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Contraceptive considerations in obese women

      Abstract

      Contraceptive failure is the primary cause of unintended pregnancy in the United States. With obesity rates at epidemic proportions, any association between obesity and strategies that prevent undesired pregnancies constitutes a significant public health and economic concern. Unfortunately, the relationship between obesity and contraception has not been extensively studied. Evidence from several epidemiological studies suggests that obesity may increase failure of some hormonal contraceptives resulting in unplanned pregnancies. Obesity may make procedure-dependent contraceptive methods (i.e., sterilization and intrauterine devices) more technically challenging for the provider to perform. Hormonal contraceptives, on the whole, do not appear to adversely affect body weight and provide important noncontraceptive benefits (i.e., cancer protection). Some surgical interventions to treat bariatric issues may compromise the efficacy of orally dosed contraceptive methods. Overall, the Society of Family Planning strongly encourages the use of both hormonal and nonhormonal methods of contraception in obese women desiring pregnancy prevention with very few restrictions. Further studies are needed to determine the interrelationship between obesity and contraception. In addition, future contraceptive efficacy studies need to include women of differing BMIs to better reflect the population of women using these methods.

      Keywords

      Background

      The rate of obesity worldwide is at epidemic proportions with 1 billion and 300 million adults meeting the criteria for overweight and obese, respectively [

      World Health Report 2002. Overweight, obesity, and high body mass, p 60. Accessed and downloaded 1.27.09. http://www.who.int/whr/2002/en/whr02_en.pdf. [Evidence grade: III].

      ]. Currently, the obesity rate in Europe and the United States is approximately 30% and rising [

      World Health Report 2002. Overweight, obesity, and high body mass, p 60. Accessed and downloaded 1.27.09. http://www.who.int/whr/2002/en/whr02_en.pdf. [Evidence grade: III].

