Differences in cardiac geometry in relation to body size among neonates with abnormal prenatal growth and body size at birth.

OBJECTIVES: Both excessive and restricted fetal growth are associated with changes in cardiac geometry and function at birth. There are significant issues when indexing cardiac parameters for body size in the neonatal period. The aims of this study were to determine to what extent cardiac geometry is dependent on body size in term and preterm neonates with restricted or excessive fetal growth and how this is affected by adiposity. METHODS: This was a cross-sectional study of neonates born between 31 and 42 weeks of gestation, divided into three groups: (1) small-for-gestational age (SGA, birth weight > 2 SD below the mean); (2) large-for-gestational age (LGA, birth weight > 2 SD above the mean); and (3) appropriate-for-gestational-age controls (AGA, birth weight ≤ 2 SD from the mean). Cardiac geometry and function were compared between the study groups, adjusting for body size. The potential impact of infant adiposity and maternal disease was assessed. RESULTS: In total, 174 neonates were included, of which 39 were SGA, 45 were LGA and 90 were AGA. Body size was reflected in cardiac dimensions, with differences in cardiac dimensions disappearing between the SGA and AGA groups when indexed for body surface area (BSA) or thoracic circumference. The same was true for the differences in atrial and ventricular areas between the LGA and AGA groups. However, left ventricular inflow and outflow tract dimensions did not follow this trend as, when indexed for BSA, they were associated negatively with adiposity, resulting in diminished dimensions in LGA compared with AGA and SGA neonates. Adiposity was associated positively with left ventricular mass, right ventricular length and area and right atrial area. The SGA group showed increased right ventricular fractional area change, possibly reflecting differences in the systolic function of the right ventricle. We found evidence of altered diastolic function between the groups, with the mitral valve inflow E- to lateral E'-wave peak velocity ratio being increased in the LGA group and decreased in the SGA group. CONCLUSIONS: Cardiac geometry is explained by body size in both term and preterm AGA and SGA infants. However, the nature of the relationship between body size and cardiac dimensions may be influenced by adiposity in LGA infants, leading to underestimation of left ventricular inflow and outflow tract dimensions when adjusted for BSA. Adjustments for thoracic circumference provide similar results to those for BSA. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Transgenerational effects of maternal obesity and gestational diabetes on offspring body composition and left ventricle mass: the Finnish Gestational Diabetes Prevention Study (RADIEL) 6-year follow-up.

AIM: To investigate the influence of maternal adiposity and gestational diabetes on offspring body composition and left ventricle mass in early childhood. METHODS: The observational follow-up study included 201 mother-child pairs, a sub-cohort from the Finnish Gestational Diabetes Prevention Study, who were recruited 6.1 ± 0.5 (mean ± SD) years postpartum, aiming for an equal number of mothers with and without gestational diabetes. RESULTS: Maternal pre-pregnancy BMI (mean ± SD; 30.5 ± 5.6 kg/m2 ) was associated with child body fat percentage [0.26 (95% CI; 0.08, 0.44)% increase in child body fat per 1 kg/m2 increase in pre-pregnancy BMI of mothers with obesity] and was reflected in child BMI Z-score (mean ± SD; 0.45 ± 0.93). Left ventricle mass, left ventricle mass index and left ventricle mass Z-score were not associated with gestational diabetes, pre-pregnancy BMI or child body fat percentage. After adjusting for child sex, body fat percentage, systolic blood pressure, pre-pregnancy BMI and maternal lean body mass, left ventricle mass increased by 3.08 (95% CI; 2.25, 3.91) g for each 1 kg in child lean body mass. CONCLUSIONS: Left ventricle mass at 6 years of age is determined predominantly by lean body mass. Maternal pre-gestational adiposity is reflected in child, but no direct association between left ventricle mass and child adiposity or evidence of left ventricle mass foetal programming related to gestational diabetes and maternal adiposity was observed in early childhood.

The implementation of a nationwide anomaly screening programme improves prenatal detection of major cardiac defects: an 11-year national population-based cohort study.

