Alcoholic Beverages As a Source of Estrogens

Home , Congener (beverages), Estrogenic substances, Phytoestrogen

Alcoholic Beverages as a Source of Estrogens

Judith S. Gavaler, Ph.D.

Alcoholic beverages contain not only alcohol but also numerous other substances (i.e., congeners) that may contribute to the beverages’ physiological effects. Plants used to produce alcoholic beverages contain estrogenlike substances (i.e., phytoestrogens). Observations that men with alcoholic cirrhosis often show testicular failure and symptoms of feminization have suggested that alcoholic beverages may contain biologically active phytoestrogens as congeners. Biochemical analyses have identified several phytoestrogens in the congeners of bourbon, beer, and wine. Studies using subjects who produced no estrogen themselves (i.e., rats whose ovaries had been removed and postmenopausal women) demonstrated that phytoestrogens in alcoholic beverage congeners exerted estrogenlike effects in both animals and humans. Those effects were observed even at moderate drinking levels. KEY WORDS: alcoholic beverage; congener; estrogens; male; female; plant; alcoholic liver cirrhosis; testicular dysfunction; feminization; hypothesis testing; biochemical mechanism; animal model; ovary; moderate AOD use; prolactin; follicle stimulating hormone; luteinizing hormone; cholesterol; globulins; literature review

he excessive consumption of drinking also includes people who con- in addition to alcohol itself (i.e., con- alcoholic beverages is associated sume alcoholic beverages only occasionally geners), which determine a beverage’s Twith numerous serious medical, and corresponds to the recommended taste, color, and aroma. Alcoholic bev- social, and legal problems that exact a limits for low-risk alcohol consumption erages differ in both the composition high human and economic price. Despite (U.S. Department of Agriculture and and quantity of congeners. These varia- the monumental problems caused by U.S. Department of Health and Human tions result from the different methods alcohol abuse and dependence, however, Services 1995). the fact is that most people who drink When discussing the risks and bene- consume moderate amounts of alcoholic fits associated with alcoholic beverages, JUDITH S. GAVALER, PH.D., is a profes- beverages. Indeed, an additional direction most people think in terms of the bev- sor at the Oklahoma Medical Research for alcohol research has been generated erages’ alcohol contents. Consequently, Foundation and an adjunct professor of by reports of the beneficial effect of mod- much of the research aimed at determin- biostatistics and epidemiology at the erate drinking on the risk of coronary ing how alcoholic beverages affect the University of Oklahoma College of Public heart disease (CHD) (Klatsky 1994). body has been conducted using alcohol Health, Oklahoma City, Oklahoma. Thus, studies have found that compared solutions to approximate the effects of with abstainers and heavier drinkers, alcoholic beverages. Alcoholic beverages, This work has been supported by National moderate drinkers (i.e., women who con- however, contain numerous substances Institute on Alcohol Abuse and Alcoholism sume up to one standard drink1 per day grants AA–06772 and AA–11184, and men who consume up to two drinks 1A standard drink is defined as a 12-ounce bottle the Office of Research on Women’s per day) have a significantly reduced risk of beer or wine cooler, a 5-ounce glass of wine, or Health, and the Office of Research of CHD. This definition of moderate 1.5 ounces of 80-proof distilled spirits. on Minority Health.

