Cerebrospinal fluid and behavioral changes after methyltestosterone administration - Preliminary findings

Background: Anabolic androgen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem. The biological mechanisms underlying behavioral symptom development are poorly understood. Subjects and Methods: We examined levels of monoamine metabolites, neurohormones, and neuropeptides in the cerebrospinal fluid (CSF) of 17 healthy men, at baseline and following 6 days of methyltestosterone (MT) administration (3 days of 40 mg/d, then 3 days of 240 mg/d). Subjects received MT or placebo in a fixed sequence, with neither subjects nor raters aware of the order. Potential relationships were examined between CSF measures, CSF MT levels, and behavioral changes measured on a visual analog scale. Results: Following MT administration, lei els of 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly lower (mean+/-SD, 103.8+/-47 vs 122.0+/-50.7 pmol/mL; P<.01), and 5-hydroxyindoleacetic acid (5- HIAA) levels were significantly higher (mean+/-SD, 104.7+/-31.3 vs 86.9+/-23.6 pmol/mL: P<.01). No significant MT-related changes were observed in CSF levels of corticotropin, norepinephrine, cortisol, arginine vasopressin, prolactin, corticotropin-releasing hormone, P-endorphin, and somatotropin release-inhibiting factor. Changes in CSF 5-HIAA significantly correlated with increases in activation symptoms (energy, sexual arousal, and diminished sleep) (r=0.55; P=.02). No significant correlation was observed between changes in CSF and plasma MT, CSF MHPG, and behavioral symptoms. Conclusions: Short-term anabolic androgenic steroid use affects brain neurochemistry, increasing CSF 5-HIAA and decreasing MHPG. Changes in 5-HIAA levels caused by anabolic androgenic steroids are related to the behavioral changes we observed. In this small sample, we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT.