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*

Abstract

In normal men, chronic testosterone (T) administration results in negative feedback suppression of gonadotropin and sperm production. However, azoospermia is achieved in only 50-70% of men treated with high dosages of T. Furthermore, the relative sensitivity of LH and FSH secretion to chronic administration of more physiological dosages of T is unclear. We determined whether a T dosage higher than those previously given would be more or less effective in suppressing spermatogenesis and whether, within the physiological range, T would exert a more selective effect on LH than on FSH secretion. After a 4- to 6-month control period, 51 normal men were randomly assigned to treatment groups (n = 9-12/group) receiving either sesame oil (1 mL) or T enanthate (25, 50, 100, or 300 mg, im) weekly for 6 months. Monthly LH and FSH levels by RIA and twice monthly sperm counts were determined. During treatment, T levels were measured daily between two weekly injections. Chronic T administration in physiological to moderately supraphysiological dosages resulted in parallel dose-dependent suppression of LH, FSH, and sperm production. T enanthate (50 mg/week) suppressed LH and FSH levels and sperm counts to 50% of those in placebo-treated men (ED50). T enanthate (300 mg/week), was no more effective than 100 mg/week in suppressing LH, FSH, and sperm production. Serum T levels in men who received 100 and 300 mg/week T enanthate were 1.5- and 3-fold higher than those in placebo-treated men, respectively. Except for mild truncal acne, weight gain, and increases in hematocrit, we detected no significant adverse health effects of chronic high dosage T administration. We conclude that 1) LH and FSH secretion are equally sensitive to the long term negative feedback effects of T administration; 2) sperm production is suppressed in parallel with the LH and FSH reductions induced by chronic T administration; and 3) even at the clearly supraphysiological dosage of 300 mg/week, T enanthate does not reliably induce azoospermia in normal men. However, there was also no evidence of a stimulatory effect of this T dosage on spermatogenesis. Furthermore, we found no evidence of major adverse health effects of T administered chronically even at the highest dosage.