220 Alcohol Health & Research World Alcoholic Beverages as a Source of Estrogens and materials (e.g., grains, fruits, and The estrogen-receptor complexes then compounds, including phytoestrogens. hops) from which the beverages are move into the cell nucleus, where the The hypothesis has been tested in bio- produced. This article explores the transported estrogen is transferred to chemical analyses, animal models, and hypothesis that congeners, particularly nuclear estrogen receptors. The nuclear human studies. The results of those phytoestrogens, contribute to the effects complexes, in turn, interact with a certain analyses are summarized in the follow- of alcoholic beverages on the body. type of genetic molecule (i.e., ribonucleic ing sections. acid [RNA]) in the nucleus, thereby influencing the activity of certain genes Evidence of the Estrogenic and modifying the cell’s function. The Biochemical Analyses Activity of Congeners strength (i.e., specificity and affinity) with which estrogens bind to their recep- To investigate the hypothesis that some Researchers’ interest in the congeners tors differs among the molecules. Thus, of the effects of alcoholic beverages result of alcoholic beverages first was spurred steroidal estrogens exhibit greater affin- from estrogenic congeners, researchers by various reports in the agricultural ity and specificity for estrogen receptors removed all of the alcohol, other volatile literature. For example, some studies than do nonsteroidal phytoestrogens substances, and most of the water con- reported that grazing animals feeding on (Rosenblum et al. 1993; Hertog et al. tained in various alcoholic beverages (e.g., particular forages and grasses showed 1993; Miksicek 1995; Makela et al. 1995) bourbon, wine, and beer) using a tech- evidence of impaired reproduction. Sub- and therefore generally are more pow- nique called rotoevaporation (see figure sequently, using those forages, researchers erful in their actions. 1). The resulting congener concentrates isolated substances that exhibited estro- then were subjected to sophisticated genlike activity and later identified them Phytoestrogens in Alcoholic biochemical analyses, such as gas chro- as estrogenlike substances of plant origin Beverages—A Hypothesis matography and mass spectrometry, (i.e., nonsteroidal phytoestrogens) (see to isolate and identify any estrogenic the following section). Finally, studies Case studies have shown that men with demonstrated that the phytoestrogens liver damage resulting from excessive found in milled by-products and oils alcohol consumption (i.e., alcoholic made from various grains, hops, corn, cirrhosis) often suffer from testicular and rice exhibited biological activity both failure—the inability of the testes to Alcoholic beverage in experimental animals and in studies produce male sex hormones. In addi- (e.g., wine, using cultured cells (see Gavaler et al. tion, those men also frequently show bourbon, 1987a,b; 1995a,b; and references therein). signs and symptoms of feminization, beer) such as enlarged breasts and a redistri- Estrogens and Their Activities bution of body fat into a pattern that mimics that of women (for reviews, see Rotoevaporation Estrogens are female sex hormones that Wright et al. 1992; Gavaler and Van remove are produced primarily in the ovaries. Thiel 1988). These signs and symptoms ¥ Alcohol These hormones play essential roles in are consistent with exposure to high (ethanol) the development and maintenance of levels of estrogen. Surprisingly, however, ¥ Other the female reproductive organs and the levels of the steroidal estrogens in volatile breasts as well as in pregnancy and cirrhotic, feminized men are similar substances lactation. In men, small amounts of to or only slightly elevated compared ¥ Most of the water estrogens are produced in the testes. with the levels in age-matched non- Congener (For more information on estrogens alcoholic men. concentrate for administration to and their functions, see the article by The fact that alcoholic beverages are OVEX rats and Hiller-Sturmhöfel and Bartke, pp. made from many plants and plant by- postmenopausal 153–164.) Based on the structure of products that contain phytoestrogens women the molecules, two main classes of has led to the hypothesis that alcoholic estrogens exist: steroidal and non- beverages contain biologically active steroidal. The steroidal estrogens— phytoestrogens as congeners. According estradiol and estrone—are generated to this hypothesis, two factors might Figure 1 Schematic representation of by the body. Nonsteroidal estrogens, contribute, at least in part, to the femi- the preparation of alcoholic beverage also known as phytoestrogens, are nization observed in men with alcoholic congener concentrates, which can be produced by certain plants. cirrhosis: (1) prolonged exposure to the used to investigate the effects of those Estrogens exert their effects by entering phytoestrogens contained in alcoholic congeners in rats whose ovaries have their target cells, where they bind to beverage congeners and (2) the impaired been removed (OVEX rats) and in docking molecules (i.e., receptors) in the ability of the alcohol-damaged liver to postmenopausal women. fluid that fills the cell (i.e., the cytosol). adequately metabolize and excrete many

