Objective: The aim of the present study was to evaluate the effect on insulin secretion and insulin sensitivity of hormone replacement therapy (HRT) with short-term unopposed transdermal 17beta-estradiol and, after 1 year, when combined with intermittent medroxyprogesterone acetate (MPA).
Methods: Ninety-nine postmenopausal women with coronary artery disease (CAD), but without diabetes mellitus, consecutively recruited from patients referred for invasive coronary investigations at a tertiary university clinic, were randomized to either HRT or a control group. Unopposed estradiol was given for 3 months, and MPA was added in cycles of 14 days every 3 months. Clinical investigations were undertaken at baseline and after 3 months and 12 months. Insulin sensitivity index (HOMA-IR) and insulin secretion (HOMA-BCF) were calculated using the homeostasis model assessment.
Results: Compared with the control group, treatment with unopposed transdermal 17beta-estradiol caused a significant decrease in HOMA-IR, that is, improved insulin sensitivity, but after combination with MPA and 12 months of HRT, no change was observed in HOMA-IR. Similarly, a transient decrease was observed for plasma levels of C peptide after unopposed 17beta-estradiol. HOMA-BCF remained unchanged throughout the study period. Sex hormone-binding globulin (SHBG) was related to HOMA-IR but not to HOMA-BCF at baseline. The association with HOMA-IR grew stronger after unopposed transdermal estradiol. No deleterious effect of HRT on glucose metabolism was found in postmenopausal women with CAD.
Conclusions: Short-term treatment with unopposed transdermal estradiol caused a decrease in insulin resistance, but long-term treatment after intermittent MPA was introduced had no effect on either insulin secretion or insulin resistance.