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Testosterone therapy decreases leptin levels in men with obesity
In healthy men with obesity and low levels of total testosterone, testosterone therapy reduced levels of leptin beyond the effects of diet alone, according to findings from Australia.
“The novelty in our study stems from the fact that we simultaneously investigated the effects of testosterone in the context of a rigorous weight-loss program,” Mathis Grossmann, MD, PhD, FRACP, professor in the department of medicine at the University of Melbourne, told Endocrine Today. “This allowed us to conclude that testosterone treatment reduces leptin over and above the effects of weight loss, suggesting testosterone reduces leptin resistance.”
In a prespecified secondary analysis of a randomized controlled trial, Grossman and colleagues analyzed data from 100 men with obesity (BMI 30 kg/m²) and low testosterone levels (two fasting total testosterone level measurements 12 nmol/L) assigned to a very low-energy diet for 10 weeks (640 kcal per day), followed by 46 weeks of weight maintenance, based on the Australian Commonwealth Scientific and Industrial Research Organisation (CSIRO) Total Wellbeing diet. Men in the cohort were randomly assigned either 56 weeks of 1,000 mg intramuscular testosterone undecanoate therapy (Reandron, Bayer; n = 49; cases) or a matching placebo (n = 51; controls); 82 men completed the study. The study was conducted between April 2013 and November 2015. For the secondary analysis, primary outcomes were between-group differences during follow-up in levels of leptin, adiponectin, ghrelin, glucagon-like peptide-1, gastric inhibitory polypeptide, peptide PYY, pancreatic polypeptide and amylin.
After the diet phase, men assigned to testosterone therapy lost a mean of 12 kg vs. 13.5 kg in controls; weight loss was maintained at study end (–11.4 kg vs. –10.9 kg). At the end of the rapid weight-loss phase, both cases and controls experienced changes in adipokines, with decreases in leptin and increases in adiponectin, as well as decreases in PYY and amylin and increases in pancreatic polypeptide and ghrelin.
At 56 weeks, men assigned testosterone therapy had reduced leptin levels vs. controls (mean adjusted difference, –3.6 ng/mL; 95% CI, –5.3 to –1.9). Researchers noted that the between-group changes in leptin were dependent on baseline fat mass; the mean adjusted difference for the three-way interaction per 1 kg of fat mass were –0.28 ng/mL (95% CI, –0.35 to –0.13) at 10 weeks and –0.26 ng/mL (95% CI, –0.31 to –0.26) at 56 weeks, respectively. There were no significant between-group differences for other hormones at 56 weeks, according to the researchers.
“The negative effect of testosterone on other adipokines and gut hormones in the context of weight loss suggests that testosterone treatment reduces fat mass by mechanisms other than appetite, in itself an important finding,” Grossman said. “Finally, by demonstrating the persistent changes of gut hormones and adipokines after weight maintenance, we not only confirm the [prior findings], but extend their findings to a controlled setting in a larger, exclusively male population.” – by Regina Schaffer
For more information:
Mathis Grossman, MD, PhD , FRACP , can be reached at Austin Health Endocrinology, Austin Health, Level 7, Room 3, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC 3084, Australia; email: mathisg@unimelb.edu.au.
Disclosure: Grossman reports receiving research funding from Bayer Pharma, Eli Lilly, Novartis and Weight Watchers, as well as speaker’s honoraria from Besins Healthcare. Another researcher reports receiving research funding from Bayer Pharma.