Low- and standard-estrogen dosage in oral therapy: dose-dependent effects on insulin and lipid metabolism in healthy postmenopausal women

Objective To evaluate the influences of different doses of daily oral unopposed 17-estradiol compared with placebo, both on glucose tolerance and lipid metabolism in healthy postmenopausal women. Patients and methods Forty-eight normoinsulinemic postmenopausal women were enrolled in the study. Patients were assigned to receive randomly 1mg (group A) or 2mg (group B) of oral micronized estradiol therapy daily or to the placebo (group C), for 12 weeks. Results The low-dose estradiol treatment determined an improvement of the peripheral insulin sensitivity, made evident by a significant increase both in the metabolic index and oral glucose insulin sensitivity index (p0.01 and p0.05, respectively) as well as a decrease in the homeostasis model assessment-estimated insulin resistance (p0.01). Conversely, in the standard-dose group, the metabolic index significantly decreased (p0.05), showing a slight deterioration in insulin sensitivity. For lipid metabolism, the 1mg dose showed a neutral effect, while 2mg had a beneficial effect on low density lipoprotein cholesterol, but caused an increase in triglycerides (p0.01 and p0.05, respectively). Conclusions The oral low dose of unopposed estradiol therapy had a favorable effect on glycoinsulinemic metabolism in healthy postmenopausal women; however, the standard dose caused a slight but significant deterioration in insulin sensitivity.