Dr. Sellers is assistant clinical professor in the Department of Psychiatry, Division of Alcoholism and Drug Abuse,  at New York University School of Medicine in New York City.



Disclosure: The author reports no affiliation with or financial interest in any commercial organization that might pose a conflict of interest.



Please direct all correspondence to: Brealyn Sellers, MD, 26 West 9th St, PH-B, New York, NY 10011; Tel: 917-912-1604.


 

Focus Points

• Historically, there has been a limited amount of literature describing the effects on women. However, current research shows significant gender differences in the physiological, psychiatric, and social impact of alcohol abuse.

• Important physiological distinctions between men and women exist with regard to the rate of alcohol metabolism and the effect a unit of alcohol has on total blood alcohol level.
• Women demonstrate more severe medical implications with the same quantity and time course of exposure to alcohol as men, with accelerated disease processes demonstrated in cardiovascular disease, alcoholic liver disease, osteoporosis, brain damage, breast cancer, and obstetric complications.
• Differences in social and cultural expectations for men and women mediate the vulnerability to alcoholism and access to treatment.

Abstract

Is the disparity between men and women with alcohol use disorders (AUDs) significant enough to warrant different treatment approaches? Factors governing the development of AUDs are diverse, including social, psychological, cultural, and medical factors; therefore, the impact of problem drinking between the sexes varies widely. However, AUDs in women have been the focus for scientific inquiry only in the last three decades, thus there are still significant unanswered questions regarding the manifestation of these differences. This article presents a review of the current knowledge on women with AUDs, including epidemiology, pharmacology, medical, reproductive, and psychiatric pathophysiology, as well as sociocultural factors. It also describes significant findings in the areas of assessment and treatment, and concludes with recommendations for further study.

Introduction

In response to the dearth of information on women and alcohol use, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) initiated the first formal literature review on the subject in 1978 and met to discuss their findings.1 Previously, most research on alcoholism had been conducted using male subjects, which implied either that there were no differences between the sexes with respect to this disorder, or that alcoholism was not of great significance to women. In the decades following, it has been shown that neither of these assumptions is correct. The differences manifest themselves in every facet of the biopsychosocial model. Plentiful evidence suggests that women have an enhanced vulnerability to acute and chronic complications of alcoholism compared to their male counterparts.2 Still, the subject of alcoholism in women continues to be marginalized, as its designation as a special populations category implies. Sex bias in the field of addiction research persists, as does the presumption that findings in the male population can be extrapolated to females.3 This article attempts to clarify the fallacy in this presumption and describe some of the more important findings specific to alcohol use disorders (AUDs) in women.

Prevalence

Epidemiology

Data regarding the incidence and prevalence of drug and alcohol use is collected as part of the Substance Abuse and Mental Health Services Administration-sponsored National Survey on Drug Use and Health (NSDUH), formerly known as the National Household Survey on Drug Abuse.4 Although this is the most comprehensive, large-scale data collection on the subject, the survey does not by design include subjects living outside of households. Therefore the data do not take into account homeless people or those living in transitional settings such as jails, treatment centers, or military bases. These settings are likely to house populations with increased vulnerability to substance use disorders of all types. Therefore,  the data reported by this survey should be regarded as conservative.

In 2002, 120 million (51.0%) Americans ≥12 years of age reported current alcohol use, which is defined as having had one drink in the past 30 days. Except for the group 12–17 years of age, males were more likely to report alcohol consumption than females (57.4% of males ≥12 years of age versus 44.9% of females ≥12 years of age.) For the group comprised of subjects 12–17 years of age, males and females demonstrated comparable rates of use, with 17.4% of the males and 17.9% of the females reporting current use. Heavy drinking, defined as having ≥5 drinks/day on at least 5 of the past 30 days, was reported by 6.7% of Americans ≥12 years of age, or 15.9 million.4  

Using nationally representative data derived from the NIAAA’s 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC, N=43,093) and NIAAA’s 1991–1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES, N=42,862), Grant and colleagues5 compared 12-month prevalence rates of abuse and dependence using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)6 diagnostic criteria to distinguish between the two AUDs. Over the course of the decade, the prevalence rates of the sexes were shown to converge. The male to female ratio for alcohol abuse declined from 3.09 in 1991–1992 to 2.72 in 2001–2002. Convergence was also shown in the prevalence of dependence between the two time intervals, but only in the groups 30–44 (2.46–1.91) and 45–64 (2.85–2.32) year of age.

