Hormone therapy and insulin resistance in non-diabetic postmenopausal women: a systematic review and meta-analysis

Climacteric. 2025 Dec;28(6):673-681. doi: 10.1080/13697137.2025.2509844. Epub 2025 Jun 18.

Abstract

Objective: Menopause increases the risk of insulin resistance and cardiometabolic diseases. This study summarizes the effects of hormone therapy (HT) on insulin resistance in non-diabetic postmenopausal women.

Method: The study analyzed randomized controlled trials (1998-2024) that assessed the impact of HT on insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) in non-diabetic postmenopausal women. Raw mean differences (RMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analysis compared estrogen alone (E alone) and estrogen plus progestogen (E + P) to placebo.

Results: Seventeen randomized controlled trials with 5772 women (3644 on HT: E alone [n = 1259] or E + P [n = 2385]; 2128 on placebo) were included. The weighted mean (standard deviation) age was 56.91 (5.95) years, with treatment lasting 8 weeks to 3 years. HT significantly reduced HOMA-IR (RMD = -0.24 [-0.32 to -0.16], p < 0.001, I2 = 60.3%). Subgroup analysis showed reductions in both E alone (RMD = -0.42 [-0.55 to -0.29], p < 0.001, I2 = 35%) and E + P (RMD= -0.14 [-0.23 to -0.04], p = 0.005, I2 = 13.7%) compared to placebo.

Conclusion: HT significantly lowers insulin resistance in healthy, non-diabetic postmenopausal women, with E alone yielding greater reductions than combination therapy.

Keywords: Hormone therapy; cardiovascular disease risk factors; estrogen therapy; insulin resistance; postmenopausal women.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Estrogen Replacement Therapy* / methods
  • Estrogens / administration & dosage
  • Female
  • Humans
  • Insulin Resistance*
  • Middle Aged
  • Postmenopause*
  • Progestins / administration & dosage
  • Randomized Controlled Trials as Topic

Substances

  • Estrogens
  • Progestins