Acute Ethanol Ingestion Research Articles

Effects of ethanol on responses of isolated rabbit urinary bladder and urethra.

Acute ethanol ingestion increases the risk of urinary retention in patients with benign prostatic hyperplasia (BPH). To elucidate the mechanism of this effect, we investigated the in vitro effects of ethanol on lower urinary tract function in rabbits. The responses to various stimuli of muscle strips isolated from male rabbit bladder and urethra were determined in the presence of 0%, 0.5%, 1.0%, and 3.0% ethanol. Basal tension of tissue strips taken from the bladder and the urethra was reduced by ethanol in a dose-dependent manner, as were bladder contractions induced by field stimulation, bethanechol, and ATP. Ethanol also reduced phenylephrine-induced contractions of the prostatic urethra. A high (3%) concentration of ethanol significantly reduced KCl-induced contraction of both the bladder and urethra, as well as urethral relaxation induced by field stimulation following contraction with 200 mumol/L phenylephrine. Responsiveness of the rabbit lower urinary tract was significantly reduced by exposure to ethanol. A similar decrease in tonus and contractility of the detrusor and inhibition of relaxation in the prostatic urethra may lead to urinary retention in men following acute ingestion of ethanol.

Influence of exercise and ethanol on cholinesterase activity and lipid peroxidation in blood and brain regions of rat

1. 1. This study elucidates the interaction of acute exercise and single ethanol intake on cholinergic enzyme and its relationship to lipid peroxidation in the blood and brain regions of the rat. 2. 2. Butyrylcholinesterase (BuChE) in plasma and acetylcholinesterase (AChE) in brain regions as well as lipid peroxidation (MDA) were assayed in 1) sedentary control rats; 2) after acute exercise (100% VO 2max); 3) ethanol 20% (1.6 gm/Kg P.o.); 4) exercise and then ethanol 20% (1.6 gm/Kg P.o.). 3. 3. Acute exercise significantly increased BuChE activity (155% of control) in plasma and decreased AChE activity (60% of control) in the corpus striatum with a significant increase in the striatal MDA level (254% of control). Ethanol significantly decreased AChE activity only in striatum (86% of control) with a significant increase in striatal MDA level (132% of control). 4. 4. The combination of exercise and ethanol 20% (l.6gm/Kg P.o.) significantly increased BuChE activity (123% of control) in plasma, and decreased AChE activity (76% of control) in striatum with significant increase in striatal MDA level (147% of control). 5. 5. Acute exercise, single ethanol 20% (1.6 gm/Kg P.o.) intake and the combination selectively inhibited striatal AChE, and the inhibition was correlated with increased lipid peroxidation indicating perturbation of motor function. The combination reduced the peripheral stress response caused by exhaustive exercise.

A PET Study on the Acute Effect of Ethanol on Striatal D2 Dopamine Receptors with [11C]Raclopride in Healthy Males

The effect of acute oral ethanol intake (1·0 g/kg) on cerebral D2-receptors ([11C]raclopride binding) was studied in seven healthy volunteers, using water and alcohol in two separate 59-min PET sessions. In the alcohol experiments, the blood ethanol concentration at the beginning of the imaging was 26·4±3·8 mmol/l and remained stable during the PET session. Ethanol was not found to influence binding of [11C]raclopride to the dopamine D2 receptors in the human striatum, as indicated by the unchanged ratio Bmax/Kd of the whole (left and right) striatum. The Tmax values of the control and ethanol experiments did not differ in the whole striatum, but the right to left difference of striatal Tmax was turned from negative to positive by ethanol (P=0·02). However, the difference between hemispheres in Bmax/Kd was not significantly altered by ethanol intake. There was considerable interindividual variation in the response of all the above parameters to acute ethanol exposure. According to the present results, the acute effects of peroral ethanol exposure on striatal D2 receptor binding potential are of relatively small magnitude in man. However, the changes in Tmax suggest that ethanol may influence the right–left difference of [11C]raclopride binding. © 1997 by John Wiley & Sons, Ltd.

Does concurrent acute ethanol ingestion during omeprazole therapy affect pituitary gonadal axis in male subjects?

