Hormone therapy and insulin resistance in non-diabetic postmenopausal women: a systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 40531213 · doi:10.1080/13697137.2025.2509844
What was done
A systematic review and random-effects meta-analysis of randomized controlled trials published from 1998 to 2024 evaluating the effect of hormone therapy (HT) on insulin resistance—measured via the homeostasis model assessment of insulin resistance (HOMA-IR)—in non-diabetic postmenopausal women compared to placebo. Subgroup analyses compared estrogen alone (E alone) and estrogen plus progestogen (E + P) against placebo.
What was found
Across 17 RCTs involving 5,772 non-diabetic postmenopausal women (3,644 on HT [1,259 on E alone, 2,385 on E + P] and 2,128 on placebo; mean age 56.91 ± 5.95 years; follow-up 8 weeks to 3 years): - Overall HT significantly reduced HOMA-IR compared to placebo (raw mean difference [RMD] = -0.24, 95% CI [-0.32 to -0.16], p < 0.001, I² = 60.3%). - Estrogen alone produced a larger reduction in HOMA-IR (RMD = -0.42, 95% CI [-0.55 to -0.29], p < 0.001, I² = 35%). - Estrogen plus progestogen also reduced HOMA-IR, but to a lesser degree (RMD = -0.14, 95% CI [-0.23 to -0.04], p = 0.005, I² = 13.7%).
Why it matters
This meta-analysis demonstrates that postmenopausal hormone therapy improves surrogate measures of insulin sensitivity in women without diabetes, while indicating that the addition of progestogen attenuates estrogen's beneficial effect.
Limits
The primary pooled outcome displayed moderate heterogeneity (I² = 60.3%). Findings are restricted to a surrogate laboratory index (HOMA-IR) rather than clinical metabolic endpoints (such as new-onset diabetes). Study durations varied widely (8 weeks to 3 years), and the abstract provides no subgroup breakdown by route of administration (e.g., transdermal vs. oral) or progestogen formulation.
Cited by
- supports The loss of estrogen from the body makes a person more insulin resistant.