Alcohol consumption is associated with an increased risk of breast cancer, increasing linearly even with a moderate consumption and irrespectively of the type of alcoholic beverage. It shows no dependency from other risk factors like menopausal status, oral contraceptives, hormone replacement therapy, or genetic history of breast cancer. The precise mechanism for the effect of drinking alcohol in mammary cancer promotion is still far from being established. Studies by our laboratory suggest that acetaldehyde produced in situ and accumulated in mammary tissue because of poor detoxicating mechanisms might play a role in mutational and promotional events. Additional studies indicated the production of reactive oxygen species accompanied of decreases in vitamin E and GSH contents and of glutathione transferase activity. The resulting oxidative stress might also play a relevant role in several stages of the carcinogenic process. There are reported in literature studies showing that plasmatic levels of estrogens significantly increased after alcohol drinking and that the breast cancer risk is higher in receptor ER-positive individuals. Estrogens are known that they may produce breast cancer by actions on ER and also as chemical carcinogens, as a consequence of their oxidation leading to reactive metabolites. In this review we introduce our working hypothesis integrating the acetaldehyde and the oxidative stress effects with those involving increased estrogen levels. We also analyze potential preventive actions that might be accessible. There remains the fact that alcohol drinking is just one of the avoidable causes of breast cancer and that, at present, the suggested acceptable dose for prevention of this risk is of one drink per day.

The idea of the presence of androgens in females may sound peculiar as androgens generally refer to male hormones. Although produced in small amounts in women, androgens have direct and significant effects on many aspects of female physiology. Moreover, androgens are precursors to estrogens, which are the predominant female sex hormones. The measurement of androgens in blood is important in the diagnosis of both gonadal and adrenal functional disturbances, as well as monitoring subsequent treatments. The accuracy of such measurements is crucial in sports medicine and doping control. Therefore, the concentration of androgens in female subjects is frequently measured. Analysing such compounds with accuracy is especially difficult, costly and time consuming. Therefore, laboratories widely use direct radioimmunoassay kits, which are often insensitive and inaccurate. It is especially complicated to determine the level of androgens in women, as the concentration is much lower compared to the concentration found in males. Additionally, the amount of androgens in fluids tends to decrease with aging. Analyses of hormone concentrations are influenced by a myriad of factors. The factors influencing the outcome of these tests can be divided into in vivo preanalytical factors (e.g., aging, chronobiological rhythms, diet, menstrual cycle, physical exercise, etc.), in vitro preanalytical factors (e.g., specimen collection, equipment, transport, storage, etc.) and as mentioned before, analytical factors. To improve the value of these tests, the strongly influencing factors must be controlled. This can be accomplished using standardised assays and specimen collection procedures. In general, sufficient attention is not given to the preanalytical (biological) factors, especially in the measurement of androgens in females. Biological factors (non-pathological factors) that may influence the outcome of these tests in female subjects have received little attention and are the topic of the present review.

Alcoholic myopathy is a common pathology characterized by wasting due to reduced protein synthesis, although the mechanisms involved remain unclear. Women are particularly sensitive and malnutrition exacerbates the myopathy. This study aimed to address (i) whether long-term alcohol feeding alters expression of heat shock proteins (HSPs) in male and female rats; (ii) the effect of immediate alcohol dosing with or without raised levels of endogenous acetaldehyde; and (iii) the effect of starvation. To address this, (i) male and female rats were fed alcohol in the long-term (6-7 weeks as 35% of energy in a liquid diet) and compared to controls fed the same diet with isoenergetic glucose; (ii) male rats given an immediate bolus (75 mmol ethanol per kilogram body weight intraperitoneally) 2.5 hours before sacrifice and compared to controls given a dose of saline (with or without pretreatment with cyanamide-an acetaldehyde dehydrogenase inhibitor which raises endogenous acetaldehyde); (iii) male rats starved for 1 or 2 days then immediately dosed with alcohol. Protein levels of HSP 27, HSP 60, and HSP 70 were measured in muscles of male rats fed alcohol and pair-fed control rats by SDS-PAGE and Western blotting in study I. Levels of HSP 27, HSP 60, HSP 70, and HSP 90 mRNA were analyzed in hind limb skeletal muscle by reverse transcription-polymerase chain reaction with an endogenous internal standard, glyceraldehyde-3-phosphate-dehydrogenase. (i) Long-term alcohol dosage reduced HSP 27 in male rats but not in females, whereas HSP 90 mRNA increased in long-term alcohol-fed female rats but not in male rats. These changes were reflected by a similar trend in HSP protein content, although statistical significance was not achieved. (ii) There was no effect on any of the HSP mRNAs in rats dosed immediately with alcohol or in combination with cyanamide. (iii) Starvation per se for 2 days was associated with an increase in HSP 27 mRNA. Alcohol administration after 2 days starvation caused a blunting of the increased HSP 27 mRNA in starvation alone. This suggests that long-term alcohol exposure affects HSP gene expression and that this effect is moderated by sex and starvation. This may contribute to, or reflect, the biochemical lesion in alcoholic myopathy.

Systemic alcohol exposure lowers plasma testosterone (T) levels in adult males, but the relative role of impaired luteinizing hormone (LH)-releasing hormone synthesis and decreased pituitary LH release versus that of a direct ability of circulating alcohol to inhibit testicular steroidogenesis remains poorly understood. We had reported preliminary evidence that alcohol might stimulate a pituitary-independent, neural pathway between the hypothalamus and the testes whose activation blunts T secretion in response to human chorionic gonadotropin (hCG). The present work was done to further investigate the influence of alcohol on this pathway by comparing the effect of the intragastric (i.g.) and intracerebroventricular (i.c.v.) injection of alcohol on the T response to hCG, to probe the role of LH and corticotropin-releasing factor (CRF) in both models, and to examine potential changes in levels of the cholesterol transfer protein steroidogenic acute regulatory (StAR) protein.

Male Sprague Dawley rats were implanted with chronic i.c.v., i.g., and/or intravenous cannulae that allowed drug delivery and blood sampling in nonanesthetized, undisturbed animals. T blood levels were measured by radioimmunoassay. The role of LH and of hormones of the hypothalamic-pituitary-adrenal axis such as adrenocorticotropic hormone and corticosterone was investigated in rats pretreated with an LH-releasing hormone antagonist or CRF antibodies. The potential presence of neuronal damage was assessed by Fluoro-Jade methodology. StAR protein levels were measured by Western blot in Leydig cells isolated from rats injected with the vehicle or alcohol.

Although it was not accompanied by measurable blood alcohol levels, i.c.v. administered alcohol, at a dose (5 microl of 200 proof, 86 microM) that did not cause neuronal damage and did not lead to detectable levels of the drug in the cerebrospinal fluid of the fourth ventricle of the brain, significantly blunted hCG-induced T release. The ig injection of alcohol, which in contrast induced significant increases in blood alcohol levels, also significantly interfered with the ability of hCG to induce T release. This effect was comparable in 40- and 65-day-old rats. Neither prior blockade of LH-releasing hormone receptors with a potent LH-releasing hormone antagonist nor immunoneutralization of endogenous CRF altered the inhibitory effect of alcohol injected i.c.v. or i.g. on T secretion. Preliminary results suggested that testicular levels of StAR protein may be slightly decreased by both alcohol regimens.

Collectively, our results indicate that alcohol can act within the brain to influence testicular activity independently of LH, independently of hormones of the hypothalamic-pituitary-adrenal axis, and/or independently of the presence of the drug in the circulation. Our present working hypothesis is that the i.c.v. injection of alcohol stimulates an inhibitory neural pathway that connects the hypothalamus to the testes.