Rev Endocr Metab Disord DOI 10.1007/s11154-011-9177-1

Putting risk into perspective: The US medical eligibility criteria for contraceptive use Kathryn M. Curtis & Naomi K. Tepper & Polly A. Marchbanks

# Springer Science+Business Media, LLC (outside the USA) 2011

Abstract Unintended pregnancy remains a considerable problem in the United States, with health risks for both mother and infant. These risks may be increased among women with medical conditions, for whom pregnancy can lead to severe adverse outcomes. Highly effective and safe contraceptive methods are available to prevent unintended pregnancy. However, women with medical conditions and their providers also may be concerned about potential risks associated with contraceptive method use. Evidence-based guidance documents can be helpful tools for clinicians to efficiently use evidence and put risks into perspective. The US Medical Eligibility Criteria for Contraceptive Use, 2010, provides evidence-based recommendations for the safety of contraceptive use among women with medical conditions and other characteristics. While some contraceptive methods pose risks for some women, these must be considered in context and weighed against such considerations as the absolute risk of adverse events and the risks associated with pregnancy. Most women, even women with medical conditions, can safely use highly effective methods of contraception and promoting their use will further efforts to reduce unintended pregnancy. Keywords Contraception . Diabetes . Evidence-based guidelines . Inflammatory bowel disease . Obesity . Risk

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. K. M. Curtis (*) : N. K. Tepper : P. A. Marchbanks Division of Reproductive Health, Centers for Disease Control and Prevention, MS K-34, 4770 Buford Highway NE, Atlanta, GA 30341, USA e-mail: [email protected]

1 Introduction Rates of unintended pregnancy remain high in the United States and have changed little in the last two decades [1]. About half of all pregnancies are unintended, and one in ten women ages 18–24 will have an unintended pregnancy every year [1]. Women who experience an unintended pregnancy are at increased risk for adverse pregnancy behaviors and outcomes, including increased rates of abortion, later entry into prenatal care, decreased likelihood of smoking cessation and increased incidence of low birth weight [2, 3]. For women with underlying medical conditions, the consequences of an unintended pregnancy can be even more serious, including substantial risk of morbidity and even death for the woman and increased risk for birth defects, prematurity, and death of the infant. Safe and highly effective contraceptive methods are available to prevent unintended pregnancy. While all contraceptive methods have the potential for side effects and, rarely, serious adverse events, most women – even those with medical conditions – can safely use most methods of contraception. Most contraceptive methods also have noncontraceptive benefits, such as decreased risk of ovarian and endometrial cancer for oral contraceptive users and decreased vaginal bleeding for users of progestin-only methods [4]. The goal of contraceptive decision making is to maximize the effectiveness of the contraceptive method while minimizing any potential risks. Both provider and patient perception of contraceptive method effectiveness and risks and benefits play an important role in making these decisions. However, many providers and patients have misperceptions about contraceptive risks [5–7] – both risks of adverse events and risk of contraceptive failure – and, therefore, it is critical to be able to put these risks into perspective in order to make informed choices about contraceptive methods.

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Evidence-based guidance is one tool that can assist providers in accurately assessing risks and benefits. The Centers for Disease Control and Prevention (CDC) recently published the U. S. Medical Eligibility Criteria for Contraceptive Use, 2010 [8], which provides evidence-based recommendations for the safe use of contraceptive methods for women with medical conditions and other characteristics. This guidance document should help providers in accurately assessing contraceptive safety for specific women, especially women with serious medical conditions, who need to choose a method that they can use effectively in order to prevent serious sequelae associated with unintended pregnancy.

