OC52 - Temporal trends in testosterone and luteinizing hormone levels indicate an ongoing resetting of hypothalamic-pituitary-gonadal function in healthy men

Background/Introduction Recent evidence suggested that semen parameters are showing a progressive worsening over time in men, likely due to a combination of lifestyle and environmental factors. While semen quality has been extensively studied, data on long-term trends in testosterone serum levels remain scarce. Purpose The aim of this study was to investigate the existence of a temporal trend in serum testosterone levels among healthy men. Methods A systematic search of the literature covering studies published between 1971 and July 2024 was conducted, focusing on studies reporting testosterone serum levels in healthy adult men. Exclusion criteria included: (i) age under 18, (ii) conditions affecting testosterone levels, (iii) subjects’ enrolment based on testosterone levels and (iv) blood examinations performed in a time-frame interval >10 years. When available, data on luteinising hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG) and body mass index (BMI) were also collected as secondary endpoints. Results A total of 1,256 articles comprising 1,504 study groups and 1,064,891 subjects (mean age 42.0 ± 7.0 years) were included. A significant negative linear regression between serum testosterone levels and year of measurement was detected (p=0.033) and confirmed by meta-regression analysis, after adjusting for study sample size, subjects’ age and BMI (Coefficient -0.6, standard error (SE):0.2, p<0.001). No significant temporal trend was observed for BMI (p=0.617). LH serum levels also declined significantly over time after adjusting for subjects’ age (Coefficient -0.1, SE:0.1, p<0.001), while no trend was observed for FSH (p=0.143). The testosterone trend persisted even after adjusting data according to the assay used for testosterone measurement and after matching with environmental and demographic data. Conclusion(s) This study is the first comprehensive meta-regression analysis showing a consistent decline in serum testosterone and LH levels in healthy men over the past decades, independent of age and BMI. The parallel reduction in both hormones may reflect an ongoing resetting of the hypothalamic-pituitary-testicular axis, potentially linked to changing environmental exposures or lifestyle factors.