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Cerebrospinal Fluid and Behavioral Changes After Methyltestosterone Administration
Preliminary Findings
Robert C. Daly, MB, MRCPsych, MPH;
Tung-Ping Su, MD;
Peter J. Schmidt, MD;
David Pickar, MD;
Dennis L. Murphy, MD;
David R. Rubinow, MD
Arch Gen Psychiatry. 2001;58:172-177.
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, 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, ß-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.
From the Behavioral Endocrinology Branch (Drs Daly, Schmidt, and Rubinow),
the Experimental Therapeutics Branch (Dr Pickar), and the Laboratory of Clinical
Sciences (Dr Murphy), National Institute of Mental Health, Bethesda, Md; and
the Division of Psychiatry, National Yang-Ming University, and the Department
of Psychiatry, Veteran's General Hospital, Taipei, Taiwan (Dr Su).
Corresponding author and reprints: Robert C. Daly, MB, MRCPsych,
MPH, Behavioral Endocrinology Branch, National Institute of Mental Health,
Bldg 10, Room 3N242, 10 Center Dr, MSC 1277, Bethesda, MD 20892-1277 (e-mail: dalyr{at}intra.nimh.nih.gov).
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