Vol. 22, No. 3, 1998 221 compounds present. Those analyses identified two phytoestrogens—sitosterol and biochanin A—in bourbon; two A additional phytoestrogens—daidzein Ovariectomized rats and genistein—were present in beer (Rosenblum et al. 1987, 1991). Other 0 Begin daily adminis- phytoestrogens have been identified in tration of water, wine (Hertog et al. 1993). bourbon congeners, In addition, both the congener con- Week 1 or red wine concentrates and the purified phytoestro- geners equivalent to gens were examined for their ability to one drink (low dose) bind to estrogen receptors and to com- Week 2 or two drinks (high pete with estradiol for binding to dose) per day estrogen receptors in the cytosol (Gavaler et al. 1987b; Hertog et al. 1993; Makela Week 3 et al. 1995). Those analyses found that compared with estradiol, phytoestrogens bound less strongly to the estrogen Week 4 End of experiment receptors and were less able to compete for binding to the receptors. It is impor- tant to note, however, that although Determine uterus weight and levels of FSH and LH those studies were able to determine the relative ability of phytoestrogens to interact with estrogen receptors in the cytosol, they provided no information about whether the molecules B also were transported to the nucleus Postmenopausal women and bound to nuclear receptors. Draw blood for 0 Provide subject with baseline hormone seven vials of the levels Experimental Analyses of congener preparation Week 1 to be taken during the Role of Phytoestrogens Draw blood the following week in Animal Models (one vial per day) Week 2 The Experimental Animal Model To maximize the probability of detect- Week 3 ing a response to biologically active phytoestrogens in alcoholic beverage congeners, researchers needed to use Week 4 animals that produced no or very little estrogen themselves. One such model Draw blood for recovery hormone is a female rat whose ovaries have been Week 5 End of experiment levels removed (i.e., an OVEX rat). In the absence of the ovaries and thus of cyclic ovarian function, the animal’s estrogen Subsequently, measure levels of prolactin, FSH, production is greatly diminished. (This LH, high-density lipoprotein cholesterol, and sex type of rat also can serve as a model for hormone-binding globulin postmenopausal women, whose ovaries have ceased to produce estrogen.) The loss of ovarian hormone produc- Figure 2 Protocol of experiments to evaluate potential estrogenlike effects of tion induces several changes in the body alcoholic beverage congeners in (A) rats whose ovaries have been that can serve as markers of the level of removed (i.e., ovariectomized) and (B) postmenopausal women. ovarian function. First, the body sub- stantially increases the levels of certain NOTE: FSH = follicle-stimulating hormone; LH = luteinizing hormone. hormones (i.e., gonadotropins) that

222 Alcohol Health & Research World Alcoholic Beverages as a Source of Estrogens

regulate ovarian estrogen production and secretion, thereby attempting to A 300 enhance estrogen production by the Bourbon Red Wine unresponsive, or absent, ovaries. Two gonadotropins exist—follicle-stimulating 250 hormone (FSH) and luteinizing hormone (LH)—whose levels in the blood 200 can be measured easily. Thus, when OVEX rats are exposed to exogenously 150 administered estrogenic substances, such as phytoestrogens, the levels of both FSH 100 and LH would be expected to decline compared with unexposed control ani- Level in Control Animals) in Control Level Uterus Weight (% of Mean Weight Uterus 50 mals, because the body would no longer need to stimulate ovarian activity to the same extent. Second, estrogen depriva- 0 tion results in shrinkage, or atrophy, of Control Low High Control Low High the uterus and fallopian tubes, the extent animals dose dose animals dose dose of which can be measured by determin- Group ing those organs’ weights. Accordingly, exposure to phytoestrogens would be expected to increase the weight of B the uterus (which in the rat includes Bourbon Red Wine the fallopian tubes) compared with 110 untreated animals. For the experiments with OVEX rats, 90 concentrates of red wine and bourbon congeners were prepared the same way 70 as for the biochemical analyses described in the previous section. The concentrates then were diluted so that 100 milliliters 50 (mL) of the animals’ drinking water contained the amount of congeners present 30 in one (low-dose) or two (high-dose)

