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

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.