WHO Medical Eligibility Criteria for Contraceptive Use

Publication date: 2004

WHO Library Cataloguing-in-Publication Data World Health Organization. Medical eligibility criteria for contraceptive use. -- 3rd ed. 1.Contraception - methods 2.Family planning - methods 3.Eligibility determination - standards 4.Quality assurance, Health care 5.Health services accessibility 6.Guidelines I.Title. ISBN 92 4 156266 8 (NLM classification: WP 630) © World Health Organization 2004 All rights reserved. Publications of the World Health Organization can be obtained from Marketing and Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: bookorders@who.int). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to Publications, at the above address (fax: +41 22 791 4806; email: permissions@who.int). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. The World Health Organization does not warrant that the information contained in this publication is complete and correct and shall not be liable for any damages incurred as a result of its use. Printed in Table of contents Acknowledgements Executive summary and Overview Tables Low-dose combined oral contraceptives (COCs) Combined injectable contraceptives, patch and ring (CICs/P/R) Progestogen-only contraceptives (POCs) Emergency contraceptive pills (ECPs) Intrauterine devices (IUDs) Copper IUD for emergency contraception (E-IUD) Barrier methods (BARR) Fertility awareness-based methods (FAB) Lactational amenorrhoea method (LAM) Coitus interruptus (CI) Surgical sterilization procedures (STER) Summary tables (SUMM) Annex Annex 1. COCs and antiretroviral therapies Annex 2. List of participants Acknowledgements This document is the result of collaboration between the World Health Organization’s Department of Reproductive Health and Research and a large number of international agencies and organizations active in the field of family planning policies and programmes. Funding and other support for this project was provided by the Government of the United States of America (through the US Agency for International Development, the Centers for Disease Control and Prevention, and the National Institute of Child Health and Human Development), the International Planned Parenthood Federation and the United Nations Population Fund. This support is gratefully acknowledged. Representatives of 10 agencies and organizations, along with 19 other individuals, served as experts at the meeting that achieved consensus on these recommendations for contraceptive use. We would like to express our deep appreciation to all of them for contributing their time and expertise towards the consensus-building process. The evidence on which the decisions in this document were based was in large part obtained from systematic reviews of the literature conducted and summarized by Dr KM Curtis, Dr ME Gaffield, Ms AP Mohllajee, Dr K Nanda, and Dr JS Smith, who also provided substantial support to Secretariat. Dr H Peterson was overall coordinator of the project for the WHO Secretariat, which included Ms K Church, Ms K Curran, Ms S Johnson and Ms G Lamptey. Ms C Hamill, who was also a part of Secretariat, contributed substantially to the meeting and was responsible for the design and layout of the publication. Ms M NíMhearáin was responsible for the cover design. We would like to express our deep appreciation to these individuals as well as to Drs L Edouard, C Huezo and J Shelton for their strong support of this endeavour. We are grateful to the following individuals who served as peer reviewers for the Continuous Identification of Research Evidence (CIRE) system: Dr T Chipato, Dr P Corfman, Dr M Cravioto, Dr V Cullins, Dr J Diaz, Dr S Diaz, Dr A Glasier, Dr J Guillebaud, Dr M Gulmezoglu, Dr K Hagenfeldt, Dr P Hannaford, Dr R Hatcher, Dr C Huezo, Dr V Jennings, Dr P Lynam, Dr P Marchbanks, Dr O Meirik, Dr S Mittal, Dr K Nanda, Dr E Otolorin, Dr A Pollack, Dr H Rees, Dr R Rivera, Dr D Skegg, Dr C Smith, Dr B Sood, and Dr E Weisberg. Partial funding for the printing and dissemination of this publication was provided by the United Nations Population Fund and is gratefully acknowledged. For any further information on this publication, please contact the Department of Reproductive Health and Research, World Health Organization, 1211 Geneva 27, Switzerland. Direct fax: + 41 22 791 4189; e-mail: reproductivehealth@who.int Further copies may be obtained from: Documentation Centre, Department of Reproductive Health and Research, World Health Organization, 1211 Geneva 27, Switzerland. Direct fax:+ 41 22 791 4189; telephone: + 41 22 791 4447; e-mail: rhrpublications@who.int. The document is also available through WHO’s reproductive health web site at www.who.int/reproductive-health. Any updates of the information contained in this document will appear in the first instance on this site. Table of contents Executive summary & Overview Executive summary. 1 Overview . 2 Goal . 3 Background . 3 Reproductive and sexual health care . 3 Issues of service quality and access that affect method use. 4 Effectiveness of method. 5 Conditions that expose a woman to increased risk as a result of unintended pregnancy . 8 Return to fertility . 8 STIs and contraception: Dual protection . 9 Method of work. 9 How to use this document. 11 Using the tables .11 Classification of categories.12 Using the categories in practice .13 Programmatic implications . 13 Clients with special needs. 14 Adolescents .14 Summary of changes from the second edition. 15 Medical eligibility criteria for contraceptive use – Page 1 Executive summary This document is one important step in a process for improving access to quality of care in family planning by reviewing the medical eligibility criteria for selecting methods of contraception. It updates the second edition of Improving access to quality care in family planning: medical eligibility criteria for contraceptive use, published in 2000, and summarizes the main recommendations of an expert Working Group meeting held at the World Health Organization, Geneva, 21−24 October 2003. (Please see Annex 2 for the list of participants.) The Working Group brought together 36 participants from 18 countries, including representatives of many agencies and organizations. The document provides recommendations for appropriate medical eligibility criteria based on the latest clinical and epidemiological data and is intended to be used by policy-makers, family planning programme managers and the scientific community. It aims to provide guidance to national family planning/reproductive health programmes in the preparation of guidelines for service delivery of contraceptives. It should not be seen or used as the actual guidelines but rather as a reference. The document covers the following family planning methods: low-dose combined oral contraceptives (COCs), combined injectable contraceptives (CICs), combined patch (P), combined vaginal ring (R), progestogen-only pills (POPs), depot medroxyprogesterone acetate (DMPA), norethisterone enantate (NET-EN), levonorgestrel (LNG) and etonogestrel (ETG) implants, emergency contraceptive pills (ECPs), copper intrauterine devices (Cu- IUDs), levonorgestrel-releasing IUDs (LNG-IUDs), copper-IUD for emergency contraception (E-IUD), barrier methods (BARR), fertility awareness-based methods (FAB), lactational amenorrhoea method (LAM), coitus interruptus (CI), and female and male sterilization (STER). WHO will update and add to the recommendations in this document at appropriate intervals through expert Working Group meetings every three to four years and through input from its family planning Guidelines Steering Group on an as-needed basis. These recommendations will be made available on the WHO web site (www.who.int/reproductive- health). The web site will also provide additional information determined by WHO to be relevant to these recommendations, pending the next formal consensus Working Group meeting. Such updates may be particularly warranted for issues where the evidence base may change rapidly. WHO encourages research to address key unresolved issues for establishing medical eligibility criteria for contraceptive use. WHO also invites comments and suggestions for improving this guidance. Medical eligibility criteria for contraceptive use – Page 2 Overview In 1999, WHO reviewed its family planning guidance and determined that the creation of new evidence-based guidelines was warranted. Accordingly, WHO initiated a new series of evidence-based family planning guidelines beginning with the second edition of Improving access to quality care in family planning. Medical eligibility criteria for contraceptive use, published in 2000. The first two cornerstones of this evidence-based series (Figure 1) are this document, the Medical eligibility criteria for contraceptive use, which provides guidance regarding “who” can use contraceptive methods safely and the Selected practice recommendations for contraceptive use, which provides guidance regarding “how” to use contraceptive methods safely and effectively. These two documents provide evidence- based guidance for choosing (the Medical eligibility criteria for contraceptive use) and for using (the Selected practice recommendations for contraceptive use) contraceptive methods. The third and fourth cornerstones, a decision-making tool for family planning clients and providers and a handbook for family planning providers, are being prepared as practical tools to improve the quality of family planning counselling and service delivery. These two tools incorporate the Medical eligibility criteria for contraceptive use and the Selected practice recommendations for contraceptive use. All four cornerstones are best interpreted and used in a broader context of reproductive and sexual health care. Figure 1. The four cornerstones of family planning guidance Medical eligibility criteria for contraceptive use – Page 3 Goal The goal of this document is to provide policy- and decision-makers and the scientific community with a set of recommendations that can be used for developing or revising national guidelines on medical eligibility criteria for contraceptive use. The document does not provide rigid guidelines but rather gives recommendations that provide a basis for rationalizing the provision of various contraceptives in view of the most up-to-date information available on the safety of the methods for people with certain health conditions. Because country situations and programme environments vary so greatly, it is inappropriate to set firm international guidelines on criteria for contraceptive use. However, it is expected that national programmes will use these for updating or developing their own contraceptive eligibility guidelines in the light of their national health policies, needs, priorities and resources. The intent is to help improve access to, and quality of, family planning services. These improvements must be made within the context of users' informed choices and medical safety. Adaptation is not always an easy task and is best done by those well-acquainted with prevailing health conditions, behaviours, and cultures. Background Over the past 30 years, there have been significant advances in the development of new contraceptive technologies, including transitions from high-dose to low-dose combined oral contraceptives, and from inert to copper- and levonorgestrel-releasing vaginal IUDs. In addition, combined injectable contraceptives, a combined hormonal patch and ring, and progestogen-only injectables and implants have been introduced. However, current policies and health care practices in some countries are based on scientific studies of contraceptive products that are no longer in wide use, on long-standing theoretical concerns that have never been substantiated, or on the personal preference or bias of service providers. These outdated policies or practices often result in limitations to both the quality of, and the access to, family planning services for clients. This document is intended to update the medical eligibility criteria used in the provision of all hormonal contraceptives, IUDs, barrier methods, fertility awareness-based methods, coitus interruptus, lactational amenorrhoea method, male and female sterilization, and emergency contraception. Reproductive and sexual health care “Reproductive rights embrace certain human rights that are already recognised in national laws, international human rights documents and other relevant consensus documents. These rights rest on the recognition of the basic right of all couples and individuals to decide freely and responsibly the number and spacing and timing of their children and to have the information and means to do so, and the right to attain the highest standard of sexual and reproductive health.” (para. 95, Beijing Platform for Action, 1995) Medical eligibility criteria for contraceptive use – Page 4 Reproductive and sexual health care including family planning services and information is recognized not only as a key intervention for improving the health of men, women and children but also as a human right. All individuals have the right to access, choice, and the benefits of scientific progress in the selection of family planning methods. A rights-based approach to the provision of contraceptives assumes a holistic view of clients, which includes taking into account clients’ sexual and reproductive health care needs and considering all appropriate eligibility criteria in helping clients choose and use a family planning method. While this document primarily addresses medical eligibility criteria for contraceptive use, considerations of social, behavioural, and other non-medical criteria, particularly client preference, must be taken into account. To provide contraceptive choices to clients in a way that respects and fulfils their human rights necessitates enabling clients to make informed choices for themselves. Women’s choices, however, are often imposed or limited by direct or indirect social, economic and cultural factors. From the women’s point of view, choices are made in a particular time, societal and cultural context; choices are complex, multifactorial and subject to change. Decision-making for contraceptive methods usually requires the need to make trade-offs among the different methods, with advantages and disadvantages of specific contraceptive methods varying according to individual circumstances, perceptions, and interpretations. Delivery of care in accordance with the client’s human and reproductive rights is fundamental to quality of care. The development of international norms for medical eligibility criteria and practice recommendations for contraceptive use is only one aspect of improving the quality of reproductive health care. Many family planning programmes have included screening, treatment and follow-up procedures that reflect high standards of public health and clinical practice but should not be seen as eligibility requirements for specific contraceptive methods. These procedures include the screening and treatment of cervical cancer, anaemia and sexually transmitted infections (STIs), and the promotion of breastfeeding and cessation of smoking. Such procedures should be strongly encouraged if the human and material resources are available to carry them out, but they should not be seen as prerequisites for the acceptance and use of family planning methods when they are not necessary to establish eligibility for the use or continuation of a particular method. Issues of service quality and access that affect method use While this document chiefly addresses medical eligibility criteria, there are many other considerations in the appropriate provision of contraceptive methods including the following service delivery criteria which are universally relevant to the initiation and follow-up of all contraceptive method use. a) Clients should be given adequate information in order to make an informed, voluntary choice of a contraceptive