Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis

Background:

There is an increased risk of venous thromboembolism among women taking oral contraceptives. However, whether there is an additional risk among women with polycystic ovary syndrome (PCOS) is unknown.

Methods:

We developed a population-based cohort from the IMS LifeLink Health Plan Claims Database, which includes managed care organizations in the United States. Women aged 18–46 years taking combined oral contraceptives and who had a claim for PCOS (n = 43 506) were matched, based on a propensity score, to control women (n = 43 506) taking oral contraceptives. Venous thromboembolism was defined using administrative coding and use of anticoagulation. We used Cox proportional hazards models to assess the relative risk (RR) of venous thromboembolism among users of combined oral contraceptives with and without PCOS.

Results:

The incidence of venous thromboembolism among women with PCOS was 23.7/10 000 person-years, while that for matched controls was 10.9/10 000 person-years. Women with PCOS taking combined oral contraceptives had an RR for venous thromboembolism of 2.14 (95% confidence interval CI] 1.41–3.24) compared with other contraceptive users. The incidence of venous thromboembolism was 6.3/10 000 person-years among women with PCOS not taking oral contraceptives; the incidence was 4.1/10 000 person-years among matched controls. The RR of venous thromboembolism among women with PCOS not taking oral contraceptives was 1.55 (95% CI 1.10–2.19).

Interpretation:

We found a 2-fold increased risk of venous thromboembolism among women with PCOS who were taking combined oral contraceptives and a 1.5-fold increased risk among women with PCOS not taking oral contraceptives. Physicians should consider the increased risk of venous thromboembolism when prescribing contraceptive therapy to women with PCOS.Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. The National Institutes of Health criteria estimates its prevalence in the United States to be between 6% and 10%, while the Rotterdam criteria estimates the prevalence to be as high as 15%.¹ Although its cause is not entirely known, the diagnostic criteria include oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenism, and polycystic ovaries.² Women often present with clinical manifestations of high androgen levels, including facial hair growth (hirsutism), acne vulgaris and hair loss on the scalp. Previous studies reported the prevalence of impaired glucose tolerance to be 31.1%–35.2% and the prevalence of type 2 diabetes to be 7.5%–9.8% among women with PCOS.^3,4 A recent consensus workshop reported that the prevalence of several known risk factors for cardiovascular disease (hypertension, diabetes, abdominal obesity, psychological factors, smoking, altered apoA1/ApoB ratios) are doubled among women with PCOS compared with matched controls.^1,5Combined oral contraceptives are the mainstay treatment for PCOS. However, they are also known to elevate the risk of venous thromboembolism and cardiovascular disease.⁶ To date, contraceptive studies involving women with PCOS have focused mainly on efficacy, evaluating the effect of combined oral contraceptives on the reduction of hirsutism and hyperandrogenism.^7,8 Two studies assessed the metabolic effects of combined oral contraceptives in PCOS, but these studies had small sample sizes and could not evaluate for cardiovascular events.^9,10Although women with PCOS have an increase in both cardiovascular risk factors and subclinical cardiovascular disease,¹¹ recent guidelines have concluded there are no data in the literature assessing the association between the use of oral contraceptives and cardiovascular disease among women with PCOS.² Because combined oral contraceptives are the mainstay treatment, our objective was to determine whether women with PCOS taking combined oral contraceptives have a greater risk of venous thromboembolism compared with other contraceptive users. We also examined whether women with PCOS not taking oral contraceptives had an increased risk of venous thromboembolism compared with the general population.