Effects of testosterone administration (and its 5‐alpha‐reduction) on parenchymal organ volumes in healthy young men: findings from a dose‐response trial

Abstract

Context Animal data shows that testosterone administration increases the volume of some parenchymal organs. However, the effects of exogenous testosterone on solid abdominal organs in humans remain unknown. Objective To evaluate the effects of testosterone administration on the volume of liver, spleen and kidneys in a dose-response trial. Participants Young healthy men aged 18 to 50 years participating in the 5α-Reductase (5aR) Trial. Interventions All participants received monthly injections of 7.5 mg leuprolide acetate to suppress endogenous testosterone secretion and weekly injections of 50, 125, 300 or 600 mg of testosterone enanthate, and were randomized to receive either 2.5 mg dutasteride (5 α-reductase inhibitor) or placebo daily for 20 weeks. Liver, spleen and kidney volumes were measured at baseline and the end of treatment using 1.5-Tesla magnetic resonance imaging. Outcomes The dose-effect of testosterone on changes in the volume of parenchymal organs was evaluated by linear regression model. The association between changes in total testosterone (TT) levels and changes in organ volumes were assessed. Results Testosterone administration increased liver volume dose-dependently (17.4 cm3 per 100 mg of weekly testosterone enanthate; p=0.031); the increase in liver volume was positively associated with changes in TT levels (R2=0.08, p=0.024). A dose-dependent, but non-significant, increase in kidney volumes was also seen. Inclusion of dutasteride use into the models showed an independent association of randomization to dutasteride group with liver volume increase. Conclusion Testosterone administration increased the liver volume in a dose-dependent manner. The potential changes in parenchymal organs should be considered when interpreting apparent changes in lean mass in response to anabolic interventions.

Hepatotoxicity of anabolic androgenic steroids in sport

“…AAS, likewise testosterone, may cause dose-related increase in the hepatic volume. It complies with the research performed on the animals and the fact that male liver is statistically larger than a female one [23].…”

Role of the renal androgen receptor in sex differences in ammonia metabolism

“…The first evidence that this involved a testosterone-dependent signaling pathway was the observation that excess androgen administration qualitatively increased rat proximal tubule size (57). Further evidence in adult males suggests that there is a dosedependent increase in kidney volume, with an estimated 4.04-cm 3 increase per 100 mg of weekly testosterone supplementation (58). We have recently shown that male mice have greater kidney and proximal tubule size than do female mice (20,22) and that these differences were testosterone dependent (22).…”

Sexual Dimorphism of Corticosteroid Signaling during Kidney Development

“…A direct effect of testosterone on renal volume has been demonstrated in mouse models of young castrated males secondarily exposed to testosterone or vehicle [ 96 ]. The trophic effect of testosterone on organ development, including the kidney, has also been demonstrated in human clinical studies [ 97 ]. Thus, sexual dimorphism in renal organogenesis as early as the third trimester in the human species could be related to testosterone secretion by male fetuses in utero [ 98 ].…”