Estrogen Alone Provides No Overall Benefit to Postmenopausal Women, Complete Analysis of WHI Trial Shows

BUFFALO, N.Y. -- Results of the clinical trial of estrogen supplementation for postmenopausal women who have had a hysterectomy, an arm of the Women's Health Initiative, show there is no overall health benefit to taking the hormone.

Full results of the trial, which involved 10,739 women who had a hysterectomy and who took estrogen-alone therapy or placebo for an average of 6.8 years, appear in the current issue of the Journal of the American Medical Association (JAMA). The trial, initially planned to continue until 2005, was halted in February because preliminary analysis of the data showed estrogen didn't reduce the risk of heart disease, a key hypothesis of the trial, and increased the risk of stroke.

"This study makes it clear that women should not be taking estrogen long-term for prevention of heart disease," said Jean Wactawski-Wende, Ph.D., an author on the study and co-director of the WHI Vanguard Clinical Center at the University at Buffalo. Approximately 300 women were enrolled in this trial through the UB center.

The estrogen-alone arm of the WHI trial was intended to continue until March 2005. The full analysis published in JAMA confirms the preliminary findings released this March. In addition to finding no effect on cardiovascular disease, results showed that estrogen-alone therapy significantly increased the risk of both stroke and deep-vein blood clots, but reduced the risk of hip and other fractures. There also was a small but statistically insignificant decrease in breast cancer.

The trial of estrogen plus progestin in women who had not had a hysterectomy was ended early also, in July 2002, because the risks -- increases in heart disease, stroke, breast cancer and blood clots -- outweighed the benefits.

"The overall message is that for women without a uterus, estrogen replacement does not protect against heart disease," said Wactawski-Wende. "There are other therapies available that have been shown to lower the risk of heart disease, such as statins, and other several other treatments to prevent osteoporosis and fracture.

"The findings of a small reduction in the risk of breast cancer in these women is intriguing, but requires further investigation."

Wactawski-Wende said the breakdown of results by age at the time women enrolled in the trial also is interesting, and open up many avenues for continued research. "It appears that younger women aged 50-59 who took estrogen had less risk of developing heart disease than women aged 60-79. However these findings are very preliminary and need further investigation. Additional analyses are underway.

"Until we can look at each of the outcomes separately -- cardiovascular disease, stroke, venous thrombosis, breast and colon cancer, fractures and death -- and analyze the impact of other health factors, we have limited understanding of the potential effect of estrogen therapy," she said.

The health of all women currently enrolled in both arms of the WHI hormone trials will continue to be monitored closely.

The WHI dietary intervention and calcium and vitamin D clinical trials will continue until 2005. Findings from those studies should be available in late 2005.

The NIH has also announced plans to continue to follow the health of all WHI participants after the end of the current study for an additional 5 years, until 2010.

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