Also see:
Estrogen, Endotoxin, and Alcohol-Induced Liver Injury
How does estrogen enhance endotoxin toxicity? Let me count the ways.
PUFA and Liver Toxicity; Protection by Saturated Fats
Endotoxin: Poisoning from the Inside Out
Fish Oils Increase Intestinal Permeability
Estrogen and Liver Toxicity
Single Bout of Binge Drinking Linked to Immune System Effects

Alcohol and Alcoholism (2000) 35 (5): 417-423.
THE EFFECTS OF MODERATE ALCOHOL CONSUMPTION ON FEMALE HORMONE LEVELS AND REPRODUCTIVE FUNCTION
Studies that have investigated the effect of moderate alcohol consumption on the level of oestrogens and progesterone in both pre- and post-menopausal women are reviewed. It is concluded that several lines of evidence point to an alcohol-induced rise in natural or synthetic oestrogen levels in women. Proposed mechanisms include an increased rate of aromatization of testosterone or a decreased rate of oxidation of oestradiol to oestrone. Moderate alcohol consumption has also been linked to decreased progesterone levels in pre-menopausal women. The relevance of these findings to female health, fertility and the timing of the menopause is considered.

Cancer Epidemiol Biomarkers Prev. 1998 Mar;7(3):189-93.
Alcohol consumption and total estradiol in premenopausal women.
P Muti, M Trevisan, A Micheli, V Krogh, G Bolelli, R Sciajno, H J Schünemann and F Berrino
The present paper analyzes the relation between alcohol intake and serum total estradiol in premenopausal women while attempting to control or reduce several sources of variability of serum estradiol. Sixty premenopausal women were recruited, and alcohol intake was estimated by a semiquantitative questionnaire. Interviews, anthropometric measurements, and blood drawings (after overnight fasting) were conducted twice, 1 year apart. Both blood samples were obtained on the same day of the luteal phase of the cycle, in the same month and in the same hour and minute of the day. Samples from the first drawing were stored at -80 degrees C. Serum from both drawings was assayed simultaneously and in blind fashion. A significant association between alcohol intake and estradiol was found when estradiol was averaged across the two visits (Spearman’s r = 0.29; P < 0.05). To control for intraindividual variability of estradiol over time, participants were then divided into tertiles of hormone distribution for each of the two sets of measurements and classified based on their consistency in estradiol across the two visits. Women showing consistently high estradiol levels at both visits were characterized by a significantly higher alcohol intake (92.8 g/week) in comparison with those showing consistently low estradiol at both visits (31.6 g/week). Furthermore, the prevalence of drinkers in the group with consistently high estradiol was significantly higher than in the group with consistently low estradiol. The present report indicates that drinkers seem to be characterized by consistently higher estradiol than nondrinkers, and that when the variability of estradiol in premenopause is considered, it is possible to identify a relationship between alcohol intake and estradiol.

Psychopharmacology (Berl). 1988;94(4):464-7.
Acute alcohol effects on plasma estradiol levels in women.
Mendelson JH, Lukas SE, Mello NK, Amass L, Ellingboe J, Skupny A.
Acute administration of alcohol (0.695 g/kg) to healthy adult women resulted in peak blood alcohol levels between 70 and 75 mg/dl within 50-60 min after initiation of drinking. Alcohol induced a significant increase (means = 18 pg/ml) in plasma estradiol levels (P less than 0.01). In contrast, after placebo ingestion, plasma estradiol levels did not change significantly. After alcohol intake, plasma estradiol levels reached peak values at 25 min following initiation of drinking when blood alcohol levels averaged 34 mg/ml. It is postulated that the alcohol-induced increase in plasma estradiol is due to changes in hepatic redox states associated with the catabolism of ethanol.

Oncology. 1991;48(6):490-4.
Diet and urine estrogens among postmenopausal women.
Katsouyanni K, Boyle P, Trichopoulos D.
Creatinine-adjusted levels of estrone, estradiol and estriol were determined in overnight urine specimens from 88 postmenopausal women from Athens, Greece, and were correlated with daily nutrient intakes estimated through a semiquantitative food frequency questionnaire. Although obesity was positively and significantly related to all three urinary estrogens and their total, none of the investigated macro- or micronutrients was significantly or suggestively associated to any of these urinary estrogens, after controlling for energy intake, reproductive and biosocial variables. These results suggest that quantitative rather than qualitative aspects of nutrition affect the levels of postmenopausal estrogens, although endogenous factors could also be responsible for the association of these estrogens with obesity. Alcohol intake was also positively associated with urinary estrogens (mainly estrone and estradiol), after controlling for energy intake, obesity and the other indicated variables.

