Study offers women more complete picture of HRT risks, benefits

Detailed results of the “estrogen-alone” study within the Women’s Health Initiative (WHI), which was terminated in early March 2004, are providing some of the first answers to questions about the efficacy of estrogen alone to prevent chronic disease in healthy, postmenopausal women who have had a hysterectomy. WHI researchers, including investigators at Brigham and Women’s Hospital (BWH), have shown that after 6.8 years of study on more than 10,000 women nationwide, estrogen-alone hormone replacement therapy (HRT) in postmenopausal women increased the risk of stroke, reduced the risk of hip fracture, and had minimal effect on the risk of heart disease and breast cancer. In addition, the research suggests that women who start estrogen earlier in life may receive more heart health benefits than those who start later in life. These findings are published in the April 14 issue of the Journal of the American Medical Association.

According to JoAnn Manson, chief of preventive medicine and principal investigator of the WHI at BWH, “These results suggest that the risks and benefits of estrogen therapy are fairly balanced, but these hormones should not be taken to prevent cardiovascular disease. More research is needed to understand if the benefits outweigh the risks in younger women beginning estrogen shortly after menopause. Estrogen therapy still has a role in the short-term treatment of menopausal symptoms, but the lowest dose should be used for the shortest duration of time possible.”

The estrogen-alone study involved 10,739 women ages 50 to 79 years who were studied for 6.8 years. Study participants were randomly assigned either a daily dose of hormone replacement therapy (HRT) – 0.625 mg/day conjugated equine estrogen (CEE) – or a placebo. The study’s main goal was to determine the impact estrogen alone has on coronary heart disease risk, but like the “estrogen plus progestin” study, which was stopped in 2002, an increased risk of stroke was found. Specific findings related to estrogen-alone HRT include:

• Coronary heart disease risk did not increase or decrease
• Stroke risk increased 39 percent with the most pronounced increase occurring among women who were 60 years old and older
• Breast cancer risk decreased by 23 percent, which was not statistically significant and indicates that further study is necessary to determine estrogen impact on breast health
• Pulmonary embolism risk increased 34 percent
• Hip fractures decreased by 39 percent
• Evidence for a small increase in dementia and mild cognitive impairment were observed in women age 65 and older. A separate research report will be issued at a later date on these findings.According to Manson, who is also a professor of medicine at Harvard Medical School, “In the early 1990s, an estimated 15 million women were taking HRT without clear information about the health benefits or risks associated with its use. These study results will help women and their clinicians make more informed choices about the use of estrogen therapy.”The Women’s Health Initiative involves more than 161,000 women who are either participating in a set of clinical trials to test preventive measures for heart disease, fractures, breast and colorectal cancer, or in a large observational study. In addition to the trials of estrogen alone and estrogen plus progestin, other WHI trials are studying a low-fat diet pattern and calcium/Vitamin D supplementation. These trials are continuing.