      ,
      • Hedley A.A.
      • Ogden C.L.
      • Johnson C.L.
      • Carroll M.D.
      • Curtin L.R.
      • Flegal K.M.
      Overweight and obesity among US children, adolescents, and adults, 1999–2002.
      ]. The prevalence of unintended pregnancy rivals that of obesity. Forty-nine percent of all pregnancies per year in the United States are unintended (3.1 million), and roughly half a million of these are related to oral contraceptive failures [
      • Finer L.B.
      • Henshaw S.K.
      Disparities in rates of unintended pregnancy in the United States, 1994 and 2001.
      ]. Obesity is known to affect the health of both present and future generations with higher rates of both maternal and fetal morbidity and mortality, and increased rates of obesity and diabetes in offspring [
      • Rode L.
      • Nilas L.
      • Wojdemann K.
      • Tabor A.
      Obesity-related complications in Danish single cephalic term pregnancies.
      ,
      • Nohr E.
      • Bech B.
      • Davies M.
      • Frydenberg M.
      • Henriksen T.
      • Olsen J.
      Prepregnancy obesity and fetal death: a study within the Danish national birth cohort.
      ,
      • Catalano P.M.
      • Ehrenberg H.M.
      The short- and long-term implications of maternal obesity on the mother and her offspring.
      ,
      • Boney C.M.
      • Verma A.
      • Tucker R.
      • Vohr B.R.
      Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus.
      ,
      • Whitaker R.C.
      Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy.
      ]. Thus, any association between obesity and the ability to prevent pregnancies constitutes a significant public health and economic concern. Unfortunately, most contraceptive research has excluded women above 130% of ideal body weight, making it difficult to counsel these women regarding their risk for contraceptive failure [
      • Grimes D.A.
      • Shields W.C.
      Family planning for obese women: challenges and opportunities.
      ].
      Use of a safe and effective contraceptive method in women with chronic medical conditions, like obesity, is paramount since these women are at higher risk of pregnancy-related complications. In addition, many contraceptive methods may offer important noncontraceptive benefits for these women [
      • World Health Organization
      Endometrial cancer and combined oral contraceptives: the WHO Collaborative Study of Neoplasia and Steroid Contraceptives.
      ,
      World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives
      Depot-medroxyprogesterone acetate (DMPA) and risk of endometrial cancer.
      ,
      • Guleria K.
      • Agarwal N.
      • Mishra K.
      • Gulati R.
      • Mehendiratta A.
      Evaluation of endometrial steroid receptors and cell mitotic activity in women using copper intrauterine device: Can Cu-T prevent endometrial cancer?.
      ,
      • Varma R.
      • Sinha D.
      • Gupta J.K.
      Non-contraceptive uses of levonorgestrel-releasing hormone system (LNG-IUS)—A systematic enquiry and overview.
      ]. However, obese women are less likely to use contraception or to receive preventative health care services as compared to women with a normal BMI [
      • Cohen S.S.
      • Palmieri R.T.
      • Nyante S.J.
      • Koralek D.O.
      • Kim S.
      • Bradshaw P.
      • et al.
      Obesity and screening for breast, cervical, and colorectal cancer in women: a review.
      ,
      • Chuang C.H.
      • Chase G.A.
      • Bensyl D.M.
      • Weisman C.S.
      Contraceptive use by diabetic and obese women.
      ]. It is unclear whether this disparity is related to patient, provider or systems issues. In regard to contraceptive care, perhaps there is an assumption that fertility is impaired and contraception is unnecessary, other health issues supersede contraceptive counseling or there is a perception that contraception would be riskier than a pregnancy. However, it is essential that the risks of contraceptive use in obese women and the potential impact of obesity on contraceptive efficacy be compared to the health, financial and personal implications of an unplanned pregnancy. The use of contraception in obese women will always prevent more pregnancies than no contraception even in the event of impaired contraceptive effectiveness and is universally always less risky to these women than a pregnancy.
      The inherent efficacy of hormonal contraception in obese users has not been well studied. The research is inconsistent and demonstrates either no difference between BMI categories or an increase in contraceptive failures in the obese group [
      • Holt V.
      • Cushing-Haugen K.
      • Daline J.
      Body weight and risk of oral contraceptive failure.
      ,
      • Holt V.
      • Scholes D.
      • Wicklund K.
      • Cushing-Haugen K.
      • Daling J.
      Body mass index, weight, and oral contraceptive failure risk.
      ,
      • Norris P.
      • Kamat A.
      • Estes C.
      • Medina C.
      • Pietro P.
      • Whitted W.
      Oral abstract presentation: contraceptive failure in overweight patients taking combination oral contraceptive pills.
      ,
      • Brunner Huber L.R.
      • Hogue C.J.
      The association between body weight, unintended pregnancy resulting in a livebirth, and contraception at the time of conception.
      ,
      • Brunner L.R.
      • Hogue C.J.
      The role of body weight in oral contraceptive failure: results from the 1995 National Survey of Family Growth.
      ,
      • Brunner Huber L.R.
      • Toth J.L.
      Obesity and oral contraceptive failure: findings from the 2002 National Survey of Family Growth.
      ,
      • Kaneshiro B.
      • Edelman A.
      • Carlson N.
      • Nichols M.
      • Jensen J.T.
      The relationship between body mass index and unintended pregnancy results from the 2002 National Survey of Family Growth.
      ,
      • Brunner Huber L.R.
      • Hogue C.J.
      • Stein A.D.
      • Drews C.
      • Zieman M.
      Body mass index and risk for oral contraceptive failure: a case-cohort study in South Carolina.
      ,
      • Zhang H.
      • LaGuardia K.
      • Creanga D.
      Higher body weight and body mass index are not associated with reduced efficacy in Ortho Tri-Cyclen Lo Users (Abstract).
      ,
      • Westhoff C.
      • Reape K.
      • Hait H.
      Subject weight and oral contraceptive efficacy in recent clinical trials (Abstract).
      ,
      • Burkman R.
      • Fisher A.
      • Wan G.
      • Barnowski C.
      • LaGuardia K.
      Association between efficacy and body weight or body mass index for two low-dose oral contraceptives.
      ,
      • Vessey M.
      • Painter R.
      Oral contraceptive failures and body weight: findings in a large cohort study.
      ,
      • Dinger J.
      • Cronin M.
      • Mohner S.
      • Schellschmidt I.
      • Minh T.
      • Westhoff C.
      Oral contraceptive effectiveness according to body mass index, weight, age, and other factors.
      ]. There are also significant limitations to most of the studies, the majority of which are retrospective and underpowered with self-reported weight or BMI, self-reported oral contraceptive use/type, and many use databases where unintended pregnancies ending in abortion are significantly underreported or not included [
      National Survey of Family Growth Cycle 6:2002 (Public use file).
      ]. Overall, self-reported weight or BMI in women is fairly accurate in that height is overreported and weight is underreported; objective measurements of weights and heights would then only strengthen the findings of positive studies [
      • Stewart A.W.
      • Jackson R.T.
      • Ford M.A.
      • Beaglehole R.
      Underestimation of relative weight by use of self reported height and weight.
      ,
      • Brunner Huber L.R.
      Validity of self-reported height and weight in women of reproductive age.
      ,
      • Engstrom J.L.
      • Paterson S.A.
      • Doherty A.
      • Trabulsi M.
      • Speer K.L.
      Accuracy of self-reported height and weight in women: an integrative review of the literature.
      ,
      • Perry G.S.
      • Byers T.E.
      • Mokdad A.H.
      • Serdula M.K.
      • Williamson D.F.
      The validity of self-reports of past body weights in US adults.
      ,
      • Troy L.M.
      • Hunter D.J.
      • Manson J.E.
      • Colditz G.A.
      • Stampfer M.J.
      • Willett W.C.
      The validity of recalled weight among younger women.
      ]. Several of the studies were based in Europe where contraceptive effectiveness has been demonstrated to be higher and thus findings would be biased towards a null result [
      • Moreau C.
      • Trussell J.
      • Rodriguez G.
      • Bajos N.
      • Bouyer J.
      Contraceptive failure rates in France: results from a population-based survey.
      ]. Many of these studies were performed at a time where the prevalence of obesity and morbid obesity was less than currently exists. Most importantly, no studies address the potential, if any, biological mechanism for failure of hormonal contraception.
      Obesity is defined based on body mass index (BMI), which is an indirect measure of body fat. BMI has been shown to correlate well to direct assessments of body fat [i.e., dual-energy X-ray absorptiometry, underwater weighing and air displacement plethysmography (BOD POD)] [
      • Mei Z.
      • Grummer-Strawn L.M.
      • Pietrobelli A.
      • Goulding A.
      • Goran M.I.
      • Dietz W.H.
      Validity of body mass index compared with other body-composition screening indexes for the assessment of body fatness in children and adolescents.
      ,
      • Garrow J.S.
      • Webster J.
      Quetelet's index (W/H2) as a measure of fatness.
      ]. BMI is calculated by dividing weight in kilograms by height in meters squared. Although BMI is not a perfect indicator of body fat, it is reliable, inexpensive and easy to perform in a clinical setting. BMI categories are defined by The Centers for Disease Control and Prevention and The World Health Organization as [
      • Perry G.S.
      • Byers T.E.
      • Mokdad A.H.
      • Serdula M.K.
      • Williamson D.F.
      The validity of self-reports of past body weights in US adults.
      ,
      • World Health Organization
      ,
      • The Centers for Disease Control and Prevention
      ]:
      • Underweight <18.5 kg/m2
      • Normal 18.5–24.9 kg/m2
      • Overweight 25–29.9 kg/m2
      • Obese 30–39.9 kg/m2 or Class I obesity 30–34.9 kg/m2 and Class II obesity 35–39.9 kg/m2
      • Very obese ≥40 kg/m2 or otherwise referred to as severe, extreme, morbid or Class III obesity
      This document will review the current evidence regarding the interrelationship between contraception and obesity.

