As alcohol consumption rates appear to be escalating, the long and short-term effect of this trend on women’s health must be evaluated. Cognitive impairment and susceptibility to developing a considerable number of health problems is greater in women after heavy alcohol consumption than in men. In addition, the fluctuations observed in female hormones even after modest drinking are disturbing and are thought to possibly promote tumourigenesis in breast cancer patients. Further reliable research is required to assess the risks to women of developing adverse health consequences from alcohol intake and communicated appropriately to the general public. Simple questioning techniques and effective biochemical markers must also be devised to ensure women abusing alcohol are identified successfully by medical practitioners so that the current situation does not prevail.

Alcohol Abuse in Women - An Increasing Problem
Alcohol consumption rates in women are increasing at an uncomfortable pace and the trends and patterns of drinking habits suggest that this upsurge is likely to continue. In a large longitudinal population-based study published in Sweden the number of women abstaining from alcohol decreased considerably between 1968 and 1993 (1). In the USA, current use of alcohol is highest amongst women between the ages of 26-34 and the level of ‘binge drinking’ peaks among 18-25 year-olds. Similar patterns have been observed in the UK but the most striking alteration over the recent years has been the rapid escalation in alcohol consumption amongst professional women. What is perhaps more concerning is the development of an apparent social acceptance of drinking excessive amounts of alcohol. It is estimated that five percent of men and two percent of women suffer from alcohol-related health problems and this figure is likely to be a severe underestimation of the situation as a large proportion of alcohol abuse cases remain undiagnosed (2, 15). The ratio of alcohol-related liver cirrhosis is now about 1.5:1 compared to 5:1 (men: women) twenty years ago (3). The general population is made aware of these statistics regularly via the media, but little action is being taken to counteract this negative trend.

Why Women are More Vulnerable
It is well documented that the effects of equal measures of alcohol are considerably disparate and often more detrimental in women than in men. For example, women are known to develop alcohol-induced liver conditions more rapidly than men and are more liable to die as a result of liver cirrhosis, even though they may consume smaller volumes of alcohol (4). Abuse of alcohol has been held accountable for encouraging the depletion of grey and white matter from the brain, the extent of which appears to be more significant in women. In addition, females are considered to be more susceptible to alcohol-induced brain damage (10) and recover short-term memory functioning at a markedly slower rate than males (5). The sensitivity of cardiac and striated muscle to alcohol toxicity is also more pronounced in females (4). One of the most concerning pieces of evidence is the increased frequency of breast cancer cases in women abusing alcohol (2). The underlying cause of the different responses to alcohol is in part explained by the variation in body composition of the two sexes. Several other hypotheses have also emerged attempting to explain these discrepancies including the contribution of the menstrual cycle, pregnancy and oral contraception to the heightened response to alcohol in women (6, 7, 8). However, little firm evidence has been generated from these studies. A detailed evaluation of the harmful effects of alcohol on women is what is perhaps more urgently required.

Alcohol and Hormones
Alcohol consumption, be it heavy or moderate, significantly influences the hormonal balance in women. Extensive research has also concluded that heavy drinking is related to an increased frequency of cases of spontaneous abortions, recurrent amenorrhea, loss of secondary sexual characteristics, anovulation and menstrual irregularities (9, 11). It is yet to be determined whether these clinical presentations and the high incidence of breast cancer in heavy drinkers is due to the direct influence of alcohol consumption on female hormone levels. A comprehensive study carried out by Sarkola et al (1999) indicates that this is very possible as it clarifies the acute effect of alcohol intake on each major female hormone. This study in conjunction with previous research elucidated that level of prolactin transiently increases during the first few hours of intoxication (9) and cortisol levels rise only after heavy doses of alcohol, becoming apparent after eight hours of drinking (9). Amongst premenopausal women, acute alcohol intake results in elevated oestradiol levels (9, 11). Additionally, the oestradiol-oestrone ratio increased significantly in subjects using oral contraceptives (mean increase of 29% after 45 minutes and 25% after 90 minutes [95% CI, p<0.001 of increase between +16-+41 and +9-+41 respectively]) (9). This study corroborated previously ascertained evidence that the acute effect of alcohol intake has little or no effect on luteinising hormone (LH) or follicle-stimulating hormone (FSH). However, the effect of alcohol on progesterone levels appears to be variable, most often demonstrating no effect (9).

