Abstract MP041: Menopausal Age, Reproductive Lifespan And Type 2 Diabetes Risk: A Case-cohort Study (InterAct)

Abstract

Background: Early menopause and estrogen deficiency are important determinants of future health outcomes. While experimental data suggest a role for estrogens in glucose homeostasis, the relationship between menopausal age and type 2 diabetes (T2D) risk is relatively unexplored. Objective: To investigate associations of menopausal age and reproductive lifespan (defined as menopausal age minus age at menarche) with T2D risk. Methods: A case cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 3691 incident T2D cases and a random subcohort of 4408 postmenopausal women (including 235 incident diabetes cases). Prentice weighted Cox regression and random effect meta-analyses were used to investigate the associations between menopausal age, reproductive lifespan and T2D risk. Results: Earlier age at menopause was associated with an increased T2D risk. After adjustment for reproductive and classical T2D risk factors, the HRs across categories of menopausal age (< 40, 40–44, 45–49, 50–54 and ≥ 55 years) were 1.31 (1.01–1.69), 1.10 (0.91–1.34), 1.00 (0.88–1.13), 1.00 (reference) and 0.86 (0.70–1.05) respectively ( P trend = 0.01). The association between reproductive lifespan and T2D risk was weaker: HRs across quartiles of reproductive lifespan were 1.18 (0.98–1.41), 1.02 (0.86–1.22), 0.96 (0.81–1.14) and 1.00 (reference) respectively ( P trend = 0.02). No effect modification with body mass index, waist circumference or smoking status was observed ( P interaction all > 0.05). Conclusion: Earlier age at menopause and a shorter reproductive lifespan are associated with an increased T2D risk, supporting a protective role for estrogens in metabolic disease risk.