Age at menopause, reproductive life span, and type 2 diabetes risk: results from the EPIC-InterAct study.
Brand JS., van der Schouw YT., Onland-Moret NC., Sharp SJ., Ong KK., Khaw KT., Ardanaz E., Amiano P., Boeing H., Chirlaque MD., Clavel-Chapelon F., Crowe FL., de Lauzon-Guillain B., Duell EJ., Fagherazzi G., Franks PW., Grioni S., Groop LC., Kaaks R., Key TJ., Nilsson PM., Overvad K., Palli D., Panico S., Quirós JR., Rolandsson O., Sacerdote C., Sánchez MJ., Slimani N., Teucher B., Tjonneland A., Tumino R., van der A DL., Feskens EJ., Langenberg C., Forouhi NG., Riboli E., Wareham NJ., InterAct Consortium None.
OBJECTIVE: Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk. RESEARCH DESIGN AND METHODS: Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied. RESULTS: Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages <40, 40-44, 45-49, and ≥55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05). CONCLUSIONS: Early menopause is associated with a greater risk of type 2 diabetes.