Genetic and environmental influences of daily and intra-individual variation in testosterone levels in middle-aged men

Background: Testosterone regulates numerous physiological processes, and evidence suggests that it plays a critical role in male aging. It has yet to be determined whether the heritability of testosterone varies in accordance with its diurnal rhythm. Similarly, it is unclear whether changes in testosterone level throughout the day are genetically influenced. The aim of the present study was to determine the degree to which genetic and environmental factors contribute to individual differences in testosterone throughout the day in middle-aged men.

Methods: Saliva-based measures of free testosterone, sampled at multiple time-points both at-home and in-lab, were collected from 783 male twins (193 monozygotic pairs, 196 dizygotic pairs, 5 unpaired twins) as part of the Vietnam Era Twin Study of Aging (VETSA). The average age of participants was 55.9 years (SD=2.6).

Results: Testosterone levels declined substantially over the course of the day, with 32-39% of the change occurring in the first 30min after waking. Heritability estimates for specific time-points ranged from .02 to .39. The heritability of the average at-home and in-lab testosterone values were notably higher (.42 and .47 respectively). Daily rates of change showed some evidence of genetic influence, with heritability estimates ranging from .15 to .29, whereas there were no observable genetic influences on coefficients of variation.

Conclusions: Genetic influences account for a significant proportion of the variance in average testosterone levels, while environmental factors account for the majority of intra-individual variability. These results highlight the need to explore both genetic and individual-specific environmental factors as determinants of free testosterone levels in aging men.