Sex Hormones Selectively Modulate Growth Hormone in Healthy Older Men

As men age, growth hormone (GH) levels naturally decline, contributing to various age-related changes. Sex steroids, such as estrogen and dihydrotestosterone (DHT), are known to influence GH regulation, but the precise mechanisms by which they modulate somatostatin (a GH inhibitor) and growth hormone secretagogue (GHS) actions in older men remain unclear. This study aimed to disentangle the specific roles of estrogen and DHT in regulating the GH axis while maintaining stable testosterone levels.

The study revealed distinct roles for estrogen and DHT in GH regulation. Aromatase inhibition by anastrozole significantly reduced estradiol levels by 75% (p<0.001), leading to a 43% increase in GH pulsatility and a 2.5-fold increase in the amplitude of GH pulses. Conversely, 5alpha-reductase inhibition by finasteride reduced DHT levels by 88% (p<0.001) but had no significant effect on basal GH secretion or pulsatility. However, finasteride treatment did enhance the GH response to a GHS by 20% (p<0.05), suggesting altered GHS receptor sensitivity. The most significant finding was that estrogen suppression, not DHT suppression, was the primary driver of increased endogenous GH secretion in older men, demonstrating a selective modulation of the somatotropic axis. This indicates that estrogen plays a more dominant inhibitory role on GH release compared to DHT.