      Clinical questions and recommendations

      1. Are obese women at increased risk for pregnancy as compared to their normal BMI counterparts?

      Abnormalities in metabolism and extremes in body weight can adversely affect the reproductive system. Obesity is a known risk factor for reduced fertility because of menstrual abnormalities, anovulation, polycystic ovarian disease and insulin resistance [
      • Speroff L.
      • Glass R.H.
      • Kase N.G.
      Clinical gynecologic endocrinology and infertility.
      ,
      • Farrow A.
      • Hull M.
      • Northstone K.
      • Taylor H.
      • Ford W.C.
      • Golding J.
      Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception.
      ]. However, the majority of women, both thin and obese, ovulate on a regular basis and are at risk for pregnancy [
      • Speroff L.
      • Glass R.H.
      • Kase N.G.
      Clinical gynecologic endocrinology and infertility.
      ].
      The rate of sexual activity and use of contraception also affect the risk of pregnancy. Many assume that obese women engage in less frequent sexual activity, making them at less risk of pregnancy. An analysis of the 2002 National Survey of Family Growth (NSFG) demonstrated no differences in sexual behaviors between BMI categories in sexually active reproductive-age women [
      • Kaneshiro B.
      • Jensen J.T.
      • Carlson N.E.
      • Harvey S.M.
      • Nichols M.D.
      • Edelman A.B.
      Body mass index and sexual behavior.
      ]. In regard to contraceptive use, an analysis of the Family Planning Module of the Behavioral Risk Factor Surveillance System (BRFSS; 7943 women) found that obese women were significantly less likely to use contraception as compared to normal BMI women [
      • Chuang C.H.
      • Chase G.A.
      • Bensyl D.M.
      • Weisman C.S.
      Contraceptive use by diabetic and obese women.
      ]. It is unclear whether this disparity is due to patient, provider and/or systems issues. Of note, these obese women were also more likely to be older, Black, Hispanic, married, less educated and without health insurance.
      Available information regarding female adolescent sexual activity based on weight differences is somewhat conflicting. A longitudinal study of 200 teens demonstrated that “thinner” girls dated more and thus had more opportunity for and higher frequency of petting and coital activity as compared to “heavier” girls [
      • Halpern C.
      • Udry J.R.
      Effects of body fat on weight concerns, dating, sexual activity: a longitudinal analysis of black and white adolescent girls.
      ]. A survey of 522 African-American female adolescents found that obese adolescents were more likely to have body image dissatisfaction and lower self-esteem issues. These factors were felt to lead to earlier coital debut (<14 years old), fear of abandonment when trying to negotiate condom use, less confidence to refuse an unsafe sexual encounter and higher rates of unprotected intercourse [
      • Wingood G.M.
      • Diclemente R.J.
      • Harrington K.
      • Davies S.L.
      Body image and African American females' sexual Health.
      ].
      Based on these findings, obese adult and adolescent women appear to be at a similar or higher risk of pregnancy as compared to normal BMI women.