2 Evidence-based guidance for contraceptive use: the US Medical Eligibility Criteria for Contraceptive Use, 2010 Many clinicians rely on evidence-based guidelines to efficiently use the best scientific evidence when making decisions about patient care. Clinical practice guidelines have been defined by the Institute of Medicine as “systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances” [9]. Evidence-based guidelines are those that are based on a critical appraisal of the scientific literature, most often through systematic reviews and metaanalyses, and link the recommendation to the scientific evidence [9]. Evidence-based guidelines are intended to be “assistive rather than directive,” [10] and are not meant to replace clinical judgment [11]. A critical component of evidence-based guidance is weighing potential harms and benefits of the recommendations [12], and therefore, must take competing risks into account. In the early 1990’s, the World Health Organization (WHO) and others became concerned about unnecessary medical barriers to contraceptive access that were not based on scientific evidence, with particular concern that some medical conditions or other characteristics were being mistakenly perceived as contraindications to contraceptive use [13]. In many parts of the world, this resulted in women with medical conditions being denied contraceptive methods [13]. This placed women at risk of unintended pregnancy and, for those with existing medical conditions, potentially severe consequences. WHO sought to examine the scientific evidence and develop a guidance document that would restrict contraceptive access to women with specific conditions when it was necessary to protect health, but more often remove unnecessary medical barriers and expand access to a wide range of contraceptive methods to assist women in preventing unintended pregnancy. In 1996, WHO published the first edition of the Medical Eligibility Criteria for Contraceptive Use (MEC). This global guidance document provided recommendations for the safe use of specific contraceptive methods among women with

particular medical conditions, for example, whether a woman with diabetes can use combined hormonal contraceptive (CHC) methods or whether a women can have an intrauterine device (IUD) inserted immediately postpartum. Currently, the WHO MEC is in its fourth edition and contains recommendations for 18 contraceptive methods and over 160 medical conditions or characteristics [14]. Each medical condition and contraceptive method combination is given a classification from 1 to 4 (Table 1), denoting whether or not the contraceptive method is safe to use for women with that medical condition or characteristic. WHO always intended for its global guidance to be reviewed and adapted for best implementation at the local level. The Centers for Disease Control and Prevention (CDC) collaborates with WHO on the development of the global guidance, and recently adapted the WHO MEC for use by health care providers in the United States [15]. Through the adaptation process, CDC determined that the majority of the WHO guidance could be taken directly for use in the United States. However, there were a small number of recommendations that were considered for adaptation, either because of new scientific evidence or the context of family planning provision in the United States. CDC also determined the need to add recommendations for a small number of additional medical conditions that were not currently included in the WHO MEC. Systematic reviews of the scientific evidence on these topics were conducted and peer reviewed by experts in the United States. CDC convened a meeting of experts, during which the scientific evidence was discussed and draft recommendations were made. Research gaps in the areas addressed were also identified [16]. The outcome of this meeting was the US Medical Eligibility Criteria for Contraceptive Use, 2010 (US MEC). [8] This document is intended to assist health care providers when counseling women, men, and couples about contraceptive choice and to be used as a source of clinical guidance. It is anticipated that this guidance will expand contraceptive options for many women in the United States with medical conditions or other characteristics, while Table 1 United States medical eligibility criteria for contraceptive use classifications Classification

Definition

1

No restriction for the use of the contraceptive method The advantages of using the method generally outweigh the theoretical or proven risks The theoretical or proven risks usually outweigh the advantages of using the method An unacceptable health risk if the contraceptive method is used

2 3 4

Source: US Medical Eligibility Criteria for Contraceptive Use, 2010 [8]

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appropriately limiting access in cases where there is evidence for increased risk of adverse health outcomes. Once a clinical guideline is produced, dissemination, implementation, and evaluation of the guideline are essential. A critical component of CDC’s dissemination and implementation plan is working closely with partners who provide family planning services or who represent family planning providers in order to effectively disseminate and implement this new guidance. The US MEC is available on CDC’s website (http://www.cdc.gov/reproductivehealth/Unintended Pregnancy/USMEC.htm), along with tools and job aids for providers, speaker presentations, and any updates that are made based on new scientific evidence. Additional implementation activities include developing training curricula for different providers and incorporating the guidance into existing clinical standards and guidelines used by various organizations. Evaluation activities include conducting baseline and follow-up surveys of attitudes and practices among family planning providers, monitoring where the guidance has been incorporated into clinical practice, and obtaining feedback from individual providers and organizations. In addition, CDC will examine new scientific results and update the recommendations as new evidence warrants.

