Alcohol's Effects on Testosterone
New Study May Explain Aggressive Behavior in Some Drinkers
Even though testosterone is often referred to as a "male sex hormone," it is in actuality common to both genders of animals and humans. The overwhelming majority of research conducted in the past 25 years in both animals and humans has found that alcohol inhibits testosterone secretion. However, a new study in the January issue of Alcoholism: Clinical & Experimental Research has found that acute administration of alcohol can induce a rapid increase in plasma and brain concentrations of testosterone in some rodents
We have demonstrated that there are very different results in the way two different groups of male rats form testosterone after acute administration of alcohol," said Robert H. Purdy, senior staff scientist in the department of neuropharmacology at The Scripps Research Institute and senior author of the study. "These differences in animals may reflect similar individual differences in humans, and provide new insights for understanding individual differences in the behavioral and endocrine pathology associated with alcohol abuse."
Fourfold Increase
Researchers injected either alcohol or 1,1-dideuteroethanol (2 g alcohol/kg body weight) into the abdominal cavities of two groups of rats, 30 un-operated and 24 adrenalectomized and castrated (ADX/GDX) Wistar males. 1,1-dideuteroethanol is a nonradioactive form of alcohol in which two of the hydrogen atoms on carbon atom #1 of ethanol have been replaced by deuterium atoms, which can then be traced.
Study authors used mass spectrometry, a very precise measure of the mass and structure of compounds derived from extracts of tissues and body fluids, to determine both the amount of neuroactive steroids present and the degree of deuterium incorporation into specific neuroactive steroids isolated from brain samples.
They found that concentrations of testosterone increased fourfold in the frontal cortex and threefold in the plasma of the un-operated rats 30 minutes after alcohol administration. ADX/GDX rats had testosterone concentrations that were only five percent of those found in the un-operated rats following alcohol administration. Tracing the effects of 1,1-dideuteroethanol demonstrated that alcohol oxidation is directly linked to testosterone biosynthesis.
Unanticipated Results
"Our finding of a direct link between alcohol administration and the level of the neuroactive steroid testosterone in the brain of these experimental animals was unanticipated from prior studies with another species of rats," Purdy said.
"Although many other studies clearly demonstrate that chronic consumption of high dosages of alcohol appears to be consistently inhibitory and suppresses reproductive function," said Dennis D. Rasmussen, research associate professor in the department of psychiatry at the University of Washington, "this study raises the possibility that episodes of alcohol consumption may also at least temporarily increase testosterone levels, with the direction of the response likely being dependent upon a variety of factors, including dosage and personal characteristics.
"This particular dosage produced blood alcohol levels and behavioral responses consistent with intoxication. So, alcohol consumption, under at least some conditions and by at least some individuals, may acutely stimulate testosterone levels in the plasma and brain of both males and females and thus could elicit some of the behavioral effects associated with increased testosterone levels, such as increased libido or aggression."
The Role of Testosterone
Rasmussen added that these findings join those of two other studies in which alcohol administration increased plasma testosterone levels in a gender- and dose-dependent manner. "Together these studies are important," he said, "because they illustrate that what has become a largely accepted principal - that alcohol consumption inhibits plasma testosterone levels and reproductive function - is not universally true."
Rasmussen suggested that future research build upon and add to previous findings regarding alcohol's effects on testosterone. "It would be important to determine whether lower dosages of alcohol, which do not induce rapid pronounced intoxication and ataxia, would also produce the acute increase in testosterone, and whether this response to lower dosages would be consistent across different strains of rats. Also, does tolerance develop with repeated administrations?
"Does this increase in testosterone occur following elective self-administration of alcohol? Finally, and probably most interesting, what role might the demonstrated changes in testosterone play in behavioral responses to acute ethanol consumption? Are there gender differences in these responses? And, if the responses do occur in females, are they different during different stages of a woman's cycle?"
Co-authors of the Alcoholism: Clinical & Experimental Research paper included: Ahmed A. Alomary of the Department of Neuropharmacology at The Scripps Research Institute, and the Veterans Affairs Healthcare Center, and Veterans Medical Research Foundation in San Diego Diego (Dr. Alomary currently resides in Jordan); Laura E. O'Dell, George F. Koob, and Monique Vallée of the Department of Neuropharmacology at The Scripps Research Institute (Dr. Vallée currently resides in France); and Robert L. Fitzgerald of the Veterans Affairs Healthcare Center, the Veterans Medical Research Foundation, and the Department of Pathology at the University of California in San Diego. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.
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