      2. Does obesity affect oral contraceptive effectiveness?

      Contraceptive effectiveness relies on medication compliance, sexual behavior (discussed above), fecundity and the inherent efficacy of the medication. Poor medication compliance has been blamed for the majority of oral contraceptive failures. Using an electronic device implanted in pill packages, researchers compared patient self-report and electronic data regarding compliance. Self-reported data significantly underestimated the number of pills missed [
      • Potter L.
      • Oakley D.
      Measuring compliance among oral contraceptive users.
      ]. However, obese women have never been demonstrated to be less compliant with medication than normal BMI women.
      In general, the effect of obesity on drug pharmacokinetics is poorly understood. A study comparing the pharmacokinetics and hypothalamic-pituitary-ovarian activity of obese (BMI >30 mg/k2) and normal (BMI <25 mg/k2) BMI women using a 20-mcg ethinyl estradiol (EE) /100-mcg levonorgestrel oral contraceptive demonstrated that the obese group had a significantly longer levonorgestrel half-life (52.1±29.4 vs. 25.6±9.3 h, p<.05) which correlated with a lower maximum levonorgestrel serum level and a longer time to reach steady state (10 vs. 5 days) [
      • Edelman A.
      • Carlson N.
      • Cherala G.
      • Munar M.
      • Stouffer R.
      • Cameron J.
      • et al.
      Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity.
      ]. There were no significant differences in volume of drug distribution between the BMI groups. Consistent with these pharmacokinetic findings, more obese women demonstrated hormonal changes associated with recruitment and maturation of a dominant follicle, and even ovulation, but the sample size was too small to achieve statistical significance. It is unknown whether these findings translate into an actual risk of pregnancy.
      A few studies support an association between weight or BMI and combined oral contraceptive failure. Holt et al. [
      • Holt V.
      • Cushing-Haugen K.
      • Daline J.
      Body weight and risk of oral contraceptive failure.
      ] performed a retrospective cohort analysis of women from a single health maintenance organization (HMO) in Seattle, WA, who were involved in a dietary study. In the highest overall weight quartile (≥70 kg) and the highest weight quartile of women using oral contraceptives with ≤35 mcg EE, the relative risk of contraceptive failure was significantly increased [RR 1.6 (CI 1.1–2.4) and RR 4.5 (CI 1.4–14.4), respectively]. The study was limited by no weight documentation immediately prior to the contraceptive failure, and self-reported contraceptive failure (no confirmation of pregnancy) and type of oral contraceptive used. In addition, the highest weight quartile was equivalent to the mean weight for the overall population and not reflective of an obese population.
      Holt et al. [
      • Holt V.
      • Scholes D.
      • Wicklund K.
      • Cushing-Haugen K.
      • Daling J.
      Body mass index, weight, and oral contraceptive failure risk.
      ] followed this report with a case-controlled study of women in the same HMO. Women with a BMI of 27.4–32.2 kg/m2 were found to have increased odds of combined oral contraceptive failure [OR 1.58 (CI 1.11–2.24) and OR 1.72 (CI 1.04–2.82)]. Pregnancies were confirmed in this study, but weight in the reference month was self-reported, more cases than controls had been previously pregnant and subjects were excluded if they missed five or more pills in the reference month.
      A case control study using the 1999 Pregnancy Risk Assessment Monitoring System (PRAMS) also found that both overweight and obese women using contraception (type not specified) had an increased chance of contraceptive failure [OR 1.73 (CI 1.2–2.36) and OR 1.75 (CI 1.21–2.52)] [
      • Brunner Huber L.R.
      • Hogue C.J.
      The association between body weight, unintended pregnancy resulting in a livebirth, and contraception at the time of conception.
      ]. This study was limited by self-reported BMI and contraceptive type, and cases were only limited to unintended pregnancies leading to live births because abortions were not tracked. Although the type of contraception in this study was not specified, one could assume that the majority of the study group was using combined oral contraception since that is the most common form of hormonal contraception used in the United States.
      A secondary analysis of a large prospective randomized trial (N=2812 women) evaluated the relationship between contraceptive efficacy and weight/BMI. The primary study compared oral contraceptives containing 25 mcg EE/180/215/250 norgestimate vs. 20 mcg EE/1 mg norethindrone [
      • Burkman R.
      • Fisher A.
      • Wan G.
      • Barnowski C.
      • LaGuardia K.
      Association between efficacy and body weight or body mass index for two low-dose oral contraceptives.
      ]. For the secondary analysis, body habitus indices were dichotomized to either <70 or ≥70 kg or <25 or ≥25 kg/m2. A slight but not statistically significant increase in the relative risk of pregnancy was found in the ≥70 kg and ≥25 kg/m2 groups [RR 1.25 (CI 0.63–2.46) and 1.85 (CI 0.98–3.45), respectively]. This study excluded women with a BMI of >32 kg/m2 and thus does not provide us with information in a truly obese population.
      In contrast, several studies have shown no association between weight or BMI and oral contraceptive failure. Retrospective analyses of the 1995 and the 2002 NSFG showed no evidence of decreased contraceptive efficacy or increased unintended pregnancies in different BMI categories after adjusting for confounders [
      • Brunner L.R.
      • Hogue C.J.
      The role of body weight in oral contraceptive failure: results from the 1995 National Survey of Family Growth.
      ,
      • Brunner Huber L.R.
      • Toth J.L.
      Obesity and oral contraceptive failure: findings from the 2002 National Survey of Family Growth.
      ,
      • Kaneshiro B.
      • Edelman A.
      • Carlson N.
      • Nichols M.
      • Jensen J.T.
      The relationship between body mass index and unintended pregnancy results from the 2002 National Survey of Family Growth.
      ]. The NSFG is limited by self-reported BMI, oral contraceptive use, oral contraceptive type (does not differentiate between combined and progestin-only) and pregnancies. In addition, abortions are significantly underreported (only 43%) in the NSFG [
      National Survey of Family Growth Cycle 6:2002 (Public use file).
      ]. Using the 1999 BRFSS and the 2000 PRAMS for South Carolina, a case-cohort study was performed and found no decreased contraceptive efficacy in obese women after adjusting for confounders [
      • Brunner Huber L.R.
      • Hogue C.J.
      • Stein A.D.
      • Drews C.
      • Zieman M.
      Body mass index and risk for oral contraceptive failure: a case-cohort study in South Carolina.
      ]. As previously mentioned, these databases are limited by self-reported height, weight, pregnancies and oral contraceptive use/type. In addition, only live births were tracked and very small numbers of overweight/obese women were included (overweight n=44, obese n=28). A reanalysis of several recent combined oral contraceptive trials found no change in contraceptive efficacy for heavier women, but again these studies were limited by either small samples sizes — only 55 out of 1673 women studied were >198 lb [
      • Zhang H.
      • LaGuardia K.
      • Creanga D.
      Higher body weight and body mass index are not associated with reduced efficacy in Ortho Tri-Cyclen Lo Users (Abstract).
      ] — or a nontraditional dosing pattern (extended 91-day regimen) [
      • Westhoff C.
      • Reape K.
      • Hait H.
      Subject weight and oral contraceptive efficacy in recent clinical trials (Abstract).
      ] which may have altered the risk of failure.
      Finally, two large longitudinal studies in Europe found no effect of weight on oral contraceptive efficacy [
      • Vessey M.
      • Painter R.
      Oral contraceptive failures and body weight: findings in a large cohort study.
      ,
      • Dinger J.
      • Cronin M.
      • Mohner S.
      • Schellschmidt I.
      • Minh T.
      • Westhoff C.
      Oral contraceptive effectiveness according to body mass index, weight, age, and other factors.
      ]. A study of British progestin-only pill users demonstrated no increase in contraceptive failures for obese women. This study had several significant limitations, including no report of the number of overweight/obese women, measurement of weight only at recruitment (1968–1974), study timing (the study occurred prior to the current obesity epidemic). The European Active Surveillance Study on Oral Contraceptives (EURAS-OC) monitored 59,510 combined oral contraceptive users from 2000 to 2005 with an impressively small lost to follow-up rate (2.4%) [
      • Dinger J.
      • Cronin M.
      • Mohner S.
      • Schellschmidt I.
      • Minh T.
      • Westhoff C.
      Oral contraceptive effectiveness according to body mass index, weight, age, and other factors.
      ]. No association between BMI or weight and contraceptive failure was found with the exception of a small effect in pills with the progestin chlormadinone acetate (not currently available in the US market). The actual number of obese women in the study was not mentioned, but the mean BMI for the study population was in the normal range (<25 kg/m2). As mentioned earlier, it is possible the results from these two studies are not generalizable to the US as European women tend to have a higher contraceptive effectiveness rate than the US women [
      • Moreau C.
      • Trussell J.
      • Rodriguez G.
      • Bajos N.
      • Bouyer J.
      Contraceptive failure rates in France: results from a population-based survey.
      ].
      When all of the data is considered, overweight and obese oral contraceptive users (both combined and progestin-only) appear to be at a similar or slightly higher risk of pregnancy as compared to normal BMI women. However, even if this risk is higher, that actual increase (attributable risk) would be minimal. If the results in the studies by Holt et al. [
      • Holt V.
      • Scholes D.
      • Wicklund K.
      • Cushing-Haugen K.
      • Daling J.
      Body mass index, weight, and oral contraceptive failure risk.
      ] are considered to be causal, then only two to four extra pregnancies per 100 women-years would be expected in women with a BMI >27.3 as compared to women with a lower BMI.

