Abstract
A gender difference in alcohol pharmacokinetics has been suggested to explain why women are more vulnerable to ethanol’s toxic effects. The results of animal experiments suggest that females exhibit higher alcohol metabolic rates than males as a result of hormonal differences. Experimental results examining gender differences in human alcohol metabolism have been inconsistent; the diversity of experimental protocols and variety of pharmacokinetic parameters reported have made comparisons of these studies very difficult. Variability in alcohol metabolic rate between individuals of the same sex is often significant, preventing an assessment of gender differences in some studies. This chapter attempts to summarize the findings of studies from the last decade that examined the role of gender and sex hormone differences on ethanol metabolism in men and women. The role of body composition, genetic factors, gastric and hepatic alcohol dehydrogenase, and gastric absorption in creating gender differences in alcohol metabolism is discussed. Suggestions are offered that may result in better cross-study comparisons and more consistent experimental results.
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References
Spain DM: Portal cirrhosis of the liver: A review of two hundred necropsies with references to sex differences. Am J Pathol 15:215–218, 1945.
Morgan MY, Sherlock S: Sex-related differences among 100 patients with alcoholic liver disease. Br Med J 1:939–941, 1977.
Wilkinson P, Santamaria JN, Randin JG: Epidemiology of alcoholic cirrhosis. Aust Ann Med 18:222–226, 1969.
Saunders JB, Walters JRF Davies P, et al: A 20-year prospective study of cirrhosis. BR Med J 282:263–266, 1981.
Gavaler JS: Sex-Related Differences in ethanol-induced liver disease: Artifactual or real? Alcohol Clin Exp Res 6:186–196, 1982.
Eriksson CJP, Malmstrom KK: Sex differences in consumption and elimination of ethanol in albino rats. Ann Med Exp Fenn 45:398–392, 1967.
Wilson JR, Erwin VG, DeFries JC, et al: Ethanol dependence in mice: Direct and correlated responses to ten generations of selective breeding. Behav Genet 14:226–232, 1984.
Collins AC, Yeager TN, Lebsack ME, Panter SS: Variations in alcohol metabolism: Influence of sex and age. Pharmacol Biochem Behav 3:973–978, 1975.
Rachamin G, MacDonald JA, Wahid S, et al: Modulation of alcohol dehydrogenase and ethanol metabolism by sex hormones in the spontaneously hypertensive rat. Biochem J 186:483–490, 1980.
Sorrell MF, Tuma DJ: Hypothesis: Alcoholic liver injury and covalent binding of acetaldehyde. Alcohol Clin Exp Res 9:306–309, 1985.
Lin RC, Lumeng L: Alcohol and hepatic protein modification in liver pathology and alcohol, in Watson RR (ed): Liver Pathology and Alcohol, Totowa, NJ, Humana Press, 1991, pp 221–240.
Wilkinson PK: Pharmacokinetics of ethanol: A review. Alcohol Clin Exp Res 4:6–21, 1980.
Holford NHG: Clinical pharmacokinetics of ethanol. Clin Pharmacokinet 13:273–292, 1987.
Wilkinson PK: Pharmacokinetics of ethanol: A review. Alcohol Clin Exp Res 4:6–21, 1980.
Lundquist F, Wolthers H: The kinetics of alcohol elimination in man. Acta Pharmacol Toxicol 14:265–286, 1958.
Von Wartburg J-P: Pharmacokinetics of alcohol, in Crow KE, Batt RD (eds): Human Metabolism of Alcohol. Boca Raton, FL, CRC Press, 1989, vol 11, pp 9–22.
Kalant H: Absorption, diffusion, distribution and elimination of ethanol: Effects on biological membranes, in Kissin B, Begleiter H (eds): The Biology of Alcoholism. New York, Plenum Press, 1971, vol 1, p 1046.
Kopun M, Propping P: The kinetics of ethanol absorption and elimination in twins an supplementary repetitive experiments in singleton subjects. Eur J Clin Pharmacol 11:337–344, 1977.