Alcohol. 1992 Sep-Oct;9(5):395-401.
Ethanol decreases progesterone synthesis in human placental cells: mechanism of ethanol effect.
Ahluwalia B, Smith D, Adeyiga O, Akbasak B, Rajguru S.
Fetal alcohol syndrome (FAS) is a set of signs and symptoms in offsprings born to mothers who abuse alcohol during pregnancy. We postulated that impairment in the placental endocrine function contribute to FAS. In this study, we examined in vitro effects of ethanol on the placental cells’ (cytotrophoblast cells) capacity to synthesize progesterone. Cytotrophoblast cells were isolated from normal term placenta and were incubated (2 x 10(6)) with 20-, 30-, and 40-mM doses of ethanol for 6 h. Progesterone was measured in the incubate by RIA. The results showed that, at the 20-mM dose of ethanol, progesterone synthesis was significantly decreased (p less than 0.01), at the 30-mM dose level there was a further decrease of 20%. The differences between 30- and 40-mM ethanol dose levels were not significant. To determine the mechanism of ethanol effects on progesterone synthesis, cytotrophoblast cells were preincubated with 30 mM ethanol followed by 10 microliters of LDL (10 microliters LDL = 80 micrograms cholesterol) and vice versa. The results showed that ethanol effects on progesterone synthesis was dependent on whether ethanol was added prior to or following the addition of LDL in the medium. If ethanol was added in the medium prior to LDL, progesterone synthesis was decreased significantly (p greater than 0.01); however, when ethanol was added after the LDL, ethanol had no effect on progesterone synthesis. In the experiment where ethanol and LDL were added simultaneously in the medium, ethanol blunted the stimulatory effect of LDL on progesterone synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Clin Exp Res. 1996 Oct;20(7):1192-5.
Estrogen-related acetaldehyde elevation in women during alcohol intoxication.
Eriksson CJ, Fukunaga T, Sarkola T, Lindholm H, Ahola L.
Alcohol is more often unpleasant and causes tissue damage more rapidly in women than men. The present study was designed to find out whether acetaldehyde, the primary metabolite of alcohol, could play a crucial role in these actions. Special emphasis was focused on the appropriate determination of blood acetaldehyde and hormonal factors. Occurrence of elevated blood acetaldehyde levels during alcohol oxidation was established in both normally cycling women and ones taking oral contraceptives, but not in men. An association between elevated acetaldehyde levels and high estrogen phases was observed in both groups of women. Estrogen-related acetaldehyde elevation is suggested to be the key factor explaining the gender differences of the adverse effects of alcohol.

Alcohol Clin Exp Res. 1992 Feb;16(1):87-92.
The association between moderate alcoholic beverage consumption and serum estradiol and testosterone levels in normal postmenopausal women: relationship to the literature.
Gavaler JS, Van Thiel DH.
The major source of endogenous estrogens in postmenopausal women is the aromatization of androgens to estrogens; because alcohol is known to increase aromatization, the relationship between moderate alcoholic beverage consumption and serum estradiol levels was evaluated in 128 normal postmenopausal women. Alcohol intake was based on a composite of self-report and food record information. Among the 78.8% of women reporting alcohol use, weekly intake was 4.8 +/- 0.6 drinks. Among abstainers, estradiol levels were 100.8 +/- 12.1 pmol/liter, significantly lower than in alcohol users, 162.6 +/- 11.9 pmol/liter. Significant bivariate correlations were found between the logarithm of estradiol and total weekly drinks. In multiple linear regression analyses inclusion of alcohol as a variable increased the amount of explained variation in estradiol. Similar findings were demonstrable when the crude estimator of aromatization, the estradiol:testosterone ratio logarithm was the dependent variable. Together, these findings suggest that moderate alcohol use is an important factor for postmenopausal estrogen status and may offer a partial explanation for the reported protective effect of moderate alcohol consumption with respect to postmenopausal cardiovascular disease risk.

