Association of endogenous sex hormones and insulin resistance among postmenopausal women: results from the Postmenopausal Estrogen/Progestin Intervention Trial

J Clin Endocrinol Metab. 2003 Apr;88(4):1646-52. doi: 10.1210/jc.2002-021375.


Most studies of sex hormones and insulin resistance (IR) have focused on androgens; few have examined the association of endogenous estrogens and IR. We determined the cross-sectional association of endogenous levels of total and bioavailable testosterone and estradiol and SHBG with IR among 845 healthy, postmenopausal women aged 45-65 yr. Women were within 10 yr of menopause and not using hormone replacement therapy. Total adiposity was estimated by body mass index, visceral adiposity by waist to hip ratio (WHR), and IR by the homeostasis model assessment. We defined homeostasis model assessment-IR as the highest quartile (cutpoint, 2.1) of the distribution in this cohort. In logistic regression analyses, the odds for IR were significant and increased in a dose-response fashion across each quartile of total estradiol, bioavailable estradiol, and bioavailable testosterone (all P < 0.001 for linear trend). These associations remained significant after adjusting for WHR; adjusted odds ratios were 4.0, 6.1, and 2.7 for total estradiol, bioavailable estradiol, and bioavailable testosterone, respectively, comparing the highest to the lowest quartile (all P < 0.001). Adjusting for body mass index and WHR together eliminated the linear association of IR with total estradiol and bioavailable testosterone, but the association with bioavailable estradiol remained (adjusted odds ratio, 2.7; P < 0.001, comparing the highest to the lowest quartile). IR was not associated with total testosterone before or after adjusting for adiposity. Lower SHBG levels were associated with higher odds of IR, independent of adiposity. These results suggest that estrogen may be equally or more important than testosterone in the pathway to IR in healthy, young postmenopausal women, with differences not entirely explained by body size.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue
  • Aged
  • Biological Availability
  • Body Composition
  • Body Constitution
  • Body Mass Index
  • Estradiol / blood
  • Estrogen Replacement Therapy*
  • Female
  • Gonadal Steroid Hormones / blood*
  • Homeostasis
  • Humans
  • Insulin Resistance*
  • Logistic Models
  • Middle Aged
  • Postmenopause*
  • Progestins / administration & dosage
  • Sex Hormone-Binding Globulin / analysis
  • Testosterone / blood
  • Viscera


  • Gonadal Steroid Hormones
  • Progestins
  • Sex Hormone-Binding Globulin
  • Testosterone
  • Estradiol