method. Information given to clients to help them make this choice should at least include: understanding of the relative effectiveness of the method; correct use of the method; how it works; common side-effects; health risks and benefits of the method; signs and symptoms that would necessitate a return to the clinic; information on return to fertility after discontinuing method use; and information on STI protection. Medical eligibility criteria for contraceptive use – Page 5 b) For those methods that require surgical approaches, insertion, fitting and/or removal by a trained health provider (sterilization, implants, IUDs, diaphragms, cervical caps), appropriately trained personnel in adequately equipped facilities must be available in order for those methods to be offered, and appropriate infection prevention procedures must be followed. c) Adequate and appropriate equipment and supplies need to be maintained and held in stock (for example, contraceptive commodities, equipment and supplies for infection prevention procedures). d) Service providers should be provided with guidelines (or client cards or other screening tools) to enable them to screen clients appropriately for conditions in which use of certain contraceptive methods would carry unacceptable health risks. e) Service providers must be trained in providing family planning counselling to help clients make informed and voluntary decisions about their fertility. Counselling is a key element in quality of care and is also an important part of both initiation and follow-up visits and should respond to clients' needs not only in contraception but also related to sexuality and the prevention of STIs, including infection with the human immunodeficiency virus (HIV). Effectiveness of method Contraceptive choice is in part dependent on the effectiveness of the contraceptive method in preventing unplanned pregnancy, which, in turn, is dependent for some methods not only on the protection afforded by the method itself, but also on how consistently and correctly it is used. Table 1 compares the percentage of women experiencing an unintended pregnancy during the first year of contraceptive method use when the method is used perfectly (consistently and correctly) and when it is used typically. Both consistent and correct use can vary greatly with such characteristics as age, income, users' desires to prevent or delay pregnancy, and culture. Methods that depend on consistent and correct use by clients have a wide range of effectiveness. Most men and women tend to be more effective users as they become more experienced with a method. However, programmatic aspects also have a profound effect on how effectively the method will be used. Medical eligibility criteria for contraceptive use – Page 6 Table 1. Percentage of women experiencing an unintended pregnancy during the first year of use and the percentage continuing use at the end of the first year, United States of America. % of women experiencing an unintended pregnancy within the first year of use % of women continuing use at one year3 Method (1) Typical use1 (2) Perfect use2 (3) (4) No method4 85 85 Spermicides5 29 18 42 Withdrawal 27 4 43 Periodic abstinence 25 51 Calendar 9 Ovulation method 3 Sympto-thermal6 2 Post-ovulation 1 Cap7 Parous women 32 26 46 Nulliparous women 16 9 57 Sponge Parous women 32 20 46 Nulliparous women 16 9 57 Diaphragm7 16 6 57 Condom8 Female (Reality) 21 5 49 Male 15 2 53 Combined pill and minipill 8 0.3 68 Combined hormonal patch (Evra) 8 0.3 68 Combined hormonal ring (NuvaRing) 8 0.3 68 DMPA (Depo-Provera) 3 0.3 56 Combined injectable (Lunelle) 3 0.05 56 IUD ParaGard (copper T) 0.8 0.6 78 Mirena (LNG-IUS) 0.1 0.1 81 LNG implants (Norplant and Norplant-2) 0.05 0.05 84 Female sterilization 0.5 0.5 100 Male sterilization 0.15 0.10 100 Emergency contraceptive pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%. Lactational amenorrhea method: LAM is a highly effective, temporary method of contraception.9 Source: Trussell J. Contraceptive efficacy. In Hatcher RA, Trussell J, Stewart F, Nelson A, Cates W, Guest F, Kowal D. Contraceptive Technology: Eighteenth Revised Edition. New York NY: Ardent Media, 2004. Note: This table has been adapted from the source document by changing the title, changing the trade names of methods to generic names and by modifying footnotes. Medical eligibility criteria for contraceptive use – Page 7 Notes: 1 Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. Estimates of the probability of pregnancy during the first year of typical use for spermicides, withdrawal, periodic abstinence, the diaphragm, the male condom, the pill, and Depo-Provera are taken from the 1995 National Survey of Family Growth corrected for underreporting of abortion; see original source (Trussel J, 2004) cited above for the derivation of the estimates for the other methods. 2 Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason; see original source (Trussel J, 2004) cited above for the derivation of the estimates for each method. 3 Among couples attempting to avoid pregnancy, the percentage who continue to use a method for 1 year. 4 The percentages becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among populations where contraception is not used, about 89% become pregnant within 1 year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within 1 year among women now relying on reversible methods of contraception if they abandoned contraception altogether. 5 Foams, creams, gels, vaginal suppositories, and vaginal film. 6 Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. 7 With spermicidal cream or jelly. 8 Without spermicides. 9 However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches 6 months of age. Medical eligibility criteria for contraceptive use – Page 8 Conditions that expose a woman to increased risk as a result of unintended pregnancy Women with conditions that may make pregnancy an unacceptable health risk should be advised that, because of their relatively higher typical-use failure rates, sole use of barrier methods for contraception and behaviour-based methods of contraception may not be the most appropriate choice for them. These conditions are noted in Table 2. Table 2. Conditions that expose a woman to increased risk as a result of unintended pregnancy Breast cancer Complicated valvular heart disease Diabetes: insulin-dependent; with nephropathy/retinopathy/neuropathy or other vascular disease; or of > 20 years' duration Endometrial or ovarian cancer High blood pressure (systolic >160 mm Hg or diastolic >100 mm Hg)† HIV/AIDS* Ischaemic heart disease Malignant gestational trophoblastic disease Malignant liver tumours (hepatoma) Schistosomiasis with fibrosis of the liver Severe (decompensated) cirrhosis Sickle cell disease STI* Stroke Thrombogenic mutations Tuberculosis † Throughout this document, blood pressure measurements are given in mm Hg. To convert to kPa, multiply by 0.1333. For example, 120/80 mm Hg = 16.0/10.7 kPa. * Dual protection is strongly recommended for protection against HIV/AIDS and other STIs when a risk of STI/HIV transmission exists. This can be achieved through the simultaneous use of condoms with other methods or the consistent and correct use of condoms alone. Return to fertility The use of contraceptive methods, with the exception of male and female sterilization, does not result in an irreversible change in fertility. Return to fertility is prompt with all methods, with the exception of DMPA and NET-EN; the median delay in return to fertility with these methods is 10 and 6 months, respectively, from the date of the last injection, regardless of the duration of their use. Male and female sterilization should be regarded as permanent methods and all individuals and couples considering these methods should be counselled accordingly. No other methods result in permanent infertility. Medical eligibility criteria for contraceptive use – Page 9 STIs and contraception: Dual protection While the development of international norms for contraceptive provision is essential for quality of care in services, the social, cultural and behavioural context of each client must also be considered. In this regard, the problems of exposure to STIs, including HIV, deserve special consideration because of the equal importance of preventing pregnancy and preventing transmission of infection. When a risk of STI/HIV transmission exists, it is important that health care providers strongly recommend dual protection to all persons at significant risk, either through the simultaneous use of condoms with other methods or through the consistent and correct use of condoms alone for both pregnancy prevention and disease prevention. Women and men seeking contraceptive advice must always be reminded of the importance of condom use for preventing the transmission of STI/HIV and such use should be encouraged and facilitated where appropriate. Male latex condoms are proven to be highly effective against STI/HIV when used consistently and correctly. Method of work This document builds on a process initiated in 1994 that culminated in the 1996 publication of the document, Improving access to quality care in family planning: medical eligibility criteria for contraceptive use. In the initial process, which was created to reach agreement on appropriate eligibility criteria for widely used contraceptive methods, a number of agencies and organizations collaborated in an in-depth review of the epidemiological and clinical evidence relevant to medical eligibility criteria of well established contraceptive methods. The process involved comparing the eligibility criteria used by different agencies for various contraceptives, preparing summaries of published medical and epidemiological literature relevant to medical eligibility criteria, and preparing a draft classification for review by a larger group of experts and agencies. Two expert Working Group meetings were organized by WHO, in March 1994 and May 1995, to review the background classifications and to formulate recommendations; publication of the document followed in 1996. The first revision of the 1996 document was based on the recommendations of an expert Working Group meeting held at WHO on 8-10 March 2000, that brought together 32 participants from 17 countries, including representatives of many agencies and organizations. The Working Group reviewed new evidence since the last Working Group meetings in 1994 and 1995. This new evidence was primarily obtained from a systematic review of the most recent literature, which was conducted to identify and summarize new evidence for medical eligibility criteria of contraceptive methods. This third edition of the document is based on the recommendations of an expert Working Group meeting held at WHO on 21–24 October 2003, that brought together 36 participants from 18 countries, including representatives of many agencies and organizations. The Working Group was comprised of international family planning experts, including clinicians, epidemiologists, policy-makers and programme experts. The Working Group also included experts in evidence identification and synthesis and users of the guideline. A Guideline Steering Group was established for this edition. All members of the Working Group were asked to declare conflicts of interests and none were declared. Using a system to identify new evidence on an ongoing basis (the Continuous Identification of Research Evidence or CIRE, www.infoforhealth.org/cire/cire_pub.pl), WHO identified 151 Medical eligibility criteria for contraceptive use – Page 10 current recommendations for which new evidence was available since the second edition. WHO also decided to develop recommendations for 3 new conditions and 3 new contraceptive methods in this third edition. Systematic reviews were conducted to appraise the complete body of evidence for these 151 recommendations and for the new conditions and new methods. A systematic, comprehensive search of bibliographic databases, such as MEDLINE, yielded all primary studies, through August 2003, that described use of contraceptive methods among women with certain conditions (e.g., the risk of stroke for women with migraines who use COCs). The purpose of these systematic reviews was to identify direct evidence for the appropriateness of contraceptive method use by women with selected conditions. Information on indirect evidence or theoretical considerations was obtained for these recommendations when direct evidence was sought but not available. The strength and quality of the evidence was graded using the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) system (www.gradeworkinggroup.org). The grading of the evidence was provided to the Working Group as each relevant recommendation was considered. Issues of cost were considered primarily in terms of availability and access to contraceptive services, as well as potential resource constraints. Programmatic implications of the recommendations were also considered by the Working Group. The recommendations primarily concern safety issues and these issues were considered in light of their applicability in a variety of settings. For most recommendations (method/condition combinations), there are a limited number of studies that address the use of a specific method by women with a specific condition. Thus, most of the decisions regarding eligibility criteria using evidence were often necessarily based on extrapolations from studies that primarily included healthy women, as well as on theoretical considerations and expert opinion. Evidence was particularly limited for newer products and for those with limited usage. The total body of evidence considered by the Working Group included: „ evidence based on direct studies or observations of the contraceptive method used by women (or men) with the condition; „ evidence derived from effects of the contraceptive method used by women (or men) without the condition; „ indirect evidence or theoretical concerns based on studies of suitable animal models, human laboratory studies, or analogous clinical situations. Where the Working Group had a systematic review of the evidence to consider as they made a recommendation, the evidence is cited in this document alongside the recommendation. The recommendations for which no evidence is cited were based on expert opinion and/or evidence obtained from sources other than systematic reviews. As noted below, over 1000 of the recommendations in this edition are unchanged from those made in the first edition. The evidence for the first edition was provided to the 1994 and 1995 Working Groups in a series of background papers prepared for the project. The second edition included 1287 recommendations. These recommendations are widely used globally and, therefore, WHO determined that any changes should be based on new evidence unless there was a compelling reason to do otherwise. The Guideline Steering Group, which convened on 21 October 2003, proposed that the expert Working Group consider only those recommendations from the second edition for which there was new evidence or for which a compelling case had been made. The Working Group concurred Medical eligibility criteria for contraceptive use – Page 11 with this proposal on 22 October and, thus, the remainder of the Working Group meeting was focused on 151 current recommendations, three new conditions and three new contraceptive methods. The Working Group was charged with determining the eligibility criteria for each condition and method of contraception by selecting a category (1 through 4, as described below). Where the Working Group determined that guidance in addition to the category was required, that guidance was provided by the Working Group as a "Clarification". Where new evidence was considered by the Working Group, this evidence has been summarized and presented under the heading “Evidence,” in the column labelled "Clarifications/Evidence”. In addition to the clarifications of