| Abstract: | Context The association between menopausal hormone replacement therapy and ovariancancer is unclear. Objective To determine whether hormone replacement therapy using estrogen only,estrogen-progestin only, or both estrogen only and estrogen-progestin increasesovarian cancer risk. Design A 1979-1998 cohort study of former participants in the Breast CancerDetection Demonstration Project, a nationwide breast cancer screening program. Setting Twenty-nine US clinical centers. Participants A total of 44 241 postmenopausal women (mean age at start of follow-up,56.6 years). Main Outcome Measure Incident ovarian cancer. Results We identified 329 women who developed ovarian cancer during follow-up.In time-dependent analyses adjusted for age, menopause type, and oral contraceptiveuse, ever use of estrogen only was significantly associated with ovarian cancer(rate ratio RR], 1.6; 95% confidence interval CI], 1.2-2.0). Increasingduration of estrogen-only use was significantly associated with ovarian cancer:RRs for 10 to 19 years and 20 or more years were 1.8 (95% CI, 1.1-3.0) and3.2 (95% CI, 1.7-5.7), respectively (P value fortrend <.001), and we observed a 7% (95% CI, 2%-13%) increase in RR peryear of use. We observed significantly elevated RRs with increasing durationof estrogen-only use across all strata of other ovarian cancer risk factors,including women with hysterectomy. The RR for estrogen-progestin use afterprior estrogen-only use was 1.5 (95% CI, 0.91-2.4), but the RR for estrogen-progestin–onlyuse was 1.1 (95% CI, 0.64-1.7). The RRs for less than 2 years and 2 or moreyears of estrogen-progestin–only use were 1.6 (95% CI, 0.78-3.3) and0.80 (95% CI, 0.35-1.8), respectively, and there was no evidence of a durationresponse (P value for trend = .30). Conclusion Women who used estrogen-only replacement therapy, particularly for 10or more years, were at significantly increased risk of ovarian cancer in thisstudy. Women who used short-term estrogen-progestin–only replacementtherapy were not at increased risk, but risk associated with short-term andlonger-term estrogen-progestin replacement therapy warrants further investigation. |