Alcohol Clin Exp Res. 1999 Jun;23(6):976-82.
Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol, and luteinizing hormone in premenopausal women.
Sarkola T, Mäkisalo H, Fukunaga T, Eriksson CJ.
BACKGROUND:
Heavy alcohol consumption is associated with menstrual irregularities, including anovulation, luteal-phase dysfunction, recurrent amenorrhea, and early menopause. In addition, moderate to heavy alcohol intake has been found to increase the risk of spontaneous abortions and breast cancer. These adverse effects could at least in part originate from alcohol-mediated changes in hormone levels.
METHODS:
The acute effect of alcohol on the hormone balance in women using oral contraceptives (OC+) and also in nonusers (OC-), was evaluated in 30 OC- and 31 OC+ subjects, representing the whole period of the menstrual cycle. It was also evaluated in 40 OC- and 47 OC+ subjects during the midcycle phase and in 10 OC+ subjects with unknown cycle phase.
RESULTS:
We found that among subjects who used oral contraceptives, estradiol levels increased and progesterone levels decreased after intake of alcohol (0.5 g/kg). No dose effect (0.34-1.02 g/kg) on progesterone was observed in a substudy on 10 OC+ subjects. With regard to estrone levels, no effect was observed, although a significant increase was found in the estradiol-to-estrone ratio. Among subjects not using oral contraceptives, progesterone levels decreased after intake of alcohol (0.5 g/kg). No effect was found in estradiol, estrone, or the estradiol-to-estrone ratio during midcycle in this study group. A transient elevating effect of alcohol (0.5 g/kg) on prolactin levels was observed in both study groups. We found that alcohol (0.5 g/kg) had no significant effect on luteinizing hormone (LH) levels among subjects not using oral contraceptives, and observed a decline among subjects using oral contraceptives at midcycle.
CONCLUSIONS:
We suggest that the estradiol and progesterone effects are related to decreased steroid catabolism, resulting from the alcohol-mediated increase in the hepatic NADH-to-NAD ratio. The transient effect on prolactin levels may reflect acute changes in opioid and dopamine levels in the hypothalamus. The present findings regarding female sex steroids may be of relevance in the association between moderate to heavy alcohol consumption and the development of breast cancer.

Alcohol Clin Exp Res. 1993 Aug;17(4):786-90.
Alcohol and estrogen levels in postmenopausal women: the spectrum of effect.
Gavaler JS, Deal SR, Van Thiel DH, Arria A, Allan MJ.
Compared with alcohol-abstaining normal postmenopausal women, estradiol levels are known to be statistically increased in normal postmenopausal women who consume alcoholic beverages moderately, and to be even further increased in alcoholic postmenopausal women with cirrhosis. This study was undertaken to evaluate whether or not there is a spectrum of changes in levels of sex steroids and pituitary hormones associated with alcohol abstinence, alcohol use, and alcohol-induced cirrhosis in the absence of current alcohol abuse. For levels of estradiol and testosterone, as well as for the estradiol to testosterone ratio, all three groups differed significantly from each other; for the pituitary hormones, levels in the abstainers and alcohol users were similar and statistically different from levels in the alcoholic cirrhotic women. Compared with the alcohol-abstaining women, the relationships of age and estradiol with levels of the other hormones were disturbed for 4 of 11 correlations examined among the alcohol users, and for 9 of 11 correlations evaluated among the alcoholic cirrhotic women. These findings suggest that not only are hormonal relationships markedly disrupted among alcoholic cirrhotics, but also that alcoholic beverage consumption in the range of 0.1-28 total weekly drinks results in detectable perturbations of the normal hormonal relationships expected in postmenopausal women.

Hepatology. 1992 Aug;16(2):312-9.
Hormonal status of postmenopausal women with alcohol-induced cirrhosis: further findings and a review of the literature.
Gavaler JS, Van Thiel DH.
The derangements of levels of sex hormones and gonadotropins in alcoholic cirrhotic men are well delineated. The countersituation in alcoholic cirrhotic women has not yet been fully described. This study was performed in postmenopausal women among whom menstrual cycle variations in hormones no longer occur; with such a study population, it is possible to control for confounding factors and thus optimize detection of differences in levels of hormones and hormone interrelationships. Both estradiol levels and a rough estimate of aromatization of testosterone to estradiol, the estradiol to testosterone ratio, were significantly elevated in the 20 alcoholic subjects with alcohol-induced cirrhosis, as compared with the 27 normal controls; similarly, testosterone, luteinizing hormone and follicle-stimulating hormone were all significantly reduced in the alcoholic cirrhotic women. In addition, the normal relationships of estradiol with luteinizing hormone, follicle-stimulating hormone, body mass and the estradiol/testosterone ratio were detected in the control group but not in the group of cirrhotic women. Further, among the alcoholic cirrhotic postmenopausal women, testosterone, luteinizing hormone, follicle-stimulating hormone and the estradiol/testosterone ratio were all significantly correlated with the Child’s liver disease severity score. That the hormone levels and their interrelationships differ markedly between normal and alcoholic cirrhotic women extends previous findings in both men and postmenopausal women; the correlations of hormone levels and markers of liver disease will require further investigation.

