Abstract

Abstract Study question Is polycystic ovary syndrome (PCOS) associated with epithelial ovarian cancer and borderline ovarian tumors? Summary answer Overall, no association between PCOS and epithelial ovarian tumors was seen, however, we observed an increased risk of ovarian cancer among postmenopausal women with PCOS. What is known already Few studies have investigated the association between PCOS and epithelial ovarian tumors. In general, studies have reported conflicting results, possibly due to methodological differences and varying confounder adjustments. For ovarian cancer, most studies have reported no associations, while two studies reported an increased risk for women with PCOS compared to women without PCOS. For borderline ovarian tumors, most studies found no associations while one study observed an increased risk for serous borderline ovarian tumors among women with PCOS. Only a few studies have investigated the risk associated with PCOS according to menopausal status and histological subtypes of these tumors. Study design, size, duration This is a nationwide cohort study including all women born in Denmark between January 1, 1940 and December 31, 2000. The study cohort consisted of 1,7 million women after exclusion of women who emigrated, died, were diagnosed with cancer, or had bilateral oophorectomy before study start. Participants/materials, setting, methods The study cohorts for ovarian cancer analyses and borderline ovarian tumor analyses were linked to national registers to obtain information on PCOS diagnosis, cancer diagnosis, covariates, migration, and vital status. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for ovarian cancer and for borderline ovarian tumors, as well as separately for histological subtypes and according to menopausal status (landmark analysis at attained age of 51 years). Main results and the role of chance During a median 26.0 years of follow-up, 6,490 women were diagnosed with epithelial ovarian cancer and 2,990 women were diagnosed with borderline ovarian tumors. Overall, we found no marked associations for ovarian cancer and borderline ovarian tumors among women with PCOS compared to women without PCOS after adjustments for highest obtained level of education and obesity (HR 1.32 95% CI 0.80-2.20 and HR 1.59 95% CI 0.92-2.75, respectively). However, we found an increased risk of ovarian cancer among postmenopausal women (HR 2.18 95% CI 1.04-4.57). Lastly, we observed an increased risk for serous borderline ovarian tumors (HR 2.98 95% CI 1.64-5.42) for women with PCOS. Limitations, reasons for caution The low number of exposed cases, despite the large study population, is a main limitation. Although the register-based exposure data are highly valid, diagnosis of PCOS is challenging, and we are not able to account for changes in diagnostic practices over time. Wider implications of the findings The results from our study and previous studies should be taken into consideration when revising clinical guidelines for the management of long-term health outcomes for women with PCOS. Low statistical precision is an important limitation in our study and in previous studies, and larger studies with pooled analyses are warranted. Trial registration number not applicable

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