Age-dependent changes in the concentration of active sex steroids, precursors, metabolites, and regulatory agents in blood serum of male subjects

Abstract

We measured blood concentration of active and non-active sex steroids, metabolites, and precursors and compared to changes in protein and peptide hormones controlling the reproductive axis (total 14 hormones and hormone-like substances) in male subjects aged 18 to 72 y.o. We found a significant decrease in serum concentration of precursors for active sex steroids (pregnenolone, progesterone, dehydroepiandrosterone, and DHEA-sulfate), free testosterone, androstenedione (non-active metabolite of testosterone) as well as 5α-dihydrotestone after the age of 35. However, the level of total testosterone and estradiol (another active testosterone metabolite) remained steady. The systems regulated production of active sex steroids resisted a higher load associated with age and caused the increase in luteinizing and follicle-stimulating hormones in hypophysis and activin in steroidogenic glands directly correlating with age; negative correlation for these hormones was confirmed with certain sex steroids explaining the negative feedback. Decrease in level of hypopheseal adrenocorticotropic hormone with age demonstrated a more substantial role for adrenal glands compared to that of testicles in reduction of blood concentration of active sex steroids. In general, despite the reduced activity of steroidogenic glands in 60-to 70-year old male subjects the level of testosterone and estradiol remained unchanged due to associated growth of level of luteinizing and follicle-stimulating hypopheseal hormones as well as activin in steroidogenic glands that stimulated biosynthesis of sex steroids. Also androgen effects were inhibited due to the reduced level of free (unbound) testosterone and 5α-dihydrotestone.