Gonadal hormonal factors before menopause and incident type 2 diabetes in women: A 22-year follow-up of 83 799 women from the E3N cohort study: A 22-year follow-up of 83 799 women from the E3N cohort study

Background: In many populations the incidence of type 2 diabetes is higher in men than in women. This may be explained by exposure to female gonadal hormones, but so far, there is no consensus on their role over the life course in type 2 diabetes etiology. Methods: Data are from 83 799 French women from the E3N (Etude Épidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale) cohort study, followed for 22 years. Multivariable Cox models including classical risk factors were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) between gonadal hormonal factors and incident type 2 diabetes. Results: Older age at menarche, more menstrual cycles, older age at menopause, longer duration of exposure to gonadal hormones and breastfeeding were inversely associated with incident type 2 diabetes cases (n = 4806). While a longer duration of menstrual cycles (HR = 1.23 [95% CI: 1.07-1.41] comparing ≥32 vs ≤24 days) and use of contraceptive pills (HR = 1.33 [1.25-1.42]) were associated with a greater risk of type 2 diabetes. Conclusions: In women, a longer exposure to endogenous gonadal hormones with a later menopause as well as breastfeeding were associated with a lower risk of developing type 2 diabetes, independently of classical diabetes risk factors. In contrast, the use of contraceptive agents was associated with incident diabetes, but the influence of each type of contraception and of exposure duration remain to be investigated.