Level in Control Animals) in Control Level standard drinks of each type of alcoholic 10 beverage. The OVEX rats received the Luteinizing Hormone (% of Mean congener-supplemented drinking water 0 daily for 4 weeks (see figure 2). Control Control Low High Control Low High animals received plain drinking water. animals dose dose animals dose dose After the experimental period, the Group animals’ uterus weight and LH and FSH levels were determined.

Figure 3 The effects of bourbon and red wine congeners on (A) uterus weight and (B) luteinizing hormone (LH) levels of rats whose ovaries had been Results removed. The animals received congeners corresponding to one standard drink (low dose) or two standard drinks (high dose) daily in their drinking The congeners of both bourbon and water for 4 weeks. Uterus weights and LH levels in the congener- red wine exerted a dose-dependent exposed animals are expressed as the percentage of the mean level in estrogenic effect on the OVEX rats’ unexposed control animals (defined as 100 percent). The uterus weights uterus weights and LH levels (see fig- are corrected for the animals’ body weights. Both bourbon and red wine ure 3) (Gavaler et al. 1987b, 1995a). congeners induced estrogenlike effects (i.e., increased uterus weight Thus, the animals’ mean uterus weights and reduced LH levels). Moreover, red wine congeners induced more increased, and the LH levels decreased pronounced changes than did bourbon congeners. compared with control OVEX rats that

NOTE: The wide bars represent mean values, whereas narrow brackets represent the standard had received no congeners. Interestingly, error of the mean. A star above a bar indicates a statistically significant difference from the the estrogenic effects on both uterus value in the control animals (p < 0.05). weight and LH levels were more pronounced in the animals exposed

Vol. 22, No. 3, 1998 223 A 90 Red Wine White Wine Beer Bourbon All

60 FSH (IU/L) 50

Basal Basal Basal Basal Basal Trough Trough Trough Trough Trough Recovery Recovery Recovery Recovery Recovery

Hormone Levels

B 30 Red Wine White Wine Beer Bourbon All

15 LH (IU/L) 10

Basal Basal Basal Basal Basal Trough Trough Trough Trough Trough Recovery Recovery Recovery Recovery Recovery

Hormone Levels

Figure 4 Effects of alcoholic beverage congeners on (A) follicle-stimulating hormone (FSH) and (B) luteinizing hormone (LH) levels in postmenopausal women. For 4 weeks, the women consumed congener amounts corresponding to those present in one standard drink of the beverage daily. Basal hormone levels were determined before the women began the experiment. Trough levels represent the lowest hormone levels that were detected during the 4-week administration period of alcoholic beverage congeners. Recovery levels were determined 1 week after the last ingestion of congeners. All congeners had estrogenlike effects (i.e., resulted in lower FSH and LH levels). The effects of the various congeners did not differ significantly.

NOTE: The wide bars represent mean values, whereas the narrow brackets represent the standard error of the mean. A star above a bar indicates a significant difference from basal levels as determined by paired T-test (p < 0.025). The differences in baseline levels result from variations in the mean levels of the subjects in the various groups. IU/L = International units per liter.

224 Alcohol Health & Research World Alcoholic Beverages as a Source of Estrogens

A 90 Red Wine White Wine Beer Bourbon All

Prl (pg/mL) 50

Basal Basal Basal Basal Basal Trough Trough Trough Trough Trough Recovery Recovery Recovery Recovery Recovery Hormone Levels

Red Wine White Wine Beer Bourbon All 80 B 70

30 HDL(mg/dL) 20

Basal Peak Basal Peak Basal Peak Basal Peak Basal Peak

Recovery Recovery Recovery Recovery Recovery Hormone Levels

140 Red Wine White Wine Beer Bourbon All

130

C 120

110

100

80 SHBG (nmol/L) 70

Basal Peak Basal Peak Basal Peak Basal Basal Peak Peak Recovery Recovery Recovery Recovery Recovery Hormone Levels

