Polycystic ovary syndrome and risk of breast cancer in premenopausal and postmenopausal women: a nationwide population-based cohort study.

PURPOSE: Although some reproductive and metabolic characteristics of polycystic ovary syndrome (PCOS) are known risk factors for breast cancer, the evidence regarding a potential association between PCOS and breast cancer is scarce. In this population-based cohort study including all 1,719,452 women born in Denmark between 1940 and 1993, we investigated the association between PCOS and breast cancer. METHODS: PCOS diagnoses, cancer diagnoses, covariates, migrations, and vital status were all obtained from national population and health registers. Hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer overall and for histological subtypes separately were calculated based on adjusted cox proportional hazards models. RESULTS: During a median follow-up of 26 years, 63,078 women were diagnosed with breast cancer. We found an increased risk of breast cancer overall among women with PCOS compared with women without PCOS (HR: 1.21, 95% CI 1.02-1.44). In analyses stratified for menopausal status, the increased risk was restricted to postmenopausal women (HR: 1.63, 95% CI 1.23-2.15). The results for ductal and lobular histological subtypes analyses separately resembled those observed for breast cancer overall. CONCLUSION: This is the first study to report an increased risk of breast cancer among women with a history of PCOS. The increased risk was seemingly confined to postmenopausal women. Our results therefore contribute to an increased knowledge of the etiology of breast cancer, but our findings should be further confirmed in other large cohort studies with an appropriately long follow-up period.

Risk of epithelial ovarian tumors among women with polycystic ovary syndrome: A nationwide population-based cohort study.

An association between polycystic ovary syndrome (PCOS) and epithelial ovarian tumors is biologically plausible as conditions inherent to PCOS such as excessive androgenic hormones, reproductive factors and obesity are also risk factors for these hormone-sensitive tumors. However, previous studies have showed conflicting results and have various methodological limitations. This population-based cohort study investigates the association between PCOS and epithelial ovarian tumors and includes all women born in Denmark between January 1, 1940 and December 31, 1993 (n = 1 719 304). PCOS diagnoses, ovarian cancer and borderline ovarian tumor diagnoses, covariates, migration and vital status were obtained from the Danish national registers. Adjusted cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for epithelial ovarian cancer and for borderline ovarian tumors overall as well as for histological subtypes separately. During median 26 years of follow-up we identified 6490 women with ovarian cancer and 2990 women with borderline ovarian tumors. Overall, we observed no marked associations between a diagnosis of PCOS and overall epithelial ovarian cancer or overall epithelial borderline ovarian tumors, irrespective of time since diagnosis. However, we found an increased risk of ovarian cancer among postmenopausal women with PCOS (HR 2.28 95% CI 1.02-5.09) and an increased risk of serous borderline ovarian tumors (HR 2.34 95% CI 1.21-4.53) in women with PCOS compared with women without PCOS. Importantly, low statistical precision is a crucial limitation of our study and in previous studies and larger studies with longer follow-up are therefore warranted.

Tumors of the central nervous system among women treated with fertility drugs: a population-based cohort study.

PURPOSE: To investigate the association between fertility drugs and tumors of the central nervous system (CNS). METHODS: This cohort study was based on The Danish Infertility Cohort and included 148,016 infertile women living in Denmark (1995-2017). The study cohort was linked to national registers to obtain information on use of specific fertility drugs, cancer diagnoses, covariates, emigration, and vital status. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all CNS tumors and separately for gliomas, meningiomas and diverse benign tumors of the brain and other parts of the CNS. RESULTS: During a median 11.3 years of follow-up, 328 women were diagnosed with CNS tumors. No marked associations were observed between use of the fertility drugs clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators and progesterone and CNS tumors. However, use of human chorionic gonadotropin was associated with a decreased rate of meningiomas (HR 0.49 95% CI 0.28-0.87). No clear associations with CNS tumors were observed according to time since first use or cumulative dose for any of the fertility drugs. CONCLUSION: No associations between use of most types of fertility drugs and CNS tumors were observed. However, our findings only apply to premenopausal women and additional studies with longer follow-up time are necessary.