      3. Does obesity affect contraceptive effectiveness for nonoral contraceptive methods?

      Compared to information on oral contraceptive methods, an even smaller number of obese women have been studied with other hormonal methods (contraceptive patch, contraceptive ring, implant, injection) [
      • Audet M.
      • Moreau M.
      • Koltun W.
      • Waldbaum A.
      • Shangold G.
      • Fisher A.
      • et al.
      Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive.
      ,
      • Zieman M.
      • Guillebaud J.
      • Weisberg E.
      • Shangold G.
      • Fisher A.
      • Creasy G.
      Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data.
      ,
      • Dieben T.
      • Roumen F.
      • Apter D.
      Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring.
      ,
      • Westhoff C.
      Higher body weight does not affect Nuvaring's efficacy.
      ,
      • Roumen F.J.M.E.
      • Apter D.
      • Mulders T.M.T.
      • Dieben T.O.M.
      Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol.
      ,
      • Croxatto H.
      • Mäkäräinen L.
      The pharmacodynamics and efficacy of Implanon®: an overview of the data.
      ,
      • Huber J.
      Pharmacokinetics of Implanon®: An integrated analysis..
      ,
      • Jain J.
      • Jakimiuk J.
      • Bode F.
      • Ross D.
      • Kaunitz A.
      Contraceptive efficacy and safety of DMPA-SC.
      ,
      ,
      • Graesslin O.
      • Korver T.
      The contraceptive efficacy of Implanon: a review of clinical trials and marketing experience.
      ]. An abstract reporting the pooled analysis of three multicentered cohort studies of the contraceptive patch reported a possible increase in contraceptive failure in women weighing ≥90 kg, but it did not report what the increase was or how many women weighing ≥90 kg were included in the analysis [
      • Zieman M.
      • Guillebaud J.
      • Weisberg E.
      • Shangold G.
      • Fisher A.
      • Creasy G.
      Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data.
      ]. In regard to the contraceptive ring, an abstract reporting a reanalysis of the Phase III trials found no increase in failure for heavier women (weight 88–272 lb, n=6047) [
      • Westhoff C.
      Higher body weight does not affect Nuvaring's efficacy.
      ]. The etonogestrel contraceptive implant has not been prospectively studied in women who weigh more than 130% of ideal body weight [
      ] and only a handful of users studied have weighed over 70 kg (n=134); however, no pregnancies were reported in this group [
      • Graesslin O.
      • Korver T.
      The contraceptive efficacy of Implanon: a review of clinical trials and marketing experience.
      ]. Accordingly, no definitive conclusions can be made regarding the impact of increased weight or BMI on their effectiveness.
      Obesity may make procedure-dependent contraceptive methods more challenging for the provider to perform. A Cochrane review of interval laparoscopic tubal ligations found an increased complication rate in obese women [
      • Jamieson D.
      • Hillis S.
      • Duerr A.
      • Marchbanks P.
      • Costello C.
      • Peterson H.
      Complications of interval laparoscopic tubal sterilization: findings from the United States Collaborative Review of Sterilization.
      ]. Placement of an IUD may require longer instruments and an exam table with a higher weight capacity. Intramuscular injections may also require longer needles to ensure proper medication administration [
      • Nisbet A.
      Intramuscular gluteal injections in the increasingly obese population: retrospective study.
      ].
      The number of overweight and obese women studied is too small to determine a difference in the inherent contraceptive effectiveness for nonoral hormonal methods. Effectiveness of intrauterine devices and sterilization should theoretically be unaffected by BMI but may be associated with an increase in technical difficulties and procedure-related complications.

