The impact of steroids on longevity prediction and health
Although they are present in relatively low concentration in our bodies, steroid hormones play a crucial role in a vast variety of biological processes, from maintaining pregnancy to regulating mineral and glucose balance in the organism. However, their roles and interactions are still far from being understood. Two recent papers investigating steroid hormones in the KORA cohort shed further light on how these powerful metabolites define health and disease.
Prof. Jerzy Adamski, one of the co-authors of the articles, summarizes the findings and their relevance:
Androgens associate with mortality risk
Although too high or too low levels of androgens are associated with osteoporosis or cardiovascular disorders, there is no established threshold level for steroids in these diseases. Furthermore, there is a need to understand all-cause mortality mechanisms on the metabolic level. Schrederecker et al. studied human serum samples for changes in sex hormone binding globulin (SHGB), testosterone and its active metabolite dihydrotestosterone (DHT) in comparison to survival in a German cross-sectional KORA F4 study. The authors found that higher SHBG concentrations were associated with increased risk of all-cause mortality both in men and women. Lower testosterone and calculated free testosterone as well as higher DHT concentrations in women were associated with increased risk of all-cause mortality. This manuscript contributes to the knowledge that androgens impact survival also in women.
Sex hormones and normoglycemia
Sexual dimorphism is observed in health and disease but the mechanisms underlying different frequencies of disorders are not fully understood. Progestogens and estrogens were considered to be of limited importance to male metabolic homeostasis up to now. However, a recent study by Lau at al. demonstrated that we might have to rethink the importance of these steroids in males. The specific research topic in this project was impact of progestogens and estrogens on normoglycemia in both women and men. The analyses of steroids were performed in the well characterized KORA study cohort and contained both cross-sectional and prospective samples. The mass spectrometry-based assay ensured specific quantification of steroids not blurred by the cross-reactivity of antibody-based assays. The outcome of this study is somewhat surprising. Progesterone, its metabolites 17α-hydroxyprogesterone and 17β-estradiol are independently associated with glycemic traits indeed in men as well as in women.
The researchers involved in the KORA study had already previously addressed the “female health-survival paradox”, i.e. the fact that in industrialized economies, women live longer but also suffer higher rates of serious health challenges. The current studies shed further light on the similarities and differences in how steroid hormones contribute to aging, disease and mortality in men and women. Most importantly, the studies add to our understanding of how progesterons and estrogens influence male health, as well as our understanding of how androgens are involved in aging in women.
Schederecker, F., Cecil, A., Prehn, C. et al.: Sex hormone-binding globulin, androgens and mortality: the KORA-F4 cohort study. (2020) Endocrine connections | https://doi.org/10.1530/EC-20-0080
Lau LHY, Nano J, Cecil A, et al.: Cross-sectional and prospective relationships of endogenous progestogens and estrogens with glucose metabolism in men and women: a KORA F4/FF4 Study. (2021) BMJ Open Diabetes Research and Care | https://doi.org/10.1136/bmjdrc-2020-001951