Insulin sensitivity in women with coronary heart disease during hormone replacement therapy

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).

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.

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.

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.