Cerebrospinal Fluid and Behavioral Changes After Methyltestosterone Administration

National Yang Ming University, T’ai-pei, Taipei, Taiwan
Archives of General Psychiatry (Impact Factor: 14.48). 02/2001; 58(2):172-7. DOI: 10.1001/archpsyc.58.2.172
Source: PubMed


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.
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.
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.
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.

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    • "ain reward system have been described in clinical studies . For example , alterations in levels of monoamine metabolites , neurohormones , and neuropeptides , which play a crucial role in the reward mechanism , have been investigated in the cerebrospinal fluid of subjects who received methyltestosterone ( MT ) with respect to placebo - treatment ( Daly et al . , 2001 ) . Results showed that levels of 5 - hydroxyindolacetic acid ( 5 - HIAA ) increased while 3 - metoxy - 4 - hydroxyphenylglycol ( MHPG ) levels decreased in cerebrospinal fluid , following MT administration . In particular , changes in cerebrospinal fluid 5 - HIAA significantly correlated with the activation of specific psychiatric symp"
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    ABSTRACT: Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies.
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    • "In healthy volunteers, short-term AAS administration increases plasma and CSF levels of ␤-endorphin (Daly et al., 2001), but little is known about the role of these ␤-endorphin increases in the development or maintenance of AAS dependence. To date, no study has examined the relationship between opioid levels and symptoms of AAS dependence among AAS users. "
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    ABSTRACT: Background Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. Method Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity x frequency of exercise, age, and education abstained from exercise for 24 hours prior to testing and provided 24-hour cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image. Results Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence. Conclusion The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence.
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    • "The administration of testosterone and the abuse of androgenic/anabolic steroids has been reported to be associated with reduce sleep time, insomnia and increased awakenings.3940 Given acutely methyltestosterone increases arousal and diminished sleep changes attributed to activation of the brain serotonergic system.4142 "
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