostly will need medical admission and oral medication conducted by a dermatologist. Psoriasis severity is measured commonly by the Psoriasis Area and Severity Index (PASI) whereby four sections of the body (head, arms, trunk, and legs) are scored according to severity of psoriasis. The scores then multiplied by a factor which represents the proportion. While useful in trials, in clinical practice the calculations can be contrived with 16 separate variables. The simplified PASI for clinical use, whereby the severity of redness, thickness and scaling of all plaques on the body, are estimated on a scale of 14. Then, these three variables are each multiplied by the estimated percentage of body surface area covered by the plaques. These are then summed to give the simplified PASI.
Guttate Guttate (drop-like) psoriasis presents with a sudden onset widespread eruption of papules to small plaques. Together with plaque psoriasis, it constitutes the overwhelming majority of psoriasis cases. It is commonly precipitated by group A b-haemolytic streptococci infection or other viral infections. Swabbing of pharynx and perianal area is recommended by some, as subclinical Streptococcus infection can at times be present. Some authors recommend post-antibiotic urinalysis to monitor for post-streptococcal glomerulonephritis. Oral antibiotics can be used to treat the throat or perianal infection; however, they are not the mainstay treatment for psoriasis. Mucosal Involvement Mucosal involvement can involve up to 5.6% of cases. It can involve oral/genital mucosa which demonstrates erythematous patches. Therapy is not commonly needed. Nail Involvement Reports range from 7% to 40%. The changes that are most common are pitting, followed by onycholysis, longitudinal striations. Other changes include subungual keratosis and discolouration. Pustular This form is rare in children. It has explosive onset and high fevers and other constitutional symptoms. The morphology is different with often annular plaques with peripheral postulation. It will often recur, then be followed by a period of typical
CLINICAL SUBTYPES
Plaque Psoriasis Plaque psoriasis constitutes 3484% of cases in many
PA EDIA TRICS
plaque psoriasis. Complications such as elevated hepatic transaminases and Ig A nephropathy have been documented.
Table 1. Criteria for psoriatic arthritis proposed by Vasey and Espinoza
Criterion I: Psoriatic skin or nail involvement Criterion II: Peripheral pattern

1. Pain and soft tissue swelling with or without limitation of movement of the distal interphalangeal joint for over 4 weeks 2. Pain and soft tissue swelling with or without limitation of motion of the peripheral joints involved in an asymmetrical peripheral pattern for over 4 weeks. This includes a sausage digit 3. Symmetrical peripheral arthritis for over 4 weeks, in the absence of rheumatoid factor or subcutaneous nodules 4. Pencil-in-cup deformity, whittling of terminal phalanges, fluffy periostitis, and bony ankylosis
Non-pharmacological strategies including counselling about the natural history of the disease is important
Criterion III: Central pattern

Arthropathy Psoriatic arthropathy is rare in children; however, it can be debilitating. It can be difficult to distinguish psoriatic from rheumatoid arthropathy. The criteria devised by Vasey and Espinoza have proven to be most sensitive (Table 1). It commonly involves the proximal and distal interphalangeal joints of the feet, proximal interphalangeal joints of the hand, knees, and ankle. Over time, it involves the wrists, metacarpophalangeal joints, elbow, and metatarsophalangeal joints.
1. Spinal pain and stiffness with the restriction of motion present for over 4 weeks 2. Grade 2 symmetric sacroiliitis according to the New York criteria 3. Grade 3 or 4 unilateral sacroiliitis
fatty acid supplementation in adults has demonstrated marginal benefit. Trauma to the skin is well known to trigger a flare (Koebner phenomenon). Pharmacological triggers include chloroquine, hydroxychloroquine, lithium, b-blockers, or, more commonly used in children, withdrawal of systemic and potent topical steroids. The treatment varies significantly from patient to patient depending on impact of disease. It is reasonable to treat minimally in young children, who are not bothered by their condition, and with aggressive combination therapy in older children, if required. All treatments are considered to be suppressive rather than curative, and most therapies are additive in combination. It is often worthwhile using a combination of therapies and encouraging maximum compliance in an attempt to clear the
TREATMENT
Non-pharmacological strategies including counselling about the natural history of the disease is important, particularly regarding patient/family fears of permanent disfigurement. Stress has been implicated in adults as an exacerbator of disease severity. There is no clear research suggesting dietary triggers or therapy in children, although omega-3
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Table 2. Possible regimes

psoriasis and then maintaining with minimal or no therapy (Table 2).
Face and flexure LPC 2% + salicylic acid 2% in aqueous cream topically at night (coal tar solution) and hydrocortisone 1% ointment topically in the morning If refractory, consider addition of tacrolimus/pimecrolimus and/or bursts of more potent topical steroids. Scalp Shampoos containing corticosteroids, zinc, tar or salicylic acid or calcipotriol can be used. Topical therapy for plaque psoriasis affecting the trunk and limbs 1. Coal tar prepared 1% lotion topically nocte/BD or LPC (20% coal tar in alcohol solution) 4% + salicylic acid 2% in aqueous cream nocte/BD + moderately potent corticosteroid in the morning (both LPC and salicylic concentrations can be titrated up to 10%, based on response.) 2. Add calcipotriol 0.005% OD or BD. 3. Add tazarotene 0.05% at night + moderate steroid in the morning. 4. If the above fail, consider light therapy in older children, or biologics/systemic therapy (see below). (Seek dermatologic participation in management will be required.) Genital area 1. Hydrocortisone 1% BD 2. In cases of poor response after 2 weeks, a moderately potent corticosteroid cream applied OD. Younger children in nappies: Moderately potent corticosteroid cream and anti-candidal cream (nystatin/imidazole). Recent streptococcal throat infection To eliminate this precipitant, commence phenoxymethylpenicillin 12.5 mg/kg up to 500 mg orally BD for 10 days, or roxithromycin (immediate) or cephalexin if penicillin-sensitive When clear, LPC 12% in aqueous or zinc cream OD for maintenance. Acute pustular This presentation is serious and requires hospital admission.
BD = twice daily; LPC= liquor picis carbonis; OD = once daily.
All treatments are considered to be suppressive rather than curative
DISCUSSION OF MODALITIES
Topical Emollient: emollients are best used on scaling or irritated skin, and provide prompt relief. Greasier emollients are easiest to spread and are best for drier skin; however, a less greasy preparation may be best in hot weather. In order of increasing greasiness, preparations include: aqueous cream liquid paraffin, glycerol 10% in sorbolene cream, 50/50 liquid and white soft paraffin. Steroid: topical corticosteroids have antiinflammatory and anti-mitotic effects. The more potent preparations are used to treat thicker areas of skin. Facial and diaper region can be treated with mild preparations such as 1% hydrocortisone. Trunks and limbs can be treated effectively with medium- to high-potency steroids for limited periods of time. Adverse effects include atrophy in areas of thin skin, tachyphylaxis, striae, and hypothalamicpituitary-adrenal axis suppression. Coal tars: tar treatment has anti-inflammatory and antipruritic effects. It remains a popular choice in children because it obviates the systemic steroid absorption, although its odour and staining effects on skin affect compliance in older children. The preparations are in cream or liquid form. Its
PA EDIA TRICS
adverse effects include local acne, folliculitis, and irritant/contact dermatitis. When used as part of the Goeckerman regimen (daily topical coal tar and exposure to UV-A or UV-B), it has proven to be highly effective in many studies. However, it has concurrently demonstrated carcinogenic, potential increased mutagenicity and temporary genotoxicity; but a 20-year follow-up of 29 patients from Mayo Clinic did not find any cases of malignancies.
Emollients provide prompt relief of scaling or irritated skin.
Systemic therapies are usually reserved for chronic severe psoriasis refractory to topical and light therapies
Calcipotriene: this vitamin D derivative can be used where adverse effects of steroids, such as systemic absorption or atrophy, are of risk. Calcipotriene can be used as an adjunct, or less commonly as a substitute. Studies suggest equal or better response than topical steroids and anthralin with reduced side effects. However, maximal effect is initiated after 6 weeks only. Theoretical risk of hypocalcaemia is unlikely if calcipotriene is not used on large surface area. Calcineurin inhibitors: tacrolimus and pimecrolimus are calcineurin blockers. Tacrolimus is a calcineurin inhibitor that acts by preventing the production of cytokines in T cells and mast cells. While unsuitable for thick plaques owing to poor penetration and absorption, it has proven efficacious in the treatment of adults. A small paediatric study in 2007 of 11 patients showed drastic improvement
when applied to the face and intertriginous areas. Tazarotene: tazarotene is a topical synthetic retinoid best used as an adjunct to topical steroid and other therapies if control is not achieved. Local irritation is the only common side effect. Anthralin: anthralin use remains controversial in children. It can cause staining and troubling irritation. However, a study in children by Zvulunov on 58 children demonstrated remission in 81% and mild skin irritation in 20%. Use in children is rare and only as an adjunct.
SYSTEMIC
Systemic therapies are usually reserved for chronic severe psoriasis refractory to topical and light therapies. Safety of treatment beyond 1 years duration has not been well established.
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Coal tar medications remain a popular choice in children as they are considered to be safe.
There have been advances in the use of biologic therapies for paediatric autoimmune disease
Cyclosporin At doses of 35 mg/kg, cyclosporine has proven efficacious in paediatric psoriatic patients. Close monitoring for renal function and blood pressure is required. Theoretical risks of malignancy and lymphoproliferative disorders seem to be minimal owing to the low doses and limited durations of treatment in this population. Systemic Retinoid Acitretin and isotretinoin have proven beneficial as single agent therapy for pustular and erythrodermic psoriasis, however less so for plaque psoriasis. Side effects can include skin fragility, deranged liver enzymes, skeletal toxicity, and pseudotumor cerebri. Use as monotherapy is uncommon. It is often used as an adjunct to light therapy. Methotrexate Methotrexate (dosed at 0.20.7 mg/kg/wk) provides excellent clearance according to one study, conferring 75% PASI reduction in most children. Therapy is generally commenced with 7.5 mg and folate administration, with close monitoring of liver function tests and cholesterol. Common side effects include nausea and vomiting. It is a known abortifactant and teratogen, and can cause liver cirrhosis.
BIOLOGICS
Recently, there have been advances in the use of biologic therapies for paediatric autoimmune disease. Three TNF antagonist drugs have been commonly used in children for conditions such as Crohns disease and juvenile idiopathic arthritis. Owing to the recent development newness of these therapies, all potential side effects are not known.
PA EDIA TRICS
Psoriasis is believed to be mediated by tumor necrosis factor, of which increased levels are found in active plaques.
Etanercept A multicentre, randomized controlled trial has demonstrated efficacy versus placebo, with 53% of children achieving a physicians global assessment of clear by 12 weeks (versus 13% in the placebo group). Adverse events including human papillomavirus, infection, gastroenteritis and influenza were reported. Overall, it was well tolerated. It is given as subcutaneous injection once or twice weekly. Infliximab Infliximab is used for a variety of paediatric autoimmune diseases. Reports supporting infliximab in psoriasis include two case studies where both patients failed multiple therapies, topical and systemic with no side effects. Side effect profile in the treatment of other diseases has been encouraging, most commonly associated with upper respiratory
tract infection, pneumonia, but also rare cases of hepatosplenic lymphoma. It is administered as twoweekly intravenous infusion.
Adalimumab There is no literature on the use of adalimumab in paediatric psoriasis. However, it has demonstrated success in patients with juvenile idiopathic arthritis. Ustekinumab Ustekinumab is a human monoclonal antibody that inhibits interleukin receptor-mediated signalling. Multiple studies have demonstrated dose-dependent clinical responses and linear pharmacokinetics. Three recent randomized controlled trials have demonstrated 12-weekly subcutaneous ustekinumab to improve clinical and quality-of-life parameJPOG JUL/AUG 2012 145
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ters. Adverse event rates were favourable, with no indication of links with cardiovascular, malignancies, or infective morbidities. Ongoing studies shall provide data regarding adverse events over a longer period of time. These studies have not, however, been conducted in children, and as such their suitability and safety are yet to be assessed completely.
chological and emotional stress of this disease. Biologic modalities offer much promise for the efficacious and safe management of psoriasis in children.
2011 Elsevier Ltd. Initially published in Paediatrics and Child Health 2011;21(3):126131.
Further Reading LIGHT TREATMENT