J Pharmacol Exp Ther. 1990 Aug;254(2):407-11.
Alcohol effects on hCG-stimulated gonadal hormones in women.
S K Teoh, J H Mendelson, N K Mello, A Skupny and J Ellingboe
Chronic alcohol abuse is associated with derangements of reproductive function in women. The mechanism of increased risk for alcohol-related abortions and fetal alcohol syndrome is unknown. The goal of this study was to determine if acute alcohol administration affected gonadal steroid hormone levels after administration of human chorionic gonadotropin (hCG) to normal healthy women. hCG was used to simulate the hormonal milieu during the first trimester of pregnancy. Ten women were studied during the mid-luteal phase (between days 17 and 23) of their menstrual cycle. Plasma estradiol, progesterone and prolactin were measured before and after simultaneous administration of 5000 I.U. of hCG (Profasi) and alcohol or placebo solution under double-blind conditions. There was a significant increase in plasma estradiol (P less than .001) and prolactin levels (P less than .01) after hCG and alcohol administration but not after hCG and placebo administration. Plasma progesterone increased significantly (P less than .001) above base line after hCG and placebo administration but this was not observed after hCG and alcohol administration. Since progesterone is essential for the maintenance of pregnancy, alcohol’s attenuation of the expected progesterone response to hCG stimulation could increase the risk of spontaneous abortion. An alcohol-induced increase in estradiol after hCG administration could contribute to risk for fetal dysmorphology during the first trimester of pregnancy.

Maturitas. 1994 Aug;19(2):83-92.
Factors associated with onset of menopause in women aged 45-49.
Torgerson DJ, Avenell A, Russell IT, Reid DM.
This paper uses a cross-sectional sample of women aged 45-49 to investigate factors that might be associated with an early menopause. Using logistic regression analysis we found that age, smoking, age of maternal menopause, parity, social class, meat and alcohol consumption were all independently associated with an early natural menopause. Meat, alcohol consumption and maternal menopausal age do not seem to have been previously noted as associated with the timing of the menopause. These associations would merit further study, preferably using prospective data. However, this study in line with much previous work shows that smoking is associated with a reduction in menopausal age.

The Journal of Clinical Endocrinology & Metabolism June 1, 1988 vol. 66 no. 6 1181-1186
Alcohol Effects on Naltrexone-Induced Stimulation of Pituitary, Adrenal, and Gonadal Hormones During the Early Follicular Phase of the Menstrual Cycle*
SIEW KOON TEOH, JACK H. MENDELSON, NANCY K. MELLO and ALICJA SKUPNY
Chronic alcohol abuse in women is associated with severe derangements of menstrual cycle regularity. However, acute alcohol ingestion has no effect on pituitary-gonadal secretory function. The purpose of this study was to determine whether acute alcohol ingestion altered the effects of naltrexone, a long-acting opioid antagonist, on pituitary, adrenal, and gonadal hormones in normal women. Fourteen women were studied during the early follicular phase (between days 2 and 4) of their menstrual cycle. Plasma LH, PRL, estradiol, progesterone, and cortisol concentrations were measured before and after administration of 50 mg naltrexone, orally, and alcohol or placebo solution given 1 h after naltrexone, under double blind conditions. Naltrexone significantly increased mean plasma LH (P = 0.02), PRL (P = 0.003), E2 (P < 0.03), and cortisol (P < 0.001) levels. Alcohol significantly augmented the naltrexone-stimulated increases in plasma LH (P = 0.006), estradiol (P < 0.004), and cortisol (P < 0.001) levels and significantly decreased plasma progesterone levels (P = 0.001). Plasma PRL increased (P = 0.001) to the same extent after naltrexone and alcohol ingestion or naltrexone and placebo. We conclude that alcohol enhances naltrexone-induced increases in plasma gonadotropins and adrenal and gonadal steroid hormones in women during the early follicular phase of the menstrual cycle.

JNCI J Natl Cancer Inst (1993) 85 (9): 722-727.
Effects of Alcohol Consumption on Plasma and Urinary Hormone Concentrations in Premenopausal Women
Marsha E. Reichman, Joseph T. Judd, Christopher Longcope, Arthur Schatzkin, Beverly A. Clevidence, Padmanabhan P. Nair, William S. Campbell and Philip R. Taylor
Background: Most epidemiologic studies of the relationship between alcohol consumption and breast cancer risk over the past decade have shown that persons who consume a moderate amount of alcohol are at 40%-100% greater risk of breast cancer than those who do not consume alcohol. Dose-response effects have been observed, but no causal relationship has been established. Purpose: This study examines the hypothesis that alcohol consumption affects levels of reproductive hormones. Methods: A controlled-diet study lasting for six consecutive menstrual cycles was conducted. Participants were randomly assigned to two groups, and a crossover design was used. During the last three menstrual cycles, alcohol consumption of the two groups was reversed. Thirty-four premenopausal women, aged 21–40 years, with a history of regular menstrual cycles, consumed 30 g of ethanol (equivalent to approximately two average drinks) per day for three menstrual cycles and no alcohol for the other three. All food and alcohol consumed were provided by the study. Caloric intake was monitored to ensure that each woman would maintain body weight at approximately the baseline level. Hormone assays were performed on pooled plasma or 24-hour urine specimens collected during the follicular (days 5–7), peri-ovulatory (days 12–15), and mid-luteal (days 21–23) phases of the third menstrual cycle for subjects on each diet. Results: Alcohol consumption was associated with statistically significant increases in levels of several hormones. Plasma dehydroepiandrosterone sulfate levels were 7.0% higher in the follicular phase (P =.05). In the peri-ovulatory phase, there were increases of 21.2% (P =.01) in plasma estrone levels, 27.5% (P =.01) in plasma estradiol levels, and 31.9% (P =.009) in urinary estradiol levels. In the luteal phase, urinary estrone levels rose 15.2% (P =.05), estradiol levels increased 21.6% (P =.02), and estriol levels rose 29.1% (P =.03). No changes were found in the percent of bioavailable estradiol, defined by the sum of percent free estradiol and percent albumin-bound estradiol. However, increased total estradiol levels in the peri-ovulatory phase suggest elevated absolute amounts of bioavailable estradiol. Conclusion: This study has shown increases in total estrogen levels and amount of bioavailable estrogens in association with alcohol consumption in pre-menopausal women. Implication: This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation.

Alcohol Clin Exp Res. 1998 Aug;22(5):994-7.
Moderate alcohol consumption and estrogen levels in postmenopausal women: a review.
Purohit V.
This report reviews the literature to evaluate association between moderate alcohol consumption and estrogen levels in healthy postmenopausal women. Of the eight studies available in literature on postmenopausal women who were not on estrogen therapy, two analyzed urine samples and six analyzed blood samples for estrogen levels. Of the two urine sample studies, only one reported positive association (p < 0.05) between alcohol consumption and estrogen (estrone and estradiol) levels that increased by 16 to 20%. Of the six blood sample studies, only two–one in American women and one in European women–reported significant increases (p < 0.05) in estradiol levels in response to alcohol consumption. In the American women study, estradiol levels increased only with wine and not with beer or whiskey. In the European women study, estradiol levels increased in Danish and Portuguese women, but not in Spanish women. Thus, further studies are required to establish correlation between moderate alcohol consumption and estrogen levels in postmenopausal women. Of the two studies on postmenopausal women who were on estrogen replacement therapy, one administered estradiol through transdermal patch (0.15 mg) and one orally (1 mg/day). In both studies, blood estradiol levels were measured after administering a single dose of ethanol orally (0.7-0.75 g/kg of body weight). Estradiol levels were increased by 22 and 300% in the transdermal patch and oral studies, respectively. These results suggest that alcohol consumption may increase blood estradiol levels in postmenopausal women who are on estrogen replacement therapy, and this may increase the risk of breast cancer.

Breast Cancer Res Treat. 1997 Jul;44(3):235-41.
Associations of alcohol, height, and reproductive factors with serum hormone concentrations in postmenopausal Japanese women. Steroid hormones in Japanese postmenopausal women.
Nagata C, Kabuto M, Takatsuka N, Shimizu H.
We measured serum levels of estradiol (E2), sex hormone-binding globulin SHBG), progesterone, and dehydroepiandrosterone sulfate (DHEAS) in 61 postmenopausal women drawn from female residents in a community in Japan to evaluate the relationships between these hormone levels and potential breast cancer risk factors. The information on reproductive history, body size, alcohol use, and physical activity was obtained by means of a self-administered questionnaire. There was a significant trend in increasing E2 level with increasing height after taking account of age and body mass index (BMI) (p for trend = 0.04). BMI was inversely associated with SHBG level after controlling age (p for trend = 0.01). Decreasing progesterone with increasing BMI was observed after controlling age and history of hysterectomy (P = 0.05). Alcohol consumption was positively associated with E2 level and there was a strong linear trend after controlling for age, height, and BMI (p for trend = 0.001). Trend for increasing DHEAS with alcohol consumption was also statistically significant after controlling for age and history of hysterectomy (p for trend = 0.01). Reproductive factors as well as physical activity were not related to any of the hormone levels.