much, if not all, of the bone mineral density is regained upon discontinuation of DMPA [20]. These findings have led to concern about the potential for fracture among DMPA users. However, bone mineral density is one measure of bone strength and has not been shown to be predictive of fracture risk in women of reproductive age [18]. The surrogate endpoint of bone mineral density does not assess the effect of DMPA on risk of fracture [18]. Valid surrogate end points must not only correlate with the clinical outcome of interest but must also capture the effect of the treatment on the outcome of interest [18]. Therefore, it is critical to assess whether the surrogate endpoint is an accurate proxy for the adverse outcome of interest. Finally, while women frequently have a range of contraceptive options to choose from, each with different risks and benefits, it is necessary to take into account the risk of adverse events associated with pregnancy, in order to gain full perspective of the risks. For example, while the use of combined hormonal methods increases the risk of venous thromboembolism (VTE) by a factor of 3–6 and the absolute risk remains low [21], the risk of VTE during the postpartum period increases 10-fold as compared to the risk among non-pregnant women [22]. 3.1 Obesity

3 Putting risk into perspective Evaluating risk and putting risk into perspective can be challenging for providers and patients. Risks are not always presented in ways that are easy to understand and many times understanding of risk is influenced by media reports, anecdotal reports from friends, and individual experiences of providers. Often risks are presented in the scientific literature as relative risks (risk ratios or odds ratios), which compare the risk of an adverse event in an “exposed” group to the risk of the adverse event in an “unexposed” group. For example, women who use combined oral contraceptives (COCs) are about twice as likely to have a stroke than women who are not using COCs, for a relative risk of approximately 2 [17]. However, the absolute risk of a woman of reproductive age experiencing a stroke is very low – around 4 per 100,000 women over 1 year [17]. Therefore, two times that number brings the absolute risk of stroke for COC users to 8 per 100,000 COC users over 1 year – still a rare event [17]. Therefore, it is critical to put relative risks into perspective by examining the absolute risk of the event occurring over time. Another area that can lead to misperceptions of risk is the use of surrogate endpoints when information on clinical events is not available [18]. For example, numerous studies have shown that women who use depot-medroxyprogesterone (DMPA) lose small amounts of bone mineral density [19];

The prevalence of obesity is increasing rapidly in the United States and currently one-third of US women ages 20–39 are obese (body mass index (BMI)≥30 kg/m2) [23]. Obesity is associated with several poor pregnancy outcomes, including gestational diabetes, pre-eclampsia, VTE, cesarean section, and mortality [24]. Maternal obesity is also associated with several negative consequences for the infant including macrosomia, congenital abnormalities, and perinatal death [24]. Therefore, obese women need highly effective contraceptive methods to decrease the risk of unintended pregnancy. However, there have been concerns about both increased risk of contraceptive failure and increased risk of adverse effects among obese women who use hormonal contraception. Hormonal contraceptives may be less effective in obese women due to greater body mass or to metabolic changes in obesity [25]. Two recent reviews examined studies of hormonal contraceptive failure among women who were overweight or obese [25, 26]. Overall, the body of evidence was fairly inconsistent, with some studies finding increases in hormonal contraceptive failure with higher BMI or body weight, while others found no association. However, the increased relative risks were modest (odds ratios around 2.0 or less). Limitations of these studies include reliance on selfreported weight, lack of reliable measures of contraceptive use, and inadequate sample sizes. Given these limitations, there is a possibility that the observed results may be biased.