UV-B UV-B has been demonstrated to be safe and efficacious in children. Narrowband therapy reduces dose of UV, and combination with topical/systemic modalities two to three treatments a week can be common. Side effects include erythema and hyperpigmentation. Carcinogenicity has not been demonstrated. PsoralenUV-A A psoralen is administered before UV therapy in this regime as a photosensitizer, either orally for generalized photosensitization or topically for local effect. However, psoralenUV-A therapy is uncommon since the advent of narrowband UV-B, as it has demonstrated an increased risk of squamous cell carcinoma and melanoma.
Dermatology Expert Group. Therapeutic guidelines: dermatology. Version 3. Melbourne: Therapeutic Guidelines Limited, 2009. Duffy DKL, Spelman LS, Martin NG. Psoriasis in Australian twins. J Am Acad Dermatol 1993;29:428434. Duvic M, Asano AT, Hagar C, Mays S. The pathogenesis of psoriasis and the mechanism of action of tazarotene. J Am Acad Dermatol 1998;4:S129S133. Fredriksson T, Pettersson U. Severe psoriasisoral therapy with a new retinoid. Dermatologica 1978;157:238244. Henseler T. The genetics of psoriasis. J Am Acad Dermatology 1997;37:S1S11. Lebwohl M, Ali S. Treatment of psoriasis. Part 1. Topical therapy and phototherapy. J Am Acad Dermatology 2001;45:487498. Lewkoweiz D, Gottlieb AB. Pediatric psoriasis and psoriatic arthritis. Dermatol Ther 2004;17:364375. Louden BA, Pearce DJ, Lang W, Feldman SR. A Simplified Psoriasis Area Severity Index (SPASI) for rating psoriasis severity in clinic patients. Dermatol Online J 2004;10:7. Morris A, Rogers M, Fischer G, Williams K. Childhood psoriasis a clinical review of 1262 cases. Pediatr Dermatol 2001;18:188198. Rasmussen JE. The relationship between infection with group A beta haemolytic streptococci and the development of psoriasis. Pediatr Infect Dis J 2000;19:153154. Raychaudhuri SP, Gross J. A comparative study of paediatric onset psoriasis with adult onset psoriasis. Pediatr Dermatol 2000;17:174178. Rogers M. Childhood psoriasis. Curr Opin Pediatr 2002;14:404409. US FDA. Highlights of prescribing information: Stelara ustekinumab). Available from: http://www.accessdata.fda.gov /drugsatfda_docs/label/2009/125261lbl.pdf.
CONCLUSION
Considering that a significant proportion of adult cases of psoriasis develops in children, it is important to diagnose and establish early management. Early intervention can maintain clearance, limit severity of the disease as well as reduce the psy-
About the Authors
Vyom Sharma is a hospital medical officer at the Royal Melbourne Hospital, Parkville, Melbourne, Australia. Conflict of interest: None. David Orchard is Staff Specialist in the Department of Dermatology, Royal Childrens Hospital, Melbourne, Victoria, Australia. Conflict of interest: None.
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Dysmenorrhoea Dysmenorrhoea
Shilpa Kolhe, MBBS, MD, MRCOG; Shilpa Deb, MBBS, DGO, MRCOG Shilpa Kolhe, MBBS, MD, MRCOG; Shilpa Deb, MBBS, DGO, MRCOG
BACKGROUND
Dysmenorrhoea is a medical condition characterized by severe uterine pain during menstruation manifesting as cyclical lower abdominal or pelvic pain, which may also radiate to the back and thighs. The term dysmenorrhoea is derived from the Greek words dys meaning difficult, painful or abnormal, meno meaning month, and rrhea meaning flow. It is commonly divided into primary dysmenorrhoea, where there is no coexistent pathology, and secondary dysmenorrhoea where there is an identifiable pathological condition known to contribute to painful menstruation. Symptoms of primary dysmenorrhoea begin a few hours before the start of menstruation and are often relieved during the first few days of bleeding. The initial onset of primary dysmenorrhoea is usually shortly after menarche (612 months), when ovulatory cycles are established. Secondary dysmenorrhoea can also occur at any time after menarche but is most commonly observed in women in their third and fourth decade of life in association with an existing condition. Since dysmenorrhoea is a symptom that could be perceived differently by different women, it is difficult to establish its true incidence. However, the reported prevalence is age-related, increasing from around 40% in girls aged 12 years, to 70% in girls at 17 years of age. An epidemiological study showed that the prevalence of dysmenorrhoea among adolescent females ranges from 60% to 93%, but decreases with advancing age. One systematic review of community and hospital surveys estimated the overall prevalence to be 4595% whilst a second age-based systematic review suggested 2550% of adult women and as many as 75% of adolescents experience pain with menJPOG JUL/AUG 2012 147
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struation. Pain is significant in 520% who report severe dysmenorrhoea or pain that prevents them from participating in their usual activities. One community survey of adolescents aged 1218 years showed dysmenorrhoea as one of the most common biomedical problems causing health risk behaviours and psychosocial problems, such as cigarette or alcohol use, dieting, infrequent/never seat belt use, and feeling depressed. It is one of the most commonly reported reasons for absenteeism from school or work with some studies suggesting that 1045% of women miss or reduce time at work, school or other activities. In the United States, the annual economic loss has been estimated at 600 million work hours and 2 billion dollars. These reports suggest a significant socio-economic and psychosocial impact of dysmenorrhoea on female health during the reproductive years.
strual cycle. (The hypothesis that prostaglandins released from the endometrium at the time of menses contribute to dysmenorrhoea is supported by the observation that endometrial concentrations of prostaglandin E2 (PGE2) and prostaglandin F2 (PGF2) correlate with the severity of dysmenorrhoea, that cyclo-oxygenase inhibitors decrease menstrual fluid prostaglandin levels and decrease pain, and that the clinical manifestations of dysmenorrhoea are similar to those with prostaglandin-induced labour or medical management of miscarriage. In contrast to the uterine contractions in normal menstruation, contractions in women with primary dysmenorrhoea often begin with elevate basal tone, reach higher active pressures (frequently more than 150 mm Hg), and are non-rhythmic or in coordinate. In addition to stimulating uterine contractions, PGF 2 and PGE 2 can cause contraction of bronchial, bowel, and vascular smooth muscle resulting in bronchoconstriction, nausea, vomiting, diarrhoea, and hypertension. Di-
PATHOPHYSIOLOGY
The most important physiological event reported with dysmenorrhoea is increased myometrial activity with accompanying uterine ischaemia (uterine angina), which stimulates the type C afferent pain neurones. Doppler flow studies have supported this hypothesis by showing higher uterine and arcuate artery resistance on the first day of menses in women with primary dysmenorrhoea than in controls. While the pathophysiological mechanisms that cause this are not entirely understood, it is thought that this myometrial activity is modulated and augmented by prostaglandin synthesis. This may reflect the increase in circulating levels of prostaglandin F 2, which is a potent myometrial stimulant and vasoconstrictor. It is also found that the levels of prostaglandins in endometrial fluid in the early follicular phase of menstrual cycle are less than levels in late luteal phase of menJPOG JUL/AUG 2012 148
arrhoea and nausea are commonly associated with primary dysmenorrhoea. The other reported factors in the causation of increased myometrial activity are increased levels of circulating vasopressin and leukotrienes. This effect is mediated via myometrial oxytocin and vasopressin V1a receptors. The role of vasopressin may relate to prostaglandin synthesis and release; leukotrienes, as well as PGE2, may increase the sensitivity of pain fibres in the uterus. Increased endometrial expression of leukotrienes has been demonstrated in women with primary dysmenorrhoea resistant to prostaglandin antagonists. Psychosocial factors may play a role in the perception and the severity of the pain.
CLINICAL FEATURES
History is critical in establishing the diagnosis of
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Table 1. Differential characteristics of primary and secondary dysmenorrhoea
Primary
Age (years) Onset of pain Pathophysiology Symptoms 1625 Just prior to menstruation (spasmodic) Excess prostaglandins, vasopressin, leukotrienes Usually self-limiting, lasts for first 13 days menstruation Responds to COCP and NSAIDs Periods normal or light Unremarkable
Secondary
3045 Pain often progresses through late luteal (congestive) Underlying disorder Associated with other features related to underlying disease Resistant to COCP and NSAIDs Periods often heavy Dependent on cause but may include a tender, enlarged, fixed, retroverted uterus with adnexal tenderness and a mass
Signs
COCP = combined oral contraceptive; NSAIDs = non-steroidal anti-inflammatory drugs.
dysmenorrhoea and also in differentiating between primary and secondary dysmenorrhoea. A thorough menstrual history including the age at menarche and at the onset of pain, cycle length and regularity, duration and amount of menstrual flow, and an assessment of the onset, duration, type, cyclicity and severity of pain and associated symptoms such as nausea, vomiting, bloating, diarrhoea and fatigue is essential in the diagnosis of dysmenorrhoea. It is then important to exclude the secondary causes of dysmenorrhoea such as pelvic infection, sexually transmitted disease, endometriosis, subfertility, abdominopelvic surgery and difficult childbirth which could present with additional symptoms of deep dyspareunia, intermenstrual, postcoital bleeding, and subfertility. One should specifically determine the factors that exacerbate or ameliorate the symptoms, as secondary dysmenorrhoea is more commonly refractory to simple treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) and the combined oral contraceptive (COCP). Social and family history should be considered as they may have direct or indirect bearing on the causation and help in optimizing the treatment (Table 1).
PRIMARY DYSMENORRHOEA
Primary dysmenorrhoea almost invariably occurs in young women with ovulatory cycles and usually appears within a year after menarche. The pain classically begins just before or with the onset of menstruation lasting through the first 12 days and is typically described as spasmodic lower abdominal or pelvic pain superimposed over a constant dull aching pain, which may radiate to the back and along the thighs. Menstrual bleeding is usually normal. Associated symptoms such as malaise and fatigue (85%), irritability (72%), dizziness (28%), headache (45%), lower backache (60%), diarrhoea (60%), and nausea and vomiting (89%) may be present. The diagnosis of primary dysmenorrhoea is made primarily based on history and then by exclusion of existing pathology. Pelvic or rectal examination where appropriate may be helpful to exclude common problems of young age such as pelvic inflammatory disease and endometriosis, and provide reassurance through a negative assessment. Psychosexual factors may be contributing to dysmenJPOG JUL/AUG 2012 149
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orrhoea and should be considered where medical treatment is unsuccessful.
menorrhoea is endometriosis. Women with endometriosis who present with secondary dysmenorrhoea have physical findings approximately 40% of the time. It is important to remember that absence of abnormal findings does not exclude secondary dysmenorrhoea and should be complemented with a transvaginal ultrasound. A small but significant minority of adolescent girls will have secondary dysmenorrhoea, which is largely due to endometriosis, ovarian cyst or presence of congenital anomaly in the urogenital tract. Endometriosis may be an isolated finding or associated with a uterine abnormality, which is more likely when dysmenorrhoea occurs during the first or second cycles after menarche. Adnexal, rectovaginal and uterine tenderness associated with cervical excitation is seen in 76% of adolescents with endometriosis, reiterating the importance of pelvic examination in this group of patients. More extensive disease will manifest similarly to that seen in older women with nodular disease over the uterosacral ligaments and rectovaginal septum, decreased uterine mobility, and unilateral or bilateral adnexal masses. Similar findings may be seen in adolescents with acute or chronic pelvic inflammatory disease.
SECONDARY DYSMENORRHOEA
Secondary dysmenorrhoea mainly occurs in the third and fourth decade of reproductive life. The pain is different to that of primary dysmenorrhoea and is described as pelvic heaviness and back pain increasing progressively throughout the late luteal phase and peaking with the onset of menstruation. This pattern of pain is often referred to as congestive pain in contrast to the spasmodic pain seen with primary dysmenorrhoea. The pain associated with secondary dysmenorrhoea is more likely to coincide or be temporally associated to other gynaecological symptoms, such as cycle irregularity, heavy periods, dyspareunia, vaginal discharge, intermenstrual bleeding, and postcoital bleeding.
Major Causes of Secondary Dysmenorrhoea Gynaecologic disorders: Endometriosis Adenomyosis Pelvic inflammatory disease Fibroids Endometrial polyps Ovarian cysts Intrauterine contraceptive device Intrauterine adhesions Congenital obstructive mullerian malformations Pelvic congestion syndrome Cervical stenosis Non-gynaecologic disorders: Inflammatory bowel disease Irritable bowel syndrome Urogenital disease Psychogenic disorders The most common cause of secondary dysJPOG JUL/AUG 2012 150
INVESTIGATIONS
Careful analysis of the clinical findings should be made and investigations directed towards the likely underlying causes. There are no specific tests to diagnose primary dysmenorrhoea, which is largely made on clinical findings. Routine blood tests are not usually indicated in patients with isolated dysmenorrhoea, but a full blood count to exclude anaemia should be undertaken in women with associated menorrhagia. Microscopy and culture of swabs from the endocervix for Chlamydia and gonorrhoea should be obtained together with a high vaginal swab
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from the posterior vaginal fornix for other sexually transmitted diseases. A raised white cell count suggests infection and may be associated with a raised erythrocyte sedimentation rate and C-reactive protein in patients with chronic pelvic inflammatory disease. These tests are non-specific but may be used to monitor disease progression or response to therapy. The same is true of the tumour marker CA-125, which is raised in some cases of endometriosis. Underlying causes of secondary dysmenorrhoea such as fibroids, intrauterine contraceptive devices and ovarian cysts including endometriomas are best assessed with ultrasound. Transvaginal ultrasound is preferable to transabdominal as it offers more resolution and can also be used as an extension of the pelvic examination to qualify tenderness and uterine mobility. To improve the sensitivity and specificity of ultrasound in the detection of endometrial lesions including polyps and submucosal fibroids, consideration should be given to saline infusion sonography, which is shown to be comparable with hysteroscopy in diagnosing endometrial lesions (Tables 1 and 2). Three-dimensional ultrasound offers the benefit of assessing organs in coronal plane and, therefore, can prove beneficial in the diagnosis of endometrial pathology. Four-dimensional ultrasound may have a role in assessing the frequency and intensity of myometrial activity associated with dysmenorrhoea. In certain cases, to ascertain or clarify diagnosis, a diagnostic laparoscopy may be required. Laparoscopy is the gold standard in investigation of peritoneal endometriosis, adhesions and chronic pelvic inflammatory disease, also allowing treatment at the same time. Hysteroscopy may be indicated to evaluate intrauterine pathology suggested by imaging and may be combined with resection of an endometrial polyp or sub-mucosal fibroid.
Table 2. Evidence-based treatment options for dysmenorrhoea
Grade A NSAIDs (other than aspirin) Combined oral contraceptives Grade B & C Aspirin, paracetamol, and compound analgesics Magnesium Thiamine Vitamin B1, B6, E Fish oil High-frequency TENS Topical heat (about 39C) Exercise Japanese and Chinese herbal medicine Unknown Levonorgestrel intrauterine system Surgical interruption of pelvic nerve pathways Acupuncture Behavioural interventions Magnet therapy Vasopressin antagonists Low-frequency TENS No benefit Spinal manipulation
