Menopausal hormone therapy decreases the likelihood of diabetes development in peri‑menopausal individuals with prediabetes

Background: The influence of menopausal hormone therapy (MHT) on the probability of developing diabetes mellitus in individuals with prediabetes remains uncertain. Methods: This retrospective cohort study, utilizing the TriNetX U.S. Collaborative Network, investigated cohorts, implemented propensity score matching, and analyzed outcomes associated with diabetes mellitus. The study focused on individuals aged 46–60 with prediabetes prior to menopause, categorizing them into MHT and non-MHT groups. Further stratified analyses, including variables such as age and race, were conducted to thoroughly examine potential variations in outcomes. Results: The study involved 6566 individuals (MHT and non-MHT), with propensity score matching ensuring balanced cohorts. Over a 20-year follow-up, the MHT group demonstrated a lower incidence of diabetes mellitus compared to the non- MHT group, with a Hazard Ratio of 0.693 (95 % CI: 0.577, 0.832). Stratified analyses revealed age-specific nuances, with significant protective effects in individuals aged 46–50 and 55–60. Additionally, ethnicity played a role, with MHT demonstrating significant benefits in White individuals but not in the Black or Asian populations. BMI analysis indicated a significant risk reduction with MHT in individuals with BMI less than or equal to 24.9 and 25–29.9 kg/m 2, but not in those with BMI greater than or equal to 30 kg/m 2. Conclusion: In our study, we demonstrate a sustained 20-year decrease in the risk of diabetes among premenopausal individuals with prediabetes who undergo menopausal hormone therapy.