Oral Contraceptives in Polycystic Ovary Syndrome: Risk-Benefit Assessment

Bulent O. Yildiz, M.D.


Semin Reprod Med. 2008;26(1):111-120. 

In This Article

OCP Use and the Risk of Cardiovascular Disease

The association of OCP use and coronary thrombosis was first reported in 1963 shortly after the OCPs were introduced to the clinic.[10] Studies suggested the use of OCPs as a risk factor for venous and arterial thrombosis.[11,12] To lower these risks, various modifications of OCPs including the reduction of estrogen dose and changes in the progestin compound were attempted.

An increased risk of venous thrombosis in OCP users have been consistently reported.[13] The rates of venous thrombosis in OCP users are three- to fourfold higher than that rate in nonusers. This risk is highest during the first year of use.[14] Third-generation OCPs containing desogestrel or gestodene had about twice the risk of nonfatal venous thrombosis when compared with second-generation OCPs containing levonorgestrel (3 vs. 1.5 events per 10,000 women-years, respectively).[15] These rates in non-OCP users and pregnant women are found to be 0.5 to 1.1 and 6 events per 10,000 women-years, respectively.[15] Overall, these data suggest that although the OCP use increases the relative risk of venous thrombosis, the background risk in young women is low, and the absolute risk is even smaller than the actual risk associated with pregnancy.

There has been less consistency in the results of studies examining the risk of arterial thrombosis in OCP users. An increased risk of myocardial infarction, stroke, or peripheral arterial disease associated with the use of low-dose OCPs has been found in some, but not all, studies. Two recent meta-analyses have addressed this issue.[16,17] Based on 19 case-control studies and 4 cohort studies that met the predefined inclusion criteria, Khader et al have found that current OCP users compared with never-users have an overall adjusted odds ratio (OR); of myocardial infarction of 2.48 (95% confidence interval [CI], 1.91 to 3.22). The risk of myocardial infarction for past OCP users was not significantly different from that of never-users (OR, 1.15; 95% CI, 0.98 to 1.35).[16] Stratified analysis based on the generation of OCPs in this study showed that first- and second-generation OCP users have an increased risk of myocardial infarction than that of never-users, whereas that risk was similar between the current third-generation OCP users and never-users.[16] The other meta-analysis by Baillargeon et al evaluated the results from 18 independent study populations from 15 articles.[17] The risk estimates with current use of low-dose OCPs were 1.84 (95% CI, 1.56 to 2.86); for myocardial infarction and 2.12 (95% CI, 1.63 to 2.48); for ischemic strokes. Stratified analysis in this study showed that current use of second-generation OCPs significantly increased both the risk of myocardial infarction and ischemic stroke. On the other hand, current use of third-generation OCPs was associated only with increased risk of ischemic stroke but not with the increased risk of myocardial infarction.[17]

Interestingly, increased cardiovascular disease (CVD); risk associated with current use of OCPs does not continue after the OCP is stopped.[17,18] In fact, four independent studies included in the meta-analysis by Baillargeon et al reported a significant reduction of risk for myocardial infarction[19] and ischemic stroke[20,21] in past users of low-dose OCPs compared with never-users.[17] Similarly, a recent multicenter trial, measuring coronary artery disease by quantitative coronary angiography, reported that past OCP use is associated with less coronary artery disease among postmenopausal women with suspected myocardial ischemia.[18] These data support the hypothesis that past OCP use during reproductive years might provide protection from CVD later in life.

A study by Schwingl et al estimated the annual risk of death in the United States from CVD attributable to low-dose OCPs through use of data from studies published in 1980-1997 and from age-specific mortality rates for 1993 and 1994.[22] Four CVD categories were included: myocardial infarction, venous thromboembolism and pulmonary embolism, ischemic stroke, and hemorrhagic stroke. The overall risk of death from CVD among nonsmoking users of low-dose OCPs was 0.06/100,000 for women in the 15- to 34-year age group and 3.03/100,000 for women in the 35- to 44-year age group. For young nonsmokers, the excess mortality risk associated with OCP use was smaller than the risk of death from pregnancy, whereas this risk among smoking OCP users over 35 years of age was higher than the risk of death from pregnancy. The results of this study suggested that there is virtually no excess attributable risk of death from CVD related to OCP use in women younger than 35 years of age, whereas women over 35 years of age who smoke should not be permitted to use OCPs because of the excess attributable risk of death from CVD.[22]

Taken together, available data about the OCPs and CVD risk indicate that (i); OCP use regardless of the progestin type is associated with an increased risk of venous thrombosis especially during the first year although the absolute risk is smaller than the actual risk associated with pregnancy, (ii); third-generation OCPs are safer than second-generation pills in terms of CVD risk, (iii); the increased risk of CVD does not continue once OCPs are stopped and past use of OCPs regardless of the generation have no remaining risk from that exposure, and (iv); low-dose OCPs appear not to be associated with arterial thrombosis risk in healthy young nonsmoker women.


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