The 1994 National Comorbidity Survey7 looked at psychiatric disorders amongst subjects 15–54 years of age throughout the United States. Substance dependence of any kind is more prevalent in men than in women, with lifetime prevalence for men (35.4) nearly twice that for women (17.9). The difference between the sexes for alcohol dependence (men=20.1, women=8.2) is larger than the difference between the sexes for drug dependence (men=9.2, women=5.9).

Risk Factors

There are areas of vulnerability specific for women with AUDs which impact the rate of progression of the disease process relative to men. The telescoping phenomenon described by Piazza and colleagues8 in 1989 refers to the decreased time interval between the age when alcohol consumption is initiated and when treatment is sought for women as compared to men. Women also demonstrate an accelerated course through the development of alcoholism, with briefer periods between such landmarks as drinking regularly or loss of control of drinking.9 The truncated time course in the disease process also implies that there is less opportunity for intervention.10

Gender differences in genetic predisposition toward the development of AUDs have not been well-defined to date. Recent evidence supports the heritability of alcoholism in women, a phenomenon well-described in the male population. In an epidemiologic-based twin study, Kendler and colleauges11 demonstrated that the concordance for alcoholism was higher in monozygotic twins than in dizygotic twin pairs, which suggests a heritability of liability toward alcoholism in women (range, 50% to 60%).

Pharmacology of Alcoholism in Women

Among the most important physiological differences between males and females with respect to the metabolism of alcohol are rate of absorption and resulting blood alcohol levels. A unit of ingested alcohol will result in a higher blood alcohol concentration in women than in men when corrected for body weight.12 Alcohol undergoes first-pass metabolism to a large degree in the gastric mucosa, where it is oxidized by alcohol dehydrogenase.13 Under standard conditions, normal female subjects metabolize approximately one quarter of the amount of ingested alcohol that men do. This is due to a significantly lower level of alcohol dehydrogenase in the gastric mucosa of women, and results in higher blood alcohol concentrations in the female cohort. In a study by Frezza and colleagues,13 both male and female alcoholics had less gastric alcohol dehydrogenase than normal subjects, but the level was shown to be significantly lower amongst the women. Consequently, the ratio of alcohol consumed to alcohol absorbed in alcoholic female subjects approached 1:1.13

The difference in quantity of ingested alcohol versus blood alcohol concentrations between men and women can also be explained by differences in the respective body compositions of the sexes. Men have a higher average content of body water at 65%±2% than do women at 51%±2%,14 which means the quantity of alcohol that is absorbed will be distributed over a smaller volume of water in women, leading to higher blood alcohol levels.

Sociocultural Factors Uniquely Affecting Female Drinkers

Social and cultural forces are significant determinants in all aspects of substance use, as well as important factors in shaping gender-related behaviors for both men and women. The stereotype of the “party girl,” which implies a relationship between drinking and promiscuity, is one that has been pervasive both historically and in contemporary thinking.15 A correlation has been made between a woman’s vulnerability to rape and acute intoxication in a study16 that surveyed approximately 24,000 college women. Approximately 1 in 20 women reported being raped, and nearly 75% of the victims reported having been intoxicated at the time. In addition, teenage girls who drink are more likely to be sexually active and to have unprotected sex. According to a report by the National Center for Addiction and Substance Abuse,17 adolescent girls who use alcohol >5 times/month are five times likelier to be sexually active and one-third less likely to use condoms than girls who do not use alcohol. Social stigma can also pose as an obstacle to seeking care among women with children who reported being reluctant to identify themselves as alcoholic for fear of losing custody of their children.18

Sociocultural influences may also confer some protective benefits for women compared to men. An analysis of family history studies done in 197819 showed that social factors were strong deterrents to problematic drinking behaviors in females as opposed to males. Such deterrents included less social pressure to drink, fewer gender-specific social situations where drinking is integral, and different drinking practices. That the gap between the prevalence of male versus female problem drinking is closing may be attributable in part to gradual changes in some of these social norms.

Evaluation

Because of gender differences in physiology and the more rapid acceleration of course in women, the process of assessment and evaluation of women with AUDs should begin earlier. Women with substance use disorders of all types are more likely than men to seek treatment as a consequence of health or family problems.20 This finding underscores the importance of the role of primary care physicians in early identification of alcoholism in their female patients. In a study that investigated the role of informal support and community services on the 5-year course of AUDs, Weisner and colleagues21 observed that interventions from medical and mental health agencies correlated with reduced alcohol consumption. Outside the discipline of psychiatry, there exist opportunities for detection of alcoholism if the clinician is alert to the advanced rate of pathophysiological changes seen in women. A greater emphasis should be placed on the detection of substance use disorders of all types by primary care residency training programs in order to reach more of these patients.