NSAID = non-steroidal anti-inflammatory drug; TENS = transcutaneous electrical nerve stimulation.
MANAGEMENT
Treatment for dysmenorrhoea is aimed at relieving symptoms and is best treated with analgesics that are prostaglandin inhibitors so as to affect the physiological mechanisms behind menstrual pain and by directing treatment at the underlying pathology. Many studies have employed patient self-reporting using a visual analogue or other pain scale, quality of life scales, or other similar measures such as the menstrual distress or menstrual symptom questionnaires. Additional measures include analysis of the proportion of women requiring analgesics in addition to their assigned treatment and recording the percentage of women reporting activity restriction of social activities or absenteeism from work or school. Whichever system is used, grading dysmenorrhoea according to severity of
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pain and limitation of daily activity will help guide the treatment strategy and catalogue the response to treatment (Table 2).
Cox-2 inhibitors are more expensive. It should be remembered, however, that NSAIDs are associated with adverse effects including headache, drowsiness, dizziness and dryness in addition to gastrointestinal effects like nausea and indigestion. Gastrointestinal ulceration and haemorrhage were less prominent side effects, probably owing to the short-term administration only. When treating women with risk factors for NSAID-induced ulceration which include previous clinical history of gastroduodenal ulcer or perforation, gastrointestinal bleeding, or the concomitant use of medications known to increase the likelihood of upper gastrointestinal adverse events, such as corticosteroids and anticoagulants the potential risks and benefits of using an NSAID should be considered and discussed with the patient. If an NSAID is offered in this situation, a gastro-protective agent should also be prescribed. NSAIDs are also contraindicated in patients with renal insufficiency, bleeding diatheses, and aspirin hypersensitivity because of their pharmacokinetic and pharmacodynamic drug interactions and possible effects on platelet aggregation. However, because they are generally used for short periods in otherwise healthy young women, they are frequently well tolerated and free of serious toxicity in most patients. It is unclear which NSAIDs have better efficacy or safety and when is the optimal time to initiate treatment. While all NSAIDs are thought to be effective, relieving pain by up to 70%, naproxen and ibuprofen appear significantly better than mefenamic acid and aspirin in terms of the need for rescue analgesia. NSAIDs that achieve peak serum concentrations within 3060 minutes and have a faster onset of action (eg, ibuprofen, naproxen, meclofenamate) may be preferred. Some recommended doses are as follows: naproxen 250275 mg four to eight hourly; ibuprofen 400 mg three,
Medical Treatments
NSAIDs (Other Than Aspirin)
NSAIDs are the mainstay of treatment for primary dysmenorrhoea. It is proposed that NSAIDs relieve primary dysmenorrhoea mainly by suppressing the production of endometrial prostaglandins, thus alleviating cramps and restoring normal uterine activity. In addition, there may be direct analgesic action on the central nervous system (Dawood 2006). NSAIDs inhibit cyclooxygenase (Cox) type 1 and 2 pathways, thus inhibiting synthesis of prostaglandins. A recent Cochrane review analysed 73 randomized controlled trials (RCTs). Nineteen different types of Cox-1 NSAIDs and two Cox-2 NSAIDs (meloxicam and etoricoxib) were evaluated. NSAIDs (with an exception of aspirin) were significantly superior to placebo in reducing the pain associated with primary dysmenorrhoea (odds ratio, OR, 4.50; 95% confidence interval, CI, 3.85 5.27). NSAIDs were also significantly more effective for pain relief than paracetamol (OR, 1.90; 95% CI, 1.053.44). NSAIDs with the exception of Cox-2 inhibitors may also benefit social interaction, with evidence from one systematic review that their use is associated with a reduced restriction of daily activities, absenteeism, and the need for additional analgesia compared with placebo. When NSAIDs were compared with each other, there was no significant difference found in their efficacy (P > 0.05). Etoricoxib did not differ significantly in efficacy from naproxen, and meloxicam was significantly less effective for pain relief than diclofenac. Although known to have reduced gastrointestinal toxicity, neither Cox-2 NSAIDs differed significantly in tolerability from the Cox-1 comparators. Besides,
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four or six times daily; diclofenac 200 mg/day in divided doses; mefenamic acid 250 mg eight hourly; nimesulide 50100 mg twice daily; meloxicam 7.515 mg daily. Pareek et al found that fixed-dose combination of aceclofenacdrotaverine (NSAID + antispasmodic) was superior to monotherapy with aceclofenac in women with primary dysmenorrhoea. Another RCT concluded that one to two tablets of combination of ibuprofen and paracetamol provided superior analgesic efficacy than placebo.
Aspirin, Paracetamol and Compound Analgesics
and, therefore, the oestrogen-dependent proliferation of the endometrium and reduced secretion of progesterone. This in turn reduces the amount of prostaglandin produced by glands in the lining of the uterus, which then reduces both uterine blood flow and cramps. A Cochrane systematic review of the efficacy of COCPs for primary dysmenorrhoea analysed 10 RCTs out of the 23 identified. Improvement in pain was reported in five studies that compared COCP to placebo (OR, 2.01; 95% CI, 1.323.08). Combined oral contraceptive pills containing less than 35 g of oestradiol have been shown to control symptoms of dysmenorrhoea effectively and therefore should be the preferred choice of COCP. There is strong evidence to support the use of COCPs containing low-dose oestrogen for the treatment of dysmenorrhoea. Tricycling COCP has been used to treat women with severe dysmenorrhoea especially that associated with endometriosis. The extended cycle regimen might be associated with less menstrual pain than the monthly regimen. However, future trials comparing the two regimes are warranted. A Cochrane systematic review on the efficacy of modern COCP (low-dose oestrogen) found COCP as effective as gonadotrophin-releasing hormone analogue in treating painful symptoms of endometriosis. Transdermal and vaginal ring contraceptives have a favourable impact on dysmenorrhoea similar to that noted with the use of COCP. There were no studies identified that directly compared COCP to NSAIDs in the management of dysmenorrhoea.
Other Hormonal Therapies
Paracetamol was shown to offer no additional pain relief than placebo, aspirin or naproxen in two systematic reviews. Coproxamol (paracetamol and dextropropoxyphene) appears to be superior to placebo, but is associated with more side effects than naproxen and is less effective than mefenamic acid. One systematic review found that aspirin was significantly more effective than placebo for pain relief but not as effective as ibuprofen, naproxen and mefenamic acid (number needed to treat for aspirin was 10, compared with only 2 or 3 for other NSAIDs).
Combined Oral Contraceptives
COCPs are commonly used as second-line therapy for primary dysmenorrhoea where NSAIDs are ineffective, poorly tolerated or contraindicated. Over 90% of adolescents with primary dysmenorrhoea report a reduction in pain within 3 months of commencing a COCP containing at least 30 g of oestrogen. Zahradnik et al suggested that COCPs should be used as a first-line therapy in women with dysmenorrhoea who also wish contraception. This method of approach eliminates the risks associated with taking NSAIDs for pain relief. COCP is thought to work by inhibiting ovulation
Other hormonal therapies such as progestogens (depomedroxyprogesterone acetate and levonorgestrel), danazol and gonadotrophin-releasing hormone analogues again work by inhibiting ovulaJPOG JUL/AUG 2012 153
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tion and suppressing the menstrual cycle and can occasionally be used for resistant dysmenorrhoea. They are frequently used for short periods of no more than 6 months to provide a few months of amenorrhoea and relief from symptoms in women debilitated by their pain. The levonorgestrel-releasing intrauterine system, although not licensed for the treatment of dysmenorrhoea, can be of benefit in treating coexistent menorrhagia.
the benefits of magnesium; however, the results of three small trials comparing magnesium with placebo showed that magnesium was more effective than placebo for pain relief and the need for additional medication was less. The dose and regimen of treatment with magnesium to be used is still unclear. Pyridoxine pyridoxine (vitamin B 6) is shown to be more effective at reducing pain when compared with placebo and a combination of magnesium and vitamin B 6. Omega-3 fatty acids (fish oil) one RCT has shown that the use of omega-3 fatty acids may reduce pain, although more research is needed to quantify this effect. Adverse effects associated with fish oil treatment were mild and included nausea and worsening of acne. Vitamin B 1 one large trial showed vitamin B 1 to be more effective than placebo in reducing pain. Vitamin E a RCT showed vitamin E alone (500 units per day or 200 units twice per day, beginning 2 days before menses and continuing through the first 3 days of bleeding) was more effective than placebo for relieving dysmenorrhoea in adolescents randomly assigned to either therapy, although both active drug and placebo reduced pain. Japanese herbal medicine one small trial showed the natural herbal remedy tokishakuyaku-san to be more effective for pain relief than placebo and less use of additional pain medication. There is some evidence supporting the benefits of a low-fat vegetarian diet on dysmenorrhoea in parous women. Chinese herbal medicine there is some promising evidence supporting the use of Chinese herbal medicine for primary dysmenorrhoea. However, results are limited by the poor methodological quality of the trials.
Surgical Treatments Surgical intervention may be necessary to treat the underlying cause of secondary dysmenorrhoea. It is generally not indicated for treating primary dysmenorrhoea. Although there is insufficient evidence to support its routine use, surgical procedures such as laparoscopic uterine nerve ablation and presacral neurectomy may be performed for symptomatic relief of pain in refractory cases of dysmenorrhoea. These two surgical procedures interrupt most of the cervical sensory nerve fibres (thus diminishing uterine pain). Dependent upon the aetiology, this may necessitate conservative laparoscopic or open surgery with adhesiolysis, ovarian cystectomy, salpingectomy and ablation or excision of endometriotic deposits or hysteroscopic resection of endometrial polyps, intrauterine adhesions and sub-mucosal fibroids. In severe cases of endometriosis resistant to medical therapy, hysterectomy, with or without bilateral oophorectomy, may be required. Conservative Treatments
Herbal Products and Dietary Supplements
Thiamine a single large randomized controlled trial has shown beneficial effects of thiamine (100 mg daily) on menstrual pain when used for 2 months or more. A total of 87% of patients were cured up to 2 months after treatment. Magnesium there is limited evidence on
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Alternative remedies
Acupuncture there is limited evidence from controlled trials to support the use of complementary alternative medicine (acupuncture, yoga) for treatment of dysmenorrhoea. Three trials compared acupuncture to sham acupuncture; all three observed a reduction in pain in both groups, but only one trial noted greater pain reduction in the real versus the sham acupuncture group. More data from controlled trials demonstrating safety and efficacy need to be done before these modalities can be recommended. Spinal manipulation spinal manipulation may improve spinal mobility and pelvic blood flow, hence reducing menstrual pain. This has been reported as an effective alternate treatment for dysmenorrhoea in two small, limited-quality RCTs. A larger and better designed RCT found no significant difference between spinal manipulation and placebo manipulation after 1 month. Overall, there is no evidence to suggest that spinal manipulation is effective in the treatment of primary or secondary dysmenorrhoea.
Other Non-hormonal Therapies
Exercise systematic review on the use of exercise for relief of dysmenorrhoea included a single randomized trial that provided some evidence that exercise reduces menstrual symptoms. Topical heat treatment heat to abdomen appears to be as effective as oral analgesics for relief of dysmenorrhoea. A trial randomly assigned women with dysmenorrhoea to an abdominal heat wrap (40C) which was worn for 8 hours, a placebo wrap, acetaminophen (1,000 mg every 5 hours, four times per day for 1 day), or placebo pills. The heat wrap provided better pain relief than acetaminophen and was well tolerated. Transcutaneous electrical nerve stimulation transcutaneous electrical nerve stimulation (TENS) seems to work by altering the bodys ability to receive or perceive pain signals. TENS is thought to have two effects: (1) it raises the threshold for pain signals from uterine hypoxia and hypercontractility by sending a volley of afferent impulses through the large diameter sensory fibres of the same nerve root, resulting in lower perception of painful uterine signals; and (2) it stimulates release of endorphins from the peripheral nerves and the spinal cord. A meta-analysis from the Cochrane database including three trials (n = 124 women) found that high-frequency (50120 Hz) TENS was more effective than placebo TENS for relief of dysmenorrhoea but is less effective than ibuprofen. Behavioural interventions a systematic review concluded that behavioural interventions may be of benefit in treating women with dysmenorrhoea. These include attempts at modification of the way the woman thinks about her pain (eg, desensitization-based procedures, hypnotherapy, imagery, coping strategies) and attempts at modification of her response to pain (eg, biofeedback, electromyographic training, Lamaze exercises, and relaxation training).
Alverine citrate, an anticholinergic antispasmodic, is licensed for the treatment of dysmenorrhoea, but there is a lack of published evidence on its efficacy for this indication and it is unlikely to be as effective as NSAIDs or the COCP. Beta-agonists and calcium channel blockers are reported to be of some benefit in dysmenorrhoea, but none is licensed for this indication. Transdermal glyceryl trinitrate is useful as a modulator of uterine contractility and an alternative for the management of primary dysmenorrhoea, although is limited by its side effect of headache. There are trials underway assessing the role of vasopressin antagonists, antispasmodics, magnesium, vitamin K, and magnet therapy in the treatment of dysmenorrhoea.
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Practice points
supportive providing symptomatic relief, and more directive surgical treatment should be reserved for specific secondary causes of dysmenorrhoea or for refractory cases.
2011 Elsevier Ltd. Initially published in Obstetrics, Gynaecology and Reproductive Medicine 2011;21(11):311316.
Around 4070% of women suffer with dysmenorrhoea Increased myometrial activity induced by an excessive production of prostaglandin causing ischaemia is the most accepted pathophysiological mechanism Primary dysmenorrhoea is seen in young women with ovulatory cycles and is characterized by spasmodic menstrual pain starting just before menstruation lasting for 2448 hours. There is no coexisting pathology Secondary dysmenorrhoea is always associated with an underlying pathology and is characterized by congestive menstrual pain, which increases progressively through the late luteal phase, peaking with onset of menstruation History is critical in establishing the diagnosis of dysmenorrhoea Treatment is aimed at symptomatic relief with analgesics especially NSAIDs and at treating the underlying pathology
Further Reading
Chantler I, Mitchell D, Fuller A. The effect of three cyclo-oxygenase inhibitors on intensity of primary dysmenorrheic pain. Clin J Pain 2008;24:3944. Cho SH, Hwang EW. Acupuncture for primary dysmenorrhoea: a systematic review. BJOG 2010;117:509. Tugay N, Akbayrak T, Demirturk F, et al. Effectiveness of transcutaneous electrical nerve stimulation and interferential current in primary dysmenorrhea. Pain Med 2007;8:295 300.
Cochrane Reviews PROGNOSIS