guidance and the summaries of the evidence, comments have been provided at the end of each contraceptive method section by the WHO Secretariat for selected methods/conditions. The final list of 1705 recommendations was approved by all members of the Guideline Steering Group and the Working Group at the completion of the meeting on 24 October 2003. How to use this document The present document is intended to be used by policy-makers, family planning programme managers and the scientific community. It aims to provide guidance to national family planning/reproductive health programmes in the preparation of guidelines for service delivery of contraceptives. It should not be seen or used as the actual guidelines but rather as a reference. The guidance in this document is intended for interpretation at country and programme levels in a manner that reflects the diversity of situations and settings in which contraceptives are provided. While it is unlikely that the classification of categories in this document would change during this process, it is very likely that the application of these categories at country level will vary. In particular, the level of clinical knowledge and experience of various types of providers and the resources available at the service delivery point will have to be taken into consideration. Using the tables The Working Group addressed medical criteria for the initiation and continuation of use of all methods evaluated. The issue of continuation criteria is clinically relevant whenever a woman develops the condition while she is using the method. When the Working Group determined that categories for initiation and continuation were different, these differences are noted in the columns 'I=Initiation' and 'C=Continuation'. Where I and C are not denoted, the category is the same for initiation and continuation of use. On the basis of this classification system, the eligibility criteria for initiating and continuing use of a specific contraceptive method are presented in this document in a set of tables. The first column indicates the condition. Several conditions were subdivided to differentiate between varying degrees of the condition. The second column classifies the condition for Medical eligibility criteria for contraceptive use – Page 12 initiation and/or continuation into one of the four categories described below. If necessary, the third column gives clarification or evidence regarding the classification, as described in the section above. A summary table is included at the end of the document covering medical eligibility criteria by condition for hormonal methods and IUDs. A summary of the conditions or categories that were revised for this edition is included at the end of this section. TYPE OF CONTRACEPTIVE CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/ EVIDENCE Condition Condition classified from 1 to 4 The categories for fertility awareness-based methods and surgical sterilization are described at the beginning of the relevant section. Clarifications and evidence regarding the classification NA denotes a condition for which a ranking was not given by the Working Group but for which clarifications have been provided. Classification of categories The medical eligibility criteria in this document were based on the method of work described above and aim to ensure an adequate margin of safety. Each condition was defined as representing either an individual's characteristics (e.g., age, history of pregnancy) or a known pre-existing medical/pathological condition (e.g., diabetes, hypertension). It is expected that national and institutional health and service delivery environments will decide the most suitable means for screening for conditions according to their public health importance. Client history will often be the most appropriate approach. The conditions affecting eligibility for the use of each contraceptive method were classified under one of the following four categories: 1. A condition for which there is no restriction for the use of the contraceptive method. 2. A condition where the advantages of using the method generally outweigh the theoretical or proven risks. 3. A condition where the theoretical or proven risks usually outweigh the advantages of using the method. 4. A condition which represents an unacceptable health risk if the contraceptive method is used. Medical eligibility criteria for contraceptive use – Page 13 Using the categories in practice Categories 1 and 4 are self-explanatory. Classification of a method/condition as category 2 indicates the method can generally be used, but careful follow-up may be required. However, provision of a method to a woman with a condition classified as category 3 requires careful clinical judgement and access to clinical services; for such a woman, the severity of the condition and the availability, practicality, and acceptability of alternative methods should be taken into account. For a method/condition classified as category 3, use of that method is not usually recommended unless other more appropriate methods are not available or acceptable. Careful follow-up will be required. Where resources for clinical judgement are limited, such as in community-based services, the four-category classification framework can be simplified into two categories. With this simplification, a classification of Category 3 indicates that a woman is not medically eligible to use the method. CATEGORY WITH CLINICAL JUDGEMENT WITH LIMITED CLINICAL JUDGEMENT 1 Use method in any circumstances 2 Generally use the method Yes (Use the method) 3 Use of method not usually recommended unless other more appropriate methods are not available or not acceptable 4 Method not to be used No (Do not use the method) Programmatic implications Programmatic issues that need to be addressed include: „ informed choice, „ elements of quality of care, „ essential screening procedures for administering the methods, „ provider training and skills, „ referral and follow-up for contraceptive use as appropriate. In the application of the eligibility criteria to programmes, service delivery practices that are essential for the safe use of the contraceptive should be distinguished from practices that may be appropriate for good health care but are not related to use of the method. The promotion of good health care practices unrelated to safe contraception should be considered neither as a prerequisite nor as an obstacle to the provision of a contraceptive method, but as complementary to it. Medical eligibility criteria for contraceptive use – Page 14 As a next step, the recommendations on eligibility criteria need to be considered in light of country circumstances, so as to be applicable to providers at all levels of the service delivery system. Countries will need to determine how far and by what means it may be possible to extend their services to the more peripheral levels. This may involve upgrading both staff and facilities where feasible and affordable, or may require the extension of the skills of certain categories of health personnel or a modest addition of equipment and supplies, and redeployment of space. It will also be necessary to address questions of misperceptions sometimes held by providers and users on the risks and side-effects of the methods and to look closely at the needs and perspectives of women and men in the context of informed choice. Clients with special needs Medical eligibility criteria address contraceptive use by people with specific medical conditions. In addition, contraceptive provision to people with special needs requires further consideration. Individuals with a physical disability represent such a group. Decisions on appropriate contraception must take into account the nature of the disability, the expressed desires of the individual and the nature of the method. Decisions must be based on informed choice. Similar considerations should be given to individuals with mental disability or with serious psychiatric disease. Where the nature of the condition does not allow for informed choice, contraceptives should be provided only after full discussion with all parties including guardians or care-givers. The reproductive rights of the individual must be considered in any such decisions. Adolescents In general, adolescents are eligible to use any method of contraception and must have access to a variety of contraceptive choices. Age alone does not constitute a medical reason for denying any method to adolescents. While some concerns have been expressed regarding the use of certain contraceptive methods in adolescents (e.g., the use of progestogen-only injectables by those below 18 years), these concerns must be balanced against the advantages of avoiding pregnancy. It is clear that many of the same eligibility criteria that apply to older clients apply to young people. However, some conditions (e.g., cardiovascular disorders) that may limit use of some methods in older women do not generally affect young people since these conditions are rare in this age group. Social and behavioural issues should be important considerations in the choice of contraceptive methods by adolescents. For example, in some settings, adolescents are also at increased risk for STIs, including HIV. While adolescents may choose to use any one of the contraceptive methods available in their communities, in some cases, using methods that do not require a daily regimen may be more appropriate. Adolescents, married or unmarried, have also been shown to be less tolerant of side-effects and therefore have high discontinuation rates. Method choice may also be influenced by factors such as sporadic patterns of intercourse and the need to conceal sexual activity and contraceptive use. For instance, sexually active adolescents who are unmarried have very different needs from those who are married and want to postpone, space or limit pregnancy. Expanding the number of method choices offered can lead to improved satisfaction, increased acceptance and increased prevalence of contraceptive use. Proper education and counselling both before and at the time of method selection can help adolescents address their specific Medical eligibility criteria for contraceptive use – Page 15 problems and make informed and voluntary decisions. Every effort should be made to prevent service and method costs from limiting the options available. Summary of changes from the second edition A summary of the classification changes or major condition modifications from the second edition is given in Table 3. It is recognized that some of the eligibility criteria in this report will need to be reviewed in the light of new research findings from studies being completed and/or currently in progress. It is intended that this document will be updated on a continual basis in order to reflect the latest scientific evidence and findings. Medical eligibility criteria for contraceptive use – Page 16 Table 3. Summary of changes from the second edition (Conditions for which there was a classification change for one or more methods or a major modification to the condition description. Changed classifications are highlighted in blue.) CONDITION COC CIC POP DMPA NET-EN LNG/ ETG Cu-IUD LNG-IUD I = Initiation, C = Continuation PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY OBESITY >30 kg/m2 body mass index (BMI) 2 2 1 1 1 1 1 CARDIOVASCULAR DISEASE KNOWN THROMBOGENIC MUTATIONS (e.g. Factor V Leiden; Prothrombin mutation; Protein S, Protein C and Antithrombin deficiencies) 4 4 2 2 2 1 2 DEPRESSIVE DISORDERS DEPRESSIVE DISORDERS 1 1 1 1 1 1 1 REPRODUCTIVE TRACT INFECTIONS AND DISORDERS UTERINE FIBROIDS a) Without distortion of the uterine cavity 1 1 1 1 1 1 1 b) With distortion of the uterine cavity 1 1 1 1 1 4 4 PELVIC INFLAMMATORY DISEASE (PID) a) Past PID (assuming no current risk factors of STIs) I C I C (i) with subsequent pregnancy 1 1 1 1 1 1 1 1 1 ii) without subsequent pregnancy 1 1 1 1 1 2 2 2 2 b) PID - current 1 1 1 1 1 4 2 4 2 Medical eligibility criteria for contraceptive use – Page 17 CONDITION COC CIC POP DMPA NET-EN LNG/ ETG Cu-IUD LNG-IUD I = Initiation, C = Continuation STIs I C I C a) Current purulent cervicitis or chlamydial infection or gonorrhoea 1 1 1 1 1 4 2 4 2 b) Other STIs (excluding HIV and hepatitis) 1 1 1 1 1 2 2 2 2 c) Vaginitis (including trichomonas vaginalis and bacterial vaginosis) 1 1 1 1 1 2 2 2 2 d) Increased risk of STIs 1 1 1 1 1 2/3 2 2/3 2 HIV/AIDS I C I C HIGH RISK OF HIV 1 1 1 1 1 2 2 2 2 HIV-INFECTED 1 1 1 1 1 2 2 2 2 AIDS 1 1 1 1 1 3 2 3 2 Clinically well on ARV therapy See ANTIRETROVIRAL THERAPY below 2 2 2 2 DRUG INTERACTIONS DRUGS WHICH AFFECT LIVER ENZYMES a) Rifampicin 3 2 3 2 3 1 1 b) Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine) 3 2 3 2 3 1 1 ANTIBIOTICS (excluding rifampicin) a) Griseofulvin 2 1 2 1 2 1 1 b) Other antibiotics 1 1 1 1 1 1 1 I C I C ANTIRETROVIRAL THERAPY 2 2 2 2 2 2/3 2 2/3 2 Medical eligibility criteria for contraceptive use – Page 18 In addition, the following changes were made which are not included in the summary of changes: 1. Patch, ring and etonogestrel implants Three new methods (patch, ring and etonogestrel implants) were added. The patch and ring are grouped with CICs but are given the same category ratings as COCs. The etonogestrel implants are grouped with, and are given the same category ratings as, the levonorgestrel implants. 2. Barrier methods For the conditions of high risk of HIV, HIV-infected, and AIDS, spermicide use is a Category 4. For the conditions of high risk of HIV, HIV-infected, and AIDS, diaphragm (with spermicide) and cervical cap are Category 3. 3. Female surgical sterilization The condition of known thrombogenic mutations (e.g. Factor V Leiden; Prothrombin mutation; Protein S, Protein C, and Antithrombin deficiencies) has been added for female surgical sterilization and is Category A. The condition of depressive disorders has been added for female surgical sterilization and is a Category C. For the condition of other STIs (excluding HIV and hepatitis), female surgical sterilization is Category A. For the condition of previous abdominal or pelvic surgery, female surgical sterilization is Category C. 4. Male surgical sterilization The condition of young age has been added for male surgical sterilization and is Category C. The condition of depressive disorders has been added for male surgical sterilization and is Category C. Table of contents Low-dose combined oral contraceptives PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY . 1 Pregnancy.1 Age .1 Parity.1 Breastfeeding.1 Postpartum .1 Post-abortion.1 Past ectopic pregnancy.1 History of pelvic surgery.1 Smoking.2 Obesity.2 Blood pressure measurement unavailable.2 CARDIOVASCULAR DISEASE. 2 Multiple risk factors for arterial cardiovascular disease.2 Hypertension.2 History of high blood pressure during pregnancy.3 Deep venous thrombosis (DVT)/pulmonary embolism (PE).3 Known thrombogenic mutations.4 Superficial venous thrombosis .4 Current and history of ischaemic heart disease .4 Stroke .4 Known hyperlipidaemias .4 Valvular heart disease .4 NEUROLOGIC CONDITIONS. 5 Headaches.5 Epilepsy .5 DEPRESSIVE DISORDERS . 5 Depressive disorders .5 REPRODUCTIVE TRACT INFECTIONS AND DISORDERS. 5 Vaginal bleeding patterns .5 Unexplained vaginal bleeding .6 Endometriosis .6 Benign ovarian tumours .6 Severe dysmenorrhoea.6 Trophoblast disease.6 Cervical ectropion .6 Cervical intraepithelial neoplasia (CIN) .6 Cervical cancer .6 Breast disease .6 Endometrial cancer .7 Ovarian cancer.7 Uterine fibroids.7 Pelvic inflammatory disease (PID) .7 STIs .7 HIV/AIDS . 8 High risk of HIV.8 HIV-infected .8 AIDS .8 OTHER INFECTIONS . 8 Schistosomiasis .8 Tuberculosis.8 Malaria .8 ENDOCRINE CONDITIONS . 9 Diabetes.9 Thyroid disorders .9 GASTROINTESTINAL CONDITIONS . 9 Gall-bladder disease .9 History of cholestasis .9 Viral hepatitis .9 Cirrhosis.10 Liver tumours .10 ANAEMIAS. 10 Thalassaemia.10 Sickle cell disease.10 Iron-deficiency anaemia.10 DRUG INTERACTIONS . 