Breast Cancer and Alcohol
As alcohol intake appears to directly alter hormone levels, it is feasible that the resulting imbalance perpetuates the proliferation of breast cancer tissue. Increasing evidence identifies a possible link between increased oestrogen levels and the incidence of breast cancer. Interestingly, many breast cancer patients possess oestrogen-receptor-positive tumours and drugs such as tamoxifen are employed to obstruct their activity. It has been speculated that the enzyme 17-ß hydroxysteroid, which catalyses the oxidation of oestradiol to oestrone and the production of progesterone, may experience alcohol-mediated changes in the redox state (9). This enzyme has been detected in epithelial cells of breast glands (9) and may thus explain cases of breast cancer arising in correlation to greater alcohol consumption. Further research to investigate this proposition is essential and the probable link between heavy alcohol consumption and breast cancer risk needs to be clarified. If this information was readily available to the general public women may be forced to reconsider their lifestyles, which may ultimately lead to a reduction in cases of the most prevalent cancer killing women in Britain today.

Is a ‘Moderate’ Intake of Alcohol Safe?
The damaging effects of moderate drinking are less well documented and the adverse health consequences that women face as a result remain even more obscure. As mentioned earlier, women are left more impaired than men after drinking equivalent, moderate amounts of alcohol. It is not surprising, therefore, that women have a higher risk of driver fatality at similar blood alcohol concentrations (BACs) (10). The effects of non-biological factors, such as pace of drinking and beverage type also need to be investigated in relation to women and, if the findings are significant, made available to the general population. Light to moderate consumption of alcohol may even provide a protective effect from ischaemic strokes and cerebral infarctions in young women (10, 12). However, the overall ‘costs’ and ‘benefits’ of moderate alcohol intake must be evaluated if the average consumer is to make an informed decision and adopt drinking habits that may be less detrimental to their health. The economic implications of these findings may well be severe as the government's income from tax and duties from the liquor industry may face a sharp decline in the long term. If, however, the situation is left to commercial forces, alcohol consumption is likely to continue to rise (13), and the impending social and economic ramifications of this trend will become evident.

Detecting the Problem at a Patient Level
The necessity to successfully identify individuals abusing alcohol is evident and it appears the currently used protocols for this purpose are inefficient, as far as female patients are concerned. At the primary care level the CAGE questionnaire is probably the most widely used, but a study of its effectiveness demonstrated it had a poor sensitivity and specificity (15, 16). The AUDIT-C questionnaire appeared to perform better but still was not sufficient to identify a satisfactory number of female alcohol abusers (15, 16 and 17). In addition to this, the most ‘promising’ biomarker of alcohol abuse, carbohydrate-deficient transferrin (CDT) is presently considered to be unreliable and invalid for female patients (14). The opportunity to develop a suitable biomarker for alcohol abuse in women is obvious and must be realized. Much interest has also been directed towards uncovering candidate genes underlying an individual’s risk of developing alcohol dependence. However, this research remains in its early stages, but it is vital to proportionally represent female subjects in such studies in order to have any significant impact on the health of the nation.

It is evident that improved guidelines for General Practitioners as well as other health care professionals are required for the early detection of alcohol abuse in women. However, specialized prevention strategies targeting women are also essential in addition to treatment programs designed to meet their specific needs. Further research is crucial to establish the detrimental effects of moderate and heavy alcohol consumption on women's health. Once risk factors have been identified, these must be communicated to women of all age groups so that positive lifestyle alterations can be adopted on an individual basis. Ultimately, medical practitioners should accept responsibility for conveying this information to their patients and understand the importance of their early intervention.

Editors Note: a longer version of this article was originally submitted as a special study module (SSM) under the supervision of Prof. T. Peters, Clinical Biochemistry, King's College Hospital.

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