Cross-sectional and prospective relationships of endogenous progestogens and estrogens with glucose metabolism in men and women: A KORA F4/FF4 Study

Abstract

Introduction Relationships between endogenous female sex hormones and glycemic traits remain understudied, especially in men. We examined whether endogenous 17?-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 (?) 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) (?=-0.067, 95% CI-0.120 to-0.013) and fasting insulin (?=-0.074, 95% CI-0.118 to-0.030), and positively associated with Quantitative Insulin Sensitivity Check Index (QUICKI) (?=0.061, 95% CI 0.018 to 0.105). Progesterone was inversely associated with fasting insulin (?=-0.047, 95% CI-0.088 to-0.006) and positively associated with QUICKI (?=0.041, 95% CI 0.001 to 0.082). E2 was inversely associated with fasting insulin (?=-0.068, 95% CI-0.116 to-0.020) and positively associated with QUICKI (?=0.059, 95% CI 0.012 to 0.107). fE2 was positively associated with glycated hemoglobin (HbA 1c) (?=0.079, 95% CI 0.027 to 0.132). In women, 17-OHP was positively associated with fasting glucose (FG) (?=0.068, 95% CI 0.014 to 0.123). fE2 was positively associated with FG (?=0.080, 95% CI 0.020 to 0.141) and HbA 1c (?=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. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.