Impact Alcoholism on Female Sexual and Reproductive Functioning

The effects of alcohol on sexual and reproductive functioning in women are complex and multifactorial. The existing data further underscore the limitations of viewing the sexes indiscriminantly. An association between alcohol use and increased risk for breast cancer has been demonstrated,22 where alcohol use is defined as two or more drinks per day. The greatest risk shown in this study is for women who are heavy drinkers, postmenopausal, and have a history of benign breast disease and use hormone replacement therapy.23 Alcohol consumption has not been linked conclusively with increased risk for ovarian cancer.24

There is a correlation between premenstrual syndrome (PMS) and increased alcohol intake, and a higher rate of abuse and dependence occurs among females diagnosed with PMS.25 There is also an association between premenstrual dysphoric disorder and increased use of alcohol and marijuana during this part of the monthly cycle.26

Though it is difficult to evaluate the influence of alcohol on sexuality without taking social conditions into account, studies separating the impact of pharmacology from socially influenced determinants have been conducted. These studies have demonstrated differences in the impact of single doses of alcohol on sexual arousal in men and women.27 Women who believed they had consumed alcohol reported greater arousal in response to sexual stimuli, demonstrating an expectation effect, a response duplicated in the male subjects studied. The physiological response was decreased, however, among the female subjects who had actually received alcohol. This dissociation between perceived arousal and physiological arousal also held true for orgasmic response,28 which is diminished in proportion to the quantity of alcohol consumed. The converse is also true. Though it is a commonly held fear for women in recovery that sobriety will inhibit their sexuality, there is empirical evidence that in the context of a monogamous relationship, significant enhancement of sexual functioning occurred once abstinence was achieved.29

The teratogenic effects of alcohol consumption by pregnant women on the growing fetus have been well-researched. In addition to fetal alcohol syndrome, which occurs only in the offspring of alcohol-consuming women, low birth weight and spontaneous abortion also occur at a higher incidence amongst this group than in the general population. The consumption of alcohol in pregnant women is the most commonly known teratogenic cause of mental retardation, with an estimated incidence of 1–3 cases/1,000 live births.

Fetal Alcohol Syndrome is one of the three most frequently occurring birth defects associated with mental retardation, along with Down’s syndrome and spina bifida.2 The abnormalities attributed to heavy fetal exposure to alcohol include growth deficiency, craniofacial abnormalities, and central nervous system defects.

Implications of Alcoholism on the General Medical Condition of Women

Women appear to be more susceptible to the toxic effects of alcohol, and develop alcohol-related health problems at similar rates but at lower levels of consumption than men.30 Medical complications include alcoholic liver disease, osteoporosis, cardiovascular disease, and neurological disorders, as well as breast cancer and the obstetric and gynecological implications discussed above. In addition to previously mentioned differences in metabolism, there is also evidence suggesting a link between high estrogen phases and disproportionately elevated levels of acetaldehyde,31 a metabolite of alcohol implicated in the pathogenesis of many alcohol related disorders.

While the risk for alcoholic liver disease is higher for women at any level of consumption, the relative risk is significantly greater when the rate of consumption is between 7–13 alcoholic beverages/week for women, as opposed to 14–27/week for men.32 Bone mass has been shown to be depleted by chronic heavy exposure to alcohol, particularly when the abuse occurs from adolescence to early adulthood, and can be permanent even with cessation of alcohol exposure.33 While the risk of heart disease is decreased among women who drink moderately compared with those who are abstinent,34 there are also data which support the conclusion that female alcoholics will develop cardiomyopathy at only 60% of the alcohol consumption of men drinking over the same period of time.35 Other increased cardiovascular risks associated with drinking in women include hypertension.36

Development of brain damage in alcoholic women is consistent with the overall pattern of women’s greater sensitivity to the toxic effects of alcohol in comparison to men. Brain mass is diminished to the same degree in both groups, though the women had significantly shorter periods of exposure.37 Imaging studies demonstrated that grey matter is disproportionately smaller in alcoholic women than in alcoholic men, in addition to significantly smaller overall brain volume in women.38 Both acute and chronic neurotoxic effects of heavy alcohol exposure on cognitive, sensory, and motor function will likely be shown to be more pronounced in females compared to males.

