The Minimum Effective Dose of Estrogen for Prevention of Postmenopausal Bone Loss

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The present authors report a 2-year study of estrogen therapy for the prevention or reduction of postmenopausal bone loss. The aim of the investigation was to determine the minimum effective dose of estrogen for postmenopausal and oophorectomized women. Of the 150 patients enrolled in the study, 108 completed 2 years of therapy. Thirty patients were allocated to each of four dose levels of conjugated equine estrogens: 1.25, 0.625, 0.3, and 0.15 mg per day. All patients were allocated randomly to a dose level and were compared with 30 patients randomly given nonmatching placebo tablets (Table 1). The mean heights and weights of the groups were comparable and did not change significantly throughout the study. Total serum calcium (corrected for changes in serum albumin) and phosphate were significantly reduced by 0.625 and by 1.25 mg of conjugated estrogens per day but not by any of the lower doses. In the measurements taken before treatment, serum calcium was significantly higher in the group given 0.625 mg per day than in all other groups. Serum phosphate also was higher in the 0.625-mg and 1.25-mg groups before therapy. The reasons for these differences are obscure, but the finding does not interfere with the interpretation of the results. In conjunction with the changes in serum levels, urinary calcium was reduced only in those groups given 0.625 and 1.25 mg of estrogen per day. In the pretreatment measurements, urinary calcium was somewhat reduced in the group given 0.625 mg per day, as compared with other groups. This is perhaps compatible with the slightly higher level of serum calcium. Despite this lower starting point, 0.625 mg of conjugated equine estrogens per day reduces urinary calcium significantly. Urinary hydroxyproline also was significantly reduced at 0.625 and 1.25 mg per day but not at the lower dose levels. Bone mineral content, estimated by single photon absorptiometry, fell significantly in the placebo (0.15− and 0.3− mg-treated) groups, with no significant difference in behavior between groups. Conjugated equine estrogens at 0.625 and 1.25 mg per day afforded significant protection against bone loss. Construction of a dose-response curve suggested that a 50 per cent response rate would be obtained at 0.45 mg of estrogens per day.