ESPE Yearbook of Paediatric Endocrinology

Sci Adv. 2025 Mar 28;11(13):eadu6094. doi: 10.1126/sciadv.adu6094

Brief Summary: In this human observational cohort study, involving 949 healthy adults, half male, half female, aged 20 to 69 years, the authors measured the levels of 17 steroid hormones by targeted mass spectrometry (MS), and investigated associations between steroid levels and biological sex, age, clinical and demographic data, genetics, and plasma proteomics. Furthermore, to identify associations between steroid hormone levels and health status, they assessed a subset (n=415) of the original cohort 10 years after the initial study.

While confirming expected age- and sex-related hormone changes, such as the decline of estrogens in older women compared to younger individuals, the study also uncovered unexpected relationships. Oral hormonal contraception influenced circulating levels of multiple steroid hormones in women, while BMI and smoking were related to altered hormone levels in men only. Importantly, the finding that testosterone decline in men may be linked more to health status than to aging challenges prevailing assumptions about andropause.

The data highlight how socioeconomic and lifestyle factors, including housing, employment, and smoking habits, significantly correlate with hormone variations, underscoring the importance of considering these factors in medical research and treatment. The associations found between steroid hormones and genetic and plasma protein markers suggest new avenues for understanding hormone regulation.

Despite certain limitations, such as the genetic homogeneity of the cohort and measurement constraints, the study’s findings are valuable for guiding future mechanistic studies. By revealing the complex interactions between hormones, sex, lifestyle, and health, this work has the potential to influence clinical management of hormone-related conditions and inform public health strategies. Overall, it lays a foundation for advancing research in endocrinology, metabolism, immunology, aging, and gender medicine contributing to a more holistic understanding of human health and how it might be shaped by environmental factors and gender behaviors.