A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women and the attenuating effect of added progestin

Abstract

Objective: To determine the effects of estrogen and of added progestin on carbohydrate tolerance in postmenopausal women.

Design: An insulin tolerance test (ITT) was used to assess insulin resistance in healthy post-menopausal women and to determine the effects of oral estrogen with and without added progestin on insulin sensitivity.

Setting: A menopause research clinic at a University Medical Center.

Patients: Fifteen healthy postmenopausal and nine premenopausal women were studied after having not received any hormone preparations for > or = 4 weeks.

Interventions: All subjects received a baseline ITT and postmenopausal women were then randomized to receive either 0.625 mg conjugated equine estrogen, 0.625 mg conjugated equine estrogen/10 mg progestin, or 1.25 mg conjugated equine estrogen for 2 months at which time a second ITT was performed. In the former two groups the women were treated for an additional 4 months to assess the long-term effects of treatment and had a third ITT performed at the end of 6 months.

Main outcome measures: Fasting serum insulin and glucose were measured and K(itt) values were obtained at each visit in each group.

Results: Forty-four percent of nonobese healthy postmenopausal women were found to have insulin resistance. The three groups differed significantly in their K(itt) responses. Estrogen replacement improved insulin sensitivity (K(itt) increased by 25%). However, 1.25 mg of conjugated equine estrogen caused a 24.7% decrease in K(itt) values and progestins attenuated the beneficial effects of 0.625 mg conjugated equine estrogen from baseline values (K(itt) decreased by 17.0%). Two- and 6-month values did not differ.

Conclusions: Insulin resistance is prevalent in healthy postmenopausal women. A moderate dose of estrogen appears to increase insulin sensitivity but higher doses may attenuate this benefit and progestins may cause a decrease in insulin sensitivity.