10 Drugs which affect liver enzymes.10 Antibiotics .10 Antiretroviral therapy.11 Additional comments . 12 References for low-dose combined oral contraceptives. 14 * See also additional comments at end of table Low-dose combined oral contraceptives – Page 1 LOW-DOSE COMBINED ORAL CONTRACEPTIVES LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY PREGNANCY NA Clarification: Use of COCs is not required. There is no known harm to the woman, the course of her pregnancy, or the fetus if COCs are accidentally used during pregnancy. AGE* a) Menarche to < 40 years 1 b) > 40 years 2 PARITY a) Nulliparous 1 b) Parous 1 BREASTFEEDING* a) < 6 weeks postpartum 4 b) > 6 weeks to < 6 months postpartum (primarily breastfeeding) 3 c) > 6 months postpartum 2 POSTPARTUM* (in non-breastfeeding women) a) < 21 days 3 b) > 21 days 1 POST-ABORTION a) First trimester 1 Clarification: COCs may be started immediately post- abortion. b) Second trimester 1 c) Immediate post- septic abortion 1 PAST ECTOPIC PREGNANCY* 1 HISTORY OF PELVIC SURGERY 1 * See also additional comments at end of table Page 2 – Low-dose combined oral contraceptives LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE SMOKING a) Age < 35 years 2 b) Age > 35 years (i) <15 cigarettes/day 3 (ii) >15 cigarettes/day 4 Evidence: COC users who smoked were at increased risk of cardiovascular diseases, especially myocardial infarction, compared with those who did not smoke. Studies also showed an increased risk of myocardial infarction with increasing number of cigarettes smoked per day.1-12 OBESITY > 30 kg/m2 body mass index (BMI) 2 Evidence: Obese women who used COCs were at increased risk of VTE compared with non-users. The absolute risk of VTE remained small. Data are limited regarding the impact of obesity on COC effectiveness.6, 13, 14 BLOOD PRESSURE MEASUREMENT UNAVAILABLE NA Clarification: It is desirable to have blood pressure measurements taken before initiation of COC use. However, in some settings blood pressure measurements are unavailable. In many of these settings pregnancy morbidity and mortality risks are high, and COCs are one of the few methods widely available. In such settings, women should not be denied use of COCs simply because their blood pressure cannot be measured. CARDIOVASCULAR DISEASE MULTIPLE RISK FACTORS FOR ARTERIAL CARDIOVASCULAR DISEASE (such as older age, smoking, diabetes and hypertension) 3/4 Clarification: When a woman has multiple major risk factors, any of which alone would substantially increase the risk of cardiovascular disease, use of COCs may increase her risk to an unacceptable level. However, a simple addition of categories for multiple risk factors is not intended; for example, a combination of two risk factors assigned a category 2 may not necessarily warrant a higher category. HYPERTENSION* For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist, risk of cardiovascular disease may increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive. a) History of hypertension, where blood pressure CANNOT be evaluated (including hypertension in pregnancy) 3 Clarification: Evaluation of cause and level of hypertension is recommended, as soon as feasible. Evidence: Women who did not have a blood pressure check before COC use had an increased risk of acute myocardial infarction and stroke.15-19 * See also additional comments at end of table Low-dose combined oral contraceptives – Page 3 LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE HYPERTENSION (Cont’d) b) Adequately controlled hypertension, where blood pressure CAN be evaluated 3 Clarification: Women adequately treated for hypertension are at reduced risk of acute myocardial infarction and stroke as compared with untreated women. Although there are no data, COC users with adequately controlled and monitored hypertension should be at reduced risk of acute myocardial infarction and stroke compared with untreated hypertensive COC users. c) Elevated blood pressure levels (properly taken measurements) (i) systolic 140-159 or diastolic 90-99 3 Evidence: Among women with hypertension, COC users were at increased risk of stroke, acute myocardial infarction, and peripheral arterial disease compared with non-users.1, 3, 9-11, 15-31 (ii) systolic >160 or diastolic >100 4 d) Vascular disease 4 HISTORY OF HIGH BLOOD PRESSURE DURING PREGNANCY (where current blood pressure is measurable and normal) 2 Evidence: Women who had a history of high blood pressure in pregnancy, who also used COCs, had an increased risk of myocardial infarction and venous thromboembolism, compared with COC users who did not have a history of high blood pressure during pregnancy. The absolute risks of acute myocardial infarction and venous thromboembolism in this population remained small.11, 17-19, 21, 32-37 DEEP VENOUS THROMBOSIS (DVT)/ PULMONARY EMBOLISM (PE)* a) History of DVT/PE 4 b) Current DVT/PE 4 c) Family history of DVT/PE (first-degree relatives) 2 d) Major surgery (i) with prolonged immobilization 4 (ii) without prolonged immobilization 2 e) Minor surgery without immobilization 1 * See also additional comments at end of table Page 4 – Low-dose combined oral contraceptives LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE KNOWN THROMBOGENIC MUTATIONS (e.g., Factor V Leiden; Prothrombin mutation; Protein S, Protein C, and Antithrombin deficiencies) 4 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening. Evidence: Among women with thrombogenic mutations, COC users had a two to twenty-fold higher risk of thrombosis than non-users.38-51 SUPERFICIAL VENOUS THROMBOSIS* a) Varicose veins 1 b) Superficial thrombophlebitis 2 CURRENT AND HISTORY OF ISCHAEMIC HEART DISEASE* 4 STROKE* (history of cerebrovascular accident) 4 KNOWN HYPERLIPIDAEMIAS 2/3 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening. While some types of hyperlipidaemias are risk factors for vascular disease, the category should be assessed according to the type, its severity, and the presence of other cardiovascular risk factors. VALVULAR HEART DISEASE* a) Uncomplicated 2 b) Complicated (pulmonary hypertension, risk of atrial fibrillation, history of subacute bacterial endocarditis) 4 * See also additional comments at end of table Low-dose combined oral contraceptives – Page 5 LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE NEUROLOGIC CONDITIONS HEADACHES* I C a) Non-migrainous (mild or severe) 1 2 Clarification: Classification depends on accurate diagnosis of those severe headaches that are migrainous and those that are not. Any new headaches or marked changes in headaches should be evaluated. Classification is for women without any other risk factors for stroke. Risk of stroke increases with age, hypertension and smoking. b) Migraine (i) without aura Age < 35 2 3 Age > 35 3 4 (ii) with aura, at any age 4 4 Evidence: Among women with migraine, women who also had aura had a higher risk of stroke than those without aura.52-54 Among women with migraine, those who used COCs had a 2 to 4-fold increased risk of stroke compared with women who did not use COCs.20, 26-28, 53-58 EPILEPSY 1 Clarification: If a woman is taking anticonvulsants, refer to the section on drug interactions. Certain anticonvulsants lower COC effectiveness. DEPRESSIVE DISORDERS DEPRESSIVE DISORDERS 1 Clarification: The classification is based on data for women with selected depressive disorders. No data on bipolar disorder or postpartum depression were available. There is a potential for drug interactions between certain antidepressant medications and hormonal contraceptives. Evidence: COC use did not increase depressive symptoms in women with depression compared to baseline or to non- users with depression.59-61 REPRODUCTIVE TRACT INFECTIONS AND DISORDERS VAGINAL BLEEDING PATTERNS* a) Irregular pattern without heavy bleeding 1 b) Heavy or prolonged bleeding (includes regular and irregular patterns) 1 Clarification: Unusually heavy bleeding should raise the suspicion of a serious underlying condition. * See also additional comments at end of table Page 6 – Low-dose combined oral contraceptives LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE UNEXPLAINED VAGINAL BLEEDING* (suspicious for serious condition) Before evaluation 2 Clarification: If pregnancy or an underlying pathological condition (such as pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation. ENDOMETRIOSIS* 1 BENIGN OVARIAN TUMOURS (including cysts) 1 SEVERE DYSMENORRHOEA 1 Evidence: There was no increased risk of side-effects with COC use among women with dysmenorrhoea compared to women not using COCs. Some COC users had a reduction in pain and bleeding.62, 63 TROPHOBLAST DISEASE a) Benign gestational trophoblastic disease 1 b) Malignant gestational trophoblastic disease 1 Evidence: Among women with benign or malignant gestational trophoblastic disease, there was no difference in mean times to hCG normalization or incidence of postmolar trophoblastic disease for COC users compared to non- hormonal users.64-71 CERVICAL ECTROPION* 1 CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) 2 Evidence: Among women with persistent HPV infection, long-term COC use (> 5 years) may increase the risk of carcinoma in situ and invasive carcinoma.72 CERVICAL CANCER* (awaiting treatment) 2 BREAST DISEASE* a) Undiagnosed mass 2 Clarification: Evaluation should be pursued as early as possible. b) Benign breast disease 1 c) Family history of cancer 1 Evidence: Among COC users with a family history of breast cancer, there was no increased risk of breast cancer compared with non-COC users with a family history of breast cancer.73-80 Among women with BRCA1 mutations, COC users may have a small increased risk of breast cancer compared with non-users.81-83 * See also additional comments at end of table Low-dose combined oral contraceptives – Page 7 LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE BREAST DISEASE (Cont’d) d) Breast cancer (i) current 4 (ii) past and no evidence of current disease for 5 years 3 ENDOMETRIAL CANCER* 1 OVARIAN CANCER* 1 UTERINE FIBROIDS* a) Without distortion of the uterine cavity 1 b) With distortion of the uterine cavity 1 PELVIC INFLAMMATORY DISEASE (PID)* a) Past PID (assuming no current risk factors for STIs) (i) with subsequent pregnancy 1 (ii) without subsequent pregnancy 1 b) PID - current 1 STIs* a) Current purulent cervicitis or chlamydial infection or gonorrhoea 1 b) Other STIs (excluding HIV and hepatitis) 1 * See also additional comments at end of table Page 8 – Low-dose combined oral contraceptives LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE STIs (Cont’d) c) Vaginitis (including trichomonas vaginalis and bacterial vaginosis) 1 d) Increased risk of STIs 1 Evidence: Evidence suggests that there may be an increased risk of chlamydial cervicitis among COC users at high risk of STIs. For other STIs, there is either evidence of no association between COC use and STI acquisition or limited evidence to draw any conclusions.84-160 HIV/AIDS HIGH RISK OF HIV* 1 Evidence: Overall, evidence is inconsistent regarding whether there is any increased risk of HIV acquisition among COC users compared with non-users.161-198 HIV-INFECTED 1 Evidence: Limited evidence suggests no association between COC use and changes in RNA levels or CD4 counts among HIV-infected women. There is also limited evidence showing no association between COC use and female to male HIV transmission, and mixed results regarding increased risk of HIV and herpes simplex virus (HSV) shedding among HIV-infected women using hormonal contraception.161, 199-204 AIDS 1 On ARV therapy 2 Clarification: If a woman is taking antiretroviral (ARV) therapy, refer to the section on drug interactions. Because there may be drug interactions between hormonal contraceptives and ARVs, AIDS with ARV therapy is classified as Category 2. OTHER INFECTIONS SCHISTOSOMIASIS a) Uncomplicated 1 Evidence: Among women with uncomplicated schistosomiasis, COC use had no adverse effects on liver function.205-211 b) Fibrosis of liver (if severe, see cirrhosis) 1 TUBERCULOSIS a) Non-pelvic 1 b) Known pelvic 1 Clarification: If a woman is taking rifampicin, refer to the section on drug interactions. Rifampicin is likely to decrease COC effectiveness. MALARIA 1 * See also additional comments at end of table Low-dose combined oral contraceptives – Page 9 LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE ENDOCRINE CONDITIONS DIABETES* a) History of gestational disease 1 b) Non-vascular disease (i) non-insulin dependent 2 (ii) insulin dependent 2 c) Nephropathy/ retinopathy/ neuropathy 3/4 Clarification: The category should be assessed according to the severity of the condition. d) Other vascular disease or diabetes of > 20 years' duration 3/4 Clarification: The category should be assessed according to the severity of the condition. THYROID DISORDERS a) Simple goitre 1 b) Hyperthyroid 1 c) Hypothyroid 1 GASTROINTESTINAL CONDITIONS GALL-BLADDER DISEASE* a) Symptomatic (i) treated by cholecystectomy 2 (ii) medically treated 3 (iii) current 3 b) Asymptomatic 2 HISTORY OF CHOLESTASIS* a) Pregnancy-related 2 b) Past COC-related 3 VIRAL HEPATITIS* a) Active 4 b) Carrier 1 * See also additional comments at end of table Page 10 – Low-dose combined oral contraceptives LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE CIRRHOSIS* a) Mild (compensated) 3 b) Severe (decompensated) 4 LIVER TUMOURS* a) Benign (adenoma) 4 b) Malignant (hepatoma) 4 ANAEMIAS THALASSAEMIA* 1 SICKLE CELL DISEASE 2 IRON-DEFICIENCY ANAEMIA* 1 DRUG INTERACTIONS DRUGS WHICH AFFECT LIVER ENZYMES a) Rifampicin 3 b) Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine) 3 Clarification: Although the interaction of rifampicin or certain anticonvulsants with COCs is not harmful to women, it is likely to reduce the effectiveness of COCs. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. Whether increasing the hormone dose of COCs is of benefit remains unclear. Evidence: Use of rifampicin and certain anticonvulsants decreased the contraceptive effectiveness of COCs.212-237 ANTIBIOTICS (excluding rifampicin) a) Griseofulvin 2 b) Other antibiotics 1 Evidence: The contraceptive effectiveness of COCs was not affected by coadministration of most broad-spectrum antibiotics.238-290 * See also additional comments at end of table Low-dose combined oral contraceptives – Page 11 LOW-DOSE COMBINED ORAL CONTRACEPTIVES (COCs) < 35 µg of ethinylestradiol COCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CONDITION CATEGORY I=Initiation C=Continuation CLARIFICATIONS/EVIDENCE ANTIRETROVIRAL THERAPY 2 Clarification: It is important to note that antiretroviral drugs (ARV) have the potential to either decrease or increase the bioavailability of steroid hormones in hormonal contraceptives. The limited data available (outlined in Annex 1) suggest that potential drug interactions between many ARVs (particularly some non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)) and hormonal contraceptives may alter safety and effectiveness of both the hormonal contraceptives and the ARVs. It is not known whether the contraceptive effectiveness of progestogen-only injectable contraceptives (such as depot medroxyprogesterone acetate and norethisterone enantate) would be compromised, as these methods provide higher blood hormone levels than other progestogen-only hormonal contraceptives, as well as than combined oral contraceptives. Studies are underway to evaluate potential interactions between depot medroxyprogesterone acetate and selected PI and NNRTI drugs. Thus, if a woman on ARV treatment decides to initiate or continue hormonal contraceptive use, the consistent use of condoms is recommended for preventing HIV transmission and may also compensate for any possible reduction in the effectiveness of the hormonal contraceptive. Evidence: See Annex 1. Page 12 – Low-dose combined oral contraceptives Additional comments AGE Menarche to < 40 years: Theoretical concerns about the use of combined hormonal contraceptives among young adolescents have not been substantiated. > 40 years: The risk of cardiovascular disease increases with age and may also increase with combined hormonal contraceptive use. In the absence of other adverse clinical conditions, combined hormonal contraceptives can be used until menopause. BREASTFEEDING < 6 weeks postpartum: There is some theoretical concern that the neonate may be at risk due to exposure to steroid hormones during the first 6 weeks postpartum. > 6 weeks to < 6 months (primarily breastfeeding): Use of COCs during breastfeeding diminishes the quantity of breast milk, decreases the duration of lactation, and may thereby adversely affect the growth of the infant. POSTPARTUM < 21 days: There is some theoretical concern regarding the association between combined hormonal contraceptive use up to 3 weeks postpartum and risk of thrombosis in the mother. Blood coagulation and fibrinolysis are essentially normalized by 3 weeks postpartum. PAST ECTOPIC PREGNANCY The risk of future ectopic pregnancy is increased among women who have had an ectopic pregnancy in the past. Combined hormonal contraceptives provide protection against pregnancy in general, including ectopic gestation. HYPERTENSION Vascular disease: Among women with underlying vascular disease, the increased risk of arterial thrombosis associated with combined hormonal contraceptive use should be avoided. DEEP VENOUS THROMBOSIS (DVT)/ PULMONARY EMBOLISM (PE) Family history of DVT/PE (first-degree relatives): Some conditions which increase the risk of DVT/PE are heritable. Major surgery: The degree of risk of DVT/PE associated with major surgery varies depending on the length of time that a woman is immobilized. There is no need to stop combined hormonal contraceptives prior to female surgical sterilization. SUPERFICIAL VENOUS THROMBOSIS Varicose veins: Varicose veins are not risk factors for DVT/PE. CURRENT AND HISTORY OF ISCHAEMIC HEART DISEASE Among women with underlying vascular disease, the increased risk of arterial thrombosis associated with combined hormonal contraceptive use should be avoided. STROKE Among women with underlying vascular disease, the increased risk of arterial thrombosis associated with combined hormonal contraceptive use should be avoided. VALVULAR HEART DISEASE Among women with valvular heart disease, combined hormonal contraceptive use may further increase the risk of arterial thrombosis; women with complicated valvular heart disease are at greatest risk. HEADACHES Aura is a specific focal neurologic symptom. For more information on this and other diagnostic criteria, see: Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd Edition. Cephalalgia. 2004; 24 (Suppl 1): 1- 150. http://216.25.100.131/ihscommon/guidelines/pdfs/ihc_II_main_no_print.pdf VAGINAL BLEEDING PATTERNS Irregular menstrual bleeding patterns are common among healthy women. UNEXPLAINED VAGINAL BLEEDING There are no conditions that cause vaginal bleeding that will be worsened in the short term by use of combined hormonal contraceptives. ENDOMETRIOSIS Combined hormonal contraceptives do not worsen, and may alleviate, the symptoms of endometriosis. CERVICAL ECTROPION Cervical ectropion is not a risk factor for cervical cancer, and there is no need for restriction of combined hormonal contraceptive use. CERVICAL CANCER (awaiting treatment) There is some theoretical concern that combined hormonal contraceptive use may affect prognosis of the existing disease. While awaiting treatment, women may use combined hormonal contraceptives. In general, treatment of this condition renders a woman sterile. BREAST DISEASE Family history of cancer: Women with BRCA1 or BRCA2 mutations have a much higher baseline risk of breast cancer than women who do not have these mutations. Most women with a family history of breast cancer do not have these mutations. Low-dose combined oral contraceptives – Page 13 Breast cancer: Breast cancer is a hormonally sensitive tumour, and the prognosis of women with current or recent breast cancer may worsen with combined hormonal contraceptive use. ENDOMETRIAL CANCER COC use reduces the risk of developing endometrial cancer. While awaiting treatment, women may use COCs. In general, treatment of this condition renders a woman sterile. OVARIAN CANCER COC use reduces the risk of developing ovarian cancer. While awaiting treatment, women may use COCs. In general, treatment of this condition renders a woman sterile. UTERINE FIBROIDS COCs do not appear to cause growth of uterine fibroids. PELVIC INFLAMMATORY DISEASE (PID) COCs may reduce the risk of PID among women with STIs, but do not protect against HIV or lower genital tract STIs. STIs COCs may reduce the risk of PID among women with STIs, but do not protect against HIV or lower genital tract STIs. HIGH RISK OF HIV COCs may reduce the risk of PID among women with STIs, but do not protect against HIV or lower genital tract STIs. DIABETES Although carbohydrate tolerance may change with combined hormonal contraceptive use, the major concerns are vascular disease due to diabetes and additional risk of arterial thrombosis due to combined hormonal contraceptive use. GALL-BLADDER DISEASE COCs may cause a small increased risk of gall-bladder disease. There is also concern that COCs may worsen existing gall-bladder disease. HISTORY OF CHOLESTASIS Pregnancy-related: History of pregnancy-related cholestasis may predict an increased risk of developing COC- associated cholestasis. Past COC-related: History of COC-related cholestasis predicts an increased risk with subsequent COC use. VIRAL HEPATITIS Active: COCs are metabolized by the liver, and their use may adversely affect women whose liver function is compromised. 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A double-blind, placebo-controlled study on the effect of vigabatrin on in vivo parameters of hepatic microsomal enzyme induction and on the kinetics of steroid oral contraceptives in healthy female volunteers. Epilepsia, 1997, 38:702-7. 232. Crawford P et al. The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptive steroids. Contraception, 1986, 33:23-9. 233. Eldon MA et al. Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol. Neurology, 1998, 50:1146-8. 234. Fattore C et al. Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women. Epilepsia, 1999, 40:783-7. 235. Ragueneau-Majlessi I, Levy RH, Janik F. Levetiracetam does not alter the pharmacokinetics of an oral contraceptive in healthy women. Epilepsia, 2002, 43:697-702. Low-dose combined oral contraceptives – Page 23 236. Rosenfeld WE et al. 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Advances in Contraception, 1996, 12:101-9. 249. de Groot AC, Eshuis H, Stricker BH. [Inefficacy of oral contraception during use of minocycline]. Nederlands Tijdschrift voor Geneeskunde, 1990, 134:1227-9. 250. DeSano EA, Hurley SC. Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness. Fertility & Sterility, 1982, 37:853-4. 251. Devenport MH et al. Metabolic effects of low-dose fluconazole in healthy female users and non- users of oral contraceptives. British Journal of Clinical Pharmacology, 1989, 27:851-9. 252. Donley TG, Smith RF, Roy B. Reduced oral contraceptive effectiveness with concurrent antibiotic use: a protocol for prescribing antibiotics to women of childbearing age. Compendium, 1990, 11:392-6. 253. Dosseter J. Drug interaction wtih oral contraceptives. BMJ, 1984, 4:467-8. 254. Driver J. Use of antibiotics during pregnancy. British Dental Journal, 1982, 153:48. 255. el-Raghy I et al. 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Table of contents Combined injectable contraceptives, patch & ring PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY. 3 Pregnancy.3 Age .3 Parity.3 Breastfeeding.3 Postpartum .3 Post-abortion.3 Past ectopic pregnancy.4 History of pelvic surgery.4 Smoking.4 Obesity.4 Blood pressure measurement unavailable .4 CARDIOVASCULAR DISEASE. 4 Multiple risk factors for arterial cardiovascular disease.4 Hypertension.5 History of high blood pressure during pregnancy.5 Deep venous thrombosis (DVT)/Pulmonary embolism (PE) .6 Known thrombogenic mutations.6 Superficial venous thrombosis .6 Current and history of ischaemic heart disease .6 Stroke .6 Known hyperlipidaemias .7 Valvular heart disease .7 NEUROLOGIC CONDITIONS. 7 Headaches.7 Epilepsy .7 DEPRESSIVE DISORDERS . 8 Depressive disorders .8 REPRODUCTIVE TRACT INFECTIONS AND DISORDERS. 8 Vaginal bleeding patterns.8 Unexplained vaginal bleeding .8 Endometriosis .8 Benign ovarian tumours .8 Severe dysmenorrhoea.8 Trophoblast disease.8 Cervical ectropion .8 Cervical intraepithelial neoplasia (CIN) .9 Cervical cancer .9 Breast disease .9 Endometrial cancer .9 Ovarian cancer.9 Uterine fibroids.9 Pelvic inflammatory disease (PID) .9 STIs .10 HIV/AIDS . 10 High risk of HIV.10 HIV-infected .10 AIDS .10 OTHER INFECTIONS . 10 Schistosomiasis .10 Tuberculosis.10 Malaria .10 ENDOCRINE CONDITIONS. 11 Diabetes.11 Thyroid disorders .11 GASTROINTESTINAL CONDITIONS. 11 Gall-bladder disease .11 History of cholestasis .11 Viral hepatitis .12 Cirrhosis.12 Liver tumours .12 ANAEMIAS. 12 Thalassaemia.12 Sickle cell disease.12 Iron-deficiency anaemia.12 DRUG INTERACTIONS . 12 Drugs which affect liver enzymes.12 Antibiotics .12 Antiretroviral therapy.13 Additional comments . 14 References for combined injectable contraceptives, patch, and ring . 17 Combined injectable contraceptives, patch & ring – Page 1 COMBINED INJECTABLE CONTRACEPTIVES (CICs) Combined injectable contraceptives (CICs) provide for the release of a natural estrogen plus a progestogen and act through the inhibition of ovulation.1-5 Two CIC formulations, both given at four- week intervals, are considered here: 1) Cyclofem = Medroxyprogesterone acetate 25mg plus estradiol cypionate 5mg 2) Mesigyna = Norethisterone enantate 50mg plus estradiol valerate 5mg Because the estrogens in CICs may be more physiologic and may be less potent compared with the synthetic estrogens of combined oral contraceptives (COCs), the type and magnitude of estrogen- related side-effects associated with CICs may be different from those experienced by COC users. In fact, short-term studies of CICs have shown little effect on blood pressure, haemostasis and coagulation, lipid metabolism, and liver function in comparison with COCs.6-8 In addition, the parenteral administration of CICs eliminates the first-pass effect of the hormones on the liver. However, CICs are a relatively new contraceptive method, and there are few epidemiological data on their long-term effects. There is also the concern that, while the effect of the hormonal exposure associated with use of COCs and progestogen-only pills (POPs) can be reduced immediately by discontinuing their use, this is not the case with injectables, for which the effect continues for some time after the last injection. Pending further evidence, the Working Group concluded that the evidence available for COCs applies to CICs in many but not all instances. Therefore, the Working Group assigned categories for CICs somewhere between the categories for COCs and POPs. However, for severe pathologies (e.g., ischaemic heart disease), the classification of conditions was the same as for COCs. The assigned categories should, therefore, be considered a preliminary, best judgement, which will be re-evaluated as new data become available. COMBINED CONTRACEPTIVE PATCH (P) The combined contraceptive patch uses a square 20 cm2, three-layer system applied to the buttocks, torso, abdomen, or upper arm, to release ethinylestradiol and a progestogen (norelgestromin) transdermally. The contraceptive effect of the combined patch is achieved through inhibition of ovulation.9 The combined contraceptive patch currently available for consideration was: Evra = 17-deacetyl norgestimate (norelgestromin) 150µg plus ethinylestradiol 20µg (both dosages are approximate daily release rates). The combined contraceptive patch is a new contraceptive method. Relatively limited information is available on the safety of the combined contraceptive patch among healthy women and even less information is available for women with specific medical conditions. Moreover, epidemiological data on the long-term effects of the combined contraceptive patch were not available for the Working Group to review and all available studies received support from the patch manufacturer. According to available evidence, the combined contraceptive patch provides a comparable safety and pharmacokinetic profile to COCs with similar hormone formulations.9-18 Reports of transient, short-term breast discomfort and skin site reactions occurred among less than 25% of combined contraceptive patch users.10-13 Limited evidence suggests the effectiveness of the patch may decline for women weighing 90kg or more.10-11 To date, no studies have examined whether the avoidance of the first-pass effect of hormones on the liver with patch use lessens concerns about drug interactions or use of the patch among women with liver conditions. Pending further evidence, the Working Group concluded that the evidence available for COCs applies to the patch. Therefore, the patch should have the same categories as COCs. The assigned categories should, therefore, be considered a preliminary, best judgement, which will be re-evaluated as new data become available. Page 2 – Combined injectable contraceptives, patch and ring COMBINED VAGINAL RING (R) The combined contraceptive vaginal ring releases ethinylestradiol and a progestogen (etonogestrel) from a 54mm ethylene vinyl acetate copolymer ring. The contraceptive effect of the combined vaginal ring is achieved through inhibition of ovulation.19-20 The vaginal ring formulation currently available for consideration was: NuvaRing = etonogestrel 120 µg plus ethinylestradiol 15 µg (both dosages are approximate daily release rates). The combined contraceptive vaginal ring is a new contraceptive method. Relatively limited information is available on the safety of the combined contraceptive ring among healthy women and even less information is available for women with specific medical conditions. Moreover, epidemiological data on the long-term effects of the combined contraceptive ring were not available for the Working Group to review and all available studies received support from the ring manufacturer. According to available evidence, the combined contraceptive vaginal ring provides a comparable safety and pharmacokinetic profile to COCs with similar hormone formulations.20-25 Evidence among healthy women suggests the vaginal ring does not alter vaginal flora,23-24 and limited evidence on women with low-grade squamous intraepithelial lesions found use of the vaginal ring did not worsen the condition.23 To date, no studies have examined whether the avoidance of the first-pass effect of hormones on the liver with vaginal ring use lessens concerns about drug interactions or use of the ring among women with liver conditions. Pending further evidence, the Working Group concluded that the evidence available for COCs applies to the ring. Therefore, the ring should have the same categories as COCs. The assigned categories should, therefore, be considered a preliminary, best judgement, which will be re-evaluated as new data become available. * See also additional comments at end of table Combined injectable contraceptives, patch and ring – Page 3 COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY PREGNANCY NA NA NA Clarification: Use of CICs, P, or R is not required. There is no known harm to the woman, the course of her pregnancy, or the fetus if CICs, P, or R are accidentally used during pregnancy. AGE* a) Menarche to < 40 years 1 1 1 b) > 40 years 2 2 2 PARITY a) Nulliparous 1 1 1 b) Parous 1 1 1 BREASTFEEDING* a) < 6 weeks postpartum 4 4 4 b) > 6 weeks to < 6 months postpartum (primarily breastfeeding) 3 3 3 c) > 6 months postpartum 2 2 2 POSTPARTUM* (in non-breastfeeding women) a) < 21 days 3 3 3 b) > 21 days 1 1 1 POST-ABORTION