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However, if these results are true, it is important to consider the absolute effect. The two studies finding an association between body weight or BMI and COC failure reported relative risk estimates in the range of 1.5–1.6. It has been estimated that the failure rate of COCs among non-obese women would be 7.6% during typical use, under the assumption that 25% of COC users are obese [26]. If obesity increases the risk of failure by 60% (relative risk of 1.6), the failure rate would rise to 12% for obese women, which is still more effective than typical use of barrier methods. There is also concern about risk of VTE, as both CHCs and obesity are independent risk factors for VTE [21]. Although estimates from individual studies vary, a recent review estimated the absolute annual risk of VTE among CHC users of normal weight (BMI 20–24) to be 34 per 100,000 [27]. The same review estimated the risk for CHC users with BMI≥35 to be 63–176 per 100,000 women, increased but still a rare event [27]. When taking these various risks into perspective, women who are obese can use any method of contraception (US MEC 1 or 2). CHCs are classified as a US MEC 2 because of the theoretical concern about the potential for decreased contraceptive effectiveness and because of the increased risk of VTE [8]. 3.2 Inflammatory bowel disease Inflammatory bowel disease (IBD) includes two disorders of the gastrointestinal tract – ulcerative colitis and Crohn’s disease – with rates among women of 160 per 100,000 for ulcerative colitis and 103 per 100,000 for Crohn’s disease in the United States [28]. Pregnancy among women with IBD can exacerbate disease and lead to adverse maternal and infant outcomes. Among women with inactive IBD when they become pregnant, about one-third will relapse during pregnancy. For women who become pregnant while they have active disease, more than half will either continue to have active disease or experience worsening of disease activity during pregnancy [29]. Active disease increases risk of miscarriage, prematurity, and low birth weight [29, 30]. Finally, while most treatment options for IBD are considered safe during pregnancy, methotrexate is teratogenic; women using methotrexate are in need of highly effective contraception to prevent pregnancy [31]. Women with IBD may be concerned that hormonal contraceptive methods may also increase the risk for relapse or worsening of disease. A recent systematic review of the safety of contraceptive use among women with IBD summarized evidence from five cohort studies and concluded that oral contraceptive (OC) use among IBD patients did not increase the risk of relapse, including relapse rate, time to relapse or need for further surgery [32].

Women with IBD, especially those with active or extensive disease, may be at increased risk for VTE, with one study showing a 3.5 times increased risk above those without IBD [32]. While no studies have examined the risk of VTE among women with IBD who use hormonal methods of contraception, given that CHCs also increase risk of VTE, this is an area of caution. However, this theoretical concern should be considered in the context of the overall rate of VTE. Because the absolute rate of VTE among reproductive age women is low (about 1–10 per 10,000 annually) [33], any increased risk among women with IBD who use CHCs would still result in a relatively small number of events. Finally, because oral contraceptives (OCs) are absorbed in the small bowel, there has been concern about decreased absorption of OCs, which may lead to decreased contraceptive effectiveness. Evidence from two pharmacokinetic studies suggested that absorption of COCs with higher doses of estrogen and progestin than those used today did not significantly differ between women with mild ulcerative colitis and those with small resections when compared with healthy women [32]. However, there is no evidence examining lower doses of hormones or progestin-only pills, and no evidence among women with Crohn’s disease, which most commonly affects the small bowel where OCs are absorbed [32]. Women with IBD can use any contraceptive method (US MEC 1 or 2), with the exception of those who are at increased risk of VTE (for example, women with active or extensive IBD disease), for whom CHCs are classified as US MEC 3 [8]. 3.3 Diabetes Approximately 10% of women aged 20 years or greater in the United States have diabetes and the incidence is increasing [34, 35]. Women with diabetes are at increased risk of pregnancy complications, including an increased risk of progression of their diabetes as well as a two to four-fold increased risk for congenital anomalies [36–38]. For some women with severe diabetes, including those with gastroparesis, advanced nephropathy, or ischemic heart disease, risk of morbidity is so high that pregnancy is relatively contraindicated [36]. Because risks can be decreased by planning pregnancy at a time when optimal glucose levels are reached, much effort has gone into providing preconception care to women with diabetes, including contraceptive care [38]. However, women with diabetes may be presented with limited contraceptive options due to perceived risks associated with the use of various contraceptive methods, including metabolic or vascular complications [39]. Studies examining the effects of hormonal contraceptives among diabetic women have looked at a variety of outcomes.

