Influence of Age and Sex on Alcohol Metabolism and Acute Responses

Previous studies, including our studies using the alcohol clamp, have shown that alcohol pharmacokinetics differ between women and men. Some of the factors that may contribute to these sex differences in absorption, distribution and metabolism include variation in lean body mass (and total body water), liver size and differences in activity or capacity of alcohol metabolizing enzymes in the stomach and livers of women and men. A fundamental difference between men and women is in the levels of the sex hormones estrogen and testosterone, which can influence several of the above factors. Sex differences in alcohol pharmacokinetics, and estrogen itself, have been postulated as determinants of the increased susceptibility of women to alcohol-related liver disease. An additional area of interest is sex- and age-related differences in sensitivity to the effects of alcohol. The elderly are thought to be more sensitive to alcohol and show greater impairment than younger individuals. However, it is not clear if these changes are due to pharmacokinetic or pharmacodynamic factors. The objectives of this project are (I) to evaluate the influence of age and sex on alcohol elimination rates in men and women, and (II) to determine the influence of age and sex on the initial response and acute adaptation to alcohol on measures of subjective perceptions of alcohol effects and heart rate. This study will be conducted in 24 young and 24 older participants, with equal numbers of males and females in each group. Comparison of alcohol elimination rates across these groups and correlation with liver volume and sex steroid levels will provide a means to examine the influence of sex hormones, estrogen and testosterone, in age-related and sex-related differences in alcohol metabolism and liver volume. This study will examine age- and sex- related differences in response to alcohol on subjective measures of intoxication and mood, as well as on heart-rate and psychophysiological responses to emotional visual stimuli (pictures). This study will also evaluate the effect of acute alcohol administration on gene expression in peripheral blood cells. Findings from these studies will provide important new data regarding the role of sex steroids (estrogen and testosterone) on the metabolism of alcohol, and a better understanding of age- and sex-related differences in metabolic processes that may underlie medically important differences in the responses of individuals to alcohol.