a) First trimester 1 1 1 Clarification: CICs, P, or R may be started immediately post-abortion. b) Second trimester 1 1 1 c) Immediate post-septic abortion 1 1 1 * See also additional comments at end of table Page 4 – Combined injectable contraceptives, patch and ring COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE PAST ECTOPIC PREGNANCY* 1 1 1 HISTORY OF PELVIC SURGERY 1 1 1 SMOKING a) Age < 35 years 2 2 2 b) Age > 35 years (i) <15 cigarettes/day 2 3 3 (ii) >15 cigarettes/day 3 4 4 OBESITY > 30 kg/m2 body mass index (BMI) 2 2 2 Evidence: Limited evidence suggests the effectiveness of the patch may decline for women weighing 90kg or more.10-11 BLOOD PRESSURE MEASUREMENT UNAVAILABLE NA NA NA Clarification: It is desirable to have blood pressure measurements taken before initiation of CIC, P, or R use. However, in some settings blood pressure measurements are unavailable. In many of these settings, pregnancy morbidity and mortality risks are high, and CICs, P, or R may be one of the few methods available. In such settings, women should not be denied use of CICs, P, or R simply because their blood pressure cannot be measured. CARDIOVASCULAR DISEASE MULTIPLE RISK FACTORS FOR ARTERIAL CARDIOVASCULAR DISEASE (such as older age, smoking, diabetes and hypertension) 3/4 3/4 3/4 Clarification: When a woman has multiple major risk factors, any of which alone would substantially increase the risk of cardiovascular disease, use of CICs, P, or R may increase her risk to an unacceptable level. However, a simple addition of categories for multiple risk factors is not intended; for example, a combination of two risk factors assigned a category 2 may not necessarily warrant a higher category. * See also additional comments at end of table Combined injectable contraceptives, patch and ring – Page 5 COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE HYPERTENSION* For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist, risk of cardiovascular disease may increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive. a) History of hypertension, where blood pressure CANNOT be evaluated (including hypertension in pregnancy) 3 3 3 Clarification: Evaluation of cause and level of hypertension is recommended as soon as feasible. b) Adequately controlled hypertension, where blood pressure CAN be evaluated 3 3 3 Clarification: Women adequately treated for hypertension are at reduced risk of acute myocardial infarction and stroke as compared with untreated women. Although there are no data, CIC, P, or R users with adequately controlled and monitored hypertension should be at reduced risk of acute myocardial infarction and stroke compared with untreated hypertensive CIC, P, or R users. c) Elevated blood pressure levels (properly taken measurements) (i) systolic 140-159 or diastolic 90-99 3 3 3 (ii) systolic >160 or diastolic >100 4 4 4 d) Vascular disease 4 4 4 HISTORY OF HIGH BLOOD PRESSURE DURING PREGNANCY (where current blood pressure is measurable and normal) 2 2 2 * See also additional comments at end of table Page 6 – Combined injectable contraceptives, patch and ring COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE DEEP VENOUS THROMBOSIS (DVT)/ PULMONARY EMBOLISM (PE)* a) History of DVT/PE 4 4 4 b) Current DVT/PE 4 4 4 c) Family history of DVT/PE (first-degree relatives) 2 2 2 d) Major surgery (i) with prolonged immobilization 4 4 4 (ii) without prolonged immobilization 2 2 2 e) Minor surgery without immobilization 1 1 1 KNOWN THROMBOGENIC MUTATIONS (e.g., Factor V Leiden; Prothrombin mutation; Protein S, Protein C, and Antithrombin deficiencies) 4 4 4 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening. SUPERFICIAL VENOUS THROMBOSIS* a) Varicose veins 1 1 1 b) Superficial thrombophlebitis 2 2 2 CURRENT AND HISTORY OF ISCHAEMIC HEART DISEASE* 4 4 4 STROKE* (history of cerebrovascular accident) 4 4 4 * See also additional comments at end of table Combined injectable contraceptives, patch and ring – Page 7 COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE KNOWN HYPERLIPIDAEMIAS 2/3 2/3 2/3 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening. While some types of hyperlipidaemias are risk factors for vascular disease, the category should be assessed according to the type, its severity, and the presence of other cardiovascular risk factors. VALVULAR HEART DISEASE* a) Uncomplicated 2 2 2 b) Complicated (pulmonary hypertension, risk of atrial fibrillation, history of subacute bacterial endocarditis) 4 4 4 NEUROLOGIC CONDITIONS HEADACHES* I C I C I C a) Non-migrainous (mild or severe) 1 2 1 2 1 2 Clarification: Classification depends on accurate diagnosis of those severe headaches that are migrainous and those that are not. Any new headaches or marked changes in headaches should be evaluated. Classification is for women without any other risk factors for stroke. Risk of stroke increases with age, hypertension and smoking. b) Migraine (i) without aura Age < 35 2 3 2 3 2 3 Age > 35 3 4 3 4 3 4 (ii) with aura, at any age 4 4 4 4 4 4 EPILEPSY 1 1 1 Clarification: If a woman is taking anticonvulsants, refer to the section on drug interactions. Certain anticonvulsants lower COC effectiveness. The extent to which CIC, P or R use are similar to COC use in this regard remains unclear. * See also additional comments at end of table Page 8 – Combined injectable contraceptives, patch and ring COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE DEPRESSIVE DISORDERS DEPRESSIVE DISORDERS 1 1 1 Clarification: The classification is based on data for women with selected depressive disorders. No data on bipolar disorder or postpartum depression were available. There is a potential for drug interactions between certain antidepressant medications and hormonal contraceptives. REPRODUCTIVE TRACT INFECTIONS AND DISORDERS VAGINAL BLEEDING PATTERNS* a) Irregular pattern without heavy bleeding 1 1 1 b) Heavy or prolonged bleeding (includes regular and irregular patterns) 1 1 1 Clarification: Unusually heavy bleeding should raise the suspicion of a serious underlying condition. UNEXPLAINED VAGINAL BLEEDING* (suspicious for serious condition) Before evaluation 2 2 2 Clarification: If pregnancy or an underlying pathological condition (such as pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation. ENDOMETRIOSIS* 1 1 1 BENIGN OVARIAN TUMOURS (including cysts) 1 1 1 SEVERE DYSMENORRHOEA 1 1 1 TROPHOBLAST DISEASE a) Benign gestational trophoblastic disease 1 1 1 b) Malignant gestational trophoblastic disease 1 1 1 CERVICAL ECTROPION* 1 1 1 * See also additional comments at end of table Combined injectable contraceptives, patch and ring – Page 9 COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) 2 2 2 Evidence: Limited evidence on women with low-grade squamous intraepithelial lesions found use of the vaginal ring did not worsen the condition.23 CERVICAL CANCER* (awaiting treatment) 2 2 2 BREAST DISEASE* a) Undiagnosed mass 2 2 2 Clarification: Evaluation should be pursued as early as possible. b) Benign breast disease 1 1 1 c) Family history of cancer 1 1 1 d) Breast cancer (i) current 4 4 4 (ii) past and no evidence of current disease for 5 years 3 3 3 ENDOMETRIAL CANCER* 1 1 1 OVARIAN CANCER* 1 1 1 UTERINE FIBROIDS* a) Without distortion of the uterine cavity 1 1 1 b) With distortion of the uterine cavity 1 1 1 PELVIC INFLAMMATORY DISEASE (PID)* a) Past PID (assuming no current risk factors for STIs) i) with subsequent pregnancy 1 1 1 ii) without subsequent pregnancy 1 1 1 b) PID - current 1 1 1 * See also additional comments at end of table Page 10 – Combined injectable contraceptives, patch and ring COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE STIs* a) Current purulent cervicitis or chlamydial infection or gonorrhoea 1 1 1 b) Other STIs (excluding HIV and hepatitis) 1 1 1 c) Vaginitis (including trichomonas vaginalis and bacterial vaginosis) 1 1 1 d) Increased risk of STIs 1 1 1 HIV/AIDS HIGH RISK OF HIV* 1 1 1 HIV-INFECTED 1 1 1 AIDS 1 1 1 On ARV therapy 2 2 2 Clarification: If a woman is taking antiretroviral (ARV) therapy, refer to the section on drug interactions. Because there may be drug interactions between hormonal contraceptives and ARVs, AIDS with ARV therapy is classified as Category 2. OTHER INFECTIONS SCHISTOSOMIASIS a) Uncomplicated 1 1 1 b) Fibrosis of liver (if severe, see cirrhosis) 1 1 1 TUBERCULOSIS a) Non-pelvic 1 1 1 Clarification: If a woman is taking rifampicin, refer to the section on drug interactions. Rifampicin is likely to decrease COC effectiveness. The extent to which CIC, P, or R use is similar to COC use in this regard remains unclear. b) Known pelvic 1 1 1 MALARIA 1 1 1 * See also additional comments at end of table Combined injectable contraceptives, patch and ring – Page 11 COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE ENDOCRINE CONDITIONS DIABETES* a) History of gestational disease 1 1 1 b) Non-vascular disease (i) non-insulin dependent 2 2 2 (ii) insulin dependent 2 2 2 c) Nephropathy/ retinopathy/ neuropathy 3/4 3/4 3/4 Clarification: The category should be assessed according to the severity of the condition. d) Other vascular disease or diabetes of >20 years' duration 3/4 3/4 3/4 Clarification: The category should be assessed according to the severity of the condition. THYROID DISORDERS a) Simple goitre 1 1 1 b) Hyperthyroid 1 1 1 c) Hypothyroid 1 1 1 GASTROINTESTINAL CONDITIONS GALL-BLADDER DISEASE* a) Symptomatic (i) treated by cholecystectomy 2 2 2 (ii) medically treated 2 3 3 (iii) current 2 3 3 b) Asymptomatic 2 2 2 HISTORY OF CHOLESTASIS* a) Pregnancy-related 2 2 2 b) Past COC or CIC related 2 3 3 * See also additional comments at end of table Page 12 – Combined injectable contraceptives, patch and ring COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE VIRAL HEPATITIS* a) Active 3/4 4 4 b) Carrier 1 1 1 Clarification: The category should be assessed according to the severity of the condition. Clarification: In women with symptomatic viral hepatitis, CICs, P and R should be withheld until liver function returns to normal or 3 months after the woman becomes asymptomatic, whichever occurs earlier. CIRRHOSIS* a) Mild (compensated) 2 3 3 b) Severe (decompensated) 3 4 4 LIVER TUMOURS* a) Benign (adenoma) 3 4 4 b) Malignant (hepatoma) 3/4 4 4 ANAEMIAS THALASSAEMIA 1 1 1 SICKLE CELL DISEASE 2 2 2 IRON-DEFICIENCY ANAEMIA* 1 1 1 DRUG INTERACTIONS DRUGS WHICH AFFECT LIVER ENZYMES a) Rifampicin 2 3 3 b) Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine) 2 3 3 Clarification: Although the interaction of rifampicin or certain anticonvulsants with P or R use is not harmful to women, it is likely to reduce P or R effectiveness. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. ANTIBIOTICS (excluding rifampicin) a) Griseofulvin 1 2 2 b) Other antibiotics 1 1 1 * See also additional comments at end of table Combined injectable contraceptives, patch and ring – Page 13 COMBINED INJECTABLE CONTRACEPTIVES (CICs), PATCH (P), RING (R) CICs, patch, and ring do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation C=Continuation CONDITION CICs P R CLARIFICATIONS/EVIDENCE ANTIRETROVIRAL THERAPY 2 2 2 Clarification: It is important to note that antiretroviral drugs (ARV) have the potential to either decrease or increase the bioavailability of steroid hormones in hormonal contraceptives. The limited data available (outlined in Annex 1) suggest that potential drug interactions between many ARVs (particularly some non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)) and hormonal contraceptives may alter safety and effectiveness of both the hormonal contraceptives and the ARVs. It is not known whether the contraceptive effectiveness of progestogen-only injectable contraceptives (such as depot medroxyprogesterone acetate and norethisterone enantate) would be compromised, as these methods provide higher blood hormone levels than other progestogen-only hormonal contraceptives, as well as than combined oral contraceptives. Studies are underway to evaluate potential interactions between depot medroxyprogesterone acetate and selected PI and NNRTI drugs. Thus, if a woman on ARV treatment decides to initiate or continue hormonal contraceptive use, the consistent use of condoms is recommended for preventing HIV transmission and may also compensate for any possible reduction in the effectiveness of the hormonal contraceptive. Page 14 – Combined injectable contraceptives, patch and ring Additional comments AGE Menarche to < 40 years: Theoretical concerns about the use of combined hormonal contraceptives among young adolescents have not been substantiated. > 40 years: The risk of cardiovascular disease increases with age and may also increase with combined hormonal contraceptive use. In the absence of other adverse clinical conditions, combined hormonal contraceptives can be used until menopause. BREASTFEEDING < 6 weeks postpartum: There is some theoretical concern that the neonate may be at risk due to exposure to steroid hormones during the first 6 weeks postpartum. > 6 weeks to < 6 months (primarily breastfeeding): Use of combined hormonal contraceptives during breastfeeding diminishes the quantity of breast milk, decreases the duration of lactation, and may thereby adversely affect the growth of the infant. POSTPARTUM < 21 days: There is some theoretical concern regarding the association between combined hormonal contraceptive use up to 3 weeks postpartum and risk of thrombosis in the mother. Blood coagulation and fibrinolysis are essentially normalized by 3 weeks postpartum. PAST ECTOPIC PREGNANCY The risk of future ectopic pregnancy is increased among women who have had an ectopic pregnancy in the past. Combined hormonal contraceptives provide protection against pregnancy in general, including ectopic gestation. HYPERTENSION Vascular disease: Among women with underlying vascular disease, the increased risk of arterial thrombosis associated with combined hormonal contraceptive use should be avoided. DEEP VENOUS THROMBOSIS (DVT)/ PULMONARY EMBOLISM (PE) Family history of DVT/PE (first-degree relatives): Some conditions which increase the risk of DVT/PE are heritable. Major surgery: The degree of risk of DVT/PE associated with major surgery varies depending on the length of time that a woman is immobilized. There is no need to stop combined hormonal contraceptives prior to female surgical sterilization. SUPERFICIAL VENOUS THROMBOSIS Varicose veins: Varicose veins are not risk factors for DVT/PE. CURRENT AND HISTORY OF ISCHAEMIC HEART DISEASE Among women with underlying vascular disease, the increased risk of arterial thrombosis associated with combined hormonal contraceptive use should be avoided. STROKE Among women with underlying vascular disease, the increased risk of arterial thrombosis associated with combined hormonal contraceptive use should be avoided. VALVULAR HEART DISEASE Among women with valvular heart disease, combined hormonal contraceptive use may further increase the risk of arterial thrombosis; women with complicated valvular heart disease are at greatest risk. HEADACHES Aura is a specific focal neurologic symptom. For more information on this and other diagnostic criteria, see: Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd Edition. Cephalalgia. 