JAMA. 1996 Dec 4;276(21):1747-51.
Effects of Alcohol Ingestion on Estrogens in Postmenopausal Women
Elizabeth S. Ginsburg, MD; Nancy K. Mello, PhD; Jack H. Mendelson, MD; Robert L. Barbieri, MD; Siew Koon Teoh, MD; Micol Rothman; Xiaoying Gao, MD; J. Wallis Sholar
Objective. —To determine if moderate alcohol drinking increases circulating estradiol levels in postmenopausal women who are taking estrogen replacement.
Design. —Randomized, double-blind, placebo-controlled crossover study of the effects of alcohol ingestion on plasma estradiol and estrone.
Setting. —Inpatient Clinical Research Center.
Participants. —Twelve healthy postmenopausal women receiving oral estrogen (estradiol, 1 mg/day) and progestin (medroxyprogesterone acetate) replacement therapy were compared with 12 postmenopausal women who were not using estrogen replacement therapy (ERT).
Intervention. —Each group drank alcohol (0.7 g/kg) and an isoenergetic (isocaloric) placebo (randomized sequence) on consecutive days. Women who were taking ERT were studied during the estrogen-only portion of their replacement cycle, and estrogen was administered each evening at 2100 hours.
Main Outcome Measure. —The impact of alcohol ingestion on plasma estradiol and estrone levels.
Results. — Alcohol ingestion lead to a 3-fold increase in circulating estradiol in women on ERT; however, alcohol did not change estradiol significantly in control women who were not on ERT. In women using ERT, estradiol levels increased from 297 to 973 pmol/L (81 to 265 pg/mL) within 50 minutes (P<.001) during the ascending limb of the blood alcohol curve and remained significantly above baseline for 5 hours (P<.001). No significant increase in circulating estrone was detected in either group. However, estrone levels decreased after alcohol and placebo in women on ERT (P<.05). Blood alcohol levels did not differ significantly in women who used ERT and those who did not. Peak blood alcohol levels of 21 mmol/L were attained in each of the 2 groups within 50 to 60 minutes after drinking began. Changes in estradiol were significantly correlated with changes in blood alcohol levels on both the ascending (P<.001) and descending (P<.001) limb of the blood alcohol curve.
Conclusions. —Acute alcohol ingestion may lead to significant and sustained elevations in circulating estradiol to levels 300% higher than those targeted in clinical use of ERT. Potential health risks and benefits of the interactions between acute alcohol ingestion and ERT should be further evaluated.

BMJ 1998;317:505
Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy
Tina Kold Jensen, postdoctoral fellowa (tk.jensen@winsloew.ou.dk), Niels Henrik I Hjollund, physicianb, Tine Brink Henriksen, physicianc, Thomas Scheike, associate professor of biostatisticsd, Henrik Kolstad, physicianb, Aleksander Giwercman, physiciana, Erik Ernst, physicianc, Jens Peter Bonde, chief doctorb, Niels E Skakkebæk, professora, J⊘rn Olsen, professore
Objective : To examine the effect of alcohol consumption on the probability of conception.
Design : A follow up study over six menstrual cycles or until a clinically recognised pregnancy occurred after discontinuation of contraception.
Subjects : 430 Danish couples aged 20-35 years trying to conceive for the first time.
Main outcome measures : Clinically recognised pregnancy. Fecundability odds ratio: odds of conception among exposed couples divided by odds among those not exposed.
Results : In the six cycles of follow up 64% (179) of women with a weekly alcohol intake of less than five drinks and 55% (75) of women with a higher intake conceived. After adjustment for cycle number, smoking in either partner or smoking exposure in utero, centre of enrolment, diseases in female reproductive organs, woman’s body mass index, sperm concentration, and duration of menstrual cycle, the odds ratio decreased with increasing alcohol intake from 0.61 (95% confidence interval 0.40 to 0.93) among women consuming 1-5 drinks a week to 0.34 (0.22 to 0.52) among women consuming more than 10 drinks a week (P=0.03 for trend) compared with women with no alcohol intake. Among men no dose-response association was found after control for confounders including women’s alcohol intake.
Conclusion : A woman’s alcohol intake is associated with decreased fecundability even among women with a weekly alcohol intake corresponding to five or fewer drinks. This finding needs further corroboration, but it seems reasonable to encourage women to avoid intake of alcohol when they are trying to become pregnant.
Key messages
As alcohol consumption is widespread and increasing in many countries, even a minor effect on fertility is of public health interest
Some studies have found that women with high alcohol intake take longer to become pregnant, but none have found that moderate intake has an effect
The probability of conception in a menstrual cycle decreased with increasing alcohol intake in women, even among those drinking five or fewer drinks a week
Women who are trying to conceive should be encouraged to avoid intake of alcohol

