Effects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose-dependent suppression of luteinizing hormone, follicle-stimulating hormone, and sperm production.
Level 2 - randomized trial
Individual randomized controlled trial in humans
PubMed 2104626 · doi:10.1210/jcem-70-1-282
What was done
Fifty-one healthy men (mean age 29 years) completed a 4- to 6-month baseline control period and were then randomly assigned to weekly intramuscular injections for 6 months of either vehicle control (1 mL sesame oil) or testosterone enanthate at 25, 50, 100, or 300 mg (n = 9–12 per group). Researchers measured monthly serum LH and FSH via radioimmunoassay, twice-monthly sperm counts and concentrations, and daily testosterone levels between two weekly injections, alongside safety monitoring.
What was found
Testosterone administration caused parallel, dose-dependent suppression of LH, FSH, and sperm production. At 50 mg/week, LH and FSH were suppressed to 65% and 62% of control values, and sperm counts fell to 36% of control values. At 100 mg/week, LH and FSH dropped to 32% and 34% of control values, and sperm count fell to 0.8% of control. Increasing the dose to 300 mg/week produced no greater suppression of gonadotropins or sperm production than 100 mg/week, and did not reliably achieve azoospermia. Serum testosterone was 1.5-fold and 3-fold higher than control in the 100 mg/week and 300 mg/week groups, respectively. Adverse effects were limited to mild truncal acne, weight gain, and increased hematocrit.
Why it matters
This study demonstrates that LH and FSH secretion are equally sensitive to negative feedback from exogenous testosterone. It also establishes that supraphysiological dosing beyond 100 mg weekly provides no added benefit for male contraceptive suppression of spermatogenesis.
Limits
The total sample size was small (51 men split across five arms, yielding 9–12 participants per group). The study was restricted to healthy young men over a 6-month treatment duration, precluding assessment of long-term cardiovascular, metabolic, or prostate safety outcomes.
Cited by
- supports Suppression of gonadotropins occurs within days of starting exogenous testosterone administration.