There are very few longitudinal studies examining the progression and eventual outcome of primary or secondary dysmenorrhoea. Primary dysmenorrhoea often improves in the third decade of a womans reproductive life and appears to be reduced after childbirth. The prognosis of secondary dysmenorrhoea is not known, as its severity, progression and eventual outcome depend on the underlying pathology.
Brown J, Brown S. Exercise for dysmenorrhoea. Cochrane Database Syst Rev 2010;(2):CD004142. Herbal and dietary therapies for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev 2002. Marjoribanks J, Proctor ML, Farquhar C. Nonsteroidal antiinflammatory drugs for primary dysmenorrhoea. Cochrane Database Syst Rev 2010;(1):CD001751. Proctor ML, Hing W, Johnson TC, Murphy PA. Spinal manipulation for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev 2006;(3):CD002119. Proctor ML, Latthe PM, Farquhar CM, Khan KS, Johnson NP. Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev 2005;(4):CD001896. Proctor ML, Murphy PA, Pattison HM, Suckling J, Farquhar CM. Behavioural interventions for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev 2007;(3):CD002248. Wong CL, Farquhar C, Roberts H, Proctor M. Oral contraceptive pill for primary dysmenorrhoea. Cochrane Database Syst Rev 2009;(4):CD002120.
CONCLUSIONS
Dysmenorrhoea has a significant physical, behavioural, psychological and social impact, affecting 4070% of women of reproductive age. It is a leading cause of absenteeism. The exact pathophysiological processes are not fully understood, but it probably reflects increased myometrial activity induced by an excessive production of prostaglandin causing ischaemia. Mainstay treatment is generally
About the Authors