Am J Public Health. 1994 Sep;84(9):1429-32.
Infertility in women and moderate alcohol use.
Grodstein F, Goldman MB, Cramer DW.
OBJECTIVE:
The purpose of this study was to investigate the relationship between moderate alcohol intake and fertility.
METHODS:
Interviews were conducted with 3833 women who recently gave birth and 1050 women from seven infertility clinics. The case subjects were categorized based on the infertility specialist’s assignment of the most likely cause of infertility: ovulatory factor, tubal disease, cervical factor, endometriosis, or idiopathy. Separate logistic regression models were used to assess the relationship between alcohol use and each type of infertility, adjusted for age, infertility center, cigarette smoking, caffeine use, number of sexual partners, use of an intrauterine device (for tubal disease), and body mass index and exercise (for ovulatory factor).
RESULTS:
We found an increase in infertility, due to ovulatory factor or endometriosis, with alcohol use. The odds ratio for ovulatory factor was 1.3 (95% confidence interval [CI] = 1.0, 1.7) for moderate drinkers and 1.6 (95% CI = 1.1, 2.3) for heavier drinkers, compared with nondrinkers. The risk of endometriosis was roughly 50% higher in case subjects with any alcohol intake than in control subjects (OR = 1.6, 95% CI = 1.1, 2.3, at moderate levels; OR = 1.5, 95% CI = 0.8, 2.7, at heavier levels).
CONCLUSIONS:
Moderate alcohol use may contribute to the risk of specific types of infertility.

JNCI J Natl Cancer Inst (1995) 87 (17): 1297-1302.
Alcohol, Height, and Adiposity in Relation to Estrogen and Prolactin Levels in Postmenopausal Women
Susan E. Hankinson*, Walter C. Willett, JoAnn E. Manson, David J. Hunter, Graham A. Colditz, Meir J. Stampfer, Christopher Longcope and Frank E. Speizer
Background: Alcohol use, height, and postmenopausal adiposity have each been positively associated with postmenopausal breast cancer risk in most epidemiologic studies. The mechanism underlying these associations is unclear, although an effect of these factors on hormone levels has been hypothesized. Few previous studies have evaluated the relationship of either alcohol consumption or height with plasma hormone levels. A positive association between adiposity and plasma estrogen levels in postmenopausal women has been reported consistently. Purpose: Using archived frozen plasma samples and corresponding data from participants in the Nurses’ Health Study, we determined plasma hormone levels and assessed these levels in relation to alcohol consumption, height, and adiposity among postmenopausal women. Methods: Blood samples were collected from a subset of participants in the Nurses’ Health Study in 1989 and 1990, then stored in liquid nitrogen. Hormone concentrations in 217 archived plasma samples (from healthy postmenopausal women) were analyzed in 1993. Spearman correlation coefficients were calculated to assess the linear association between alcohol consumption during the previous year (mean daily intake in grams per day ascertained from semiquantitative food-frequency questionnaires completed in 1990 or 1991), height, and adiposity (as measured by body mass index [BMI] in kg/m2, with weight reported at time of blood collection), and plasma hormone levels. Two-sided P values were also calculated. Results: After controlling for age, height, smoking status, and BMI, alcohol consumption was positively associated with estrone sulfate concentrations (r =.17; P =.02); no statistically significant association was noted for the other plasma hormones measured. Mean plasma estrone sulfate levels were 159 pg/mL in women who reported no alcohol use versus 211 pg/mL in women consuming 30 g or more of alcohol per day. After adjusting for the other covariates, we observed a strong positive correlation between BMI and plasma estrogens (r ranging from.37 for estrone and estrone sulfate to.63 for bioavailable estradiol, with all P values <.01; prolactin was the only hormone unassociated with BMI, r =.01). Height was unrelated to either plasma estrogens or prolactin. Conclusions: BMI and alcohol use were positively associated with postmenopausal plasma estrogen and estrone sulfate levels, respectively. Implications: The association of alcohol consumption and postmenopausal obesity with subsequent breast cancer risk might be mediated, at least in part, through an influence on postmenopausal plasa estrogen levels. Additional studies are needed to further quantify the relationship between alcohol consumption and plasma hormone levels and to elucidate the physiologic basis for this association.

