Monoamines and neurosteroids in sexual function during induced hypogonadism in healthy men

Context: Although the behavioral effects of high-dose androgen administration may involve alterations in serotonergic activity, few studies have investigated the impact of androgen withdrawal on the central nervous system in humans. Objective: To examine the effects of pharmacologically induced hypogonadism on several cerebrospinal fluid (CSF) systems that could mediate the behavioral concomitants of hypogonadism. Design: Double-blind assessment of the effects of the short-term induction of hypogonadism and subsequent replacement with testosterone and placebo in a crossover design. Setting: National Institutes of Health, Bethesda, Md. Participants: Twelve healthy male volunteers. Interventions: We administered the gonadotropin-releasing hormone agonist leuprolide acetate (7.5 mg in-tramuscularly every 4 weeks) to the healthy male volunteers, creating a hypogonadal state, and then either replaced testosterone (200 mg intramuscularly) or administered a placebo every 2 weeks for 1 month. Main Outcome Measures: Mood and behavioral symptoms were monitored with daily self-ratings, and lumbar punctures were performed during both hypogonadal ( placebo) and testosterone-replaced conditions for CSF levels of steroids and monoamine metabolites. Results: The CSF testosterone, dihydrotestosterone, and androsterone levels were significantly lower during hypogonadism ( P = .002, .04, and .046, respectively), but no significant changes were observed in CSF measures of 5-hydroxyindoleacetic acid, homovanillic acid, dehydroepiandrosterone, or pregnenolone. Decreased sexual interest was observed during the hypogonadal state compared with both baseline and testosterone replacement (P = .009) and correlated significantly with CSF measures of androsterone during both hypogonadism and testosterone replacement (r = -0.76 and -0.81, respectively; P < .01). Moreover, the change in severity of decreased sexual interest correlated significantly with the change in CSF androsterone levels between testosterone replacement and hypogonadism (r = -0.68; P < .05). The CSF 5-hydroxyindoleacetic acid and homovanillic acid levels did not correlate significantly with any behavioral or CSF measure. Conclusion: These data suggest that the neurosteroid androsterone contributes to the regulation of sexual function in men.