Figure 5 Effects of alcoholic beverage congeners on the levels of (A) prolactin (Prl), (B) high-density lipoprotein (HDL) cholesterol, and (C) sex hormone-binding globulin (SHBG) in postmenopausal women. For 4 weeks, the women consumed congener amounts corresponding to those present in one standard drink of the beverage daily. Basal hormone levels were determined before the women began the experiment. Peak levels represent the highest hormone levels that were detected during the 4-week administration period of alcoholic beverage congeners. Recovery levels were determined 1 week after the last ingestion of congeners. All congeners had estrogenlike effects (i.e., resulted in elevated levels of Prl, HDL cholesterol, and SHBG). The effects of the various congeners did not differ significantly.

Vol. 22, No. 3, 1998 225 to red wine congeners than in the 1994). Finally, according to the so-called If the congeners contained biologically animals exposed to bourbon con- French Paradox, French people have a active phytoestrogens, the FSH and geners. In addition, the estrogenic low mortality rate from CHD despite LH levels should decrease as described effects reached statistical significance a high intake in saturated fats. This effect previously, whereas prolactin levels at lower doses of red wine congeners has been attributed to the French peo- should increase. Similarly, the levels of than of bourbon congeners. These ple’s relatively high consumption of alco- HDL cholesterol and SHBG should findings suggest that red wine con- holic beverages in general and of red wine increase following exposure to estrogenic tains a higher content and/or bio- in particular (Bordeaux Symposium alcoholic beverage congeners. logically more active phytoestrogens 1998). When analyzed together, these To determine the baseline levels of the than does bourbon. studies suggest that moderate alcohol markers before the women were exposed consumption can have effects similar to the congener preparations, blood to estrogen replacement therapy in terms samples were obtained at the onset of Experimental Analyses of reducing the drinker’s risk of CHD. the study (see figure 2, p. 222). During of the Role of Phyto- To investigate this issue in more detail, the 4-week period of daily congener estrogens in Humans researchers have used a human model ingestion, blood samples were drawn equivalent to the OVEX rats (i.e., post- each week. In addition, the subjects As described in the previous section, menopausal woman) to evaluate the were weighed weekly. Finally, blood the congeners of two types of alcoholic hypothesis that alcoholic beverage samples were obtained 1 week after the beverages, bourbon and red wine, congeners contain biologically active women had stopped ingesting the produced detectable estrogenic effects estrogenic substances that produce a beverage congeners to determine whether in OVEX rats, thereby confirming the clinically significant effect even at mod- the amounts of hormones and binding hypothesis that alcoholic beverages erate drinking levels. proteins had returned to baseline levels. contain biologically active estrogenic Thus, each woman served as her own substances. These findings also support The Human Study Sample control. The researchers then could the notion that the feminization determine the highest (i.e., peak) or observed among men with alcoholic The study recruited 24 postmenopausal lowest (i.e., trough) levels of proteins cirrhosis might result, at least in part, women ranging from ages 57 to 59 (46 and hormones achieved during the 4-week from high exposure to biologically percent from minority populations) who study period as well as the levels after active estrogenic substances in alcoholic were not using estrogen replacement exposure had been terminated for 1 full beverages. Because most people consume therapy (i.e., were estrogen deficient). week (i.e., the recovery level). For each only moderate amounts of alcoholic The women were all light social drinkers study participant, the values then were beverages, however, it is reasonable to or abstainers and consumed no alcohol compared with the corresponding levels ask whether biologically active estrogenic during the study. The study evaluated before congener exposure began. congeners could elicit a clinically rele- the effects of four types of alcoholic vant response in humans even at mod- beverage congeners (i.e., from white and Results erate drinking levels. red wine, beer, and bourbon) in the Three sets of reports, when evaluated women. Thus, six women received For all the hormones and other proteins together, support the idea that alcoholic white wine congeners, seven women examined, the levels changed as would beverages may also produce estrogenic received red wine congeners, six be expected if the congeners contained effects in moderate drinkers. First, women received beer congeners, and biologically active phytoestrogens (see numerous studies have demonstrated five women received bourbon congeners. figures 4 and 5, p. 225) (Gavaler et al. a reduced risk of CHD in postmeno- Every evening for 4 weeks, each 1995a). Thus, the levels of FSH and LH pausal women who use estrogen replace- woman consumed a congener prepara- decreased, with trough levels significantly ment therapy. One postulated mecha- tion corresponding to one standard lower than baseline levels. Conversely, nism underlying this effect involves the drink of that beverage. To evaluate the levels of prolactin, HDL choles- ability of estrogen to increase levels of whether the women showed a clinically terol, and SHBG increased during the high-density lipoprotein (HDL) choles- relevant response indicating exposure study period and reached peak levels terol, or “good” cholesterol. Second, to biologically active estrogenic substances that were significantly higher than the as described previously, several studies in the congener preparations, the baseline levels. The women’s weights have reported a decreased risk of CHD researchers measured the levels of did not change over the study period. among moderate drinkers (Klatsky several hormones and other proteins. In addition, following the recovery These included three hormones pro- period of 1 week, the levels of all five duced in the pituitary gland (i.e., FSH, markers returned to values that did not 2Prolactin is essential for the development and LH, and prolactin2) and two estrogen- differ significantly from baseline levels. growth of the mammary gland and for the initia- responsive proteins produced by the No statistically significant differences tion and maintenance of milk production in nursing women. Prolactin production is increased liver (i.e., HDL cholesterol and sex existed in the estrogenic effects of the in the presence of estrogen. hormone-binding globulin [SHBG]). various congener concentrates.