Fertil Steril. 1998 Oct;70(4):632-7.
Alcohol and caffeine consumption and decreased fertility.
Hakim RB, Gray RH, Zacur H.
OBJECTIVE:
To examine the effects of alcohol and caffeine on conception.
DESIGN:
Prospective observational study.
SETTING:
Healthy volunteers in two manufacturing facilities.
PATIENT(S):
One hundred twenty-four women who provided daily urine samples for measurement of steroid hormones and hCG, and prospective information about alcohol and caffeine consumption.
MAIN OUTCOME MEASURE(S):
Probability of conception per 100 menstrual cycles.
RESULT(S):
There was >50% reduction in the probability of conception during a menstrual cycle during which participants consumed alcohol. Caffeine consumption did not independently affect the probability of conception but may enhance alcohol’s negative effect. Women who abstained from alcohol and consumed less than one cup of coffee or its equivalent per day conceived 26.9 pregnancies per 100 menstrual cycles compared with 10.5 per 100 menstrual cycles among those who consumed any alcohol and more than one cup of coffee per day.
CONCLUSIONS:
This study revealed an independent dose-related negative effect of alcohol consumption on the ability to conceive. Our results suggest that women who are attempting to conceive should abstain from consuming alcohol.

Am J Physiol Gastrointest Liver Physiol. 2001 Dec;281(6):G1348-56.
Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines.
Nanji AA, Jokelainen K, Fotouhinia M, Rahemtulla A, Thomas P, Tipoe GL, Su GL, Dannenberg AJ.
Alcoholic liver injury is more severe and rapidly developing in women than men. To evaluate the reason(s) for these gender-related differences, we determined whether pathogenic mechanisms important in alcoholic liver injury in male rats were further upregulated in female rats. Male and age-matched female rats (7/group) were fed ethanol and a diet containing fish oil for 4 wk by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. We analyzed liver histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-kappa B (NF-kappa B) activation, and mRNA levels of cyclooxygenase-1 (COX-1) and COX-2, tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). Alcohol-induced liver injury was more severe in female vs. male rats. Female rats had higher endotoxin, lipid peroxidation, and nonheme iron levels and increased NF-kappa B activation and upregulation of the chemokines MCP-1 and MIP-2. CYP2E1 activity and TNF-alpha and COX-2 levels were similar in male and female rats. Remarkably, female rats fed fish oil and dextrose also showed necrosis and inflammation. Our findings in ethanol-fed rats suggest that increased endotoxemia and lipid peroxidation in females stimulate NF-kappa B activation and chemokine production, enhancing liver injury. TNF-alpha and COX-2 upregulation are probably important in causing liver injury but do not explain gender-related differences.

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Feminization of men:

Proc Soc Exp Biol Med. 1995 Jan;208(1):98-102.
The phytoestrogen congeners of alcoholic beverages: current status.
Gavaler JS, Rosenblum ER, Deal SR, Bowie BT.
The idea that alcoholic beverages might contain biologically active phytoestrogenic congeners stemmed from findings of overt feminization observed in alcoholic men with alcohol-induced cirrhosis. Specifically, in addition to being hypogonadal, these chronically alcohol-abusing men with cirrhosis frequently manifest gynecomastia, palmar erythema, spider angiomata, and a female escutcheon. These physical signs of exposure to active estrogen occur in the presence of normal or only minimally elevated levels of endogenous steroid estrogens. Because levels of circulating steroid hormones failed to provide a satisfactory explanation for the feminization observed, alternate explanations were considered. If the estrogenization observed was not entirely a function of tissue expose to steroid estrogens produced endogenously, then perhaps tissues were being exposed to exogenous estrogenic substances from dietary sources. Given the degree of alcohol abuse in the population in which hypotheses for feminization were being formed, alcoholic beverages became a prime candidate as a dietary source of exogenous estrogenic substances.