Psychiatric Comorbidities in Alcoholic Women

Studies of chemically dependent subjects show higher levels of comorbid psychiatric disorders across all demographic variables.4 The relationship of cause and effect in this group remains unclear. Whether a given patient’s psychiatric symptoms predate or are induced by substance abuse has been the subject of much research. According to data presented as part of the 2002 NSDUH report,4 10.5% of women were diagnosed with a serious mental illness, versus 6.0% of men.

Among female alcoholics, a strong association with major depression has been demonstrated. The relative risk for heavy drinking is 2.60 times greater in women with a history of depression as compared to women without a history of depressive disorder. In addition, an increased frequency of depressive symptoms was found to be associated with a higher risk (relative risk=1.09) for alcoholism.39 In a 1995 review of female twin studies, Kendler and colleagues40 observed that genetic influences alone, as well as the combination of genetic and environmental influences, can cause both alcoholism and psychiatric comorbidity in women. With respect to other affective disorders, significant differences in vulnerability between males and females exist, especially in regard to bipolar affective disorder (BAD). Although the lifetime prevalence of alcohol abuse/dependence is higher in BAD than in all other axis I disorders, the risk of developing alcoholism was greater for females with BAD (odds ratio=7.35) than for males with BAD (odds ratio=2.77) as compared to the general population.41 Women also have a higher incidence of premorbid anxiety disorders,42 and a greater severity of post-traumatic stress disorder symptoms than do men with similar traumatic exposures.43 Among axis II diagnoses, there is greater association between substance use disorders and obsessive-compulsive, histrionic, schizoid, and antisocial personality disorders  in women than men.44 Another significant distinction between male and female alcoholics is the frequency of suicide attempts. Alcoholic women attempt suicide four times as often as do non-alcoholic women, with the most vulnerable group being 20–29 years of age.45

Treatment

Though the ratio of women to men in substance abuse treatment is reflective of their representation among substance abusers in the general population,46 a consensus on how to most efficaciously treat women with AUDs does not presently exist. Effective treatment must address those issues unique to women. Obstacles to treatment include child care, transportation, child custody issues, and issues of stigmatization of alcoholism in women.9 Though women seek medical care more readily than do men, they are less likely to seek out specialized alcohol treatment.47 In fact, women are more likely than men to seek substance abuse treatment in a mental health setting as opposed to a specialized substance abuse treatment setting.48 This may be related to the greater number of women with comorbid axis I diagnoses discussed previously. Hasin and colleagues49 found that remission in alcoholism significantly increases the likelihood of remission of depressive symptoms. In addition to focusing on the psychiatric and physical diagnoses which commonly accompany AUDs in women, efforts to address issues of sexual abuse may significantly improve treatment success.50 The availability of child care has also been shown to improve access to treatment in the female population.51 Education regarding effects of alcohol use on pregnancy and transmission of sexually-transmitted diseases is also of special benefit to females.

Comparing outcome between alcoholic men and women treated in the same facility indicate that both sexes benefit equally.52 However, in a 2-year follow-up study comparing women who were treated in a specialized female unit with women treated in a mixed setting, women receiving treatment in the specialized female unit had overall better outcomes.53 These outcomes are difficult to interpret, however, as the women-only program offered many more services than the standard treatment. Like the data on morbidity, the mortality data for women alcoholics reflects an overall greater severity of illness than that for male alcoholics, as shown by Lindberg and Agren54 in a study which demonstrated that female alcoholics showed 5.2 times the expected rate of mortality, whereas male alcoholics showed a 3-fold increase over the expected rate of mortality. It is reasonable to conclude that successful outcome is to a great degree dependent on early detection and intervention. However, as care providers learn more about the unique manifestations of alcoholism in the female population, better treatment approach strategies will emerge.

Conclusion

As more research is focused on the alcoholic disease process unique to women, it is likely that further  need for gender-specific treatment approaches will continue to emerge. Because of the unique vulnerability of women to the social stigma of substance use disorders, the onus of early diagnosis and treatment may fall upon healthcare providers outside the addiction treatment community, a reality that necessitates more extensive training for providers outside the psychiatric profession. The telescoping phenomenon is a compelling argument for more aggressive identification of women at risk, and for the development of treatment that will adequately address the needs of nearly half of the drinking population. Although the final goal of all treatment is abstinence, the rate at which problems arise is different for men and women. The degree to which women suffer grave medical consequences requires that interventions are made earlier. As the prevalence of alcoholism among the sexes continue to converge, the disparities between the respective treatment needs of each group will become more clear. PP

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