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

J Womens Health (Larchmt). 2005 Mar;14(2):137-45. doi: 10.1089/jwh.2005.14.137.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Coronary Disease*
  • Dose-Response Relationship, Drug
  • Estradiol / administration & dosage*
  • Estradiol / adverse effects
  • Estrogen Replacement Therapy*
  • Female
  • Humans
  • Insulin / blood*
  • Insulin / metabolism
  • Insulin Resistance*
  • Insulin Secretion
  • Medroxyprogesterone Acetate / administration & dosage*
  • Medroxyprogesterone Acetate / adverse effects
  • Middle Aged
  • Norway
  • Postmenopause / drug effects
  • Time Factors
  • Women's Health


  • Insulin
  • Estradiol
  • Medroxyprogesterone Acetate