Psychopharmacology 3e Web Box 10.2 - Of Special Interest: Gender Differences in Alcohol Effects

Research into the effects of alcohol has traditionally focused on males because it is generally assumed that drinking and drinking problems are far more prevalent among men. Although males are more likely to be heavy drinkers and binge drinkers, annual National Surveys on Drug Use and Health have shown that both sexes start drinking at younger ages than in the past and that the number of females who drink excessively is increasing. Hence more research is needed in the area of gender-specific differences in the effects of alcohol on the brain and body, as well as family dynamics and the potential for alcohol-induced damage in the offspring of a female drinker.

Although the prevalence of alcohol use disorder (AUD) is higher in men (20%) than in women (5% to 6%), there is general agreement among researchers that both alcohol-induced organ damage and related medical issues are more severe in women and develop more quickly (reviewed by Ceylan-Isik et al., 2010; Erol and Karpyak, 2015). Female alcohol abusers have a significantly higher death rate than males. This vulnerability is due to metabolic, genetic, physiological, neurobiological, and hormonal factors. We have already mentioned that less efficient gastric metabolism by alcohol dehydrogenase and the smaller fluid volume in women cause more rapidly rising and higher blood levels for equivalent doses. Since BAC predicts the effects of alcohol, women experience more acute effects, including increased memory impairment, greater probability of experiencing blackouts, and increased motor impairment. Pharmacokinetic differences determine the time course of alcohol levels and the degree of organ exposure, which increase a woman’s risk and speed up the occurrence of potential liver damage, circulatory disorders, breast cancer, fertility impairment, and a range of reproductive problems. Estrogen may also speed up liver damage because of its role in inflammatory processes, and the use of oral contraceptives may contribute still further. Females are also more sensitive to acetaldehyde-induced depression of cardiac contraction, which may be the basis for the higher rates of cardiomyopathy reported in alcohol-abusing women.

Alcohol-induced brain damage and reduced brain volume in women take fewer years of heavy drinking than in men. Imaging studies have shown greater reductions in both gray and white matter in women with AUD, accompanied by expected impairments in cognitive and psychomotor function. Reduced volume of the hippocampus has been reported in alcohol-abusing adolescents compared with others of the same age, but girls are apparently more vulnerable than boys to alcohol-induced shrinkage. Thiamine deficiency is greater in women with AUD, and this may explain some of the increased risk for dementia and Wernicke–Korsakoff syndrome. Low thiamine in combination with exposure to toxins in the environment is predictive of greater teratogenic effects in pregnancy. In general, ingested lead is rapidly excreted, but under higher exposure, thiamine acts as a regulator of lead levels. Alcohol-induced thiamine reduction permits an accumulation of lead in the alcohol-dependent female in bone, hair, and liver, where impaired mitochondrial function and decreasing cellular energy reserves (adenosine triphosphate [ATP]) occur. Additionally, the lead has a synergistic effect with alcohol on the developing fetus, producing greater neurobehavioral impairment in offspring and more impaired postnatal development.

It is of significant interest that the effects of alcohol use on neurotransmitter systems vary with gender. For instance, one imaging study examined gender differences in DA release in response to alcohol consumption among social drinkers (Urban et al., 2010). PET imaging following ethanol ingestion showed significant release of DA in the nucleus accumbens, to a greater extent for males than for females. Additionally, among males but not females, there was a positive correlation between their subjective evaluation of alcohol-induced activation and the amount of DA released; this may contribute to differences in early reinforcing effects that lead to compulsive use. Of further importance was the inverse relationship found between the frequency of the maximum number of drinks consumed per 24 hours according to self-reported drinking and DA release, once again only in men. This relationship indicates that heavier-drinking individuals (i.e., those consuming more in 24 hours), who have a greater potential for addiction, release less DA. It is possible that reduced DA release may parallel the transition from social drinking to a stronger habit. Differences in DA release among men and women may provide a neurobiological mechanism to explain the increased vulnerability to AUD in men. Many other sex-specific differences in DA signaling in various brain regions have been reported, including larger numbers of DA cells in the female mesocortical tract and sex-specific specializations in DA receptor localization and number of D2 receptors. The mechanism responsible for gender differences and its significance for reward and addiction are not clear at this time, although gonadal steroid hormone modulation is a distinct possibility. Ceylan-Isik and colleagues (2010) review gender differences in the effects of alcohol on DA, as well as on GABA and glutamate.

 

References

Ceylan-Isik, A. F., McBride, S. M., and Ren, J. (2010). Sex difference in alcoholism: Who is at a greater risk for development of alcoholic complications? Life Sci., 87, 133–138.

Erol, A., and Karpyak, V. M. (2015). Sex and gender-related differences in alcohol use and its consequences: Contemporary knowledge and future research considerations. Drug Alcohol Depend., 156, 1–13.

Urban, N. B., Kegeles, L. S., Slifstein, M., Xu, X., Martinez, D., Sakr, E., et al. (2010). Sex differences in striatal dopamine release in young adults after oral alcohol challenge: A positron emission tomography imaging study with [11C]raclopride. Biol. Psychiatry, 68, 689–696.