Uterine fibroids and endometriosis may be associated with an increased risk of ovarian cancer. Less is known about the role of hysterectomy in these associations. We estimated the independent and joint associations of hysterectomy, fibroids, and endometriosis with ovarian cancer incidence in the prospective Sister Study cohort (2003-2009). We used time-varying Cox proportional hazards models to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). By the end of follow-up, 34% of 40,928 eligible participants had fibroids, 13% had endometriosis, and 7% had both. A total of 274 women developed ovarian cancer during follow-up (median=12.3 years). In mutually adjusted models, fibroids (HR=1.65, 95% CI: 1.28, 2.12) and possibly endometriosis (HR=1.16, 95% CI: 0.82, 1.63), were positively associated with ovarian cancer. Hysterectomies (20% of participants) were also positively associated with ovarian cancer (HR=1.29, 95% CI: 0.95, 1.74). There was some evidence that hysterectomies may mitigate ovarian cancer risk among women with fibroids (HR=0.83, 95% CI: 0.56, 1.24), but not among women with endometriosis (HR=1.20, 95% CI: 0.65, 2.22). Identifying these joint associations adds to our understanding of ovarian cancer etiology and may help inform decisions about how women with fibroids, endometriosis, and hysterectomies are treated and surveilled for ovarian cancer.

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