title: Neuroendocrine and behavioral effects of high-dose anabolic steroid administration in male normal volunteers.
abstract: OBJECTIVE
  Despite widespread abuse of anabolic-androgenic steroids (AAS), the endocrine effects of supraphysiologic doses of these compounds remain unclear. We administered the AAS methyltestosterone (MT) to 20 normal volunteers in an in-patient setting, examined its effects on levels of pituitary-gonadal, -thyroid, and -adrenal hormones, and examined potential relationships between endocrine changes and MT-induced psychological symptoms.
  
  
  METHODS
  Subjects received MT (three days of 40 mg/day, then three days of 240 mg/day) or placebo in a fixed sequence with neither subjects nor raters aware of order. Samples were obtained at the ends of the baseline, high-dose MT and withdrawal phases. Potential relationships between hormonal changes and visual analog scale measured mood changes were examined.
  
  
  RESULTS
  Significant decreases in plasma levels of gonadotropins, gonadal steroids, sex hormone binding globulin, free T3 and T4, and thyroid binding globulin (Bonferroni t, p<0.01 for each) were seen during high-dose MT; free thyroxine and TSH increased during high-dose MT, with TSH increases reaching significance during withdrawal. No significant changes in pituitary-adrenal hormones were observed. Changes in free thyroxine significantly correlated with changes in aggressiveness (anger, violent feelings, irritability) (r=0.5,p=0.02) and changes in total testosterone correlated significantly with changes in cognitive cluster symptoms (forgetfulness, distractibility) (r=0.52,p=0.02). Hormonal changes did not correlate with plasma MT levels.
  
  
  CONCLUSIONS
  Acute high-dose MT administration acutely suppresses the reproductive axis and significantly impacts thyroid axis balance without a consistent effect on pituitary-adrenal hormones. Mood and behavioral effects observed during AAS use may in part reflect secondary hormonal changes.
authors.affiliation: Behavioural Endocrinology Branch, National Institute of Mental Health, Building 10, Room 3N238, 10 Center Drive MSC 1277, Bethesda, MD 20892-1277, USA. dalyr@intra.nimh.nih.gov
authors.forename: R C
authors.initials: RC
authors.lastname: Daly
authors.forename: T-P
authors.initials: TP
authors.lastname: Su
authors.forename: P J
authors.initials: PJ
authors.lastname: Schmidt
authors.forename: M
authors.initials: M
authors.lastname: Pagliaro
authors.forename: D
authors.initials: D
authors.lastname: Pickar
authors.forename: D R
authors.initials: DR
authors.lastname: Rubinow
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects*; D000374:Aggression / Q000187:drug effects; D045930:Anabolic Agents / Q000494:pharmacology*; D000704:Analysis of Variance; D000728:Androgens / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008777:Methyltestosterone / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012016:Reference Values; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D045930:Anabolic Agents; D000728:Androgens; D004967:Estrogens; D012738:Sex Hormone-Binding Globulin; D013963:Thyroid Hormones; D008777:Methyltestosterone