226 Alcohol Health & Research World Alcoholic Beverages as a Source of Estrogens

Conclusions and Future produced in the body. These issues of the Society of Experimental Biology and Medicine 208:98–102, 1995a. Directions should be explored in clinical trials in which the participants are randomly GAVALER, J.S.; ROSENBLUM, E.R.; AND DEAL, S.R. The studies described in the previous assigned to receiving congeners. Hidden hormones in alcoholic beverages. In: Watson, R.R., ed. Drug and Alcohol Abuse Reviews: Volume sections strongly support the hypothe- Furthermore, researchers must address 6. Alcohol and Hormones. Totowa, NJ: Humana sis that congeners present in alcoholic the question of how the phytoestro- Press, 1995b. pp. 147–160. beverages can produce measurable genic congeners interact with the HERTOG, M.G.L.; HOLLMAN, P.C.H.; AND VAN estrogenic effects, even at moderate alcohol in alcoholic beverages. So far, DE PUTTE, B. Content of potentially anticarcino- drinking levels. Specifically, those studies the effects of these substances have genic flavonoids of tea infusions, wines and fruit found the following: only been investigated separately; juices. Journal of Agriculture and Food Chemistry however, every person who consumes 41:1242–1246, 1993. • Alcoholic beverage congeners exerted alcoholic beverages ingests both the KLATSKY, A.L. Epidemiology of coronary heart estrogenic effects both in an exper- alcohol and the congeners. Scientists disease: Influence of alcohol. Alcoholism: Clinical imental animal model and in post- have yet to determine how these and Experimental Research 18:88–96, 1994. menopausal women. potential interactions can best be MAKELA, S.; POUTANEN, M.; LEHTIMAKI, J.; evaluated. KOSTIAN, M.L.; SANTTI, R.; VIHKO, R. Estrogen- • The estrogenic effects of alcoholic specific 17B-hydroxysteroid oxidoreductase Type beverage congeners were detectable 1 (E>C>1.1.1.62) as a possible target for the action of phytoestrogens. Proceedings of the Society using a variety of estrogenic markers, Acknowledgments of Experimental Biology and Medicine 208:51–59, including the pituitary hormones 1995. LH (in OVEX rats and postmeno- The author wishes to acknowledge MIKSICEK, R.J. Estrogenic flavonoids: Structural pausal women), FSH, and prolactin the valuable contributions of Alberto requirements for biological activity. Proceedings of (in postmenopausal women); uterus Galvao-Teles, Estela Monteiro, Marilyn the Society of Experimental Biology and Medicine weight (in OVEX rats); and the Bonham-Leyba, Brian Bowie, Cesar 208:44–50, 1995. estrogen-responsive liver proteins A. Castro, Stephen R. Deal, Donald ROSENBLUM, E.R.; VAN THIEL, D.H.; CAMPBELL, HDL cholesterol and SHBG (in J. Ferguson, Susan E. Harman, and I.M.; AND GAVALER, J.S. Isolation and identifica- postmenopausal women). Elaine Rosenblum to this work. tion of phytoestrogenic compounds isolated from bourbon. Alcohol and Alcoholism Suppl. 