Literature suggests that both ethanol and omeprazole may affect the endocrine system. We studied the effect of concurrent use of ethanol and omeprazole on the pituitary gonadal axis in healthy males. Serum testosterone, luteinizing hormone, and follicle stimulating hormone levels were assessed in a fasting state before and after ingestion of 0.5 g/kg bodyweight of ethanol. Subjects then received omeprazole therapy (20 mg 2x/d for one week) followed by assessment of hormone levels before and after ethanol ingestion as done previously. Total testosterone levels before and after ethanol at baseline declined an average of 46.6 ng/dL (n = 8; p = NS). The testosterone levels before and after ethanol following omeprazole therapy rose an average of 55.4 ng/dL (n = 8; p = NS). There was no significant difference in the change of ethanol induced testosterone concentrations as a result of omeprazole therapy. Similarly the free testosterone, follicle stimulating hormone, and luteinizing hormone were also not affected by ethanol or omeprazole alone or in combination. We conclude that omeprazole and/or acute ingestion of ethanol do not affect the pituitary gonadal axis in healthy male subjects.

Distribution of Fatty Acid Ethyl Esters in Long Evans Rats Following Acute Ethanol Ingestion

Summary: Fatty acid ethyl esters (FAEEs) are members of a class of nonoxidative metabolites of ethanol. These lipophilic moieties have been detected in various animal and human tissues in vivo and in vitro. A one-step liquid-liquid extraction method with subsequent analysis by GC/MS is described for the identification and quantitation of palmitic acid ethyl ester and stearic acid ethyl ester in blood, liver, and brain from Long Evans rats administered ethanol by feeding needle. Animals received one of four doses of ethanol (1, 2, 4, and 5 g/kg) as a 25% w/v gavage solution. Control animals received tap water. One hour after gavage, a blood specimen (3-5 mL) was collected by cardiac puncture and the animals were euthanized in accordance with guidelines promulagated by the Institutional Animal Care and Utilization committee. Necropsies included the complete resection of liver and removal of whole brain. Blood ethanol concentrations (BECs) were determined by GC headspace with n-propanol as internal standard. Heptadecanoic acid ethyl ester was added as internal standard to 1.0 mL aliquots of blood or 2 g liver or whole brain homogenates and extracted in toluene-hexane (1:1) at pH 5. Extraction mixtures were throroughly mixed and centrifuged. Solvent layers were removed and evaporated to dryness under nitrogen. Reconstituted residues were injected into a GC/MS equipped with an HP INNOWax GC column. Selected ions in the SIM mode included 88, 101, and 157. BEC data and FAEE concentrations for blood, liver, and brain are reported. These results suggest that a one-step extraction method coupled with GC/MS analysis could be used in identifying and quantitating nonoxidative fatty acid ethyl ester metabolites of ethanol in vivo.

Alcohol and heart muscle disease.

Ethanol consumption may induce acute and chronic effects on the myocardium. High-dose acute ethanol intake may induce a decrease in myocardial contraction and produce a variety of rhythm disturbances. These effects are more relevant in patients with underlying cardiomyopathy. Chronic ethanol intake may induce the development of a dilated cardiomyopathy, which is clinically and functionally similar to idiopathic dilated cardiomyopathy. Alcoholic cardiomyopathy is potentially reversible with abstinence. The prognosis depends on the persistence or abstinence of ethanol intake. There is a positive correlation between alcoholic cardiomyopathy and the presence of other ethanol-related diseases, such as skeletal myopathy and cirrhosis. In patients with a specific ethanol-related disease, the possible presence of other complications of alcoholism should be ruled out. Although there are several factors potentially implicated in the pathogenesis of alcohol-related myocardial damage, ethanol itself may induce direct myocardial lesions, which are dose-related and independent of nutrition, protein or ionic deficiencies. The most relevant pathogenic studies on alcoholic cardiomyopathy are based on the disruption of membrane permeability and ionic fluxes mediated by ethanol, inducing a decrease in the calcium transients through the sarcolemma and interfering with the excitation-contraction coupling of myocytes. Cell energy depletion or protein-turnover disruption may contribute to the deleterious effect of ethanol on the myocardium.

The effect of tilsuprost on the liver mitochondria in taurocholate pancreatitis in rats with antecedent acute ethanol abuse.

