Gender Differences in Moderate Drinking Effects - women are more susceptible to short- and long-term effects of alcohol, however fewer women than men are considered heavy drinkers

Alcohol Research & Health,  Wntr, 1999  by Martin S. Mumenthaler,  Joy L. Taylor,  Ruth O'Hara,  Jerome A. Yesavage

• E-mail
• Print
• Link

Research has confirmed the observation that women become more impaired than men after drinking similar quantities of alcohol. In addition, women appear to be more susceptible than men to alcohol's long-term health effects (e.g., alcoholic liver disease). The prevalence of chronic alcohol-related problems is significantly lower among women, however, perhaps in part because only 2 percent of American women are heavy drinkers,(1) compared with 9 percent of men (Substance Abuse and Mental Health Services Administration 1998). Studies report adverse effects in men and women at even moderate drinking levels.(2) Among those effects are disturbances of sensory information processing, short-term memory, reaction time, and eye-hand coordination. These deficits can impair the ability to drive a motor vehicle and may persist to the following day, impeding one's performance at work. The potential influence of gender on the acute effects of alcohol is therefore of importance for the large number of women who are social drinkers.

This article reviews research on the differential effects of moderate drinking on men and women and the mechanisms that may underlie these differences. These mechanisms fall into two categories: (1) gender differences in the physiological processing and elimination of alcohol (i.e., alcohol pharmacokinetics) and (2) differential sensitivity of the nervous system to alcohol's effects. Finally, the article evaluates data on the influence of the menstrual cycle and female reproductive hormones on the pharmacokinetics and nervous system effects of alcohol.

OVERVIEW OF ALCOHOL PHARMACOKINETICS

Blood alcohol concentration (BAC) is determined by the rate of alcohol absorption from the gastrointestinal (GI) tract into the bloodstream, the volume of distribution in the body, and the rate of elimination. Absorption and distribution determine the proportion of an ingested drug or other chemical substance that reaches the organs (alcohol bioavailability), where it may subsequently exert its effects. Alcohol is eliminated from the body largely by a metabolic process called oxidation, which occurs mostly in the liver. Some oxidation of alcohol also occurs during the absorption phase, thereby affecting the bioavailability of alcohol.

Absorption and Distribution

Alcohol consumed by mouth is rapidly absorbed into the bloodstream from the stomach and small intestine. The rate of absorption of alcohol depends on several factors, including the amount and concentration of alcohol ingested and the quantity and composition of food in the stomach. Alcohol absorbed from the small intestine flows through the portal vein directly to the liver, where a portion of the alcohol is metabolized. The process by which a substance is metabolized before entering the general circulation is called first-pass metabolism (FPM).

Many toxic substances undergo hepatic FPM. In the first step of hepatic FPM of alcohol, an oxidative enzyme called alcohol dehydrogenase (ADH) converts alcohol into acetaldehyde.(3) Hepatic FPM is most significant with low to moderate alcohol doses of about 0.4 grams per kilogram of body weight (g/kg), which is equivalent to about two standard drinks(4) for a person weighing 70 kg (approximately 150 pounds). The extent of FPM in the liver depends on the rate of absorption of alcohol from the GI tract. If absorption is fast, the quantity of alcohol reaching the liver can exceed the metabolic capacity of available ADH. This allows a greater proportion of alcohol to escape FPM and reach the general circulation, resulting in a higher peak BAC. Conversely, slow absorption leads to a higher FPM and a lower peak BAC. For example, the presence of food in the stomach leads to slower alcohol absorption, hence more efficient FPM and a lower peak BAC. The time from last drink to peak BAC usually ranges from 30 to 90 minutes (Hardman and Limbird 1995).

Some FPM may occur in the GI tract (mostly in the stomach) as well as in the liver (Yin et al. 1997). Although earlier research reported decreased gastric ADH activity in women compared to men (Frezza et al. 1990), the relative contribution of gastric ADH activity to overall FPM in both genders is controversial. One study found the activity of gastric ADH in the rat to be approximately 14 percent that of hepatic ADH (Lee et al. 1992). Another study estimated that gastric FPM in humans accounts for 0.4 percent of a low alcohol dose, compared with 4 percent metabolized in the liver (Derr 1993).

The portion of alcohol that is absorbed from the GI system and that escapes FPM enters the general circulation and is rapidly distributed throughout the body, preferentially in body water (i.e., within the bloodstream and in the fluid within and between cells). Studies on alcohol pharmacokinetics must therefore take into account subjects' body compositions, a significant factor in gender-related studies.

Elimination

Alcohol can be oxidized by ADH in various organs, including the stomach and small intestine. Quantitatively, however, most alcohol metabolism occurs in the liver. Between 90 and 98 percent of alcohol that enters the body is eventually completely oxidized. The rate of alcohol metabolism is related to blood alcohol concentration (BAC). At BACs below approximately 0.02 percent,(5) the rate of alcohol metabolism is exponential. At higher BACs, the functional capacity of the ADH system becomes saturated, and the alcohol elimination rate remains relatively constant between approximately 0.020 and 0.065 percent BAC. The rate of elimination of larger doses of alcohol increases as BAC increases (Holford 1987; Lundquist and Wolthers 1958).