      4. What are the risks of contraceptive use in obese women?

      The use of low-dose estrogen-containing contraceptives slightly increases the incidence of deep venous thrombosis (5–10 cases in nonusers vs. 15–30 cases in users per 10,000 women per year) [
      • Brunner Huber L.R.
      • Hogue C.J.
      The association between body weight, unintended pregnancy resulting in a livebirth, and contraception at the time of conception.
      ,
      • Heinemann L.A.J.
      • Dinger J.C.
      Range of published estimates of venous thromboembolism incidence in young women.
      ]. At baseline, obesity doubles the risk of venous thromboembolism (VTE) as compared to a normal BMI [
      • Abdollahi M.
      • Cushman M.
      • Rosendaal F.
      Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.
      ]. As the absolute risk of VTE with combined contraceptives is quite small, the additional risk of obesity is still less than the VTE risk that pregnancy/postpartum poses in an obese woman [
      • Heinemann L.A.J.
      • Dinger J.C.
      Range of published estimates of venous thromboembolism incidence in young women.
      ,
      • Abdollahi M.
      • Cushman M.
      • Rosendaal F.
      Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.
      ,
      • Nightingale A.
      • Lawrenson R.
      • Simpson E.
      • Williams T.
      • Farmer K.
      The effects of age, body mass index, smoking, and general health on the risk of venous thromboembolism in users of combined oral contraceptives.
      ,
      • World Health Organization
      Venous thromboembolic disease and combined oral contraceptives: results of international multi-centre case control study.
      ,
      • Trussell J.
      • Guthrie K.
      • Schwarz E.
      Much ado about little: obesity, combined hormonal contraceptive use and venous thrombosis.
      ,
      • Larsen T.B.
      • Sorensen H.T.
      • Gislum M.
      • Johnsen S.P.
      Maternal smoking, obesity, and the risk of thromboembolism during pregnancy and the puerperium: a population-based nested control study.
      ].
      The currently used EE dosages of combined contraceptives (15 to 35 mcg) have less VTE risk than older products (≥50 mcg EE) [
      • Abdollahi M.
      • Cushman M.
      • Rosendaal F.
      Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.
      ]. However, no difference in venous thrombosis risk has been proven between very low (15–20 mcg EE) vs. low dose (30–35 mcg EE) products in the general population [
      • World Health Organization
      Cardiovascular disease and steroid hormone contraception. Report of a WHO Scientific Group.
      ]. Whether these very low dose products are safer in obese women is unknown.
      Recent attention has been focused on the possible increased VTE risk with the contraceptive patch. The three published studies addressing this issue are conflicting and range from no increase in risk (OR 0.9, 95% CI 0.5–1.6) to a slight increase in risk (OR 2.4, 95% CI 1.1–5.5) [
      • Cole J.A.
      • Norman H.
      • Doherty M.
      • Walker A.
      Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users.
      ,
      • Jick S.S.
      • Kaye J.A.
      • Russmann S.
      • Jick H.
      Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 μg of ethinyl estradiol.
      ,
      • Jick S.
      • Kaye J.A.
      • Li L.
      • Jick H.
      Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 μg of ethinyl estradiol.
      ,
      Boston Collaborative Drug Surveillance Program
      Postmarketing study of ORTHO EVRA and levonorgestrel oral contraceptives containing hormonal contraceptives with 30 μg of EE in relation to non-fatal venous thromboembolism, ischemic stroke, and myocardial infarction.
      ]. Even when using the most conservative estimate of VTE risk (OR 2.4), the VTE risk is still lower in patch users than in pregnancy. There are no published studies focusing on VTE risk in obese contraceptive patch users.
      Obese women are also at risk for comorbidities such as hypertension, hypercholesterolemia and diabetes. Increasing age is also an independent risk factor for VTE and may also be considered a comorbidity [
      • Abdollahi M.
      • Cushman M.
      • Rosendaal F.
      Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.
      ]. There is no safety information regarding the use of hormonal and nonhormonal contraception in obese women with comorbidities.
      No safety information exists regarding the use of contraception in women with a BMI ≥40 mg/kg2.