Shilpa Kolhe is a Senior Registrar in Obstetrics and Gynaecology at Queens Medical Centre, Nottingham, UK. Conflicts of interest: None declared. Shilpa Deb is a Consultant in Obstetrics and Gynaecology at Nottingham University Hospitals NHS Trust, Queens Medical Centre Campus, Nottingham, UK. Conflicts of interest: None declared.
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What Are the Benefits and Risks of HRT?

Elizabeth Farrell, AM, FRANZCOG, FRCOG
ormone replacement therapy (HRT) is the most effective treatment for menopause symptoms in peri- and postmenopausal women, in particular for the vasomotor symptoms of hot flushes and sweats and symptoms relating to the atroph-
ic changes in the urogenital tract. Over-the-counter alternative products have no better effect than placebo. About 20% of women will have moderate to severe symptoms that interfere with quality of life, and longitudinal studies have shown that significant symptoms may last up to a mean of 8 years, with about 10% of women affected having symptoms for 10 years or more. Opinions concerning the benefits and risks of HRT have varied over the past decade. This article aims to summarize the current position, as given in the most recent recommendations of the International Menopause Society.1 All menopausal women should be advised to develop a healthy lifestyle programme in addition to possibly taking HRT. This lifestyle plan should include healthy eating, cessation of smoking, limiting alcohol intake, being a healthy weight, and undertaking regular exercise, and will depend on the age of the woman at the time of her menopause.
INDICATIONS FOR HRT

The indications for prescribing HRT are the presence of moderate to severe menopausal symptoms impacting on a womans ability to function normally, and as a first-line therapy in young women with osteoporosis.
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All menopausal women should develop a healthy lifestyle, in addition to possibly taking hormone replacement therapy.
yearly after her regimen is effective in improving her symptoms and quality of life. Regular screening is recommended, with a yearly riskbenefit analysis being made. The duration of therapy should not be fixed but reassessed yearly. HRT can be ceased every 4 to 5 years to see if symptoms recur; it may be required for 5 to 10 years, or perhaps longer.
PREMATURE AND EARLY MENOPAUSE

Women experiencing a premature menopause (before the age of 40 years) or an early menopause (before the age of 45 years) are at greater health risks of early onset of osteoporosis, cardiovascular disease and perhaps also an increase in mood disorders and dementia. It is usually advised that these women take HRT at least until they are 50 years of age. These younger women often require high-dose therapy, either HRT or the oral contraceptive pill, for effective symptom control and to preserve bone density.
HRT PRESCRIBING
The HRT products available include tablets, patches, and gels. Recently, there has been a reduction in the number of products available for women because pharmaceutical companies have withdrawn various products for financial reasons (not because Some of the menopause symptoms women experience are listed in the box on page 159. of any safety issues). The dose of HRT prescribed should be the lowest effective dose that reduces symptoms and improves quality of life, but should always be individualized, sometimes requiring up to 6 months A woman who is prescribed HRT should be reviewed after 2 to 3 months, have her regimen tailored over further visits and then be seen at least
MONITORING OF PATIENTS ON HRT
to determine the appropriate combination of hormones. Combined therapy of oestrogen and a pro-
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gestogen (E+P) should be prescribed in women with a uterus, and oestrogen alone (oestrogen replacement therapy; ERT) in women who have had hysterectomies. Cyclical progestogens (E+P) are used in perimenopausal cycling women and continuous progestogen (E+P) after menopause. Tibolone is another option for postmenopausal women. Urogenital symptoms can be treated appropriately with vaginal oestrogen therapy either alone or in combination with HRT.
Menopause symptoms1
Hot flushes in 80% women significant in 20% of affected women last longer than 5 years in 25% of affected women Night sweats Muscle/joint pains Formications Anxiety, irritability Sleep disturbances Lessened memory, concentration Vaginal dryness, low libido Fatigue Overall diminished wellbeing
A recent follow-up study of the WHI showed a reduced risk of breast cancer in the women who took oestrogen alone for 7 years
various medical conditions, such as breast cancer, will also vary within our population, depending on a womans country of origin and the length of time she has lived in Australia.
NEW MESSAGE ABOUT HRT NEAR MENOPAUSE

In 2007, the Womens Health Initiative (WHI) investigators reanalysed their data about coronary heart
So-called bioidentical or natural HRT products, which are formulated from imported hormones by local compounding pharmacies, are untested for long-term safety and efficacy and avoid the safeguards of Therapeutic Goods Administration registration. They are a potential medicolegal hazard for prescribers and should not be advocated. Most studies in women using HRT have been in western industrialized countries with mainly Caucasian populations. The research literature needs to be interpreted accordingly and may not necessarily be applicable to all community groups. The incidences of menopause symptoms and of
disease (CHD) that had lead to scare headlines in 2002.2 They found that there was an absence of excess risk of CHD and the suggestion of reduced total mortality in younger women. This offered reassurance to those women initiating HRT under the age of age 60 years for symptom control. No morbidity was significantly increased in this group, which is the group normally treated with HRT. Meta-analysis of other studies supports this conclusion. A recent follow-up study of the WHI showed a reduced risk of breast cancer in the women who took oestrogen alone for 7 years. This is also reassuring for these women.3
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Each woman should be counselled about the benefits and risks of hormone replacement therapy to enable her to make an informed decision.
BENEFITS AND RISKS OF HRT

Benefits
HRT has the following beneficial effects: relieves vasomotor symptoms of hot flushes and sweats reverses urogenital atrophic symptoms, such as vaginal dryness, loss of lubrication prevents bone loss due to oestrogen deficiency associated with menopause decreases osteoporosis fractures in the spine and hip reduces risk of diabetes improves connective tissues in skin, joints, arteries, and intervertebral discs. If HRT is commenced in healthy women around the time of the final menstrual period, there may be a reduction in cardiovascular risk and a reduction of Alzheimers dementia. HRT may have beneficial effects on the followJPOG JUL/AUG 2012 160
ing menopause symptoms: aches and pains in joints and muscles insomnia or sleep problems loss of libido mood disturbance quality of life. HRT may also improve sexual function, and the specific HRT conjugated equine oestrogens plus medroxyprogesterone acetate when used for more than 4 years may reduce the risk of colon cancer.
Risks
Most studies on the risks of HRT focus on the risks of cancer associated with its use. Risks of specific cancers and of other conditions are summarized below.
Breast Cancer
The WHI study has shown no increase in the risk of breast cancer in first-time E+P HRT users 5 years
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after treatment initiation. It has shown a small increase 4 to 5 years after treatment initiation in those with prior use (less than 0.1% per year or fewer than 1 per 1,000 women per year of use). The WHI and the Nurses Health Study have shown that there was no increase in risk of breast cancer after 7 to 15 years of use of ERT.
Hormone replacement therapy is the most effective treatment for menopause symptoms in peri- and postmenopausal women.
If HRT is commenced in healthy women around the time of the final menstrual period, there may be a reduction in cardiovascular risk and a reduction of Alzheimers dementia
Little information is available on different doses, routes of administration of oestrogen, progesterone, progestogens, and androgens. Cessation of HRT leads to a lowering of risk, and after 5 years the risk is the same as the general population of the same age. Mammographic breast density is increased with HRT, and this may decrease the ability to interpret mammograms accurately.
Endometrial Cancer
proliferative effect of oestrogen. An adequate progestogen dose will reduce the risk of endometrial hyperplasia and cancer. Tibolone use is not associated with an increase in the risk of hyperplasia or endometrial cancer.
Ovarian Cancer
The risk of endometrial cancer is increased in women with an intact uterus taking unopposed oestrogen therapy. The risk will increase with increasingly higher doses of oestrogen and will remain for many years even after the oestrogen has been stopped. Therefore, women should always be given a progestogen to protect the endometrium against the
There is no evidence showing an increased risk of ovarian cancer in women taking combined HRT. A very small increase in risk has been shown with long-term oestrogen-only therapy.
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Most studies on the risks of hormone replacement therapy focus on the risks of cancer associated with its use.
Lung Cancer
Stroke
A statistically significant small increase in the risk of non-small cell lung cancer has been shown in older women taking HRT for 5 years, but there was no increased risk in women in the 50- to 59-year-old group.
Coronary Artery Disease
The age of the woman, her cardiovascular risks (such as hypertension) and the route of administration of E+P or ERT are all factors that influence the risk of stroke. The WHI and the Nurses Health Study both showed an increase in risk in women taking oral E+P or ERT of one additional stroke per 1,000 person-years. In an observational study, transdermal oestradiol at doses of 50 g or less showed no increase in risk of stroke. Tibolone is associated with a small increase in risk of stroke in older women.
Venous Thromboembolism
Increasing age at time of initiation of HRT has been shown to lead to increased risk of coronary events, especially in older women with pre-existing coronary disease. The events are increased in the first year of therapy. No increased risk of coronary events was shown when HRT was initiated near the menopause, and there may even be possible protection.
Venous thromboembolism (VTE) is the major risk associated with the taking of oral oestrogens. The
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risk also increases with increasing age, obesity, and thrombophilias, and may vary according to the type of progestogen being taken. Transdermal oestrogens seem to have a lower risk of VTE, related to the avoidance of the first-pass pathway of metabolism. Tibolone is not associated with an increased risk of VTE.
Alzheimers Dementia
Each woman should be counselled about the benefits and risks of HRT in a manner that allows her to make an informed decision. Written or website information will also help her to confirm her decision.
FURTHER READING
Anderson GL, Limacher M, Assaf AR, et al; Womens Health Initiative Steering Committee. Effects of conjugated equine oestrogen in postmenopausal women with hysterectomy: the Womens Health Initiative randomized controlled trial. JAMA 2004:291:17011712. Collins P, Rosano G, Casey C, et al. Management of cardiovascular risk in the perimenopausal women: a consensus statement of European cardiologists and gynecologists. Climacteric 2007;10:508526. Rossouw JE, Anderson GL, Prentice RL, et al; Writing Group for the Womens Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Womens Health Initiative randomized controlled trial. JAMA 2002;288:321333.
There is an increase in dementia in older women commenced on E+P/ERT. In the 65 to 79 years age group, ERT leads to an excess risk of 1.2 per 1,000 person-years and E+P to an excess risk of 2.3 per 1,000 person-years.
Gall Bladder Disease
The risk of gall bladder disease (and cholecystectomy) is increased with E+P.
2012 Medicine Today Pty Ltd. Initially published in Medicine Today April 2012;13(4):5961. Reprinted with permission.
CONCLUSION
HRT remains the most effective treatment for menopause symptoms, particularly the vasomotor symptoms and the atrophic changes. Maintaining and regularly updating ones knowledge about the menopause and HRT is paramount for each professional to be able to give information accurately.
About the Author

