Endogenous Estrogen Exposure and All-Cause Mortality Among Women with Overweight or Obesity According to Metabolic Health Status: Insights from an 18-Year Prospective Cohort Study.

BACKGROUND: Despite extensive research on estrogen and its implications, there remains a gap in understanding the relationship between the duration of endogenous estrogen exposure (EEE) and all-cause mortality among women with overweight or obesity according to their metabolic health status. Therefore, this study examined the association between EEE duration and all-cause mortality over an 18-year follow-up period, separately among women with metabolically healthy overweight/obesity (MHO) and those with metabolically unhealthy overweight/obesity (MUO). METHODS: In this large population-based cohort, 1162 post-menarcheal women aged ≥20 years with a body mass index (BMI) ≥25 kg/m2 from the Tehran Lipid and Glucose Study were included. Participants were classified into MHO and MUO phenotypes, and each phenotype was further divided into tertiles of EEE. Cox proportional hazards models were then applied to estimate incidence rates and hazard ratios (HRs) for all-cause mortality across EEE tertiles. RESULTS: During the follow-up, 62 deaths occurred (2.2 per 1000 person-years; 95% CI: 1.7-2.8), including 20 in the MHO group and 42 in the MUO group. Among individuals with MHO, incidence rates per 1000 person-years (95% CI) were 0.94 (0.42-2.11), 1.50 (0.81-2.79), and 0.60 (0.22-1.60) across the first, second, and third EEE tertiles, respectively. Corresponding rates for MUO were 6.46 (4.02-10.40), 3.42 (1.78-6.58), and 6.05 (3.71-9.88). After adjusting for confounders, the highest EEE tertile in MHO was associated with a significantly lower hazard of all-cause mortality (HR: 0.19; 95% CI: 0.05-0.76). CONCLUSION: Longer EEE durations appear to reduce the risk of all-cause mortality among women with overweight/obesity who are metabolically healthy.