In a study published in The New England Journal of Medicine, researchers suggest revisiting the approach to evaluation and management of hypogonadism due to data showing that declining levels of estrogen as well as androgens contribute to negative changes in body composition, strength and sexual desire in men.

In cohort 1, body fat percentage increased significantly among patients who received placebo or testosterone 1.25 g or 2.5 g daily vs. those who received higher doses, according to data. Additionally, lean mass and thigh-muscle area decreased in patients who received placebo and in patients who received testosterone 1.25 g daily vs. higher doses. Leg-press strength was weakened in the placebo group only, according to data.

In cohort 2, body fat percentage rose in all groups, with similar increases seen in the placebo and testosterone 1.25-g, 2.5-g and 5-g groups. Significant decreases in total-body lean mass were observed in the placebo group vs. the testosterone 1.25-g, 2.5-g or 10-g groups. Researchers found reductions in thigh-muscle area in patients receiving placebo vs. any dose of testosterone. Similar to cohort 1, leg-press strength decreased in the placebo group, researchers wrote.

Overall, sexual desire declined with decreased testosterone doses in both cohorts, they added.

“By examining these relationships with and without suppression of estrogen synthesis, we found that lean mass, muscle size, and strength are regulated by androgens; fat accumulation is primarily a consequences of estrogen deficiency; and sexual function is regulated by both androgens and estrogens,” Joel S. Finkelstein, MD, from the endocrine unit in the department of medicine at Massachusetts General Hospital, and colleagues wrote.

In an accompanying editorial, David J. Handelsman, MB, BS, PhD, director of the ANZAC Research Institute and head of the department of andrology at Concord Hospital and the University of Sydney, Australia, wrote that longer studies are required to separate the effects of testosterone on bone density and fractures or on prostate growth and diseases.

“Nevertheless, this excellent study contributes to our expanding appreciation of the complex mechanisms of action of testosterone,” Handelsman wrote.

PERSPECTIVE

·         Part of the action of testosterone is actually mediated by aromatization to estradiol. Men with genetic aromatase deficiency cannot produce estrogens and show increased adiposity, decreased bone mass and reduced libido. This study shows that in normal men estrogens are important for body fat; androgens are important for muscle; and both estrogens and androgens are important for libido. These data explain why different men have differing sexual symptoms and metabolic risk profiles, despite equivalent systemic testosterone exposure and could lead to a rational approach to developing designer androgens, with varying aromatizability that would promote certain actions and not others. The full clinical implications of this important mechanistic study require the development of these novel androgens and estrogens.

o    Peter Y. Liu, MD, PhD, FRACP

o    Visiting professor in the division of endocrinology, metabolism and nutrition
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Source: Endocrine Today