INTRODUCTION: Relationships between endogenous female sex hormones and glycemic traits remain understudied, especially in men. We examined whether endogenous 17α-hydroxyprogesterone (17-OHP), progesterone, estradiol (E2), and free estradiol (fE2) were associated with glycemic traits and glycemic deterioration. RESEARCH DESIGN AND METHODS: 921 mainly middle-aged and elderly men and 390 perimenopausal/postmenopausal women from the German population-based Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort study were followed up for a median of 6.4 years. Sex hormones were measured at baseline using mass spectrometry. We calculated regression coefficients (β) and ORs with 95% CIs using multivariable-adjusted linear and logistic regression models for Z-standardized hormones and glycemic traits or glycemic deterioration (ie, worsening of categorized glucose tolerance status), respectively. RESULTS: In the cross-sectional analysis (n=1222 men and n=594 women), in men, 17-OHP was inversely associated with 2h-glucose (2hG) (β=-0.067, 95% CI -0.120 to -0.013) and fasting insulin (β=-0.074, 95% CI -0.118 to -0.030), and positively associated with Quantitative Insulin Sensitivity Check Index (QUICKI) (β=0.061, 95% CI 0.018 to 0.105). Progesterone was inversely associated with fasting insulin (β=-0.047, 95% CI -0.088 to -0.006) and positively associated with QUICKI (β=0.041, 95% CI 0.001 to 0.082). E2 was inversely associated with fasting insulin (β=-0.068, 95% CI -0.116 to -0.020) and positively associated with QUICKI (β=0.059, 95% CI 0.012 to 0.107). fE2 was positively associated with glycated hemoglobin (HbA1c) (β=0.079, 95% CI 0.027 to 0.132). In women, 17-OHP was positively associated with fasting glucose (FG) (β=0.068, 95% CI 0.014 to 0.123). fE2 was positively associated with FG (β=0.080, 95% CI 0.020 to 0.141) and HbA1c (β=0.121, 95% CI 0.062 to 0.180). In the sensitivity analyses restricted to postmenopausal women, we observed a positive association between 17-OHP and glycemic deterioration (OR=1.518, 95% CI 1.033 to 2.264). CONCLUSIONS: Inter-relations exist between female sex hormones and glucose-related traits among perimenopausal/postmenopausal women and insulin-related traits among men. Endogenous progestogens and estrogens appear to be involved in glucose homeostasis not only in women but in men as well. Further well-powered studies assessing causal associations between endogenous female sex hormones and glycemic traits are warranted.
FörderungenState of Bavaria Helmholtz Alliance 'Aging and Metablic Programming, AMPro' International Helmholtz Research School for Diabetes German Center for Cardiovascular Research Helmholtz Zentrum Munchen German Research Center for Environmental Health German Federal Ministry of Education and Research German Center for Cardiovascular Research (DZHK) shared expertise program