New Warnings for Women Taking HRT

Estrogen-Only Hormone Therapy Linked to Ovarian Cancer

Medically Reviewed by Charlotte E. Grayson Mathis, MD
From the WebMD Archives

July 16, 2002 -- Last week, millions of women who take a combination form of hormone replacement therapy learned they are at increased risk for breast cancer, heart disease, and stroke. Now comes news that women who take estrogen alone may be at increased risk for ovarian cancer.

The new findings add to the growing body of evidence that the dangers of long-term hormone replacement therapy (HRT) may outweigh the benefits. Hormone therapy was originally prescribed solely to relieve the symptoms of menopause. But over the last two decades women who no longer had menopausal symptoms were encouraged to take HRT in the belief that it helped prevent common diseases of aging such as heart disease and osteoporosis.

Estrogen alone is given only to women who have had hysterectomies. The hormone progestin is added to estrogen (combination HRT) for the treatment of women who still have their uterus, to reduce the risk of endometrial cancer. About 38% of postmenopausal women in the U.S. use hormone replacement therapy.

In the latest study, researchers from the National Cancer Institute (NCI) followed 44,000 women taking estrogen only and found that these women had a 60% higher risk of ovarian cancer than women who had never used estrogen. Those on the hormone therapy for 20 years or more were three times as likely to develop ovarian cancer as women who did not take it at all. Women who took estrogen for 10 to 19 years had an 80% higher risk than nonusers.

Lead author James V. Lacey tells WebMD that this translates into one or two additional ovarian cancers per 10,000 women taking estrogen alone for one year.

"Our study does not prove that ... estrogen [taken by itself] causes ovarian cancer," Lacey says. "But it is becoming more and more obvious that hormone therapy influences many conditions that affect women after menopause. This is a very complicated issue."

The ovarian cancer results were reported July 17 in TheJournal of the American Medical Association. In that same issue, government researchers published the findings reported last week that prompted health officials to halt the 16,000-subject Women's Health Initiative study evaluating combined HRT. The risk of breast cancer rose by 26% in women on the combined therapy for just over five years, while heart disease risk rose by 29% and there was a 41% increase in the risk of stroke.

But the health officials did not stop the part of the study evaluating estrogen alone in 11,000 women without uteruses because these women did not appear to have the same increased risks for breast cancer as those on combined therapy. The 11,000 women have been sent letters stating this, but the issue of ovarian cancer has not been addressed.

Marcia Stefanick, MD, who leads the Women's Health Initiative steering committee, says no definitive conclusions on ovarian cancer risk can be made from the NCI study because of its design. Stefanick is an associate professor of medicine at Stanford University.

"Observational studies like this one give us great insight into what hypotheses we should test, but they don't answer the questions," she tells WebMD. "For that you need randomized, clinical trials."

Stefanick says the overall balance of risks vs. benefits is not clear for women taking estrogen alone. She hopes women taking part in the estrogen-only arm of the Women's Health Initiative trial will stay on the study, scheduled to continue until 2005.

"The risks that led us to stop the combined treatment arm of the trial were relatively small, and we have not seen those risks in women taking estrogen alone," she says. "We are committed to the safety of our study participants. We hope that women will continue on the trial so that we can get definitive answers to these questions."

Margery Gass, MD, who is president elect of the National American Menopause Society, says women taking either estrogen alone or combined therapy for relief of menopause symptoms should be reassured that short-term use appears safe.

"Both patients and physicians alike have tried to make decisions regarding hormone therapy with the information they have had at the time," she says. "Now we finally have some definable risks, and women can apply those risks to their lives and their decisions."