Wagner JG: Intrasubject variation in elimination half-lives of drugs which are appreciably metabolized. J Pharmacokinet Biopharm 1:165–173, 1973.
Jones AW: Interindividual variations in the disposition and metabolism of ethanol in healthy men. Alcohol 1:385, 1984.
Vessell ES, Page JG, Passananti GT: Genetic and environmental factors affecting ethanol metabolism in man. Clin Pharmacol Ther 12:192–201, 1971.
Wagner JG, Wilkinson PK, Ganes DA: Parameters V m and K m for elimination of alcohol in young male subjects following low doses of alcohol. Alcohol Alcohol 24:555–564, 1989.
Wagner JG: Intrasubject variation in elimination half-lives of drugs which are appreciably metabolized. J Pharmacokinet Biopharm 1:165–173, 1973.
Martin NG, Perl J, Oakeshott JG, et al: A twin study of ethanol metabolism. Behav Genet 15:93–109, 1985.
Passanati GT, Wolff CA, Vesell ES: Reproducibility of individual rates of ethanol metabolism in fasting subjects. Clin Pharmacol Ther 47:389–396, 1990.
Thomasson HR, Christian J, Reed T, Li T-K: Reproducibility of human alcohol metabolic rate testing. Alcohol Clin Exp Res 14:345, 1990.
Sedman AJ, Wilkinson PK, Sakmar E, et al: Food effects on absorption and metabolism of alcohol. J Stud Alcohol 37:1197–1214, 1976.
Cortot A, Jobin G, Ducrot F, et al: Gastric emptying and gastrointestinal absorption of alcohol ingested with a meal. Digest Dis Sci 31:343–348, 1986.
Lin, Y-J, Weidler DJ, Garg DC, Wagner JG: Effects of solid food on blood levels of alcohol in man. Res Commun Chem Pathol Pharmacol 13:713, 1976.
Keegan A, Batey R: Dietary carbohydrate accelerates ethanol elimination, but does not alter hepatic alcohol dehydrogenase. Alcohol Clin Exp Res 17:431–433, 1993.
Rogers J, Smith J, Starmer GA, Whitfield JB: Differing effects of carbohydrate, fat and protein on the rate of ethanol metabolism. Alcohol Alcohol 22:345–353, 1987.
Roine RP, Gentry T, Lim RT, et al: Effect of concentration of ingested ethanol on blood alcohol levels. Alcohol Clin Exp Res 15:734–738, 1991.
Pfeiffer A, Hogl B, Kaess H: Effect of ethanol and commonly ingested alcoholic beverages on gastric emptying and gastrointestinal transit. Clin Invest 70:487–491, 1992.
Smith T, DeMaster EG, Furne JK, et al: First-pass metabolism of ethanol is negligible in the rat. J Clin Invest 89:1801–1806, 1992.
Sturtevant RP, Sturtevant FM: Circadian rhythms in rates of ethanol metabolism, in Crow KE, Batt RD (eds): Human Metabolism of Alcohol. Boca Raton, FL, CRC Press, vol 1, pp 23–39, 1989.
Yap M, Mascord DJ, Starmer GA, Whitfield JB: Studies on the chronopharmacology of ethanol. Alcohol Alcohol 28:17–24, 1993.
Kater RMH, Carulli N, Iber FL: Differences in the rate of ethanol metabolism in recently drinking and nondrinking subjects. Am J Clin Nutr 22:1608–1617, 1969.
Mezey E, Tobon F: Rates of ethanol clearance and activities of the ethanol-oxidizing enzymes in chronic alcoholic patients. Gastroenterology 61:707–715, 1971.
Smith GD, Shaw LJ, Maini RJ, et al: Mathematical modelling of ethanol metabolism in normal subjects and chronic alcohol misusers. Alcohol Alcohol 28:25–32, 1993.
