Effects of oral and transdermal 17 beta-estradiol with cyclical oral norethindrone acetate on insulin sensitivity, secretion, and elimination in postmenopausal women

Few studies have examined the effects of 17 beta-estradiol on parameters of insulin and glucose metabolism. We studied 42 healthy, untreated postmenop ausal women seeking relief from menopausal symptoms. They were randomized t o receive either oral 17 beta-estradiol 2 mg daily combined with sequential oral norethindrone acetate (NETA) 1 mg daily from days 12 to 22, or transd ermal 17 beta-estradiol 0.05 mg daily combined with sequential oral NETA 1 mg daily from days 17 to 28. Intravenous glucose tolerance tests (IVGTTs) w ere performed at baseline and after 48 weeks (estrogen-alone phase) and 48 weeks (combined phase) of completed therapy. Mathematical modeling analysis of plasma glucose, insulin, and C-peptide concentration profiles provided measures of insulin resistance, secretion, and elimination. Both types of t herapy were associated with a decrease in fasting insulin and glucose level s. Insulin sensitivity was increased by oral estradiol during the estrogen- alone phase but was reversed by the addition of NETA. Transdermal estradiol did not affect insulin sensitivity. Hepatic insulin uptake and insulin sec retion were increased with both types of treatment. The oral regimen of est radiol therapy was favorable to both insulin elimination and sensitivity. T ransdermal estradiol therapy had relatively few effects on insulin metaboli sm. Copyright (C) 2000 by W.B. Saunders Company.