Search

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.

Objectives: It is difficult to separate the possible role of fertility drugs from underlying infertility as risk factors for ovarian cancer. The present study examined the relationship between self-reported infertility and death from ovarian cancer among married women unlikely to have been exposured to fertility drugs., Methods: Women were selected for study from the 676,526 female participants in Cancer Prevention Study II (CPS-II). After twelve years of follow-up, 797 deaths from ovarian cancer were observed among women with no prior history of cancer or hysterectomy and 40 years of age or older in 1967 when ovulatory stimulants were approved in the United States. Cox proportional hazards modeling was used to compute rate ratios (RRs) and to adjust for other potential risk factors., Results: Overall, self-reported infertility was not significantly associated with ovarian cancer mortality (adjusted rate ratio (RR) = 1.1, 95 percent confidence interval (CI) = 0.9-1.3). Ovarian cancer death rates among nulligravid women with self-reported infertility, however, were 40 percent higher than for nulligravid women who never tried to become pregnant (RR = 1.4, 95 percent CI = 0.9-2.4). Multigravid women who reported infertility problems were not at increased risk., Conclusions: These results suggest that infertility itself, without concomitant exposure to fertility drugs, may increase risk of fatal ovarian cancer among nulligravid women.

Several studies suggest that tubal sterilization may decrease the risk of ovarian cancer. Data from the Cancer Prevention Study II were analyzed to examine the relation between tubal ligation and ovarian cancer mortality in a large prospective study. A total of 396,114 women who had not had hysterectomies and who had no prior history of cancer (except nonmelanoma skin cancer) were followed prospectively for approximately 9 years from 1982 to 1991. During this time, 799 ovarian cancer deaths were observed. Tubal ligation was significantly associated with a decreased risk of ovarian cancer mortality in an age- and race-adjusted Cox proportional hazards model (hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.42-0.96), and the results were essentially unchanged when controlling for potential ovarian cancer risk factors (HR = 0.68, 95% CI 0.45-1.03). The protective effect appeared to be greater in the first 20 years after the procedure (HR = 0.49, 95% CI 0.24-0.99) than later (HR = 0.80, 95% CI 0.48-1.34). No interactions between ever having had a tubal ligation and other covariates were observed. These data suggest that tubal ligation reduces the risk of fatal ovarian cancer.

The authors examined the relation between use of estrogen replacement therapy and ovarian cancer mortality in a large prospective mortality study of 240,073 peri- and postmenopausal women, none of whom had a prior history of cancer, hysterectomy, or ovarian surgery at enrollment in 1982. During 7 years of follow-up, 436 deaths from ovarian cancer occurred. Cox proportional hazard regression was used to adjust for other risk factors. Ever use of estrogen replacement therapy was associated with a rate ratio for fatal ovarian cancer of 1.15 (95% confidence interval (CI) 0.94-1.42). The mortality rate ratio increased with duration of use prior to entry to this study to 1.40 (95 CI% 0.92-2.11) with 6-10 years of use and 1.71 (95% CI 1.06-2.77) with > or = 11 years of use. The increase in mortality associated with > or = 6 years of use was observed in both current users (rate ratio (RR) = 1.72, 95% CI 1.01-2.90) and former users at study entry (RR = 1.48, 95% CI 0.99-2.22), relative to never users. Risk associated with use was not modified by any of the other risk factors. These data suggest that long-term use of estrogen replacement therapy may increase the risk of fatal ovarian cancer.