Ethnic differences in the association between age at natural menopause and risk of type 2 diabetes among postmenopausal women: a pooled analysis of individual data from 13 cohort studies

Objective: To investigate associations between age at natural menopause, particularly premature ovarian insufficiency (POI; natural menopause before 40 years), and incident type 2 diabetes (T2DM) and identify any variations by ethnicity.

Research design and methods: We pooled individual-level data of 338,059 women from 13 cohort studies without T2DM before menopause, with six ethnic groups: White (n=177,674), Chinese (n=146,008), Japanese (n=9,061), South/Southeast Asian (n=2,228), Black (n=1,838), and Mixed/Other (n=1,250). Hazard ratios (HRs) of T2DM associated with age at menopause were estimated in the overall sample and by ethnicity, with study as a random effect. For each ethnic group, we further stratified the association by birth year, education level, and BMI.

Results: Over nine years of follow-up, 20,064 (5.9%) women developed T2DM. Overall, POI (vs menopause at 50-51 years) was associated with an increased risk of T2DM (HR:1.31, 1.20-1.44), while there was an interaction between age at menopause and ethnicity (p<0.0001). T2DM risk associated with POI was higher in White (HR:1.53, 1.36-1.73), Japanese (HR:4.04, 1.97-8.27), and Chinese women born ≥1950 (HR:2.79, 2.11-3.70); while less precise, the risk estimates were consistent in South/Southeast Asian (HR:1.46, 0.89-2.40), Black (HR:1.72, 0.95-3.12), and Mixed/Other (HR:2.16, 0.83-5.57) women. A similar pattern, but smaller increased risk of T2DM was associated with early menopause overall (HR:1.16, 1.10-1.23) and for White, Japanese, and Chinese women born ≥1950.

Conclusions: POI and early menopause are risk factors for T2DM in postmenopausal women, with considerable variation across ethnic groups, and may need to be considered in risk assessments of T2DM among women.