2004; 24 (Suppl 1): 1- 150. http://216.25.100.131/ihscommon/guidelines/pdfs/ihc_II_main_no_print.pdf VAGINAL BLEEDING PATTERNS Irregular menstrual bleeding patterns are common among healthy women. UNEXPLAINED VAGINAL BLEEDING There are no conditions that cause vaginal bleeding that will be worsened in the short term by use of combined hormonal contraceptives. ENDOMETRIOSIS Combined hormonal contraceptives do not worsen, and may alleviate, the symptoms of endometriosis. CERVICAL ECTROPION Cervical ectropion is not a risk factor for cervical cancer, and there is no need for restriction of combined hormonal contraceptive use. Combined injectable contraceptives, patch and ring – Page 15 CERVICAL CANCER (awaiting treatment) There is some theoretical concern that combined hormonal contraceptive use may affect prognosis of the existing disease. While awaiting treatment, women may use combined hormonal contraceptives. In general, treatment of this condition renders a woman sterile. BREAST DISEASE Family history of cancer: Women with BRCA1 or BRCA2 mutations have a much higher baseline risk of breast cancer than women who do not have these mutations. Most women with a family history of breast cancer do not have these mutations. Breast cancer: Breast cancer is a hormonally sensitive tumour, and the prognosis of women with current or recent breast cancer may worsen with combined hormonal contraceptive use. ENDOMETRIAL CANCER It is not known whether CIC, P, or R use reduces the risk of developing endometrial cancer, as is the case with COCs. While awaiting treatment, women may use CICs, P or R. In general, treatment of this condition renders a woman sterile. OVARIAN CANCER It is not known whether CIC, P, or R use reduces the risk of developing ovarian cancer, as is the case with COCs. While awaiting treatment, women may use CICs, P, or R. In general, treatment of this condition renders a woman sterile. UTERINE FIBROIDS COCs do not appear to cause growth of uterine fibroids and CICs, P, or R are not expected to do either. PELVIC INFLAMMATORY DISEASE (PID) COCs may reduce the risk of PID among women with STIs, but do not protect against HIV or lower genital tract STIs. Whether CICs, P or R reduce the risk of PID among women with STIs is unknown, but they do not protect against HIV or lower genital tract STIs. STIs COCs may reduce the risk of PID among women with STIs, but do not protect against HIV or lower genital tract STIs. Whether CICs, P or R reduce the risk of PID among women with STIs is unknown, but they do not protect against HIV or lower genital tract STIs. HIGH RISK OF HIV COCs may reduce the risk of PID among women with STIs, but do not protect against HIV or lower genital tract STIs. Whether CICs, P or R reduce the risk of PID among women with STIs is unknown, but they do not protect against HIV or lower genital tract STIs. DIABETES Although carbohydrate tolerance may change with combined hormonal contraceptive use, the major concerns are vascular disease due to diabetes and additional risk of arterial thrombosis due to combined hormonal contraceptive use. GALL-BLADDER DISEASE P or R, like COCs, may cause a small increased risk of gall-bladder disease. There is also concern that they may worsen existing gall-bladder disease. However, unlike COCs, CICs have been shown to have a minimal effect on liver function in healthy women, and have no first-pass effect on the liver. HISTORY OF CHOLESTASIS Pregnancy-related: History of pregnancy-related cholestasis may predict an increased risk of developing cholestasis associated with combined hormone therapy. Past COC or CIC related: History of COC- or CIC-related cholestasis predicts an increased risk associated with P or R use. Unlike COCs, CICs have been shown to have a minimal effect on liver function in healthy women and have no first-pass effect on the liver. VIRAL HEPATITIS Active: Unlike COCs, CICs have been shown to have a minimal effect on liver function in healthy women and have no first-pass effect on the liver. However, because CICs are metabolized by the liver, they could, in theory, lead to adverse effects in women whose liver function is already compromised. CIRRHOSIS Unlike COCs, CICs have been shown to have a minimal effect on liver function in healthy women and have no first-pass effect on the liver. However, because CICs are metabolized by the liver, they could, in theory, lead to adverse effects in women whose liver function is already compromised Page 16 – Combined injectable contraceptives, patch and ring LIVER TUMOURS Unlike COCs, CICs have been shown to have a minimal effect on liver function in healthy women and have no first-pass effect on the liver. However, because CICs are metabolized by the liver, they could, in theory, lead to adverse effects in women whose liver function is already compromised. IRON-DEFICIENCY ANAEMIA Combined hormonal contraceptive use may decrease menstrual blood loss. Combined injectable contraceptives, patch and ring – Page 17 References for combined injectable contraceptives, patch, and ring 1. Aedo AR et al. Pharmacokinetic and pharmacodynamic investigations with monthly injectable contraceptive preparations. Contraception, 1985, 31:453-69. 2. Garza-Flores J. Pharmacokinetics of once-a-month injectable contraceptives. 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Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters. Contraception, 1989, 39:619-32. 9. Pierson RA et al. Ortho Evra/Evra versus oral contraceptives: follicular development and ovulation in normal cycles and after an intentional dosing error. Fertility & Sterility, 2003, 80:34-42. 10. Audet M-C et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs. an oral contraceptive: a randomized controlled trial. JAMA, 2001, 285:2347-54. 11. Smallwood GH et al. Efficacy and safety of a transdermal contraceptive system. Obstetrics and Gynecology, 2001, 98:799-805. 12. Helmerhorst FM et al. Comparison of efficacy, cycle control, compliance and safety in users of a contraceptive patch vs. an oral contraceptive. XVI FIGO World Congress of Gynecology and Obstetrics [FC 2.30.06], Washington DC, USA, 3-8 September 2000. 13. Dittrich R et al. Transdermal contraception: evaluation of three transdermal norelgestromin/ethinylestradiol doses in a randomized, multicenter, dose-response study. American Journal of Obstetrics and Gynecology, 2002, 186:15-20. 14. Abrams LS et al. Pharmacokinetics of a contraceptive patch (Evra/Ortho Evra) containing norelgestromin and ethinyloestradiol at four application sites. British Journal of Clinical Pharmacology, 2002, 53:141-6. 15. Abrams LS et al. Multiple-dose pharmacokinetics of a contraceptive patch in healthy women participants. Contraception, 2001, 64:287-94. 16. Abrams LS et al. Pharmacokinetics of norelgestromin and ethinylestradiol delivered by a contraceptive patch (Ortho Evra/Evra) under conditions of heat, humidity, and exercise. Journal of Clinical Pharmacology, 2001, 41:1301-9. 17. Zieman M. The introduction of a transdermal hormonal contraceptive (Ortho Evra/Evra). Fertility & Sterility, 2002, 77(2): s1-s2. 18. Burkman, RT. The transdermal contraceptive patch: a new approach to hormonal contraception. International Journal of Fertility, 2002, 47:69-76. 19. Stone SC. Desogestrel. Clinical Obstetrics and Gynecology, 1995, 38:821-8. 20. Mulders TMT, Dieben TOM. Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation inhibition. Fertility & Sterility, 2001, 75:865-70. 21. Timmer CJ, Mulders TMT. Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clinical Pharmacokinetics, 2000, 39:233-42. 22. Bjarnadottir RI, Tuppurainen M, Killick SR. Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol. American Journal of Obstetrics and Gynecology, 2002, 186:389-95. 23. Dieben TOM, Roumen FJME, Apter D. Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstetrics and Gynecology, 2002, 100:585-93. 24. Roumen FJME et al. The cervico-vaginal epithelium during 20 cycles of use of a combined contraceptive vaginal ring. Human Reproduction, 1996, 11:2443-8. 25. Davies GC, Feng LX, Newton JR. The effects of a combined contraceptive vaginal ring releasing ethinylestradiol and 3-ketodesogestrel on vaginal flora. Contraception, 1992, 45:511-8. Page 18 – Combined injectable contraceptives, patch and ring Table of contents Progestogen-only contraceptives PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY. 1 Pregnancy.1 Age .1 Parity.2 Breastfeeding.2 Postpartum .2 Post-abortion.2 Past ectopic pregnancy.3 History of pelvic surgery.3 Smoking.3 Obesity.3 Blood pressure measurement unavailable .3 CARDIOVASCULAR DISEASE. 3 Multiple risk factors for arterial cardiovascular disease.3 Hypertension.4 History of high blood pressure during pregnancy.4 Deep venous thrombosis (DVT)/Pulmonary embolism (PE) .5 Known thrombogenic mutations.5 Superficial venous thrombosis .5 Current and history of ischaemic heart disease .5 Stroke .5 Known hyperlipidaemias .6 Valvular heart disease .6 NEUROLOGIC CONDITIONS. 6 Headaches.6 Epilepsy .6 DEPRESSIVE DISORDERS . 7 Depressive disorders .7 REPRODUCTIVE TRACT INFECTIONS AND DISORDERS. 7 Vaginal bleeding patterns.7 Unexplained vaginal bleeding .7 Endometriosis .7 Benign ovarian tumours .7 Severe dysmenorrhoea.7 Trophoblast disease.8 Cervical ectropion .8 Cervical intraepithelial neoplasia (CIN) .8 Cervical cancer .8 Breast disease .8 Endometrial cancer .8 Ovarian cancer.8 Uterine fibroids.8 Pelvic inflammatory disease (PID) .9 STIs .9 HIV/AIDS . 9 High risk of HIV.9 HIV-infected .9 AIDS .10 OTHER INFECTIONS . 10 Schistosomiasis .10 Tuberculosis.10 Malaria .10 ENDOCRINE CONDITIONS. 10 Diabetes.10 Thyroid disorders .11 GASTROINTESTINAL CONDITIONS. 11 Gall-bladder disease .11 History of cholestasis .11 Viral hepatitis .11 Cirrhosis.11 Liver tumours .12 ANAEMIAS. 12 Thalassaemia.12 Sickle cell disease.12 Iron-deficiency anaemia.12 DRUG INTERACTIONS . 12 Drugs which affect liver enzymes.12 Antibiotics .12 Antiretroviral therapy.13 Additional comments . 14 References for progestogen-only contraception. 16 * See also additional comments at end of table Progestogen-only contraceptives – Page 1 PROGESTOGEN-ONLY CONTRACEPTIVES POP = Progestogen-only pill (POP) D/NE = Depot medroxyprogesterone acetate (DMPA)/norethisterone enantate (NET-EN) LNG/ETG = Levonorgestrel implants (Norplant and Jadelle) and etonogestrel implants (Implanon) PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE PERSONAL CHARACTERISTICS AND REPRODUCTIVE HISTORY PREGNANCY NA Clarification: Use of POCs is not required. There is no known harm to the woman, the course of her pregnancy, or the fetus if POCs are accidentally used during pregnancy. However, the relationship between DMPA use during pregnancy and its effects on the fetus remains unclear. AGE* a) Menarche to < 18 years 1 2 1 Evidence: Limited evidence shows decreased bone mineral density over time among adolescent DMPA users, but not among levonorgestrel implant users. No studies have examined whether DMPA use among adolescents affects peak bone mass levels.1-5 b) 18 to 45 years 1 1 1 Evidence: In general, current DMPA users had decreased bone mineral density compared with non-users; this decrease was usually within one standard deviation of normal values.6 Results for current Norplant users were mixed.6 One study of Implanon users showed no change in bone mineral density over two years.7 c) > 45 years 1 2 1 Evidence: Older DMPA users had decreased bone mineral density compared with non-users. However, limited evidence found that women gained bone mass following discontinuation of DMPA prior to menopause. Further, among postmenopausal women, there was no difference in bone mineral density between former DMPA users and never users.8-13 See also additional comments at end of table Page 2 – Progestogen-only contraceptives PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE PARITY a) Nulliparous 1 1 1 b) Parous 1 1 1 BREASTFEEDING a) < 6 weeks postpartum 3 3 3 Clarification: There is concern that the neonate may be at risk of exposure to steroid hormones during the first 6 weeks postpartum. However, in many settings pregnancy morbidity and mortality risks are high, and access to services is limited. In such settings, POCs may be one of the few types of methods widely available and accessible to breastfeeding women immediately postpartum. Evidence: Studies have shown that among breast-feeding women less than 6 weeks postpartum, progestogen-only contraceptives did not affect breast- feeding performance and infant health and growth. However, there are no data evaluating the effects of progestogen exposure via breast milk on brain and liver development.14-38 b) > 6 weeks to < 6 months postpartum (primarily breastfeeding) 1 1 1 c) > 6 months postpartum 1 1 1 POSTPARTUM* (in non-breastfeeding women) a) < 21 days 1 1 1 b) > 21 days 1 1 1 POST-ABORTION a) First trimester 1 1 1 b) Second trimester 1 1 1 c) Immediate post- septic abortion 1 1 1 Clarification: POCs may be started immediately post-abortion. Evidence: Limited evidence suggests that there are no adverse side effects when Norplant or NET-EN are initiated after a first trimester abortion.39-42 * See also additional comments at end of table Progestogen-only contraceptives – Page 3 PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE PAST ECTOPIC PREGNANCY* 2 1 1 HISTORY OF PELVIC SURGERY 1 1 1 SMOKING a) Age < 35 years 1 1 1 b) Age > 35 years i) <15 cigarettes/day 1 1 1 ii) >15 cigarettes/day 1 1 1 OBESITY > 30 kg/m2 body mass index (BMI) 1 1 1 Evidence: Studies provide conflicting evidence regarding whether obese women are at increased risk of weight gain and bleeding problems with DMPA use relative to non-obese women with DMPA use.43-45 Studies show that obese women do not experience decreased effectiveness when using Norplant soft capsules or Jadelle.46-48 BLOOD PRESSURE MEASUREMENT UNAVAILABLE NA NA NA Clarification: It is desirable to have blood pressure measurements taken before initiation of POC use. However, in some settings blood pressure measurements are unavailable. In many of these settings, pregnancy morbidity and mortality risks are high, and POCs are one of the few types of methods widely available. In such settings, women should not be denied use of POCs simply because their blood pressure cannot be measured. CARDIOVASCULAR DISEASE MULTIPLE RISK FACTORS FOR ARTERIAL CARDIOVASCULAR DISEASE (such as older age, smoking, diabetes and hypertension) 2 3 2 Clarification: When multiple major risk factors exist, risk of cardiovascular disease may increase substantially. Some POCs may increase the risk of thrombosis, although this increase is substantially less than with COCs. The effects of DMPA and NET-EN may persist for some time after discontinuation. See also additional comments at end of table Page 4 – Progestogen-only contraceptives PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE HYPERTENSION* For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist, risk of cardiovascular disease may increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive. a) History of hypertension where blood pressure CANNOT be evaluated (including hypertension in pregnancy) 2 2 2 Clarification: It is desirable to have blood pressure measurements taken before initiation of POC use. However, in some settings blood pressure measurements are unavailable. In many of these settings pregnancy morbidity and mortality risks are high, and POCs are one of the few types of methods widely available. In such settings, women should not be denied use of POCs simply because their blood pressure cannot be measured. b) Adequately controlled hypertension where blood pressure CAN be evaluated 1 2 1 Clarification: Women adequately treated for hypertension are at reduced risk of acute myocardial infarction and stroke as compared with untreated women. Although there are no data, POC users with adequately controlled and monitored hypertension should be at reduced risk of acute myocardial infarction and stroke compared with untreated hypertensive POC users. c) Elevated blood pressure levels (properly taken measurements) i) systolic140-159 or diastolic 90-99 1 2 1 ii) systolic > 160 or diastolic > 100 2 3 2 Evidence: Limited evidence suggests that among women with hypertension, those who used POPs or progestogen-only injectables had a small increased risk of cardiovascular events compared with women who did not use these methods.49 d) Vascular disease 2 3 2 HISTORY OF HIGH BLOOD PRESSURE DURING PREGNANCY (where current blood pressure is measurable and normal) 1 1 1 * See also additional comments at end of table Progestogen-only contraceptives – Page 5 PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE DEEP VENOUS THROMBOSIS (DVT)/ PULMONARY EMBOLISM (PE)* a) History