Does HRT Increase Ovarian Cancer?

Hormone Replacement Therapy May Also Prompt Additional Testing

Medically Reviewed by Brunilda Nazario, MD on September 30, 2003
From the WebMD Archives

Sept. 30, 2003 -- More than a year after concerns about an increased risk of breast cancer among hormone replacement therapy users halted the Women's Health Initiative study, researchers still continue to examine the results of the landmark study.

The latest interpretation of that data suggests that postmenopausal women who take combined hormone replacement therapy (HRT) continuously may face a higher risk of a much-rarer form of cancer that affects the ovaries as well as increase the likelihood of needing procedures used to diagnose endometrial cancer.

The results appear in the Oct. 1 issue of The Journal of the American Medical Association.

Researchers say the findings shouldn't affect most women's decisions to take HRT to relieve moderate to severe menopausal symptoms, such as hot flashes. But the possibility of an increased ovarian cancer risk and burden of additional testing support recently revised guidelines that call for the conservative use of hormone therapy.

HRT and Ovarian Cancer Risk

The Women's Health Initiative (WHI) involved 40 research centers in the U.S. and more than 16,000 postmenopausal women who had not had a hysterectomy. The women were divided into two groups that were either treated with placebo pills or with a combined estrogen plus progestin therapy (Prempro).

After more than 5 years of follow up, at first it seemed that continuous combined HRT increased ovarian cancer rates by 58% -- totaling 15 more cases of ovarian cancer per 100,000 women per year taking HRT. This may seem like a big jump, but once the researchers looked at the findings more closely, they found that this increased risk was actually not significantly different from rates seen in women taking the placebo pills.

Researchers say these findings suggest that even if those differences are later proven to be significant, ovarian cancer remains a rare disease in women taking hormone replacement therapy.

"The possibility of an increased risk of ovarian cancer incidence and mortality [death] remains worrisome, however, and needs confirmation," write researcher Garnet L. Anderson, PhD, and colleagues, of the Fred Hutchison Cancer Research Center in Seattle.

Combined HRT May Protect Against Endometrial Cancer

Endometrial tissue growth and endometrial cancer are known to occur with estrogen-only therapy. Researchers say that progestin was added to estrogen hormone replacement therapy to reduce the risk of endometrial cancer and bleeding complications found with estrogen-only therapies in women who have not had a hysterectomy (surgical removal of the uterus).

The study confirmed that combined estrogen progestin therapy reduced endometrial cancer rates by 19%, and there were 13 fewer cases of endometrial cancer per 100,000 women taking hormone replacement therapy per year compared with the placebo group. However, researchers say this difference also could not be distinguished from chance and the rates of endometrial cancer were not different from women taking placebo pills.

Vaginal bleeding was a common side effect of combined HRT, and researchers say this led to more frequent testing for endometrial cancer -- such as biopsy and ultrasound.

"The increased need for diagnostic procedures in response to bleeding is an added burden and could reasonably affect a woman's decision to use these medicines," write the researchers.

Show Sources

SOURCE: Anderson, G. The Journal of the American Medical Association; vol 290: pp 1739-1748.

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