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Some studies have shown worsening of short-term markers of diabetes control, such as insulin requirements or blood glucose levels, in diabetic women using COCs [40, 41]. Studies have also shown that COC and DMPA use among diabetic women affected lipid levels but did not impact risk for myocardial infarction [40–42]. Studies generally have not shown effects on other sequelae such as retinopathy or renal function in diabetic women using hormonal methods [43, 44]. Interpretation of these results requires consideration of the outcomes examined. Among diabetic women, studies have focused primarily on surrogate end points, such as changes in insulin requirements or serum lipid levels, with few studies of clinical outcomes, such as progression of retinopathy or vascular disease. The use of surrogate end points in clinical studies can be preferable as a substitute for the true clinical event of interest because they often allow smaller sample sizes and shorter follow-up periods [18]. However, some studies have used surrogate end points

which do not adequately represent the clinical outcome of interest or have not been tested. Nonetheless, despite the limitations of the evidence, the risks for diabetic women using contraception must be balanced against the risks of pregnancy. Based on the available evidence, most women with diabetes, including those with gestational diabetes and those without vascular disease, can use all methods of contraception (US MEC 1 or 2). However, women with complicated or long-standing diabetes should generally not use CHCs (US MEC 3/4) or DMPA (US MEC 3) [8].

4 Contraceptive effectiveness Providers and patients often have misperceptions about the risk of contraceptive failure – both the absolute risk of failure for a given contraceptive method and the relative effectiveness

Fig. 1 Comparing effectiveness of contraceptive methods. Source: Family Health International. http://www.fhi.org/nr/shared/enFHI/Resources/ EffectivenessChart.pdf Accessed April 27, 2011

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among different methods. Contraceptive effectiveness is related to contraceptive safety, as a more effective method will lead to a greater decrease in the risks associated with unintended pregnancy. This can be more important for women with medical conditions, for whom unintended pregnancy may be associated with greater risks. For example, a woman with diabetes may be concerned about the effects of CHCs on her glucose control. However, the risks of unintended pregnancy in a woman with uncontrolled diabetes must be considered and, although CHCs may be safe for her, a more effective, longacting method (IUD or implant) may be more appropriate. The distinction between perfect use and typical use is important when assessing the effectiveness of contraceptive methods. Perfect use describes the correct and consistent use of the method; typical use describes how the method is used in the real world [45]. Methods that require little action on the part of the user (for example, IUDs) tend to be highly effective with little difference between perfect and typical effectiveness, while methods that require specific action on the part of the user (for example, taking a pill every day, inserting a diaphragm or using a condom with every act of intercourse) have lower typical effectiveness rates [45]. User satisfaction and side effects also play a role in effectiveness, as these factors affect adherence to and continued use of the method. Contraceptive effectiveness has been shown to be one of the most important factors considered by women when choosing a method of contraception [7]. However, individuals often do not have inherent understanding of comparative effectiveness of contraceptives and communication of this concept can be challenging for providers. Studies assessing different ways to communicate contraceptive effectiveness have shown that simple charts comparing one method to another perform better than more complicated charts showing pregnancy rates for each individual method [7]. WHO and other organizations use a pictorial chart that portrays contraceptive methods in four tiers of effectiveness (Fig. 1). While use of methods with high typical effectiveness, such as IUDs, is rising, their overall use remains low [46]. This is due to a variety of factors but likely largely due to concerns among women and providers about associated risks. The risks of the contraceptive methods must be weighed against the risk of unintended pregnancy resulting from contraceptive failure. Most women can use highly effective methods of contraception safely, which is a critical consideration when balanced against the risks of pregnancy particularly in women with medical conditions.

5 Conclusion Unintended pregnancy remains a significant public health problem, with risks for both mother and infant. Increasing

use of safe and highly effective methods of contraception is an important strategy to reduce unintended pregnancy, particularly for women with medical problems who might face severe consequences of pregnancy. Evidence-based guidance regarding the safety of contraceptive methods among women with medical conditions can help providers examine the scientific evidence and put risks into perspective. Most women, even women with medical conditions, can safely use highly effective methods of contraception and promoting their use will further efforts to reduce unintended pregnancy. Communication of risks and benefits, including accurate information regarding effectiveness of contraceptive methods, is critical in the dialogue between a woman and her provider with the goal of choosing the best contraceptive method for each woman.

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