of DVT/PE 2 2 2 b) Current DVT/PE 3 3 3 c) Family history of DVT/PE (first-degree relatives) 1 1 1 d) Major surgery i) with prolonged immobilization 2 2 2 ii) without prolonged immobilization 1 1 1 e) Minor surgery without immobilization 1 1 1 KNOWN THROMBOGENIC MUTATIONS (e.g., Factor V Leiden; Prothrombin mutation; Protein S, Protein C, and Antithrombin deficiencies) 2 2 2 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening. SUPERFICIAL VENOUS THROMBOSIS a) Varicose veins 1 1 1 b) Superficial thrombophlebitis 1 1 1 I C I C CURRENT AND HISTORY OF ISCHAEMIC HEART DISEASE* 2 3 3 2 3 I C I C STROKE* (history of cerebrovascular accident) 2 3 3 2 3 See also additional comments at end of table Page 6 – Progestogen-only contraceptives PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE KNOWN HYPERLIPIDAEMIAS 2 2 2 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening. Some types of hyperlipidaemias are risk factors for vascular disease. VALVULAR HEART DISEASE a) Uncomplicated 1 1 1 b) Complicated (pulmonary hypertension, risk of atrial fibrillation, history of subacute bacterial endocarditis) 1 1 1 NEUROLOGIC CONDITIONS HEADACHES* I C I C I C a) Non-migrainous (mild or severe) 1 1 1 1 1 1 Clarification: Classification depends on accurate diagnosis of those severe headaches that are migrainous and those that are not. Any new headaches or marked changes in headaches should be evaluated. Classification is for women without any other risk factors for stroke. Risk of stroke increases with age, hypertension, and smoking. b) Migraine i) without aura Age < 35 1 2 2 2 2 2 Age > 35 1 2 2 2 2 2 ii) with aura, at any age 2 3 2 3 2 3 EPILEPSY 1 1 1 Clarification: If a woman is taking anticonvulsants, refer to the section on drug interactions. Certain anticonvulsants lower POC effectiveness. * See also additional comments at end of table Progestogen-only contraceptives – Page 7 PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE DEPRESSIVE DISORDERS DEPRESSIVE DISORDERS 1 1 1 Clarification: The classification is based on data for women with selected depressive disorders. No data on bipolar disorder or postpartum depression were available. There is a potential for drug interactions between certain antidepressant medications and hormonal contraceptives. Evidence: POCs did not increase depressive symptoms in women with depression compared to baseline.50-53 REPRODUCTIVE TRACT INFECTIONS AND DISORDERS VAGINAL BLEEDING PATTERNS* a) Irregular pattern without heavy bleeding 2 2 2 b) Heavy or prolonged bleeding (includes regular and irregular patterns) 2 2 2 Clarification: Unusually heavy bleeding should raise the suspicion of a serious underlying condition. UNEXPLAINED VAGINAL BLEEDING* (suspicious for serious underlying condition) Before evaluation 2 3 3 Clarification: If pregnancy or an underlying pathological condition (such as pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation. ENDOMETRIOSIS 1 1 1 BENIGN OVARIAN TUMOURS (including cysts) 1 1 1 SEVERE DYSMENORRHOEA 1 1 1 See also additional comments at end of table Page 8 – Progestogen-only contraceptives PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE TROPHOBLAST DISEASE a) Benign gestational trophoblastic disease 1 1 1 b) Malignant gestational trophoblastic disease 1 1 1 CERVICAL ECTROPION 1 1 1 CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) 1 2 2 Evidence: Among women with persistent HPV infection, long-term DMPA use (> 5 years) may increase the risk of carcinoma in situ and invasive carcinoma.54 CERVICAL CANCER (awaiting treatment)* 1 2 2 BREAST DISEASE* a) Undiagnosed mass 2 2 2 Clarification: Evaluation should be pursued as early as possible. b) Benign breast disease 1 1 1 c) Family history of cancer 1 1 1 d) Breast cancer (i) current 4 4 4 (ii) past and no evidence of current disease for 5 years 3 3 3 ENDOMETRIAL CANCER* 1 1 1 OVARIAN CANCER* 1 1 1 UTERINE FIBROIDS* a) Without distortion of the uterine cavity 1 1 1 b) With distortion of the uterine cavity 1 1 1 * See also additional comments at end of table Progestogen-only contraceptives – Page 9 PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE PELVIC INFLAMMATORY DISEASE (PID)* a) Past PID (assuming no current risk factors for STIs) (i) with subsequent pregnancy 1 1 1 (ii) without subsequent pregnancy 1 1 1 b) PID - current 1 1 1 STIs* a) Current purulent cervicitis or chlamydial infection or gonorrhoea 1 1 1 b) Other STIs (excluding HIV and hepatitis) 1 1 1 c) Vaginitis (including trichomonas vaginalis and bacterial vaginosis) 1 1 1 d) Increased risk of STIs 1 1 1 Evidence: Limited evidence suggests that there may be an increased risk of chlamydial cervicitis among DMPA users at high risk of STIs. For other STIs, there is either evidence of no association between DMPA use and STI acquisition or too limited evidence to draw any conclusions. There is no evidence for other POCs.55-61 HIV/AIDS HIGH RISK OF HIV* 1 1 1 Evidence: Overall, evidence is inconsistent regarding whether there is any increased risk of HIV acquisition among POC users compared with non- users.62-78 HIV-INFECTED 1 1 1 Evidence: Studies are conflicting regarding whether there is an increased risk of HIV and herpes simplex virus (HSV) shedding among HIV-infected women using DMPA.79-81 See also additional comments at end of table Page 10 – Progestogen-only contraceptives PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE AIDS 1 1 1 On ARV therapy 2 2 2 Clarification: If a woman is taking antiretroviral (ARV) therapy, refer to the section on drug interactions. Because there may be drug interactions between hormonal contraceptives and ARVs, AIDS with ARV therapy is classified as Category 2. OTHER INFECTIONS SCHISTOSOMIASIS a) Uncomplicated 1 1 1 Evidence: Among women with uncomplicated schistosomiasis, limited evidence showed that DMPA use had no adverse effects on liver function.82 b) Fibrosis of liver (if severe, see cirrhosis) 1 1 1 TUBERCULOSIS a) Non-pelvic 1 1 1 Clarification: If a woman is taking rifampicin, refer to the section on drug interactions. Rifampicin is likely to decrease POC effectiveness. b) Known pelvic 1 1 1 MALARIA 1 1 1 ENDOCRINE CONDITIONS DIABETES* a) History of gestational disease 1 1 1 b) Non-vascular disease (i) non-insulin dependent 2 2 2 (ii) insulin dependent 2 2 2 * See also additional comments at end of table Progestogen-only contraceptives – Page 11 PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE DIABETES (Cont'd) c) Nephropathy/ retinopathy/ neuropathy 2 3 2 d) Other vascular disease or diabetes of >20 years' duration 2 3 2 THYROID DISORDERS a) Simple goitre 1 1 1 b) Hyperthyroid 1 1 1 c) Hypothyroid 1 1 1 GASTROINTESTINAL CONDITIONS GALL-BLADDER DISEASE a) Symptomatic (i) treated by cholecystectomy 2 2 2 (ii) medically treated 2 2 2 (iii) current 2 2 2 b) Asymptomatic 2 2 2 HISTORY OF CHOLESTASIS* a) Pregnancy-related 1 1 1 b) Past COC-related 2 2 2 VIRAL HEPATITIS* . a) Active 3 3 3 b) Carrier 1 1 1 CIRRHOSIS* a) Mild (compensated) 2 2 2 b) Severe (decompensated) 3 3 3 See also additional comments at end of table Page 12 – Progestogen-only contraceptives PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE LIVER TUMOURS* a) Benign (adenoma) 3 3 3 b) Malignant (hepatoma) 3 3 3 ANAEMIAS THALASSAEMIA 1 1 1 SICKLE CELL DISEASE 1 1 1 Evidence: Among women with sickle cell disease, POC use did not have adverse effects on haematological parameters and, in some studies, was beneficial with respect to clinical symptoms.83-90 IRON-DEFICIENCY ANAEMIA* 1 1 1 DRUG INTERACTIONS DRUGS WHICH AFFECT LIVER ENZYMES a) Rifampicin 3 2 3 b) Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine) 3 2 3 Clarification: Although the interaction of rifampicin or certain anticonvulsants with POPs and LNG/ETG implants is not harmful to women, it is likely to reduce the effectiveness of POPs and LNG/ETG implants. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. Whether increasing the hormone dose of POPs alleviates this concern remains unclear. Evidence: Use of certain anticonvulsants decreased the contraceptive effectiveness of POCs.91-93 ANTIBIOTICS (excluding rifampicin) a) Griseofulvin 2 1 2 b) Other antibiotics 1 1 1 * See also additional comments at end of table Progestogen-only contraceptives – Page 13 PROGESTOGEN- ONLY CONTRACEPTIVES (POCs) POCs do not protect against STI/HIV. If there is risk of STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Male latex condoms are proven to protect against STI/HIV. CATEGORY I=Initiation, C=Continuation CONDITION POP D/NE LNG/ETG CLARIFICATIONS/EVIDENCE ANTIRETROVIRAL THERAPY 2 2 2 Clarification: It is important to note that antiretroviral drugs (ARV) have the potential to either decrease or increase the bioavailability of steroid hormones in hormonal contraceptives. The limited data available (outlined in Annex 1) suggest that potential drug interactions between many ARVs (particularly some non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)) and hormonal contraceptives may alter safety and effectiveness of both the hormonal contraceptives and the ARVs. It is not known whether the contraceptive effectiveness of progestogen-only injectable contraceptives (such as depot medroxyprogesterone acetate and norethisterone enantate) would be compromised, as these methods provide higher blood hormone levels than other progestogen-only hormonal contraceptives, as well as than combined oral contraceptives. Studies are underway to evaluate potential interactions between depot medroxyprogesterone acetate and selected PI and NNRTI drugs. Thus, if a woman on ARV treatment decides to initiate or continue hormonal contraceptive use, the consistent use of condoms is recommended for preventing HIV transmission and may also compensate for any possible reduction in the effectiveness of the hormonal contraceptive. Page 14 – Progestogen-only contraceptives Additional comments AGE Menarche to < 18 years: For women under 18 years of age, there are theoretical concerns regarding the hypo- estrogenic effects of DMPA use, including whether these women will achieve their appropriate peak bone mass. > 45 years: For women greater than age 45, there are theoretical concerns regarding hypo-estrogenic effects of DMPA use, including whether these women will regain all lost bone mass after discontinuation of DMPA. POSTPARTUM < 21 days: POCs may be safely used by non-breastfeeding women immediately postpartum. PAST ECTOPIC PREGNANCY POPs have a higher absolute rate of ectopic pregnancy compared with other POCs, but still less than using no method. HYPERTENSION Vascular disease: There is concern regarding hypo-estrogenic effects and reduced HDL levels, particularly among users of DMPA and NET-EN. However, there is little concern about these effects with regard to POPs or LNG/ETG implants. The effects of DMPA and NET-EN may persist for some time after discontinuation. DEEP VENOUS THROMBOSIS (DVT)/ PULMONARY EMBOLISM (PE) Some POCs may increase the risk of venous thrombosis, although this increase is substantially less than with COCs. CURRENT AND HISTORY OF ISCHAEMIC HEART DISEASE There is concern regarding hypo-estrogenic effects and reduced HDL levels, particularly among users of DMPA and NET-EN. However, there is little concern about these effects with regard to POPs or LNG/ETG implants. The effects of DMPA and NET-EN may persist for some time after discontinuation. STROKE There is concern regarding hypo-estrogenic effects and reduced HDL levels, particularly among users of DMPA and NET-EN. However, there is little concern about these effects with regard to POPs or LNG/ETG implants. The effects of DMPA and NET-EN may persist for some time after discontinuation. HEADACHES Aura is a specific focal neurologic symptom. For more information on this and other diagnostic criteria, see: Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd Edition. Cephalalgia. 2004; 24 (Suppl 1): 1- 150. http://216.25.100.131/ihscommon/guidelines/pdfs/ihc_II_main_no_print.pdf There is concern that severe headaches may increase with use of NET-EN, DMPA and implants. The effects of NET-EN and DMPA may persist for some time after discontinuation. VAGINAL BLEEDING PATTERNS Irregular menstrual bleeding patterns are common among healthy women. POC use frequently induces an irregular bleeding pattern. Implant use may induce irregular bleeding patterns, especially during the first 3-6 months, but these patterns may persist longer. ETG users are more likely than LNG users to develop amenorrhoea. UNEXPLAINED VAGINAL BLEEDING POCs may cause irregular bleeding patterns which may mask symptoms of underlying pathology. The effects of DMPA and NET-EN may persist for some time after discontinuation. CERVICAL CANCER (awaiting treatment) There is some theoretical concern that POC use may affect prognosis of the existing disease. While awaiting treatment, women may use POCs. In general, treatment of this condition renders a woman sterile. BREAST DISEASE Breast cancer: Breast cancer is a hormonally sensitive tumour, and the prognosis of women with current or recent breast cancer may worsen with POC use. ENDOMETRIAL CANCER While awaiting treatment, women may use POCs. In general, the treatment of this condition renders a woman sterile. OVARIAN CANCER While awaiting treatment, women may use POCs. In general, the treatment of this condition renders a woman sterile. UTERINE FIBROIDS POCs do not appear to cause growth of uterine fibroids. Progestogen-only contraceptives – Page 15 PELVIC INFLAMMATORY DISEASE (PID) Whether POCs, like COCs, reduce the risk of PID among women with STIs is unknown, but they do not protect against HIV or lower genital tract STI. STIs Whether POCs, like COCs, reduce the risk of PID among women with STIs is unknown, but they do not protect against HIV or lower genital tract STI. HIGH RISK OF HIV Whether POCs, like COCs, reduce the risk of PID among women with STIs is unknown, but they do not protect against HIV or lower genital tract STI. DIABETES Non-vascular disease: POCs may alter carbohydrate metabolism. Nephropathy, retinopathy, neuropathy: There is concern regarding hypo-estrogenic effects and reduced HDL levels, particularly among users of DMPA and NET-EN. The effects of DMPA and NET-EN may persist for some time after discontinuation. Some POCs may increase the risk of thrombosis, although this increase is substantially less than with COCs. Other vascular disease or diabetes of > 20 years’ duration: There is concern regarding hypo-estrogenic effects and reduced HDL levels, particularly among users of DMPA and NET-EN. The effects of DMPA and NET-EN may persist for some time after discontinuation. Some POCs may increase the risk of thrombosis, although this increase is substantially less than with COCs. HISTORY OF CHOLESTASIS Theoretically, a history of COC-related cholestasis may predict subsequent cholestasis with POC use. However, this has not been documented. VIRAL HEPATITIS Active: POCs are metabolized by the liver and their use may adversely affect women whose liver function is compromised. This concern is similar to, but less than, that with COCs. CIRRHOSIS POCs are metabolized by the liver and their use may adversely affect women whose liver function is compromised. This concern is similar to, but less than, that with COCs. LIVER TUMOURS POCs are metabolized by the liver and their use may adversely affect women whose liver function is compromised. In addition, POC use may enhance the growth of tumours. This concern is similar to, but less than, that with COCs. IRON-DEFICIENCY ANAEMIA Changes in the menstrual pattern associated with POC use have little effect on haemoglobin levels. Page 16 – Progestogen-only contraceptives References for progestogen-only contraception 1. Busen NH, Britt RB, Rianon N. Bone mineral density in a cohort of adolescent women using depot medroxyprogesterone acetate for one to two years. Journal of Adolescent Health, 2003, 32:257-9. 2. Cromer BA et al. 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