The damage to the liver appears to be an important aspect of multisystem organ failure in acute pancreatitis with poor prognosis. The objective of this study was to evaluate the protective effect of stable prostacyclin analogue--tilsuprost on the liver energy metabolism in taurocholate pancreatitis in rats preceded by acute ethanol intake. The respiratory control ratio (RCR) and ADP/O ratio of liver mitochondria with glutamate+malate as substrates and mitochondrial DNP (uncoupler)-dependent ATPase activity were significantly depressed after 12 h of taurocholate pancreatitis-the effects that were not significantly aggravated by antecedent acute ethanol intake. Tilsuprost (0.3 mg/kg i.g.) given just before induction of pancreatitis partly prevented the impairment of mitochondrial oxidative and phosphorylative functions, however these positive effects were limited in acute pancreatitis preceded by acute ethanol intake. These results suggest that prostacyclin analogues could be effective in the treatment of hepatic complications in acute pancreatitis, however their effectiveness could be limited in the case of acute ethanol antecedent abuse.

The influence of acute ethanol ingestion on phospholipase D activity in rat pancreas. An in vitro and in vivo study.

Since phosphatidic acid (PA), a product of phospholipase D(PLD), is known as a second messenger probably involved in cell proliferation and differentiation, our results potentially suggest a new mechanism for pancreatic tissue injury after ethanol ingestion. The mechanisms by which ethanol causes pancreatic injury are still not clear. In vitro studies have suggested a relationship of PLD to ethanol metabolism. This study was undertaken to establish the involvement of PLD in ethanol metabolism in isolated pancreatic acini and to determine the influence of acute ethanol ingestion on PLD activity in pancreas and pancreatic growth after cerulein (Ce) infusion. Dispersed pancreatic acini prelabeled with 3H myristic acid were incubated with 500 pM Ce in the presence of different concentrations of ethanol; then labeled PA and phosphatidylethanol (PEt) production were measured under the same experimental conditions. For in vivo study, male rats were infused with Ce (0.25 microgram/kg/h) or saline; 1 h before infusion, animals were treated with 40% ethanol (5 g/kg p.o.) or saline, respectively. After 1, 2, and 48 h of Ce infusion, rats were killed; dispersed pancreatic acini were then prepared and PLD activity was measured. Pancreatic weight, protein, RNA, and DNA content were also established. The production of PEt in vitro after Ce stimulation was significantly elevated with 1% ethanol in the medium. In the presence of different concentrations of ethanol (0.5-2%), a significant inhibition of PA accumulation in in vitro experiments was observed. The decrease of PA accumulation with ethanol was parallel to the increase of PEt production under the same experimental conditions. PLD activity was significantly elevated after 1 and 2 h of Ce infusion (116 and 105%, respectively), reaching control value after 48 h. Acute ethanol ingestion significantly diminished PLD activity after 1 and 2 h. After 48 h of Ce infusion, a significant increase in pancreatic weight, protein, RNA, and DNA content in pancreatic tissue was found. Ethanol was not able to influence pancreatic weight, proteins and RNA content. However, it had the potency to diminish DNA content after 48 h of Ce infusion.

Acute effects of ethanol ingestion on signal-averaged electrocardiograms

In conclusion, we found that acute ethanol ingestion causes prolongation of both atrial and ventricular signal-averaged electrocardiograms.

Acute ethanol administration induces oxidative changes in rat pancreatic tissue.

There is mounting clinical evidence that ethanol toxicity to the pancreas is linked with glutathione depletion from oxidative stress but there is not experimental proof that this occurs. The effect of acute ethanol ingestion (4 g/kg) on the pancreatic content of reduced (GSH) and oxidised (GSSG) glutathione, malondialdehyde (MDA), and carbonyl proteins were therefore studied in the rat. Ethanol caused a significant reduction in GSH (p < 0.02) and an increase in GSSG (p < 0.005), MDA (p < 0.05), and carbonyl proteins (p < 0.05) in the rat pancreas. The GSH/GSSG ratios were significantly decreased after ethanol, especially in rats pretreated with diethylmaleate (DEM), a GSH blocker. Administration of ethanol after DEM further increased the rate of lipid and protein oxidation. Pretreatment with cyanamide (an inhibitor of aldehyde dehydrogenase) but not with 4-methylpyrazole (an alcohol dehydrogenase inhibitor) caused higher production of GSSG and MDA. These findings indicate that acute ethanol reduces the pancreatic content of GSH, which seems to be protective against ethanol toxicity, since its depletion is accompanied by increased oxidative damage to cell structures. The further increase of lipid peroxidation and GSSG production in the presence of cyanamide suggests that acetaldehyde might be responsible for the oxidative changes that occur in pancreatic cells after ethanol administration.

