Gonadal steroids and body composition, strength, and sexual function in men.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 24024838 · doi:10.1056/NEJMoa1206168
What was done
A 16-week randomized controlled trial evaluated the independent physiological roles of testosterone and estradiol in 400 healthy men aged 20 to 50 years. All participants received goserelin acetate to suppress endogenous testosterone and estradiol. Cohort 1 (n=198) was randomized to receive placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel daily. Cohort 2 (n=202) received the same testosterone gel doses alongside daily anastrozole to block the aromatization of testosterone to estradiol. Primary outcomes were changes in body fat percentage and lean mass. Secondary measures included subcutaneous and intraabdominal fat areas, thigh-muscle area, leg-press strength, and sexual function.
What was found
In men without anastrozole, body fat percentage increased in cohorts receiving placebo, 1.25 g, or 2.5 g of testosterone daily (mean testosterone levels 44±13 ng/dL, 191±78 ng/dL, and 337±173 ng/dL, respectively). Lean mass and thigh-muscle area decreased in men receiving placebo and 1.25 g testosterone without anastrozole. Leg-press strength fell only with placebo. Sexual desire declined with decreasing testosterone dose. Androgen deficiency accounted for reductions in lean mass, muscle size, and strength; estrogen deficiency primarily mediated increases in body fat; and both hormones contributed to the decline in sexual function.
Why it matters
This study establishes that estrogen deficiency, rather than androgen deficiency alone, drives body fat accumulation in hypogonadal men, and demonstrates that both hormones are necessary to preserve male sexual function.
Limits
The study included only healthy men aged 20 to 50 years undergoing acute pharmacological suppression over 16 weeks, which may not capture long-term consequences in older men with chronic hypogonadism. The abstract does not provide exact numerical effect sizes for the anastrozole-treated arms or separate regional fat measurements.
Cited by
- context Specific symptoms of testosterone deficiency emerge at distinct population thresholds: bone loss around 300 ng/dL, decreased frequency of sexual thoughts at 215 ng/dL, and loss of vigor around 290 ng/dL.