Lower birthweight and left‐/mixed‐handedness are associated with intensified age‐related sex steroid decline in men. Findings from the Men's Health 40+ Study

In males, age‐related decline in free testosterone (T) and dehydroepiandrosterone (DHEA) by 2–3% per year has been reported. Estradiol (E2) and progesterone (P) seem to decrease as well, but to a lesser extent. Lower sex steroid levels in men have been related to physical and mental symptoms. Low birthweight and left‐/mixed‐handedness (L/MH) are indicators of an adverse fetal environment during pregnancy, and both have been linked to morbidity in later life. The aim of this study is to examine the relationship between lower birthweight as well as L/MH and age‐related sex steroid decline. In a cross‐sectional study design, saliva samples were collected under standardized conditions from healthy men for subsequent steroid hormone analysis using standard luminescence immunoassays. T (M = 67.57 pg/mL), DHEA (M = 247.91 pg/mL), E2 (M = 1.29 pg/mL), and P (M = 28.20 pg/mL) have been quantified leading to a final sample of 256 men providing complete data on sex hormones (M (Age)=57.8; SD(Age )= 10.8). Information on participants’ birthweight was obtained from birth reports (N = 134), and participants were asked about their handedness (right‐handed, left‐handed, mixed‐handed) (N = 256). Multivariate‐adjusted linear regression models relating each sex hormone individually and the principal component of declining steroid hormones (DSH)—an integrated hormonal parameter—with handedness and birthweight did not identify significant associations except for handedness and E2. Moderation analysis using robust regression accounting for bias due to influential data points detected a significant association between age and DSH for handedness (β = −0.0314, p = 0.040) but only a trend for birthweight (β = 0.0309, p = 0.073). For lower birthweight, a trend toward intensified age‐related sex steroid decline in men was observed, while for L/MH, a significant association with intensified age‐related sex steroid decline was identified. These results indicate that L/MH and potentially also lower birthweight might be considered as early risk factors for endocrine health in later life.