Dr Farrell is Head of the Menopause Unit, Monash Medical Centre, Southern Health, Melbourne, Victoria, Australia, and Past President of the Australasian Menopause Society. Declaration of interests: Dr Farrell has been on advisory committees and received educational and research grants from various pharmaceutical companies over the past 10 years but does not think these associations have influenced the content of this article.
REFERENCES
1. Sturdee DW, Pines A, on behalf of the International Menopause Society Writing Group. Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health. Climacteric 2011;14:302320. 2. Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007;297:14651477. 3. Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Womens Health Initiative randomised placebo-controlled trial. Lancet Oncol 2012;13:476486.
PAEDIATRICS PAEDIATRICS
II
Peer Peer Reviewed Reviewed
Managing Imaging Paediatric Headache Managing Headache in Children Brain in Tumours Children
M A McShane, MB BCh, MRCP(UK); S J Hughes, MBBS, MRCPCH Tang Phua Hwee, MBBS, FRCR, Diagnostic Radiology M A McShane, MB BCh, MRCP(UK); S JMMed Hughes, MBBS, MRCPCH
eadache is a common symptom in children. Recurrent or persistent headache is most commonly due to one of three main headache types: migraine (with and without aura), tension headache, and chronic daily headache. There are many good reviews of head-
ache and its treatment in the clinical journals. Headache including migraine affects up to 30% of the population and often begins in childhood. The classification system for headache introduced in 1998 by the International Headache Society has been updated and is widely used in research and clinical papers. Symptom overlap between the various headache syndromes is particularly common in children, making clear definition difficult in clinical practice. This paper will focus on the clinical management of headache in children including migraine and will not dwell on classification or diagnosis.
DIAGNOSIS
When considering the management of the child with headache, the importance of a detailed history and clinical examination cannot be overemphasized. Sufficient time is required to allow a good consultation in the child presenting with headache, particularly chronic headache. All parents are concerned that there may be serious underlying pathology. It is important not to miss serious pathology, and a recent paper published in the Archives of Diseases in Childhood (2010) provides a guideline to help identify those children who might have a tumour. Delay in making a diagnosis of brain tumour occurs in many children and adolescents, and particular features which might suggest a tumour include a change in headache symptom, persistent early morning headache, short but escalating history, physical symptoms such as altered gait or visual symptoms, cognitive decline, and hormonal disturbance (for example evidence of diabetes insipidus or growth failure). Headache in the very young (children less than 5 years) also needs to be
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managed with caution. In clinical practice, serious disorders such as tumours and conditions such as a Chiari 1 malformation are relatively rare causes of headache. If there is a typical history for migraine or tension headache and a thorough clinical examination is normal, then investigation is unlikely to be helpful. There is a place for organizing a scan in some patients for reassurance, but with increasing anxiety about the potential danger associated with X-radiation this should be with magnetic resonance imaging if done routinely. The clinician also needs to be aware that it is not uncommon for magnetic resonance imaging to reveal unexpected abnormalities often with no relevance to the presenting symptom. After taking a good history and undertaking a thorough examination, most patients can be reassured following discussion and formulation of a management plan. Time well spent at this first appointment may avoid unnecessary anxiety and repeated GP and hospital visits.
be warned that there may be some initial rebound. Sleep is important for all children, and poor sleep is a common association in those with chronic headache. Children and adolescents with migraines not only have a higher rate of sleep disturbance, such as insufficient sleep, daytime sleepiness and night waking, but in addition these problems tend to increase the frequency of headache. Advice aimed to improve sleep has the potential to reduce migraines. It is important to ask about bedtime; encourage a regular calm settling regime and recommend removal of distractions such as sound systems and televisions from the bedroom. Reducing caffeine intake is often advised although most children are not heavy tea and coffee drinkers. Parents need to be aware that many fizzy drinks contain caffeine and that it is best to drink plain tap water for thirst rather than sugary drinks. We often recommend that individuals with chronic headache increase fluid intake although evidence supporting this strategy is lacking. We feel that giving some responsibility to the parent and patient in terms of adapting their lifestyle can have a positive effect on symptoms possibly by giving them some control. Dietary factors may be important in some individuals, but restrictive diets in growing children are best avoided. Missing meals with resultant relatively low blood sugar seems to be a particular trigger in some individuals, and eating meals at regular intervals may be helpful for many patients. In those who have migraines triggered by sport, a small snack before activity can be beneficial. Stress has also been historically suggested as a cause for headache. While it may not necessarily be the cause, most of us would accept that stress contributes to headache severity and frequency. It may not be possible to recognize any particular stress in every patient, but enquiry is essential and measures to reduce stress encouraged. Psychological interventions are an emerging area of interest
HEADACHE MANAGEMENT (SIMPLE AND NON-PHARMACOLOGICAL MEASURES)

When we see a child with migraine or tension headache, we usually advise the family about non-medical interventions that might help the symptoms. There is good evidence that lifestyle issues impact upon headaches and migraines. Children who are obese have increased frequency and increased disability from attacks. There is also some evidence that weight loss in such patients may reduce the impact of migraines. Analgesic headache is now well recognized, and a self-perpetuating cycle of analgesic overuse can easily occur. Often simply stopping regular analgesic treatment can improve the headache symptoms particularly in those who report that the medicine is of no benefit, although the patient needs to
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in the treatment of migraine. There is some evidence that relaxation strategies are helpful for the individual in both preventing and treating migraine episodes. Biofeedback techniques and behavioural therapies such as cognitive behaviour therapy can have a positive effect on disabling chronic illness including chronic daily headache. A recent BMJ review (2011) notes that herbal remedies, mineral supplements and vitamins are sometimes used by patients who dislike drug treatment, and some have been shown to have efficacy including butterbur (Petasites hybridus ), magnesium and coenzyme Q10, but these are not without their potential side effects and uncertainty about dosage may have practical limitations for use particularly in children. We rarely advise these interventions, but some patients will research and use alternative medicine sometimes with useful effect. Feverfew was often used as a headache treatment, but lack of effect in a clinical trial has led to it becoming less popular. In the older adolescent patient with migraine with aura, the combined oral contraceptives is usually avoided, and in some individuals the pill can exacerbate headaches. Ergot derivatives are now rarely used in adult practice and never in children.
headache has resolved.
PHARMACOLOGICAL TREATMENT
Treatment is generally undertaken in a stepwise fashion, with the aim to minimize the requirement for medication where possible. It is important to balance the side effects of any treatments against the disabling effects of the migraine. This should always be done in consultation with child and family. If the migraine is infrequent and not severe, then simple measures should be employed. In children with migraine, we recommend that they try to sleep or at least rest after taking an analgesic until the
Acute Treatment of Migraine First-line treatments consist of routine analgesics: paracetamol, NSAIDS (non-steroidal anti-inflammatory drugs), and weak opiates such as codeine. There have been few studies assessing the effectiveness of simple analgesics in non-malignant chronic pain disorders including migraine. NSAIDs, such as ibuprofen, show statistical significance in the acute treatment of migraine, and all simple analgesics are most effective when taken early in the episode. Anti-emetics mentioned in the British National Formulary for Children (BNFc) include metoclopramide, domperidone, phenothiazines and antihistamines. Rectal preparations are available, but extrapyramidal side effects need to be mentioned. Regular and long-term use should be avoided. Formulations combining paracetamol, codeine and an anti-emetic are available and can be helpful for some patients, possibly owing to the anti-emetic action. Chronic analgesics use (abuse) can produce a persisting analgesic headache. The BMJ review paper suggests that in adults, simple analgesics should be used on no more than 15 days per month and migraine-specific acute drugs should be used no more than 10 days per month. The Lancet Neurology paediatric paper suggests that simple analgesia should be used on no more than 3 days per week and migraine-specific drugs no more than 6 days per month. If first-line analgesics are unsuccessful in migraine headaches, then triptans are now the recommended second-line acute treatment. The serotonin (5-HT) 1 agonists are not licensed for use in children, but the BNFc does give dosage recommendations for the drugs sumatriptan and zolmitriptan. Sumatriptan can be prescribed from 6 years and older and zolmitriptan from 12 years. Both need to
PA EDIA TRICS
be initiated by a specialist and should be avoided in children with cardiac disease, hypertension, and epilepsy. The 5-HT agonists can be administered orally or as melt-in-the-mouth tablets. In older children, they can be administered subcutaneously via an auto-injector or be given by the intranasal route. Triptans are generally well tolerated in the paediatric age group, but it is recommended that they be given as monotherapy. These drugs can interact with other medications and the serotonin syndrome, an atypical neuroleptic malignant syndrome, can be triggered. Caution is needed with this treatment particularly when on other prescribed medications. It is relatively rare for us to recommend triptans in children in our clinical practice. Recent evidence in adults has suggested efficacy for oxygen treatment in cluster headache, but fortunately this particularly distressing headache syndrome is rare in children. Pizotifen has antihistamine and anti-serotonin actions, but the evidence that it is an effective treatment for migraine is limited. Despite this lack of evidence, it is widely used. Adverse effects include increased appetite and drowsiness. We generally use pizotifen as first-line prophylactic treatment but giving this as a single dose at night to avoid daytime sedation. The BNFc gives doses from 5 years and older. It does have mild anticholinergic actions and can potentially cause problems such as urinary retention and worsening of glaucoma, but these are rarely a problem in children. Occasional behavioural disturbance is described. Pizotifen is not recommended for children with epilepsy. Propranolol is the most commonly used -blocker for migraine prophylaxis. It should not be given to patients with a history of asthma and bronchospasm. There is good evidence that -blockers are effective in migraine, but side effects can be troublesome including fatigue, cold extremities and poor sleep. The BNFc gives a dose schedule from 2 years and older, but we rarely use this drug in younger children and often find that it is not well tolerated in some older children. Postural hypotension may be a problem in some teenagers.
Aims of prophylactic treatment include reduction of attack frequency, severity and duration, as well as increased responsiveness to acute treatment during an attack
Headache and Migraine Prophylaxis There are no agreed guidelines on when prophylactic treatment should be used, but in our practice if significant headaches are occurring more than once weekly, daily prophylaxis should be considered. The BNFc suggests more than two attacks per month, but much depends on the response of the acute headaches to simple measures and the disability caused by the attacks. The decision to start a prophylactic drug requires careful discussion. Aims of prophylactic treatment include reduction of attack frequency, severity and duration, as well as increased responsiveness to acute treatment during an attack. The adverse effects of treatment also need to be discussed, and many parents will choose to avoid regular medication for their children because of anxieties about drug-related side effects. The BNFc mentions three prophylactic drug groups for use in children. These are pizotifen, -blockers, and anti-epileptics.
Peer Reviewed
Anti-epileptics drugs are useful in the management of migraine and other disorders with chronic pain. They are also useful for patients who fail to respond to other prophylactic agents. Clinical trials have shown efficacy for topiramate and sodium valproate. Carbamazepine may also be an effective treatment in some individuals and may have a better side effect profile. The BNFc recommends that these medications should be initiated and supervised by a specialist. A number of other treatments are available to treat children with chronic headache. Amitriptyline, an old antidepressant, is widely used in the management of chronic pain disorders in children and adults. We rarely use this in children younger than 12 years. Side effects include drowsiness and sometimes agitation. Anticholinergic side effects are described but rarely troublesome in children in the small doses used for this indication. Calcium channel blocker agents can be used to treat migraine, but their use is not licensed for this indication and we rarely use them other than for extremely rare conditions such as alternating hemiplegia. Botulinum toxin has recently obtained approval for use in chronic headache in both the UK and USA in adults. This treatment is not yet widely accepted as effective in the adult population and we would think indications for use in children will be very limited. There is also some emerging evidence in adults that certain nutrients such as coenzyme, riboflavin and magnesium may be helpful, but this has not been well studied in the paediatric population yet.
expectations when changing medications should occur with the patient and their family. Advice on the timing of cessation of prophylaxis is not well studied. We recommend reviewing the effectiveness of prophylactic treatment after 1 month and continuing treatment for 36 months. We do not recommend long-term treatment in children.
CONCLUSIONS
Headache is a common symptom in children and young people and requires careful clinical assessment. Once diagnosed, treatment should progress in a stepwise fashion, using simple lifestyle strategies and a range of medications, as necessary. Treatment goals and expectations should be agreed with patient and their family. Regular medications should be reviewed after a 1-month period, using diary recording for evidence of effectiveness. Longterm treatment in children should be avoided with breaks in treatment at 36 monthly intervals.
2011 Elsevier Ltd. Initially published in Paediatrics and Child Health 2011;21(11):518520.
Further Reading
Fenstermacher N, Levin M, Ward T. Pharmacological prevention of migraine. BMJ 2011;342:d583. doi:10.1136/bmj.d583. Hershey AD. Current approaches to the diagnosis and management of paediatric migraine. Lancet Neurol 2010;9:190204. Mack KJ. An approach to children with chronic daily headache. Dev Med Child Neurol 2006;48:9971000. Wilne S, Koller K, Collier J, Kennedy C, Grundy R, Walker D. The diagnosis of brain tumours in children: a guideline to assist healthcare professionals in the assessment of children who may have a brain tumour. Arch Dis Child 2010;95:534539.
Length of Treatment In children, it is often possible to stop prophylaxis after a period of time. It is recommended that throughout treatment, setting goals and reviewing
About the Authors
M A McShane is a Consultant Paediatric Neurologist at the Childrens Hospital at the John Radcliffe Hospital, Oxford, UK. Conflicts of interest: none declared. S J Hughes is a Consultant in Paediatric Neurodisability at the Royal Berkshire Hospital, Reading, UK. Conflicts of interest: none declared.

