AIMS: Alcohol abuse and alcoholism are among the major medical problems afflicting both men and women. While men display a higher prevalence for alcoholism, it is women who suffer a much greater risk for alcoholism-associated bodily damage. Although women generally consume less alcohol compared to men, females usually suffer more severe brain and other organ damage following binge or chronic alcohol abuse. MAIN METHODS AND KEY FINDINGS: Although many biological (i.e., genetic risk and neurological abnormalities) and psychosocial (i.e., impact of positive drinking expectancies, personality characteristics and deviance proneness) factors appear to impact men and women equally. These factors especially social and environmental, physiological, genetic and neurobiological ones have been demonstrated to contribute to the sex difference in response to alcohol intake, as well as the development of alcoholic complications. A number of neurotransmitters and growth factors may be partially involved in these differences between men and women. The mesolimbic dopamine system is implicated in the development of addictive behaviors. Differences in dopamine receptor density are found between sexes where gonadal steroid hormones may play a role. Inhibitory GABAergic and stimulatory glutamatergic systems also act as neuromodulators in the brain and differences in their specific receptors have been identified between men and women (particularly GABA(A) receptors and NMDA receptors). SIGNIFICANCE: Given the variety of factors contributing to the sex difference in response to alcohol intake, alcoholism treatment should take sex dimorphism into consideration. Furthermore, future research needs to be directed towards a better understanding of the mechanism of action of alcohol in both men and women.
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