Salaspuro PM, Lieber CS: Non-uniformity of blood ethanol elimination: Its exaggeration after chronic consumption. Ann Clin Res 10:294–297, 1978.
Holtzman JL, Gebhard RL, Eckfeldt JH, et al: The effects of several weeks of ethanol consumption on ethanol kinetics in normal men and women. Clin Pharmacol Ther 38:157–161, 1985.
Pieper WA, Skeen MJ: Changes in rate of ethanol elimination associated with chronic administration of ethanol to chimpanzees and Rhesus monkeys. Drug Metab Dispos 1:634–641, 1973.
Crabb DW: The liver, in Galanter M (ed): Recent Developments in Alcoholism. New York, Plenum Press, 1993, vol 11, pp 207–230.
Bosron WF, Li T-K: Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatology 6:502–510, 1986.
Bosron WF, Crabb DW, Li T-K: Relationship between kinetics of liver alcohol dehydrogenase and alcohol metabolism. Pharmacol Biochem Behav 18(Suppl 1):223–227, 1983.
Goedde HW, Agarwal DP, Fritze G, et al: Distribution of ADH2 and ALDH 2 genotypes in different populations. Hum Genet 88:344–346, 1992.
Thomasson HR, Crabb DW, Edenberg HJ, Li T-K: Alcohol and aldehyde dehydrogenase and alcoholism. Behav Genet 23:131–136, 1993.
Mizoi Y, Ijiri I, Tatsuno Y, et al: Relationship between facial flushing and blood acetaldehyde levels after alcoholintake. Pharmacol Biochem Behav 10:303–311, 1979.
Couzigou P, Fleury B, Groppi A, et al: Role of alcohol dehydrogenase polymorphism in ethanol metabolism and alcohol-related diseases. Adv Exp Med Biol 284:263–70, 1991.
Burnell JC, Bosron WF: Genetic polymorphism of human liver alcohol dehydrogenase and kinetic properties of the isoenzymes, in Crow KE, Batt RD (eds): Human Metabolism of Alcohol. Boca Raton, FL, CRC Press, 1989, vol 2, pp 65–75.
Thomasson HR, Beard JD, Li T-K: Faster ethanol metabolic rate demonstrated in subjects with ADH2*3 alleles. Alcohol Clin Exp Res 17:495, 1993.
May DG, Thomasson HR, Martier S, et al: Ethanol metabolism in women: Relative importance of ADH genotype and intake. Alcohol Clin Exp Res 16:605, 1992.
Mizoi Y, Kogame M, Fukunaga T, et al: Polymorphism of aldehyde dehydrogenase and ethanol elimination. Alcohol 2:393–396, 1985.
Goist KC Jr, Sutker PB: Acute alcohol intoxication and body composition in women and men. Pharmacol Biochem Behav 22:811–814, 1985.
Thomasson HR, Beard JD, Li T-K: Gender differences in ethanol metabolism. Alcoholism: Clin Exp Res 18:921, 1994.
Mishra L, Sharma S, Potter JJ, Mezey E: More rapid elimination of alcohol in women as compared to their male siblings. Alcohol Clin Exp Res 13:752–754, 1989.
Arthur MJP, Lee A, Wright R: Sex differences in the metabolism of ethanol and acetaldehyde in normal subjects. Clin Sci 67:397–401, 1984.
Sutker PB, Goist KC Jr, Allain AN, Bugg F: Acute alcohol intoxication: Sex comparisons on pharmacokinetic and mood measures. Alcohol Clin Exp Res 11:507–512, 1987.
Sutker PB, Tabakoff B, Goist KC Jr, Randall CL: Acute alcohol intoxication, mood states and alcohol metabolism in women and men. Pharmacol Biochem Behav 18(Suppl 1):349–354,1983.
Marshall AW, Kingstone D, Boss M, Morgan MY: Ethanol elimination in males and females: Relationship to menstrual cycle and body composition. Hepatology 3:701–706, 1983.