      5. What are the benefits of contraceptive use in obese women?

      Pregnancy prevention is usually the primary contraceptive benefit for women of any weight desiring to avoid a pregnancy. An unplanned pregnancy in an obese woman carries greater risk than a normal-weight woman as obesity adversely affects the health of both present and future generations with higher rates of both maternal and fetal morbidity and mortality, and increased rates of obesity and diabetes in the offspring [
      • Rode L.
      • Nilas L.
      • Wojdemann K.
      • Tabor A.
      Obesity-related complications in Danish single cephalic term pregnancies.
      ,
      • Nohr E.
      • Bech B.
      • Davies M.
      • Frydenberg M.
      • Henriksen T.
      • Olsen J.
      Prepregnancy obesity and fetal death: a study within the Danish national birth cohort.
      ,
      • Catalano P.M.
      • Ehrenberg H.M.
      The short- and long-term implications of maternal obesity on the mother and her offspring.
      ,
      • Boney C.M.
      • Verma A.
      • Tucker R.
      • Vohr B.R.
      Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus.
      ,
      • Whitaker R.C.
      Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy.
      ].
      Obesity is associated with endometrial hyperplasia and cancer [
      • Brinton L.
      • Berman M.
      • Mortel R.
      • Twiggs L.
      • Barrett R.
      • Wilbanks G.D.
      • et al.
      Reproductive, menstrual, and medical risk factors for endometrial cancer: results from a case-control study.
      ]. Although not directly studied in obese women, both hormonal and nonhormonal contraception (copper IUD) have been shown to decrease the risk of endometrial hyperplasia and cancer [
      • Varma R.
      • Sinha D.
      • Gupta J.K.
      Non-contraceptive uses of levonorgestrel-releasing hormone system (LNG-IUS)—A systematic enquiry and overview.
      ,
      • World Health Organization
      Endometrial cancer and combined oral contraceptives: the WHO Collaborative Study of Neoplasia and Steroid Contraceptives.
      ,
      • Jick S.S.
      • Walker A.M.
      • Jick H.
      Oral contraceptives and endometrial cancer.
      ,
      • World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives
      Depot-medroxyprogesterone acetate (DMPA) and risk of endometrial cancer.
      ,
      • Curtis K.M.
      • Marchbanks P.A.
      • Peterson H.B.
      Neoplasia with use of intrauterine devices.
      ].

      6. Does contraception adversely affect body weight?

      Weight regulation is a major health and personal concern for many women. It is not surprising that women often blame contraception for their weight gain, as this may be the only medication they use consistently throughout their lifetime. However, adults tend to gain weight over time regardless of contraceptive use (hormonal or nonhormonal); most likely due to a combination of genetics, environment and lifestyle factors [
      • Hedley A.A.
      • Ogden C.L.
      • Johnson C.L.
      • Carroll M.D.
      • Curtin L.R.
      • Flegal K.M.
      Overweight and obesity among US children, adolescents, and adults, 1999–2002.
      ,
      • Hassan D.F.
      • Petta C.A.
      • Aldrighi J.M.
      • Bahamondes L.
      • Perrotti M.
      Weight variation in a cohort of women using copper IUD for contraception.
      ]. Women's perceptions of weight gain have been shown to be incongruent with their actual weight [
      • O'Connell K.J.
      • Osborne L.M.
      • Westhoff C.
      Measured and reported weight change for women using a vaginal contraceptive ring vs. a low-dose oral contraceptive.
      ]. Additionally, women rarely blame nonuse of contraception as a reason for weight gain when pregnancy is clearly associated with weight gain and many women have difficulty returning to their prepregnancy weight [
      • Linne Y.
      • Dye L.
      • Barkeling B.
      • Rossner S.
      Weight development over time in parous women—the SPAWN study—15 years follow-up.
      ].
      Unfortunately, discontinuation of hormonal contraception due to perceived side effects plays a major role in the rates of unplanned pregnancy in the United States. Many women will discontinue their birth control because of these perceived side effects even though they are still at risk for an undesired pregnancy. Studies of oral contraceptive users have found that a perceived weight gain is one of the leading reasons for discontinuation in US women [
      • Picardo C.M.
      • Nichols M.
      • Edelman A.
      • Jensen J.
      Women's knowledge and sources of information on the risks and benefits of oral contraception.
      ,
      • Rosenberg M.
      Weight change with oral contraceptive use and during the menstrual cycle: results of daily measurements.
      ].
      Of note, the majority of studies researching hormonal contraception and its potential impact on weight have used a population of women that are no more than 130% of ideal body weight. The effect of hormonal contraception on weight may vary depending on the initial baseline weight, but this has not been thoroughly studied. In regard to specific contraceptive methods and weight gain:
      • Nonhormonal contraception (i.e., copper intrauterine device, barrier methods) has not been associated with a change in body weight [
        • Hassan D.F.
        • Petta C.A.
        • Aldrighi J.M.
        • Bahamondes L.
        • Perrotti M.
        Weight variation in a cohort of women using copper IUD for contraception.
        ].
      • Combined hormonal contraception (pill, patch, ring) has not been associated with a change in body weight [
        • O'Connell K.J.
        • Osborne L.M.
        • Westhoff C.
        Measured and reported weight change for women using a vaginal contraceptive ring vs. a low-dose oral contraceptive.
        ,
        • Gallo M.
        • Grimes D.A.
        • Schulz K.
        • Helmerhorst F.
        Combination estrogen-progestin contraceptives and body weight: systematic review of randomized controlled trials.
        ].
      • The levonorgestrel-releasing intrauterine device, in long-term users, has been associated with a small increase in weight that is equivalent to the weight gain associated with increasing age [
        • Linne Y.
        • Dye L.
        • Barkeling B.
        • Rossner S.
        Weight development over time in parous women—the SPAWN study—15 years follow-up.
        ,
        • Ronnerdag M.
        • Odlind V.
        Health effects of long-term use of the intrauterine levonorgestrel-releasing system: a follow-up study over 12 years of continuous use.
        ].
      • The etonogestrel implant has not been well studied in regard to weight gain but appears to have little or no impact on weight [
        The Implanon US Study Group
        Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel.
        ,
        • Kiriwat O.
        • Patanayindee A.
        • Koetsawang S.
        • Korver T.
        • Coelingh Bennink H.
        A 4-year pilot study on the efficacy and safety of Implanon, a single-rod hormonal contraceptive implant, in healthy women in Thailand.
        ]
      • Depot medroxyprogesterone acetate (Depo Provera®) and weight change are more controversial. Studies have been conflicting with some showing no change in weight and others finding an increase (particularly in already obese teens) [
        • Bahamondes L.
        • Del Castillo S.
        • Tabares G.
        • Arce X.E.
        • Perrotti M.
        • Petta C.
        Comparison of weight increase in users of depot medroxyprogesterone acetate and copper IUD up to 5 years.
        ,
        • Mangan S.A.
        • Larsen P.G.
        • Hudson S.
        Overweight teens at increased risk for weight gain while using depot medroxyprogesterone acetate.
        ,
        • Bonny A.E.
        • Ziegler J.
        • Harvey R.
        • Debanne S.M.
        • Secic M.
        • Cromer B.A.
        Weight gain in obese and nonobese adolescent girls initiating depot medroxyprogesterone, oral contraceptive pills, or no hormonal contraceptive method.
        ,
        • Taneepanichskul S.
        • Reinprayoon D.
        • Khaosaad P.
        Comparative study of weight change between long-term DMPA and IUD acceptors.
        ].

