April 16, 2004

You may be receiving questions from your patients about whether or not they should continue with hormone replacement therapy due to recent publications and news reports about the Women's Health Initiative (WHI) trial. Results were published in 2002 for the estrogen/progestin arm of the study and have recently been published for the estrogen-only arm. While any decision regarding the continuation of therapy should be made together by the patient and their physician, the following information may help you discuss the current findings with your patients.

The WHI is a parallel, randomized, placebo-controlled, primary prevention trial of postmenopausal hormones. The arm that compared placebo to Premarin plus medroxyprogesterone acetate was discontinued because the combination was causing more harmful effects than beneficial effects. The increased risks of Premarin plus medroxyprogesterone compared to placebo are as follows for a 5-year period. For every 10,000 women treated with Premarin plus medroxyprogesterone, 7 more women would experience a coronary event, 8 more women would experience invasive breast cancer, 8 more women would experience a stroke, and 8 more women would experience a pulmonary embolism compared to 10,000 women treated with placebo. There were some benefits of the hormone combination. For every 10,000 women treated with Premarin plus medroxyprogesterone, 6 fewer women would experience colorectal cancer and 5 fewer women would experience a hip fracture.

The arm of the trial comparing placebo to Premarin alone in women who have previously had a hysterectomy was allowed to continue and the results were recently published. The risks of Premarin monotherapy compared to placebo are as follows for a 5-year period. For every 10,000 women treated with Premarin monotherapy, 12 more women would experience a stroke compared to 10,000 women treated with placebo. There were several benefits of Premarin monotherapy. For every 10,000 women treated with Premarin monotherapy, 7 fewer women would experience breast cancer, 56 fewer women would experience an osteoporotic fracture (including 6 fewer hip fractures and 6 fewer vertebral fractures) compared to 10,000 women treated with placebo. The risk of coronary heart disease was 9% lower with Premarin monotherapy (or 5 fewer events per 10,000 women) than placebo, although this was not statistically significant.

Copies of the trials and the accompanying editorials are attached for your convenience.

• Combination Therapy Editorial: (PDF)
• Combination Therapy Trial: (PDF)
• Premarin Alone Editorial: (PDF)
• Premarin Alone Trial: (PDF)