METABOLIC AND BEHAVIORAL-EFFECTS OF HIGH-DOSE, EXOGENOUS TESTOSTERONEIN HEALTHY-MEN

In addition to their use as replacement therapy for hypogonadal males, androgens, particularly testosterone (T), are being explored as poten tial hormonal male contraceptive agents, alone or in combination with other compounds. Androgens have regulatory effects on a variety of phy siological systems in addition to gonadotropin secretion and spermatog enesis. Therefore, as hormonal contraceptive regimens that alter serum T levels are explored, it is important to evaluate their effects on t hese aspects of normal male physiology. The effects of exogenous T on suppression of spermatogenesis in 19 healthy men were recently compare d, using a T dosage of 200 mg im/week for 20 weeks. Before treatment, the men were evaluated during a 3-month pretreatment period, and after treatment, they were followed for 4-6 months or until their sperm cou nts normalized. Because of the lack of information regarding the effec ts of exogenous T on nonreproductive physiology, we examined the effec ts of high-dose T on plasma lipids, calcium metabolism, and sexual beh avior in our subjects. Mean serum T and estradiol levels increased sig nificantly during the treatment period. Plasma high-density lipoprotei n (HDL) cholesterol levels decreased significantly within the first mo nth and remained suppressed during the duration of T administration. A t the end of the treatment period, mean plasma HDL cholesterol had dec reased by 13 +/- 2% (P < 0.05); plasma levels of HDL(2), HDL(3), and a poprotein AI also decreased significantly; mean levels of low density lipoprotein cholesterol and triglycerides were unchanged. After 1 mont h of the recovery period, plasma HDL levels had returned to the baseli ne range. Serum calcium levels decreased slightly during treatment; th is decrease was statistically significant. Urinary calcium excretion d id not change. Mean levels of serum intact PTH increased by 84 +/- 17% (P < 0.05) during T administration; in contrast, 25-hydroxyvitamin D levels decreased by 16 +/- 4% (P < 0.05), and 1,25-dihydroxyvitamin D levels did not change significantly. All markers of calcium metabolism returned to baseline during the posttreatment period. Little change w as found in self-reported sexual and aggressive be; haviors during the study. There was a trend toward increased arousal and spontaneous ere ctions during T administration, but this did not reach statistical sig nificance. Frequency of sexual intercourse, masturbation, and kissing and fondling did not change, nor was the subjects' satisfaction in the ir relationships affected by T administration. Mean body weight increa sed by 4.0 +/- 0.5 kg. Approximately half the men noted mild acne. Bod y weight and acne symptoms returned to baseline during the recovery pe riod. These data demonstrate that the serum levels of T produced by ad ministration of T enanthate, 200 mg im weekly, lead to suppressed leve ls of plasma HDL cholesterol, alterations in calcium metabolism, incre ased body weight, and in some men, mild acne. These results imply that T enanthate at this dosage is moderately supraphysiological and may b e inappropriately high for long-term administration to large groups of normal men for the purpose of contraception.