MinireviewSex difference in alcoholism: Who is at a greater risk for development of alcoholic complication?
Introduction
Alcohol abuse and alcoholism are major health problems and the cost for society and the individual is tremendous. Not surprisingly, a majority of clinical and experimental approaches has been focused on male subjects. However, drastic differences have been identified between men and women not only in the propensity for alcohol abuse but also in their bodily response to alcohol. As a matter of fact, the pattern of drinking and the amount of alcohol consumed vary between men and women, which imposes a major challenge for alcohol research and the proper management against alcoholism (Devaud et al., 1999, Piano et al., 2005). Epidemiological evidence suggests that nearly 20% of adult males have alcohol abuse or suffer from alcoholism-related complications. On the other hand, only about 5–6% of adult females are alcoholic or abuse alcohol on the regular basis (Devaud et al. 1999). In general, women tend to consume less alcohol than men and appear to be less likely to manifest certain risk factors for alcohol use and health problems. Nonetheless, women perceive greater social and health sanctions for drinking while alcohol and alcoholism may counter desirable feminine traits (e.g., nurturing). Moreover, women are less likely to display characteristics associated with excessive drinking including aggressiveness, drinking to alleviate distress, behavioral undercontrol, sensation-seeking and antisociality (Nolen-Hoeksema 2004). However, the consequence of heavy alcohol use as well as alcoholic complications may be more problematic in women than men, at least in some domains. Women tend to suffer from alcohol-related physical illnesses and display more severe cognitive and motor impairment with significantly lower alcohol exposure compared with men. Heavy alcohol use in women is known to be associated with a range of reproductive problems and fetal alcohol syndrome (Bradley et al., 1998, Hommer, 2003, Nolen-Hoeksema, 2004, Prendergast, 2004). Despite a recent effort towards sex difference under both physiological and pathophysiological conditions, the sex disparity in alcohol abuse and alcoholic complications has not been clearly elucidated. Moreover, the sex difference in pharmacokinetics of alcohol may determine the time course of blood alcohol levels following alcohol ingestion and thus the degree of organ exposure to alcohol. There is proven variability in alcohol absorption, distribution and metabolism between men and women, as a result of hormonal, genetic and environmental factors (Ramchandani et al. 2001). Finally, alcohol abuse is often associated with increased sexuality, heightening the risk for HIV/AIDS and other sexually transmitted diseases, resulting in a secondary health effect of alcoholism (Kalichman et al. 2007). This mini-review will examine some of the more recent clinical and experimental findings in sex difference of alcohol-related implications, which should be used for both proper management of alcoholic injury and public health education campaign.
Section snippets
Sex difference in alcohol metabolism and alcohol detoxification
The pharmacokinetics of alcohol determines the time course of alcohol level in blood following alcoholic intake and the degree of organ exposure to alcohol. The interplay between the metabolism and organ distribution of alcohol is rather important for the pharmacodynamic response to alcohol (Ramchandani et al. 2001). Alcohol is mainly detoxified by alcohol dehydrogenase (ADH) and mitochondrial aldehyde dehydrogenase (ALDH2) in liver (Chrostek et al., 2003, Crabb et al., 2004). These enzymes
Sex difference in alcohol consumption
Drinking is associated with pleasure, leisure and reward. Chronic stress has also been shown to play a pivotal role in the continued alcohol abuse by addicts (Koob & Le Moal, 2001, Sinha, 2001). In human alcohol addiction, one of the essential factors underlying addiction is a need for mood enhancement or relief from stress. As the stress- and reward-systems in the brain are influenced by sex hormones, the development of alcohol dependency, and approaches to recovery, may also be sex dependent
Insulin-like growth factor and alcohol-induced neurodegeneration
Alcoholism is a rather complex disorder representing an important contributor to health problems. In particular, alcohol influences the function of many hormonal and neurotransmitter systems, with the interaction at γ-aminobutyric acid (GABA) receptors which is integral for the reinforcing and withdrawal-related effects of ethanol (Finn et al. 2010). Among a wide cascade of hormones and neurotransmitters, insulin-like growth factors (IGF) I and II regulate neuronal survival, energy metabolism
Alcohol consumption and risk of dementia
The correlation between alcohol intake and risk of dementia, a complex disease with mysterious pathological machinery, is somewhat ambiguous. Evidence has suggested that health behaviors like smoking, alcohol drinking, diet, physical activity and body mass index are important factors for cognition and dementia. While some findings have confirmed a positive correlation between alcohol intake and risk of dementia (Tanev et al. 2008), others indicated that alcohol drinkers in late life have
The dopamine system
The mesolimbic dopamine system, with dopaminergic projections from ventral tegmental area (VTA) to the nucleus accumbens and other forebrain areas, has been implicated in the development and maintenance of many addictive behaviors including drug and alcohol abuse (de Bruin et al. 2005). Given the key role of this system in alcohol-associated changes in behavior, the sex difference in dopaminergic system may be responsible for certain aspects of the differences between men and women following
GABA receptors
Considerable evidence has demonstrated the importance of the mesolimbic dopamine system in the development of drug addiction and alcoholism. It is well known that this system is modulated by both inhibitory and stimulatory inputs, including GABAergic and glutamatergic neurons (Johnson 2005). Chronic alcohol usage may be associated with alteration in the subunit composition of the GABA receptors in human (Dodd et al. 2006). The GABAA receptor in particular may be pivotal in the sex disparity in
NMDA receptors
Excitatory glutamatergic inputs are important modulators of the mesolimbic dopamine system and have been implicated in the development of alcohol dependence. Chronic alcohol exposure is associated with increased NMDA receptor responsiveness and decreased GABAA receptor activation, which may be due to alterations in the receptor subunit expression for both alcohol target systems (Devaud & Morrow, 1999, Dodd et al., 2006). In glutamatergic system, neuroadaptations in the NMDA receptor system
Sex difference and overall effect of ethanol in the brain
The medical consequences of alcoholism generally develop much more rapidly in women than in men. It is well known that cirrhosis and alcohol-induced cardiomyopathy as well as peripheral neuropathy can be developed after fewer years of heavy drinking in women than men (Hommer 2003). In addition, women seem to be more vulnerable to brain damage and the neurotoxic effects of alcohol than men (Hommer, 2003, Prendergast, 2004). Both men and women alcoholics display reduced brain volume in comparison
Treatments for alcoholism
Treatment for alcoholism encompasses social, psychological and pharmacotherapeutic strategies (Kiefer and Mann 2005). In clinical practice, pharmacological intervention has been widely used for treatment of withdrawal symptoms of alcohol, while other strategies have been used for treatment of relapse and cravings, such as psychosocial intervention. Drug therapy may be useful to reduce cravings and to reduce the risk of relapse (Kiefer and Mann 2005). A few of the drugs currently available
Conclusion
As with many areas of science, basic research on the effects of alcohol has focused primarily on male subjects. Society has also had the long held belief that alcoholism and alcohol-related problems are predominantly a male phenomenon, because rates of alcohol dependence are greater in men than in women. However, alcohol dependence does affect an estimated 5% of women in the United States with rather serious consequences. Accumulating evidence has made it apparent with regards to the sex
Conflict of interest statement
None to be declared.
Acknowledgement
The research in the Ren laboratory is supported by NIH R15 AA13575 and NIH/NIAAA 1R01 AA013412. We sincerely express our apology to those authors whose important work cannot be cited here due to space limitation.
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Contributed equally to this review.