EFFECTS OF ENDOGENOUS TESTOSTERONE AND ESTRADIOL ON SEXUAL-BEHAVIOR IN NORMAL YOUNG MEN

The importance of androgens in establishing and maintaining sexual fun ction in males of most species is well recognized. Estrogens also stim ulate male sexual function in some species. In men, most studies of an drogen effects on behavior have used hypogonadal men as an experimenta l model; much less is known about the role of endogenous testosterone (T) or estradiol (E(2)) in the regulation of behavior in healthy, eugo nadal men. In a randomized, double-blind study, we used a GnRH antagon ist, Nal-Glu, without T replacement, to induce acute, profound, revers ible gonadal steroid deficiency in 9 normal men for 6 weeks (Nal-Glu a lone). We also studied the effects of partial androgen replacement by administering Nal-Glu together with T enanthate, 50 mg im weekly, to 1 0 other men. A third group of 10 men received Nal-Glu plus T, 100 mg i m weekly. We studied the role of endogenous E(2) by administering Nal- Glu plus T, 100 mg im weekly, plus an aromatase inhibitor, testolacton e (Teslac), 250 mg po qid, to 10 additional men (Nal-Glu+T+Teslac). Ni ne men received placebo injections and tablets. All subjects completed a behavioral questionnaire during the pretreatment period, at weeks 2 , 4, and 6 of treatment, and at 3 weeks posttreatment. Men who receive d Nal-Glu alone became profoundly hypogonadal within 1 week after trea tment began. Serum T levels did not change significantly in the contro ls and in the men who received full T replacement but decreased to app roximately half the baseline level in men who received partial T repla cement. E(2) levels decreased profoundly in men who received Nal-Glu a lone or Nal-Glu+T+Teslac and to a lesser degree in men who received pa rtial T replacement. In men who received Nal-Glu alone, there were cli nically and statistically significant decreases in the frequency of se xual desire, sexual fantasies, and intercourse at 4-6 weeks. These men also showed a strong trend (P = 0.55) towards decreased spontaneous e rections after 4 and 6 weeks of treatment. A significant decrease in t he frequency of masturbation was evident after 6 weeks. All measures r eturned to normal by posttreatment week 3. There was a trend toward in creased aggression in the hypogonadal men, but this did not reach stat istical significance. No changes in satisfaction or happiness with the ir partners were observed. There were no significant changes in any be havioral parameter during the study in men who received any of the oth er regimens. Our data confirm the importance of physiological levels o f T in maintaining sexual behavior in normal men. They also demonstrat e that the effects of acute hypogonadism are not manifested immediatel y, but they become clinically and statistically significant after 4-6 weeks of androgen deficiency. Sexual function is restored at approxima tely the same time that serum T returns to normal levels. Our data als o show that in experimentally hypogonadal men, replacement of androgen s at a dose of 50 mg/week is adequate to maintain normal sexual functi on and behavior, and that circulating levels of E(2) have a limited ro le in the regulation of sexual behavior in normal men. The model of ac ute, reversible hypogonadism induced by GnRH antagonists plus varying amounts of androgen replacement offers an excellent in vivo bioassay f or assessing androgen effects in men.