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Am Fam Physician. 2003;67(12):2612-2615

Combined hormone therapy recently has been shown to offer no long-term advantage in women with coronary heart disease. It is associated with an increase in adverse cardiac events during the first year of therapy. The effect of estrogen alone is less clear. In one observational study, postmenopausal women who had used estrogen had improved survival rates following coronary heart disease. Other studies have given conflicting results. The oEStrogen in the Prevention of ReInfarction Trial (ESPRIT) was designed to assess the effect of unopposed estradiol on cardiac events in postmenopausal women who survived a first myocardial infarction.

All women 50 to 69 years of age who were admitted to one of 35 participating hospitals in Britain because of proven myocardial infarction were considered for the trial if they were discharged within 31 days and had none of the specified contraindications to estrogen therapy. More than 1,000 women were randomly assigned to receive estradiol (2 mg) or a placebo. Patients received study medications from their family physicians at 12, 24, 48, and 72 weeks. The primary study outcomes were cardiac death, nonfatal reinfarction, or death from any cause. Patients were monitored for two years by questionnaires completed by their family physicians at three, six, 12, 18, and 24 months. In addition to cardiac events, the questionnaires addressed uterine bleeding, endometrial cancer, breast cancer, stroke, embolic events, fractures, and compliance with treatment. A member of the research team investigated all reports of uterine bleeding. After the study, all women in the active medication group who had not had hysterectomies were sent annual reminders (with copies to their family physicians) about their exposure to unopposed estrogen and the significance of symptoms of endometrial disease.

At the beginning of the study, the 513 women assigned to estradiol were similar to the 504 women assigned to placebo; 97 percent were white, 53 percent smoked, 24 percent had undergone hysterectomy, and 15 percent were diabetic. The mean age was 62 years. Compliance was poor in both treatment and placebo groups. By 24 months, 57 percent of the treatment group and 37 percent of the placebo group were no longer compliant with the study protocol. Uterine bleeding was reported by 56 percent of the treatment group and 7 percent of the placebo group.

Of the 71 women who died during follow-up, 38 deaths resulted from confirmed cardiac causes, and it was likely that an additional 13 resulted from cardiac causes. During the two-year follow-up period, 32 women in the treatment group died compared with 39 in the control group, and 91 women had reinfarction. The combined measure of rein-farction or cardiac death was confirmed in 123 women—62 in the treatment group and 61 in the control group. The groups did not differ significantly in any of the primary outcomes. Although the risk of death from any cause was lower in the treatment group, the difference was not significant, even after adjustment for potential confounders. There was no difference in secondary measures such as stroke, embolic events, breast cancer, or fractures.

The authors conclude that estradiol therapy is not associated with any advantage in rein-farction or cardiac death in the two years following first myocardial infarction in post-menopausal women and was associated with high rates of uterine bleeding.

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