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.


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, levels 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, beta-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.
Daly
R C
RC
Behavioral Endocrinology Branch, National Institute of Mental Health, Bldg 10, Room 3N242, 10 Center Dr, MSC 1277, Bethesda, MD 20892-1277, USA. dalyr@intra.nimh.nih.gov
Su
T P
TP
Schmidt
P J
PJ
Pickar
D
D
Murphy
D L
DL
Rubinow
D R
DR
D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects; D000374:Aggression / Q000187:drug effects; D045930:Anabolic Agents / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology*; D001526:Behavioral Symptoms / Q000134:cerebrospinal fluid / Q000139:chemically induced*; D001923:Brain Chemistry / Q000187:drug effects*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D007989:Libido / Q000187:drug effects; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D008777:Methyltestosterone / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology*; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid; D012725:Sexual Behavior / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
D045930:Anabolic Agents; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D008777:Methyltestosterone