Combined hormonal contraceptive use among obese women and risk for cardiovascular events: A systematic review.

Combined hormonal contraceptive (CHC) use may modify the risk of cardiovascular events in obese [body mass index (BMI) ≥30kg/m2] women. The objective was to evaluate from the literature whether CHC use modifies the risk of acute myocardial infarction (AMI), stroke, cerebral venous thrombosis (CVT) and venous thromboembolism (VTE) in obese women and to evaluate evidence for a dose-response relationship between BMI and VTE. We searched PubMed for all articles published between database inception and February 2016 providing direct evidence on BMI, CHCs, and cardiovascular outcomes. We also searched for indirect evidence related to a dose-response relationship between BMI and risk of VTE in the general population, as these data were lacking for CHC users. The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force. The direct evidence search yielded 3 pooled analyses, 11 case-control studies and 1 cohort study. There was conflicting evidence about the risk of AMI or stroke among obese combined oral contraceptive (COC) users compared to obese nonusers, with one study finding no increased risk for AMI or stroke for COC users overall or stratified by BMI. A second study found significantly increased risk of AMI and stroke for COC users, with the highest risk estimates for high-BMI COC users. A single study suggested that obese COC users may be at higher risk for CVT compared with normal-weight nonusers. For VTE, obese COC users consistently had a risk that was 5 to 8 times that of obese nonusers and approximately 10 times that of nonobese nonusers. Five prospective cohort studies were identified as indirect evidence, and all found increased risk for VTE as BMI increased, suggesting a dose-response relationship between BMI and risk for VTE. No studies on the contraceptive patch or vaginal ring were identified that met the inclusion criteria. Limited evidence of Level II-2, fair quality, concerning whether CHC use modifies the risk of AMI and stroke in obese women is inconclusive, while a single study of Level II-2, poor quality, found that obese COC users may be at higher risk for CVT compared with normal-weight nonusers. Both COC use and higher BMI increase risk for VTE, and the greatest relative risks are for those with both risk factors based on a body of evidence graded as Level II-2, fair to poor quality. It is not possible to estimate absolute risk of VTE among women with both of these risk factors; however, the absolute risk of VTE in healthy women of reproductive age is small.

Horton LG ，Simmons KB ，Curtis KM 《-》

Combined hormonal contraceptive use among women with known dyslipidemias: a systematic review of critical safety outcomes.

Dyslipidemias represent a spectrum of lipid disorders that are important risk factors for cardiovascular disease. In addition, elevated triglycerides are known to be associated with pancreatitis. Though less clear, it is possible that dyslipidemias may also contribute to risk for venous thromboembolism (VTE). Ethinyl estradiol and progestogen, contained within combined hormonal contraception, are known to impact lipid metabolism. To evaluate from the literature whether use of combined hormonal contraception (CHC), including combined oral contraception (COC) pills, transdermal patch, vaginal ring or injectables, modifies the relative risk of acute myocardial infarction (MI), stroke, VTE or pancreatitis among women with known dyslipidemias and to determine if existing lipid abnormalities worsen with CHC use. PubMed and the Cochrane Library databases were searched for all articles in all languages published between inception and September 2014 relevant to dyslipidemia, CHC use and serious adverse events (MI, stroke, VTE or pancreatitis). The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force. From 306 articles identified by our search strategy, 3 articles met inclusion criteria. In a poor-quality case-control study, women with hypercholesterolemia but no COC use had an increased risk of MI (adjusted odds ratio [adj OR] 3.3, 95% confidence interval [CI] 1.6-6.8), as did women who used COCs but did not have hypercholesterolemia (adj OR 2.0, 95% CI 1.4-2.8), compared with non-COC users without hypercholesterolemia; women with both COC use and hypercholesterolemia had an adjusted OR of 24.7 (95% CI 5.6-108.5) compared with women with neither risk factor. A poor-quality cohort study examined COC users and reported that women with dyslipidemia had increased risk for VTE [crude risk ratio (RR) 1.39, 95% CI 1.04-1.85] and transient ischemic attacks or cerebrovascular accidents (CVAs) (RR 1.76, 95% CI 1.51-2.06) compared to those without dyslipidemia. Another poor-quality cohort study provided direct evidence on changes in lipid levels among COC users with dyslipidemia. A minority of women with elevated total cholesterol or triglyceride levels at baseline showed normal results (25% and 28%, respectively) after 6 cycles of COC use. No evidence regarding risks associated with use of other CHC methods was identified. No evidence was identified for the outcome of pancreatitis. Limited data from poor-quality observational studies suggest that women with known dyslipidemias using CHC may be at increased risk for MI and may experience a minimal increase in risk for CVA or VTE. No evidence was identified on risk for pancreatitis in this context. The impact of CHC exposure on the status of lipid abnormalities over time, an intermediate marker for disease, is also unclear. Given the significant limitations of this body of evidence, the importance of access to effective contraception and theoretical concerns raised about the use of CHCs by women with known dyslipidemias, additional rigorous studies are needed to best estimate true associations. Contraceptive decision making should include consideration of both the known and theoretical risks of a given CHC method, safety and acceptability of alternative contraceptive methods, and risks associated with unintended pregnancy.

Dragoman M ，Curtis KM ，Gaffield ME 《-》

Nonoral combined hormonal contraceptives and thromboembolism: a systematic review.

Combined hormonal contraceptives (CHCs), containing estrogen and progestin, are associated with an increased risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE) compared with nonuse. Few studies have examined whether nonoral formulations (including the combined hormonal patch, combined vaginal ring and combined injectable contraceptives) increase the risk of thrombosis compared with combined oral contraceptives (COCs). The objectives were to examine the risk of VTE and ATE among women using nonoral CHCs compared to women using COCs. We searched the PubMed database for all English language articles published from database inception through May 2016. We included primary research studies that examined women using the patch, ring or combined injectables compared with women using levonorgestrel-containing or norgestimate-containing COCs. Outcomes of interest included VTE (deep venous thrombosis or pulmonary embolism) or ATE (acute myocardial infarction or ischemic stroke). We assessed the quality of each individual piece of evidence using the system developed by the United States Preventive Services Task Force. Eight studies were identified that met inclusion criteria. Of seven analyses from six studies examining VTE among patch users compared with levonorgestrel- or norgestimate-containing COC users, two found a statistically significantly elevated risk among patch users (risk estimates 2.2-2.3), one found an elevated risk that did not meet statistical significance (risk estimate 2.0), and four found no increased risk. Of three studies examining VTE among ring users compared with levonorgestrel COC users, one found a statistically significantly elevated risk among patch users (risk estimate 1.9) and two did not. Two studies did not find an increased risk for ATE among women using the patch compared with norgestimate COCs. We did not identify any studies examining combined injectable contraceptives. Limited Level II-2 good to fair evidence demonstrated conflicting results on whether women using the patch or the ring have a higher risk of VTE than women using COCs. Evidence did not demonstrate an increased risk of ATE among women using the patch. Overall, any potential elevated risk likely represents a small number of events on a population level. Additional studies with standard methodology are needed to further clarify any associations and better understand mechanisms of hormone-induced thrombosis among users of nonoral combined hormonal contraception.

Tepper NK ，Dragoman MV ，Gaffield ME ，Curtis KM ... -  《-》

Combined hormonal contraceptive (CHC) use among obese women and contraceptive effectiveness: a systematic review.

To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI). We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force. From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed ≥90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable. Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness.

Dragoman MV ，Simmons KB ，Paulen ME ，Curtis KM ... -  《-》

Combined oral contraceptive use among women with hypertension: a systematic review.

Curtis KM ，Mohllajee AP ，Martins SL ，Peterson HB ... -  《CONTRACEPTION》