1:551– • In both the experimental animals 555, 1987. and the postmenopausal women, References ROSENBLUM, E.R.; VAN THIEL, D.H.; CAMPBELL, the changes in the levels of all estro- I.M.; AND GAVALER, J.S. Quantitation of B-sitosterol genic markers were consistent with Bordeaux Symposium. Alcoholism: Clinical and in bourbon. Alcoholism: Clinical and Experimental the presence of biologically active Experimental Research 22:738–742, 1998. Research 15:205–206, 1991. phytoestrogens in the congeners. GAVALER, J.S., AND VAN THIEL, D.H. Gonadal ROSENBLUM, E.R.; STAUBER, R.E.; VAN THIEL, dysfunction and inadequate sexual performance D.H.; CAMPBELL, I.M.; AND GAVALER, J.S. • Red wine congeners and bourbon in cirrhotic alcoholic men. (Editorial.) Gastro- Assessment of the estrogenic activity of phyto- enterology 95:1680–1683, 1988. estrogens isolated from bourbon and beer. congeners produced similar estro- Alcoholism: Clinical and Experimental Research genic effects in experimental animals GAVALER, J.S.; IMHOFF, A.F.; POHL, C.R.; ROSEN- 17:1207–1209, 1993. and in postmenopausal women. BLUM, E.R.; AND VAN THIEL, D.H. Alcoholic U.S. Department of Agriculture and U.S. beverages: A source of estrogenic substances? Department of Health and Human Services. Various aspects of the estrogenic Alcohol and Alcoholism Suppl. 1:545–549, 1987a. Nutrition and Your Health: Dietary Guidelines for Americans. 4th ed. Home and Garden Bulletin effects of alcoholic beverage congeners, GAVALER, J.S.; ROSENBLUM, E.R.; VAN THIEL, No. 232. Washington, DC: U.S. Govt. Print. however, remain to be elucidated. For D.H.; EAGON, P.K.; POHL, C.R.; AND CAMPBELL, Off. 1995. example, it is currently unknown I.M. Biologically active phytoestrogens are present whether and how phytoestrogens in in bourbon. Alcoholism: Clinical and Experimental WRIGHT, H.I.; GAVALER, J.S.; TABASCO- alcoholic beverage congeners affect Research 11:399–406, 1987b. MINGUILLAN, J.; AND VAN THIEL, D.H. the lining of the uterus and the min- Endocrine effects of alcohol abuse in males. In: GAVALER, J.S.; ROSENBLUM, E.R.; DEAL, S.R.; Mendelson, J., and Mello, N., eds. Medical eral content of the bones, both of AND BOWIE, B.T. The phytoestrogen congeners Diagnosis and Treatment of Alcoholism. New York: which are influenced by estrogens of alcoholic beverages: Current status. Proceedings McGraw-Hill, 1992. pp. 623–638.

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