      7. Does bariatric surgery affect contraceptive efficacy?

      It makes intuitive sense that any bariatric surgery which impairs gastrointestinal absorption may impair oral contraception. These surgeries include jejunoileal bypass, biliopancreatic diversion with/without duodenal switch, and Roux-en-Y bypass (gastric bypass). Currently, there are no published studies comparing oral contraceptive effectiveness before and after bariatric surgery, but one small study reported two out of nine patients with oral contraceptive failures after biliopancreatic diversion [
      • Gerrits E.G.
      • Ceulemans R.
      • van Hee R.
      • Hendrickx L.
      • Totté E.
      Contraceptive treatment after biliopancreatic diversion needs consensus.
      ] and another found lower drug levels in morbidly obese women after jejunoileal bypass (n=7) as compared to normal-weight controls [
      • Victor A.
      • Odlind V.
      • Kral J.G.
      Oral contraceptive absorption and sex hormone binding globulins in obese women: effects of jejunoileal bypass.
      ]. Other forms of nonoral contraception, both hormonal and nonhormonal, should remain unaffected by bariatric surgery but have not been studied.

      8. What changes in contraceptive prescribing habits should be made for the obese patient?

      In general, the level of evidence regarding the efficacy of some hormonal contraceptives in overweight and obese women is limited and inconsistent (i.e., Level B). Currently, there is not enough information to change clinical prescribing practices, other than helping our patients choose a contraceptive method with the overall highest inherent efficacy (i.e., IUDs, implants, sterilization). However, hormonal contraception, both combined and progestin only, can be safely and effectively used in healthy obese women. All women using combined hormonal contraception should be counseled regarding their increased VTE risk and obese women are no exception.

      Conclusions and recommendations

      The following recommendation is based on good and consistent scientific evidence (Level A):
      • Use of contraception prevents more pregnancies in women regardless of BMI than nonuse of contraception.
      The following recommendation is based on limited or inconsistent scientific evidence (Level B):
      • Obese women, both adults and adolescents, appear to be at increased risk for pregnancy as compared to their normal BMI counterparts due to higher rates of contraceptive nonuse.
      • Effectiveness of oral contraception (combined and/or progestin only) may be impaired in overweight and obese women.
      • Healthy obese women using combined hormonal contraception (pill, patch, ring) moderately increase their risk of VTE as compared to nonobese combined hormonal contraceptive users, but this is not a contraindication to use as it is still less than the risk of VTE associated with pregnancy.
      • Overall, hormonal contraception appears to have little effect on baseline body weight when studied in a nonobese female population.
      • Effectiveness of oral contraception may be impaired in women undergoing bariatric surgery that causes gastrointestinal malabsorption (jejunoileal bypass, biliopancreatic diversion with/without duodenal switch, and Roux-en-Y bypass) and thus should be avoided.
      The following recommendation is based primarily on consensus or expert opinion (Level C):
      • No safety information exists regarding the use of any type of contraceptive method in women with a BMI ≥40 mg/kg2, but this is not an absolute contraindication to use.
      • Hormonal contraception and the copper IUD prevent endometrial hyperplasia and cancer in obese women.

      Important questions to be answered

      Although contraception has been scrutinized since its inception, there are many unanswered questions in regard to obesity and contraception. Previous contraceptive studies have deliberately excluded obese women. This practice is no longer conscionable, as obese individuals make up a significant portion of our population. Future contraceptive studies, in particular efficacy studies, must be a better reflection of our current population.

      Sources

      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and PUBMED were searched for publications regarding BMI/weight and contraception since 1970. In addition, reference lists of these identified trials or review articles were searched for any additional trials that may have been missed.

      Authorship

      These guidelines were prepared by Alison Edelman, MD, MPH, and were reviewed and approved by the Board of the Society of Family Planning.

      Conflict of interest statement

      Alison Edelman, MD, MPH., reports that she serves as a faculty trainer for the Implanon™ Clinical Training Program (Schering-Plough, Kenilworth, NJ, USA). The Society of Family Planning receives no direct support from pharmaceutical companies or other industries.

      Intended audience

      This Society of Family Planning guideline was developed for its members and other clinicians who counsel, provide and/or manage family planning services. This guideline may be of interest to other professional groups that set practice standards for family planning services. The purpose of this document is to review the medical literature regarding obesity and contraception. This evidence-based review should help to guide clinicians providing this care, but it is not intended to dictate clinical care.

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