Effects of long-term estrogen replacement therapy. I. Metabolic effects.

Two groups of hypoestrogenic women are analyzed by retrospective comparisons. Patients were observed by a single group of physicians for at least five years; 301 patients were treated with replacement estrogen and 309 patients were untreated. Incidence figures for various metabolic diseases present at entry and both during and after estrogen therapy were compared by the usual statistical analysis and by statistical adjustments for certain group differences (Mantel-Haenszel statistic). The long-term administration of estrogen to these relatively young women with hypoestrogenism was associated with significantly lower rates of development of cardiovascular disease, hypertension, osteoporosis, and fractures. Detrimental effects were a higher rate of abnormal uterine bleeding and an increase in the likelihood of developing adenocarcinoma of the endometrium. Effects of estrogen preparation, dosage, method of therapy, duration of therapy, and the addition of synthetic progestins are presented.