Plasma and Urine Salsolinol in Humans: Effect of Acute Ethanol Intake on the Enantiomeric Composition of Salsolinol

The tetrahydroisoquinoline (TIQ) salsolinol (SAL), a condensation product of dopamine and pyruvate or acetaldehyde, is one of the neuropharmacologically active alkaloids in mammals. Previous HPLC studies have shown that the R-enantiomer of SAL is largely predominant, or is the only enantiomer in the urine of healthy subjects, whereas the S-enantiomer was found predominant in the urine of alcoholics. An enzymatic pathway for SAL formation that is influenced by chronic alcohol intake was proposed. However, our analyses showed that the SAL detectable in human urine and plasma is racemic, at least in healthy subjects. No change of the enantiomeric distribution was observed after an acute alcohol ingestion (1 g alcohol/kg body weight). Using a new method for the resolution of the SAL enantiomers and gas chromatography mass spectrometry analysis, the SAL enantiomers were quantified in the urine and plasma of 24 subjects before and after the intake of alcohol. Special dietary conditions were observed to avoid interferences by the SAL of the foodstuff. Although the distribution of SAL enantiomers was not changed after alcohol intake, the total urinary SAL output and the plasma concentration of SAL were significantly influenced in different ways. Only five subjects showed a significant increase both in plasma SAL concentration and in the total urinary SAL output, whereas 19 subjects showed decreased or unchanged SAL levels after alcohol administration. Data also show that only the subjects with low baseline levels (mean of 0.148 ng SAL/ml plasma) tend to increase SAL levels after ethanol ingestion, which may imply some genetic basis for the response.

Tryptophan metabolism and disposition in relation to alcohol and alcoholism.

Tryptophan (Trp) metabolism and disposition in relation to alcohol and alcoholism are briefly reviewed. The changes observed could generally be classified into those: (1) exerted by acute or chronic alcohol administration and/or subsequent withdrawal; (2) already present in the absence of alcohol consumption, such as in naive alcohol-preferring animals or in abstinent alcoholics. In normal rats, acute ethanol administration activates liver Trp pyrrolase and exerts a biphasic effect on brain 5-HT (5-hydroxytryptamine or serotonin) synthesis, whereas chronic ethanol administration and subsequent withdrawal exert opposite effects on 5-HT synthesis mediated by corresponding changes in liver Trp pyrrolase activity. A cerebral 5-HT deficiency has been demonstrated in the alcohol-preferring C57BL mouse strain and in a number of alcohol-preferring rat lines, the mechanism of which is understood only in two models; the C57B1 mouse strain has a higher liver Trp pyrrolase activity and the P rat line from Indiana has a lower density of serotonergic fibres in cerebral cortex. In man, acute ethanol intake lowers circulating [Trp] and its availability to the brain, almost certainly by activating liver Trp pyrrolase. Some evidence exists for possible inhibition of pyrrolase activity in non-abstinent chronic alcoholics. Evidence in recently abstinent alcoholics suggests that Trp availability to the brain may be impaired and that this may be particularly so in patients with positive family history. Exploration of this latter possibility may be important in understanding the biological basis of predisposition to alcoholism.

Hepatic mitochondrial and lysosomal alterations in acute experimental pancreatitis with ethanolic coetiology in rats

In order to assess the cumulative effects of antecedent acute ethanol intake and acute pancreatitis on the liver, the mitochondrial respiratory functions and lysosomal membrane integrity of the liver were evaluated in taurocholate pancreatitis (AP) in rats, induced 6 hr after intragastric ethanol 40% (5 g/kg body wt). The oxygen consumption rate, RCR (respiratory control ratio), and ADP/O ratio were measured according to Estabrook. Fractional free activity of lysosomal hydrolases was assayed. RCR with glutamate + malate was most decreased at 12 hr of AP with partial improvement after 18 hr. The ADP/O ratio dropped maximally after 18 hr of AP. The fragility of lysosomal membranes increased significantly at 18 hr of AP. The antecedent ethanol intake abolished the partial restoration of RCR after 18 hr; however, it did not affect the ADP/O ratio or the integrity of lysosomal membranes impaired in AP at this time. In conclusion, the antecedent acute ethanol abuse could aggravate the liver mitochondrial deterioration, but not the lysosomal membrane labilization seen in AP.

Gene expression of A- and B-type natriuretic peptides in response to acute ethanol ingestion.

