LOW-DOSE ESTERIFIED ESTROGEN THERAPY - EFFECTS ON BONE, PLASMA ESTRADIOL CONCENTRATIONS, ENDOMETRIUM, AND LIPID-LEVELS

Background: Prospective studies have shown that doses equivalent to co njugated equine estrogens of 0.625 mg/d or higher are needed to produc e a significant increase in bone mineral density of the lumbar spine. Objectives: To determine the effects of unopposed esterified estrogens on bone mineral density, lipid levels, and endometrial tissue structu re, and to relate these effects to changes in plasma estradiol levels. Methods: Four hundred six postmenopausal women were given calcium, 10 00 mg/d, and randomly assigned to receive continuous esterified estrog ens (0.3, 0.625, or 1.25 mg/d) or placebo for 24 months. Bone mineral density measurements and endometrial and laboratory assessments were c onducted every 6 months; plasma estradiol concentrations were measured after 12, 18, and 24 months. Results: All doses of esterified estroge ns produced significant increases in bone mineral density of the lumba r spine compared with baseline and with placebo at 6, 12, 18, and 24 m onths. Mean plasma estradiol levels increased with esterified estrogen s dose, and individual subject bone mineral density changes appeared r elated to plasma estradiol concentrations. Clinically relevant rates o f endometrial hyperplasia were noted only in the groups receiving 0.62 5 and 1.25 mg of esterified estrogens daily. Lipid changes were dose r elated and apparent in all groups. Conclusions: Esterified estrogens a t doses from 0.3 to 1.25 mg/d, administered unopposed by progestin, pr oduce a continuum of positive changes on bone and lipids. Plasma estra diol concentrations increased with esterified estrogens dose and were related to positive bone mineral densities. The 0.3-mg dose resulted i n positive bone and lipid changes without inducing endometrial hyperpl asia.