P 3 SK
An Update on Emergency Contraception

Hang-Wun Raymond Li, MBBS, MMedSc, MRCOG, FHKAM (O&G); Sue Seen-Tsing Lo, MBBS, FRCOG, PDipCommPsyMed; Ernest Hung-Yu Ng, MBBS, MD, FRCOG, FHKCOG, FHKAM (O&G); Pak-Chung Ho, MBBS, MD, FRCOG, FHKCOG, FHKAM (O&G)
INTRODUCTION
Proper use of family planning methods is the key to preventing unplanned pregnancies. Despite the great effort spent in the research and development of contraceptive methods resulting in many new advances, none of the current methods is 100% effective. Emergency contraception (EC), also called postcoital contraception, is a back-up contraception administered to a woman after unprotected sexual intercourse (UPSI) or contraceptive failure, so as to prevent unplanned pregnancy. This may be indicated when unexpected intercourse has occurred without the use of any contraception, when there is a suspected potential failure of ones regular contraceptive method (eg, condom breakage or slippage, missed dose of hormonal contraceptive, or potential failure of an intrauterine contraceptive device), or after sexual assault. Since all contraceptive methods can have potential failure, the use of EC plays an important role in preventing unplanned pregnancies and the need for termination of pregnancies in these circumstances. However, its use has been hindered by lots of myths and misconceptions which prevent its full and proper use. The purpose of this article is to provide an updated review on the efficacy and mechanisms of action of the current methods of EC, with emphaSince ancient times, special manoeuvres such as sneezing, jumping and vaginal douching with various substances (eg, disinfectants, lemon juices or Coca-Cola) have been used for EC. The modern concept of
1
Figure 1. Proper use of family planning methods is the key to the prevention of unplanned and unwanted pregnancies.
sis on the more recent advances, as well as the potential means to improve service delivery.
of oestrogen in animals was demonstrated to prevent pregnancy. The first reported use of EC was in the early 1960s, when high-dose oestrogen regimens (eg, diethylstilboestrol 2550 mg daily, ethinylestradiol 5 mg daily, or conjugated oestrogen 30 mg daily) were used over 5 days.2 These were very effective, with pregnancy rates of 0.61.6%, but were soon abandoned because of the high incidence of side effects (nausea, 5470%; vomiting, 2433%) and teratogenicity.3 The combined highdose oestrogen and progestogen regimen,
HISTORICAL EC
hormonal methods for EC probably began in the 1920s, when postcoital administration
Figure 2. Various forms of emergency contraception provide women with a safe back-up in circumstances of unprotected sexual intercourse.
the Yuzpe regimen, was introduced in the 1970s and has remained a mainstay method for over three decades.4
adopted. The first dose needs to be taken within 72 hours of UPSI and a second dose taken 12 hours later. This Yuzpe method soon became the most popular EC regimen
were nausea (54%) and vomiting (16%) caused by the high oestrogen dose.5
THE YUZPE REGIMEN

In 1974, Yuzpe et al from Canada reported the combined regimen of 100 g of ethinylestradiol and 1 mg of dl-norgestrel for EC. An equivalent regimen consist4
THE LEVONORGESTREL-ONLY owing to its convenience, as this regimen REGIMEN

can be devised using several tablets of any combined oral contraceptive pills constituting the equivalent dose. The overall failure rate when commenced within 72 hours of UPSI is 3.2%, and the failure rate increases with increasing intercourse treatment interval. The major side effects The first randomized controlled trial (RCT) 6 on the progestogen-only regimen, consisting of two doses of LNG 0.75 mg taken 12 hours apart, was conducted in Hong Kong and the results were published in 1993. This showed a slightly but not significantly
ing of ethinylestradiol 100 g and levonorgestrel (LNG) 500 g has been widely
Table 1. Recommended methods of emergency contraception in current use Licensed use (time limit after unprotected intercourse) (h) 72 120 120 120
follicular development when administered before the luteinizing hormone surge. Administration of LNG after the onset of the luteinizing hormone surge does not
Regimen
Availabilitya
inhibit ovulation. Studies have also suggested that LNG at pharmacological dose levels does not have significant effects on
Levonorgestrel, 1.5 mg single dose Mifepristone ,10 mg or 25 mg single dose Ulipristal acetate, 30 mg single dose Copper intrauterine contraceptive device
a
Most countries Mainland China only United Kingdom, continental Europe, United States Most countries
sperm function, fertilization, endometrial receptivity, and implantation.1519 There are no data on its direct effect on tubal function.
... the use of EC plays an important role in preventing unplanned pregnancies and the need for termination
As at December 2010.
higher efficacy compared with that of the Yuzpe regimen, but a significantly reduced incidence of side effects. The clinical efficacy of the LNG regimen was later confirmed to be superior to that of the Yuzpe regimen (1.1% vs 3.2%) by a multinational, multicentre trial, which was coordinated by the World Health Organization (WHO) and published in 1998.7 The combined data showed a significantly lower pregnancy rate with LNG compared with the Yuzpe regimen (relative risk, 0.51; 95% confidence interval, 0.310.83).8 In Hong Kong, it was licensed in July 2002 and has since been the first-line hormonal EC. The current recommended regimen is a single dose of LNG 1.5 mg within 72 hours after unprotected intercourse, since it was con9
without reducing the efficacy or increasing the side effect profile compared with the two-dose regimen. 10 It has been shown that the efficacy decreases with the intercourse treatment interval,11 and the intake within 24 hours after UPSI is most effective compared with later intake. The cur8
of pregnancies in these circumstances.
MIFEPRISTONE
Mifepristone is an anti-progestogen which has also been developed as an effective EC. The use of mifepristone 600 mg within 72 hours of unprotected intercourse for EC was first reported in 1992.20,21 The later trial conducted by the WHO reported that lower doses at 50 mg and 10 mg were equally efficacious.22 A recent Cochrane review has suggested that a single dose of mifepristone at 2550 mg (and possibly at the 10-mg dose although there is less evidence) taken up to 120 hours after UPSI is the most effective among all current regimens for oral EC. 8 However, its use is limJPOG JUL/AUG 2012 171
rent evidence did not show any significant difference in efficacy when used within 72 hours versus between 72120 hours after UPSI owing to the relatively small proportion of subjects falling into the latter timeframe, and the WHO is recommending its use up to 120 hours after UPSI. The use
12
of LNG EC beyond 72 hours of UPSI, however, is outside the product licence.9 Clinical studies have shown that LNG is effective as an EC only when given before, but not after, ovulation.
13,14
firmed in a large, multicentre, randomized, controlled trial that taking LNG 1.5 mg as a single dose would simplify EC use
This may
be explained by its mechanism of action. LNG mainly acts by delaying or inhibiting
The use of emergency contraception should not replace regular contraception because of its relatively higher cumulative pregnancy rate.
ited by its availability, since mifepristone at the 10- or 25-mg dose (the recommended EC dose) is only available in Mainland China. Compared with the Yuzpe regimen, the incidence of nausea and vomiting with mifepristone was significantly lower, but some users had a delay in return of menstruation, which might be the result of
21
studies,16,18,19 although this effect remains to be proven clinically. Mifepristone does not seem to have a significant effect on fertilization, and its effect on sperm or tubal function is not clear.
17,19
and the United States only as a prescription drug. It is an orally active tablet containing 30 mg of micronized UPA. Two RCTs showed that UPA was as effective as LNG for EC within 72 hours of UPSI.23,24 One of them also studied 100 women taking UPA from 72 to 120 hours after UPSI and no pregnancy was observed.24 When the results of the two RCTs were combined in a meta-analysis, UPA had a significantly lower failure rate compared with LNG (1.36% [22/1,617] vs 2.15% [35/1,625]; P = 0.046).24 In another open-label trial of using UPA between 48 and 120 hours after UPSI, a pregnancy rate of 2.1% (26/1,241)
ULIPRISTAL ACETATE
More recently, ulipristal acetate (UPA) (CDB-2914), which is another selective progestogen receptor modulator, has been introduced for EC. This was launched in the United Kingdom and continental Europe in 2009. It is more expensive than LNG-EC and is currently approved in Britain, Europe
delayed follicular maturation and ovulation by mifepristone. The superior efficacy of mifepristone may be due to the fact that it not only delays or inhibits ovulation, but may also interfere with endometrial receptivity and embryo implantation as shown by in vitro
was observed.25 Therefore, it appeared that regular hormonal contraceptives do not ap- to their contraceptive efficacy, some usthe effectiveness of UPA as an EC is main- ply to hormonal EC because of the very short ers may have personal or religious reasons tained up to 120 hours after UPSI, which exposure. Physical and pelvic examinations for refusal of any form of EC with postis currently its licensed indication. It was are not mandatory prior to prescribing hor- fertilization effects, in which case they postulated that the better efficacy of UPA monal EC. Contraindications to the use of may have the informed choice of the LNG could be attributed to its mechanisms of Cu-IUCD are the same as its ordinary use regimen. action; apart from its effect in delaying for regular contraception, such as current ovulation,
26,27
Pregnancy is considered a contrain-
it also alters the endometrial or suspected pelvic and genital tract infec- dication only because EC is not going to
histology and may hence exert a post-ovu- tions, as well as distortion of the uterine work in a woman who is already pregnant, latory effect in influencing implantation.26,28 cavity.9,32 It is not suitable for women with but not because of any harmful effect on However, the clinical relevance of this high risk factors for sexually transmitted in- the pregnant woman. There are no data to post-ovulatory observation still remains to be determined by further studies. suggest any adverse effect on pregnancy owing to exposure to LNG-EC during early
Modern methods
pregnancy. 9,31 It was also shown in a recent meta-analysis that both LNG and mifepristone do not increase the risk of having a subsequent ectopic pregnancy.33 For women using liver enzyme-inducing drugs, Cu-IUCD is the preferred choice. If the LNG regimen is used, an increased dose of 2.25 or 3 mg as a single dose is advisable, although this is an off-label use.9
COPPER INTRAUTERINE CONTRACEPTIVE DEVICE

