Estrogen offers no overall benefit for disease prevention in postmenopausal women with hysterectomy


Taking estrogen provides no overall benefit for chronic disease prevention in postmenopausal women with previous hysterectomy, but does appear to increase the risk of stroke and decrease the risk of hip fracture, according to a study in the April 14 issue of The Journal of the American Medical Association (JAMA).

Estrogen therapy has been available to postmenopausal women for more than 60 years, according to background information in the article. Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.

The Women's Health Initiative (WHI) clinical trials of hormone therapy were undertaken to determine whether conjugated equine estrogen (CEE) alone (for women with prior hysterectomy) or in combination with progestin (medroxyprogesterone acetate) would reduce coronary heart disease (CHD) events in mostly healthy postmenopausal women. The WHI estrogen plus progestin trial was halted in July 2002 because health risks exceeded benefits, including increased risks for CHD, stroke and breast cancer.

In this new report on the estrogen alone intervention, the WHI investigators assessed the effects of CEE, the most commonly used postmenopausal hormone therapy in the U.S., on major disease incidence rates. In this randomized, double-blind, placebo-controlled disease prevention trial conducted in 40 U.S. clinical centers beginning in 1993, 10,739 postmenopausal women, aged 50-79 years, with prior hysterectomy were enrolled, including 23 percent of minority race/ethnicity. The women were randomly assigned to receive either 0.625 mg/day of CEE or placebo.

The WHI authors write that in February 2004, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Based on data for the major clinical outcomes available through February 29, 2004, the researchers found that with an average of 6.8 years of follow-up, CEE had no significant effect on reducing the risk of CHD (376 cases), but did cause a significant increase (39 percent increase) in risk of stroke (276 cases). CEE significantly reduced the risk of hip fracture (39 percent reduction, 102 cases), was associated with a non-significant reduction in risk of breast cancer, (218 cases), and had no significant effect on risk of pulmonary embolism (85 cases) or colorectal cancer (119 cases). Corresponding results for composite outcomes were a significant increase (12 percent) in the risk of total cardiovascular disease, and a significantly decreased risk (30 percent) of total fractures, but no significant effect on total cancer, total mortality, and a global index . For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10,000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10,000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10,000 person-years.

"Based on these findings, women and their health care professionals now have usable risk estimates for the benefits and harms of CEE alone. Women considering taking CEE should be counseled about an increased risk of stroke but can be reassured about no excess risk of heart disease or breast cancer for at least 6.8 years of use. At present, these data demonstrate no overall benefit of CEE for chronic disease prevention in postmenopausal women and thus argue against its use in this setting. Overall, these data support the current U.S. Food and Drug Administration recommendations for postmenopausal women to use CEE only for menopausal symptoms at the smallest effective dose for the shortest possible time," the researchers write.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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