Given that ethanol ingestion is associated with a disruption of water and electrolyte balance in addition to being a significant risk factor for cardiovascular disease, we have investigated the gene expression of ANP and BNP in response to acute doses of ethanol. Wistar rats were administered either a 5 g/kg dose of ethanol or an equivalent volume of water, and atrial and ventricular tissue samples were removed at 30, 60, and 120 min for analyses. Although no differences in ANP mRNA were observed between ethanol and water-treated rats during the time course, BNP mRNA levels in ethanol-treated rats were 43% of those present in water-treated animals in atrial tissue at 120 min. In ventricular tissue, BNP mRNA levels were reduced similarly to 38% of control. These results suggest a possible differential regulation of A- and B-type natriuretic peptides under the influence of ethanol ingestion.

Role of endotoxin in the hepatic microvascular inflammatory response to ethanol.

Kupffer cells (KC) and gut-derived bacterial endotoxin have been implicated in the aetiology of alcoholic liver disease. Using in vivo microscopic methods, we have shown that ethanol ingestion in mice causes a dose dependent increase in leucocyte adhesion and endothelial cell swelling in hepatic sinusoids. Activation of KC is elicited at low doses while depression occurs at high doses and with chronic exposure. The responses are exacerbated in the presence of endotoxaemia or sepsis and are not seen in endotoxin-resistant animals, implicating a role for endotoxin in the ethanol-induced inflammatory response. In addition, the responses are abolished with anti-TNF alpha suggesting that TNF alpha is a primary mediator of these events. Nitric oxide (NO) initially appears to play an important role in these events by stabilizing the TNF alpha-mediated hepatic microvascular inflammatory response to acute ethanol ingestion, thereby helping to protect the liver from ischaemia and leucocyte induced oxidative injury. Finally, an ongoing clinical study has confirmed a mild systemic endotoxaemia in patients hospitalized for alcoholic liver disease. All of these results support important roles for endotoxin, cytokines, nitric oxide and sinusoidal lining cells in the pathophysiology of liver injury resulting from ethanol alone or in combination with infection.

CHANGES OF G-PROTEIN LEVELS IN PLATELET MEMBRANES FROM ALCOHOLICS DURING SHORT-TERM AND LONG-TERM ABSTINENCE

The levels of G alpha i2-protein and the G beta gamma-heterodimer were measured in platelet membranes of non-alcoholics, non-alcoholics after an ethanol load (1 g/kg body weight) and of alcoholics under various conditions. The findings were correlated with the activation of the adenylyl cyclase (AC) by various agents. The activation of AC was facilitated by acute ingestion of ethanol. This could not be explained by changes of the G-proteins determined because the levels of the G alpha i2-protein increased, whereas those of the G beta gamma-proteins remained in the control range. The alcoholics were divided into two groups on the day of admission: those with ethanol still present in the blood (intoxicated alcoholics) and those acutely withdrawn within the last 48 h (ethanol absent from the blood). The intoxicated alcoholics had elevated G alpha i2-protein levels in contrast to the acutely withdrawn patients, who did not. This observation suggests rapid changes of the G-protein levels. By analysing the inhibitory efficacy of the G-proteins on AC, it was found that the concentration of the G beta gamma-heterodimer, but not that of the G alpha i2-proteins, correlated with the inhibitory efficacy. The basal activity of the AC was reduced as well as the activation by some compounds. Eight days later (short-term withdrawal) both the levels of G alpha i2 and G beta gamma were elevated. Again, the inhibitory efficacy of the G-proteins correlated with the G beta gamma-heterodimer levels but not with those of the G alpha i2-protein. Furthermore, the changes of the G beta gamma-protein levels between the first and the eighth day correlated with the changes of the inhibiting efficacy. Only a trend was observed with respect to a lowered basal activity if compared with the intoxicated non-alcoholics. The activation of AC by guanylylimidyldiphosphate [Gpp(NH)p] and Gpp(NH)p + ethanol (200 mM in vitro) was still reduced. Observations after 3 and 6 months of abstinence demonstrated elevated G alpha i2- and G beta gamma-protein levels. This suggests residual marker properties of the G-proteins whereby the activity of AC was normal. Only the reduced stimulation by Gpp(NH)p + ethanol in vitro (200 mM), compared with the respective stimulation of AC of intoxicated non-alcoholics, suggested some residual disturbances of the signal transduction during long-term abstinence.