The use of the copper intrauterine contraceptive device (Cu-IUCD) for EC had been reported since 1976.29 It is an effective EC up to 5 days after UPSI and can be left in situ for regular contraception. If the timing of ovulation can be estimated, it can be inserted beyond 5 days of UPSI, as long as it is not beyond 5 days after ovulation.
8 9
of EC provide a safe and effective back-up for UPSI and contraceptive failure, and should be part of all contraceptive counselling.
ADVICE AND FOLLOW-UP

fections, including victims of rape, or if this contraception because of its relatively
Its failure rate is less than 0.1%. It should is genuinely indicated it can be inserted un- The use of EC should not replace regular be noted that the LNG-intrauterine system der prophylactic antibiotic cover. cannot be used as an EC.30,31 The Cu-IUCD It must be emphasized that EC is not higher cumulative pregnancy rate. When
works by both pre- and post-fertilization an abortifacient and is effective only be- necessary, EC pills can be repeated within effects. It probably causes local inflam- fore a pregnancy is established, although the same menstrual cycle without major matory reaction within the endometrium both pre- and post-fertilization mecha- adverse effects except change in menstruwhich may prevent implantation, as well nisms may be in place for different forms of al bleeding. However, we generally advise as changes in the cervical mucus, thus in- EC. A judicial review in the United Kingdom abstinence or use of a barrier method until hibiting sperm penetration. in 2002 ruled that pregnancy starts at the her next menstrual period. Meanwhile, we time of implantation and not at fertiliza- should emphasize the importance of proper tion. However, some contraceptive users and compliant use of a reliable regular may have a different view and acceptance contraceptive method of her choice. The Hormonal EC is generally very safe, and of this. Although the possible post-ferti- woman should be advised to have a pregthere is no medical contraindication to its lization effects of progesterone receptor nancy test if she misses her next period use. The contraindications associated with modulators and Cu-IUCD would contribute for more than 1 week or if the menstrual
SAFETY OF EC
flow is unusually scanty. Those receiving a Cu-IUCD as an EC should have a routine follow-up after their next expected menstruation to exclude failure or IUCDrelated complications. If the woman wants to keep it for continued contraception, further follow-up is arranged as a routine. Otherwise, removal can be arranged after the next menstruation returns and an alternative contraception started.
convenient location and hours of service providers, and embarrassment. Moreover, time is crucial to the effectiveness of EC. Therefore, over-the-counter sales without the need of prescription as well as advanced provision of EC are advocated. Over-the-counter provision of EC has become the standard practice in parts of America, Britain and Europe, but there is still wide variation in its acceptance across countries. In Hong Kong, our recent studies revealed that only 25.7% of laywomen and 40.2% of doctors supported the over-the-counter provision of EC.
36,37
sion.4244 The most likely reason for this is the lack of awareness by the women towards their risk of pregnancy and hence the underuse of EC despite the availability. Nonetheless, the improved access to EC for women may still help to prevent at least some unplanned pregnancies, particularly among those who are well informed.
CONCLUSION
Modern methods of EC provide a safe and effective back-up for UPSI and contraceptive failure, and should be part of all contraceptive counselling. While the LNG-only regimen is the recommended method in most countries, progesterone receptor modulators have been studied as promising alternatives which may be more effective with a wider treatment window. Insertion of a Cu-IUCD is another alternative. Better education both to laywomen and health care providers, as well as the over-the counter sale and advanced provision, may help to reduce barriers to the access to EC and promote its use when indicated. It must be emphasized that improving access to EC does not encourage its abuse or risky sexual behaviours. About the Authors
Dr Li is Associate Consultant and Subspecialist in Reproductive Medicine, Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong. Dr Lo is Senior Doctor, The Family Planning Association of Hong Kong. Dr Ng is Associate Professor and Subspecialist in Reproductive Medicine, Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong. Professor Ho is Chair Professor and Director of Reproductive Medicine, Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, and President of The Family Planning Association of Hong Kong.
IMPROVING ACCESS TO EC
There are a number of barriers to the use of EC, namely the lack of knowledge, misconceptions, and unfavourable attitudes among women and health care providers, as well as inconvenient access to EC. The lack of knowledge or awareness about EC has been demonstrated both locally and worldwide, and even among those who know about this back-up contraceptive method it is still underutilized.
34
There is still undue concern that deregulated provision would promote irresponsible abuse of EC. Studies have shown that over-the-counter provision of EC did not promote unprotected intercourse or risky sexual behaviour, nor did it compromise the use of regular contraception.
3841
Advanced provision is another means to facilitate the timely use of EC, but its acceptance again varies largely across different ethnic groups. Local studies in Hong Kong revealed that this concept was supported by only 48.7% of laywomen and 54.2% of doctors, and only 32.5% of doctors supported the advanced provision of EC to girls aged 16 or below.
36,37
For instance, a telephone survey in United Kingdom in 1996 reported that only 12% of subjects had used EC at some time. A
35
more recent survey in Hong Kong reported that more than half of the interviewed subjects were aware of EC, but only 15.7% had ever used it. This may be because
36
Studies
of the poor alertness of women about their pregnancy risk, as well as substantial misconception about its side effects and safety, and the false but common association of EC use with casual and irresponsible sex. Inconvenient access is another barrier to the use of EC. In countries where prescription is needed for EC supply, the use can be deterred by lack of time, inJPOG JUL/AUG 2012 174
both locally and worldwide, including a recent Cochrane review, have suggested that advanced provision of EC results in increased and earlier use of EC, without either increasing the risk of UPSI or sexually transmitted infections, or compromising the compliance with regular contraception.42,43 However, advanced provision did not reduce pregnancy or abortion rates when compared with conventional provi-
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Impact on contraceptive practice of making emergency hormonal contraception available over the counter in Great Britain: repeated cross sectional surveys. BMJ 2005;331:271. 39. Harper CC, Cheong M, Rocca CH, et al. The effect of increased access to emergency contraception among young adolescents. Obstet Gynecol 2005;106:483491. 40. Moreau C, Bajos N, Trussell J. The impact of pharmacy access to emergency contraceptive pills in France. Contraception 2006;73:602 608. 41. Ranney ML, Gee EM, Merchant RC. Nonprescription availability of emergency contraception in the United States. Ann Emerg Med 2006;47:461471. 42. Lo SST, Fan SYS, Ho PC, et al. Effect of advanced provision of emergency contraception on womens contraceptive behaviour a randomized controlled trial. Hum Reprod 2004;19:24042410. 43. Polis CB, Grimes DA, Schaffer K, et al. Advance provision of emergency contraception for pregnancy prevention. Cochrane Database Syst Rev 2007;(2):CD005497. 44. Raymond EG, Trussell J, Polis CB. Population effect of increased access to emergency contraceptive pills: a systematic review. Obstet Gynecol 2007;109:181188. dispelling
misconceptions. Bull World Health Organ
CME Questions
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K One CME point will be awarded only to registered candidates for each module according to Category 5 of the MMC-CME Grading System. 3S Artikel CME: P
An Update 3on Emergency Contraception SKP
CME Points: Jawab pertanyaan di bawah ini dengan Benar atau Salah An Update on Emergency Contraception
1. The levonorgestrel-only regimen is superior to the Yuzpe regimen for emergency contraception because of its lower side Please indicate effect profile. on your answer sheet whether the following statements are True or False. 2. The levonorgestrel-only regimen is licensed for use up to 120 hours after unprotected sexual intercourse. 1. The levonorgestrel-only regimen is superior to the Yuzpe regimen for emergency contraception because of its lower side 3. Hormonal methods of emergency contraception are contraindicated in women who are smoking and older than 35 years. effect profile. who are using liver enzyme-inducing drugs and need emergency contraception can be offered an increased 4. 2. Women The levonorgestrel-only regimen is licensed for use up to 120 hours after unprotected sexual intercourse. dose of the levonorgestrel-only emergency contraceptive pill, but this is an off-label use. 3. Hormonal methods of emergency contraception are contraindicated in women who are smoking and older than 35 years. 5. If the emergency contraceptive pill fails and the woman gets pregnant, the pregnancy cannot be continued because of 4. Women who are using liver enzyme-inducing drugs and need emergency contraception can be offered an increased the adverse effects of the drug on the ongoing pregnancy. dose of the levonorgestrel-only emergency contraceptive pill, but this is an off-label use. 6. Low-dose mifepristone (10 or 25 mg) offers the best contraceptive efficacy among the existing regimens. 5. If the emergency contraceptive pill fails and the woman gets pregnant, the pregnancy cannot be continued because of 7. Mifepristone is more effective levonorgestrel for emergency contraception owing to its additional early abortifacient the adverse effects of the drugthan on the ongoing pregnancy. action. 6. Low-dose mifepristone (10 or 25 mg) offers the best contraceptive efficacy among the existing regimens. 8. Both levonorgestrel and progestogen receptor modulators work equally well as emergency contraception when taken 7. Mifepristone is more effective than levonorgestrel for emergency contraception owing to its additional early abortifacient either before or after ovulation. action. 9. Women should be discouraged from obtaining emergency contraceptive pills over the counter because of the potential 8. Both levonorgestrel and progestogen receptor modulators work equally well as emergency contraception when taken risks of abuse and adverse effects. either before or after ovulation. 10. Advanced provision of the emergency contraceptive pill encourages its timely use when indicated without compromising 9. Women should be discouraged from obtaining emergency contraceptive pills over the counter because of the potential the users compliance to regular contraception. risks of abuse and adverse effects. 10. Advanced provision of the emergency contraceptive pill encourages its timely use when indicated without compromising the users compliance to regular contraception.

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JAN/FEB 2012 JUL/aug 2012 Vol. Vol. 38 38 No. No.

Your partner in paediatric and O&G practice

ISSN 1016-0124 (INDONESIA)

Paediatric Psoriasis Managing Headache in Children

Dysmenorrhoea What Are the Benefits and Risks of HRT?

An Update on Emergency Contraception

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

J UL/ AUG 2 0 1 2 Vol. 38 No. 4

JPOG JUL/AUG 2012 i

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

J UL/ AUG 2 0 1 2 Vol. 38 No. 4

Enquiries and Correspondence

Marisa Lam Greg Town

Managing Editor Associate Editor

Agnes Chieng, Sam Shum

Edwin Yu, Ho Wai Hung, Steven Cheung

Minty Kwan Jenny Lim

JPOG JUL/AUG 2012 ii

SGM BBLR dengan

Karena Anda Mengerti yang Terbaik untuk Ananda

Wu, G.; et al. (August 2004.Journal of Nutritional Biochemistry 15 (8): 332-451)

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

J UL/ AUG 2 0 1 2 Vol. 38 No. 4

Continuing Medical Education

169 An Update on Emergency Contraception

Lisa Low, Illustrator

JPOG JUL/AUG 2012 iii

FA Iklan 20,5 x 27,5cm Synflorix-GSK.pdf

PPI use by postmenopausal women increas-

Screening and cervical cancer mortality

JPOG JUL/AUG 2012 133

replacement for smoking cessation during pregnancy. Ibid: 846847 (editorial).

Results of modern paediatric burn care

JPOG JUL/AUG 2012 134

Chlorhexidine to the umbilical cord in developing countries

Moderate or late preterm birth and health outcomes

JPOG JUL/AUG 2012 135

Oral amoxicillin for severe early childhood pneumonia in rural Pakistan

questionnaire was based on previous similar sur-

Paediatricians influence parental febrile behavior

JPOG JUL/AUG 2012 136

PATHOGENESIS AND AETIOLOGY

Figure 1. Typical well-demarcated, salmon-pink patches with silvery scale.

Figure 2. Psoriasis in the concha of the ear.

Figure 3. Napkin psoriasis.

munological basis for disease.

PA ED IATRICS Peer Reviewed

Figure 4. Differential diagnosis. a. Discoid eczema. b. Tinea corporis. c. Pityriasis rosea.

JPOG JUL/AUG 2012 139

Figure 5. Pustular psoriasis requires hospitalization.

PA ED IATRICS Peer Reviewed

Table 1. Criteria for psoriatic arthritis proposed by Vasey and Espinoza

Criterion I: Psoriatic skin or nail involvement Criterion II: Peripheral pattern

Criterion III: Central pattern

Table 2. Possible regimes

psoriasis and then maintaining with minimal or no therapy (Table 2).

All treatments are considered to be suppressive rather than curative

JPOG JUL/AUG 2012 142

PA ED IATRICS Peer Reviewed

Emollients provide prompt relief of scaling or irritated skin.

PA ED IATRICS Peer Reviewed

Further Reading LIGHT TREATMENT

About the Authors

JPOG JUL/AUG 2012 146