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.