Effect of Acute Ethanol Ingestion on Orthostatic Vital Signs

Study objective: To determine the effect of acute ethanol intoxication on the results of orthostatic tilt testing. Design: Prospective, randomized crossover study. Subjects received ethanol (1.1 gm/kg) or an equal volume of water added to nonalcoholic beer. Orthostatic vital signs, ethanol concentration, and relative volume status were checked initially and hourly for 8 hours. Participants: Twenty healthy human volunteers, 10 men, and 10 women. Results: Peak ethanol concentration was 116±18 mg/dL (mean± SD) 1 hour after ingestion. ANOVA for repeated measures revealed a significant difference in orthostatic pulse changeand relative volume deficit between the ethanol and placebo groups ( P<.05). Post hoc testing revealed significant differences between the two groups at two, five, seven and eight hours post ingestion for pulse change, and two to eight hours for volume status (Bonferroni's corrected t test, P<.0055). At 2 and 5 to 8 hours, there were significantly more positive tilt tests (±30 beat/minute increase) in the ethanol group than in the placebo group ( P<.05). Starting at 2 hours, the ethanol group had a statistically significant relative fluid deficit averaging .5 L by 3 hours. There was no difference in postural blood pressure changes between the two groups. Conclusion: In healthy volunteers, ethanol intoxication resulted in exaggerated postural pulse changes and in a greater proportion of positive orthostatic tilt test results than in a placebo group. These changes were accompanied by significant relative fluid deficits. [Tomaszewski C, Cline DM, Whitley TW, Grant T: Effect of acute ethanol ingestion on orthostatic vital signs. Ann Emerg Med May 1995;25:636-641.]

Lack of effect of omeprazole therapy and/or acute ethanol ingestion on pituitary gonadal hormonal axis: [formula omitted], SriPrakash Mokshagundam, Salman Rashid. Departments of Medicine, University of Louisville, Louisville, Kentucky and University of Arkansas, Little Rock, Arkansas

Lack of effect of omeprazole therapy and/or acute ethanol ingestion on pituitary gonadal hormonal axis: [formula omitted], SriPrakash Mokshagundam, Salman Rashid. Departments of Medicine, University of Louisville, Louisville, Kentucky and University of Arkansas, Little Rock, Arkansas

Effect of Acute Ethanol Ingestion on Prolactin in Menopausal Women Using Estradiol Replacement

Epidemiologic studies suggest that women who consume ethanol are at an increased risk for developing breast cancer. Two randomized, crossover studies were performed to examine the effects of ethanol on prolactin in menopausal women using transdermal estradiol. In study 1, transdermal estradiol patches (0.15 mg) were administered to menopausal women (n = 7) the day before ethanol administration. At 8.00 h, the women ingested ethanol (1 ml/kg, 95% ethanol) or an isocaloric carbohydrate drink. Prolactin levels were measured frequently for 6.3 h. Serum ethanol levels reached a broad peak from 40 to 100 min after initiation of ethanol ingestion. Serum prolactin levels were significantly higher after ethanol ingestion than after the isocaloric carbohydrate drink ingestion (p < 0.03). Study 2 was identical to study 1 except that the transdermal estradiol patches were removed after completion of ethanol or carbohydrate ingestion. In study 2, serum prolactin was greater after ethanol ingestion than after carbohydrate ingestion (p < 0.001). In menopausal women using transdermal estradiol, acute ethanol ingestion is associated with an increase in serum prolactin.

The Effect of Acute Ethanol Ingestion on Estrogen Levels in Postmenopausal Women Using Transdermal Estradiol

To determine whether acute alcohol ingestion raises estradiol (E2) and estrone (E1) levels in a randomized, controlled, crossover study on postmenopausal women using transdermal E2. Healthy, non-smoking postmenopausal women (n = 7) using no medications were enrolled. Transdermal E2, 0.15 mg, was applied 13 hours before the subjects ingested alcohol (1 mL/kg 95% ethanol) or isocaloric carbohydrate punch. Serum samples were obtained for 40 minutes before drink ingestion and 6 hours after drink ingestion and were assayed for E2 and E1. Ethanol levels peaked 60 minutes after the start of ethanol-drink ingestion, at 25.4 mmol/L (117 mg/dL). Estradiol levels rose significantly above the mean baseline of 657 pmol/L (179 pg/mL) after ethanol-drink ingestion (P < or = .01), with a mean peak of 804 pmol/L (219 pg/mL) 35 minutes after the start of drink ingestion, and were significantly greater than the E2 levels that followed the carbohydrate drink (P < or = .0001). There were no significant changes in E2 or E1 levels after carbohydrate-drink ingestion. We conclude that ethanol ingestion may acutely raise circulating E2 concentrations in women using transdermal E2.