Estrogen Replacement Therapy and Ovarian Cancer Mortality in a Large Prospective Study of US Women

Context: Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers. The effect of postmenopausal estrogen use on ovarian cancer is not established.

Objectives: To examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use.

Design And Setting: The American Cancer Society's Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996.

Participants: A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment.

Main Outcome Measure: Ovarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT).

Results: A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up. Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96). Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was associated with increased risk in both baseline and former users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users. Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use <15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use >/=15 years ago, 1.31; 95% CI, 0.79-2.17).

Conclusions: In this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.