Jones MB, Jones MK: Alcohol effects in women during the menstrual cycle. Ann NY Acad Sci 273:577–587, 1976.
Cole-Harding S, Wilson JR: Ethanol metabolism in men and women. J Stud Alcohol 48:380–387, 1987.
Watson PE, Watson ID, Batt RD: Total body water volumes for adult males and females estimated form simple anthropometric measurements. Am J Clin Nutr 33:27–39, 1980.
Widmark EMP: Verteilung und Umwandlung des Ethyl Alkohols in Organismus des Hundes. Biochem Z 267:128–134, 1933.
Rango RE, Kreeft JH, Sitar DS: Ethanol “dose-dependent” elimination: Michaelis-Menten vs. classical kinetic analysis. Br J Clin Pharmacol 12:667–673, 1981.
Wilkinson PK, Sedman AJ, Sakmar E, et al: Blood ethanol concentrations during and following constant-rate intravenous infusion of alcohol. Clin Pharm Ther 19:213–223, 1975.
Watson PE, Watson ID, Batt RD: Prediction of blood alcohol concentrations in human subjects: Updating the Widmark equation. J Stud Alcohol 42:547–556, 1981.
Wilson JR, Erwin VG: Rate of alcohol metabolism: Do not “correct” the β60 estimates for comparisons among ethnic groups. J Stud Alcohol 44:1093–1096, 1983.
Hutson WR, Roehrkasse RL, Wald A: Influence of gender and menopause on gastric emptying and motility. Gastroenterology 96:11–17, 1989.
Datz FL, Christian PE, Moore JA: Gender-related differences in gastric emptying. J Nucl Med 28:1204–1207, 1987.
Wald A, Van Theil DH, Hoechstetter L, et al: Gastrointestinal transit: The effect of the menstrual cycle. Clin Pharmacol Ther 17:578–584, 1975.
Mezey E, Potter JJ, Tsitouras PD: Liver alcohol dehydrogenase activity in the female rat: Effects of ovariectomy and estradiol administration. Life Sci 29:1171–1176, 1981.
Torres A, Kling OR, Zeiner AR: Effects of elevated female sex steroids on enzyme induction inrats. Alcohol Clin Exp Res 9:187, 1985.
Jones MB, Jones MK: Women and alcohol: Intoxication, metabolism, and the menstrual cycle, in Greenblatt M, Schuckit MA (eds): Alcoholism Problems in Women and Children. New York, Grune and Stratton, 1976, pp 103–136.
Hay WM, Nathan PE, Heermans HW, Frankenstein W: Menstrual cycle, tolerance and blood alcohol level discrimination ability. Addict Behav 9:67–77, 1984.
Brick J, Nathan, PE, Westrick E, et al: The effect of menstrual cycle on blood alcohol levels and behavior. J Stud Alcohol 47:472–477, 1986.
Mello NK: Some behavioral and biological aspects of alcohol problems in women, in Kalant OJ (ed): Alcohol and Drug Problems in Women. New York, Plenum Press, 1980, vol 5, pp 263–298.
Jones BM, Jones MK: Ethanol metabolism in women taking oral contraceptives. Alcohol Clin Exp Res 8:24–28, 1984.
Zeiner AR, Kegg PS: Menstrual cycle and oral contraceptive effects on alcohol pharmacokinetics in Caucasian females. Alcohol Clin Exp Res 4:233, 1980.
Zeiner AR, Kegg PS: Menstrual cycle and oral contraceptive effects on alcohol pharmacokinetics in Caucasian females, in Galanter M (ed): Currents in Alcoholism. New York, Grune and Stratton, 1981, vol 8, pp 47–56.
Sutker PB, Goist KC Jr, King AR: Acute alcohol intoxication in women: Relationship to dose and menstrual cycle. Alcohol Clin Exp Res 11:74–79, 1987.
