Risk of Dying of Ovarian Cancer Found to be Increased by Estrogen Therapy: American Cancer Society Study Says Effect Persists up to 29 Years after Cessation

American Cancer Society
Wednesday, 21 March 2001

Women who use estrogen after menopause for 10 years or more have a substantially increased risk of death from ovarian cancer, report scientists from the American Cancer Society in today's Journal of the American Medical Association.

In a new analysis of the Society's large prospective US cohort study, Cancer Prevention Study II (CPSII), Carmen Rodriguez, MD, MPH, Senior Epidemiologist, and her epidemiological research department colleagues, followed the health status of 211,581 postmenopausal women from enrollment in l982 to l996. These women had no history of cancer, hysterectomy or ovarian surgery at the time they were entered in the study.

A total of 944 ovarian cancer deaths were recorded during the 14 years of follow up. Women who were using estrogen replacement therapy (ERT), when they entered CPSII had death rates that were substantially higher than never-users, with a risk ratio (RR) of 1.51 (or a 51% excess risk). Baseline users with 10 years or more of estrogen use had a risk of dying of ovarian cancer that was more than double of that of never-users (RR of 2.20). Women who were former users of ERT, but not users at study entry, also had higher ovarian death rates, but not as high as baseline users. The increased risk of mortality persisted up to 29 years after women stopped using ERT.

Overall, women who had a current or former history of ERT had an increased death rate with a RR of 1.23. "Our findings support the hypothesis that ERT increases the rate of fatal ovarian cancer and that this risk association is greater with longer use and also greater with more recent use," observes Dr. Rodriguez. "To our knowledge, no other prospective study has examined the association between duration of ERT and ovarian cancer mortality," she added.

According to the authors, one possible mechanism to account for these findings may be that postmenopausal estrogen therapy raises levels of serum estradiol and estrogen, the forms of estrogen found circulating in the body. These substances have a direct effect on cells in the ovary. Increased exposure to estrogen is known to increase proliferation of ovarian cells and some women with ovarian cancer experience a beneficial effect when treated with the drug tamoxifen, a powerful anti-estrogen.

According to American Cancer Society Chief Medical Officer, Harmon J. Eyre, MD, the potential increase of ovarian mortality risk with ERT must be considered in the broad context of the overall balance of known risks and benefits of postmenopausal hormone therapy.

"First of all, the overall lifetime risk of American women for ovarian cancer is low, less than 2 percent on average, " said Dr. Eyre. "Additionally, this study was not able to assess the effect of current hormone therapy which commonly combines the hormone progesterone with estrogen."

"More studies will be needed to confirm these results and also to look at the effect on mortality of combined therapy or HRT as it is commonly called, against the effect of unopposed estrogen therapy. But if these current results do hold up, then we will have to list ovarian cancer among the health risks associated with 10 years or more of estrogen use," added Eyre.

The American Cancer Society is the nationwide community-based voluntary health organization dedicated to eliminating cancer as a major health problem by preventing cancer, saving lives and diminishing suffering from cancer, through research, education, advocacy and service.

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