Jeavons CM, Zeiner AR: Effects of elevated female sex steroids on ethanol metabolism and acetaldehyde metabolism in humans. Alcohol Clin Exp Res 8:352–358, 1984.
Mezey E, Oesterling JE, Potter JJ: Influence of male hormones on rates of ethanol elimination in man. Hepatology 8:742–744, 1988.
Mezey E, Potter, JJ: Effect of dihydrotestosterone on rat liver alcohol dehydrogenase activity. Hepatology 2:359–365, 1982.
Azevedo E, Smith M, Hopkinson DA, Harris H: A study of possible factors influencing the variation in liver alcohol dehydrogenase activity in individuals of the “usual” ADH phenotype. Ann Hum Genet 38:31–37, 1974.
Mezey E, Sharma S, Rennie L, Potter JJ: Sex differences in gastric alcohol dehydrogenase activity in Sprague-Dawley rats. Gastroenterology 103:1804–1810, 1992.
Crabb DW, Bosron WF, Li T-K: Ethanol metabolism. Pharmacol Ther 34:59–73, 1987.
Hayashi S-I, Watanabe J, Kawajiri K: Genetic polymorphisms in the 5’-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem 110:559–565, 1991.
Gonzalez FJ, Liu SY, Yano M: Regulation of cytochrome P450 genes:molecular mechanisms. Pharmacogenetics 3:51–57, 1993.
Frezza M, Padova C, Pozzato G, et al: High blood alcohol levels in women: The role of decreased gastric alcohol dehydrogenase activity and first pass metabolism. N Engl J Med 322:95–99, 1990.
Caballeria J, Frezza M, Hernandez-Munoz C, et al: Gastric origin of the first-pass metabolism of ethanol in humans: Effect of gastrectomy. Gastroenterology 97:1205–1209, 1989.
DiPadova C, Worner TM, Julkunen RJK, Lieber CS: Effect of fasting and chronic alcohol consumption of the first-pass metabolism of ethanol. Gastroenterology 92:1169–1173, 1987.
Thomasson HR, Nowak TV, Kalbfleisch J, Li T-K: Bioavailability of ethanol by oral and intraduodenal administration. Clinical Research 42:241A, 1994.
Lucey MR, Demo-Dananberg L, Young J, et al: The interplay of age, sex, and gastric function on ethanol metabolism. Gastroenterology 104:A945, 1993
Seitz HK, Egerer G, Simanowski UA, et al: Human gastric alcohol dehydrogenase activity: Effect of age, sex and alcoholism. Gut 34:1433–1437, 1993.
Baraona E, Yokoyama A, Ishii H, et al: Lack of alcohol dehydrogenase isoenzyme activities in the stomach of Japanese subjects. Life Sci 49:1929–1934, 1991.
Lumeng L, Lehman GA, Mathis JG, Blitz GP: The relationship of the molecular forms of alcohol dehydrogenase in human gastric mucosa to those in liver. Hepatology 1:528, 1981.
Thomasson HR, Cutler C, Stone CL, et al: Multiple forms of gastric alcohol dehydrogenase consistently identified in gastric biopsies. Gastroenterology 104:1007A, 1993c.
Stone CL, Thomasson HR, Bosron WF, Li T-K: Purification and partial amino acid sequence of a high-activity human stomach alcohol dehydrogenase. Alcohol Clin Exp Res 17:911–918, 1993.
Moreno A, Pares X: Purification and characterization of a new alcohol dehydrogenase from human stomach. J Biol Chem 266:1128–1133, 1991.
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Thomasson, H.R. (2002). Gender Differences in Alcohol Metabolism. In: Galanter, M., et al. Recent Developments in Alcoholism. Recent Developments in Alcoholism, vol 12. Springer, Boston, MA. https://doi.org/10.1007/0-306-47138-8_9
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DOI: https://doi.org/10.1007/0-306-47138-8_9
Publisher Name: Springer, Boston, MA
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