OBJECTIVE: To evaluate whether a nationwide prenatal anomaly screening programme improves detection rates of univentricular heart (UVH) and transposition of great arteries (TGA), and whether maternal risk factors for severe fetal heart disease affect prenatal detection. DESIGN: Population-based cohort study. SETTING: Nationwide data from Finnish registries 2004-14. POPULATION: A total of 642 456 parturients and 3449 terminated pregnancies due to severe fetal anomaly. METHODS: Prenatal detection rates were calculated in three time periods (prescreening, transition and screening phase). The effect of maternal risk factors (obesity, in vitro fertilisation, pregestational diabetes and smoking) was evaluated. MAIN OUTCOME MEASURES: Change in detection rates and impact of maternal risk factors on screening programme efficacy. RESULTS: In total, 483 cases of UVH and 184 of TGA were detected. The prenatal detection rate of UVH increased from 50.4% to 82.8% and of TGA from 12.3% to 41.0% (P < 0.0001). Maternal risk factors did not affect prenatal detection rate, but detection rate differed substantially by region. CONCLUSIONS: A nationwide screening programme improved overall UVH and TGA detection rates, but regional differences were observed. Obesity or other maternal risk factors did not affect the screening programme efficacy. The establishment of structured guidelines and recommendations is essential when implementing the screening programme. In addition, a prospective screening register is highly recommended to ensure high quality of screening. TWEETABLE ABSTRACT: Implementation of a nationwide prenatal anomaly screening improved detection rates of UVH and TGA.

Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study.

OBJECTIVE: Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not. METHODS: This was a retrospective multicenter study of fetuses with aortic stenosis that underwent FV between 2005 and 2012, compared with contemporaneously enrolled natural history (NH) cases sharing similar characteristics at presentation but not undergoing FV. Main outcome measures were overall survival, BV-circulation survival and survival after birth. Secondary outcomes were hemodynamic change and left heart growth. A propensity score model was created including 54/67 FV and 60/147 NH fetuses. Analyses were performed using logistic, Cox or linear regression models with inverse probability of treatment weighting (IPTW) restricted to fetuses with a propensity score of 0.14-0.9, to create a final cohort for analysis of 42 FV and 29 NH cases. RESULTS: FV was technically successful in 59/67 fetuses at a median age of 26 (21-34) weeks. There were 7/72 (10%) procedure-related losses, and 22/53 (42%) FV babies were delivered at < 37 weeks. IPTW demonstrated improved survival of liveborn infants following FV (hazard ratio, 0.38; 95% CI, 0.23-0.64; P = 0.0001), after adjusting for circulation and postnatal surgical center. Similar proportions had BV circulation (36% for the FV cohort and 38% for the NH cohort) and survival was similar between final circulations. Successful FV cases showed improved hemodynamic response and less deterioration of left heart growth compared with NH cases (P ≤ 0.01). CONCLUSIONS: We report improvements in fetal hemodynamics and preservation of left heart growth following successful FV compared with NH. While the proportion of those achieving a BV circulation outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation to 10 years' follow-up. However, FV is associated with a 10% procedure-related loss and increased prematurity compared with the NH cohort, and therefore the risk-to-benefit ratio remains uncertain. We recommend a carefully designed trial incorporating appropriate and integrated fetal and postnatal management strategies to account for center-specific practices, so that the benefits achieved by fetal therapy vs surgical strategy can be demonstrated clearly. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Clinical and biological markers of premature aging after autologous SCT in childhood cancer.

The aim of this study was to analyze the prevalence of frailty and physical health limitations among long-term survivors of high-risk neuroblastoma (HR NBL) and to investigate whether frail health is associated with variables of cardiovascular function, markers of inflammation and telomere length. A national study cohort of 19 (median age 22, range 16-30 years) long-term (>10 years) HR NBL survivors was studied and the findings were compared with 20 age- and sex-matched controls. Frailty was defined as ⩾3 of the following conditions: low muscle mass, low energy expenditure, slow running and weakness. The prevalence of frailty was significantly higher among the HR NBL survivors 9/19 (47%) than among the controls (0%). Thirteen (68%) of the survivors reported significant physical health limitations in vigorous activities, as opposed to none of the controls. The HR NBL survivors had significantly shorter telomere length and higher serum levels of high sensitivity C-reactive protein than did the controls. Frail health and poor physical functioning are prevalent among HR NBL survivors and suggest premature aging. Survivors with gonadal damage, very low fat mass percentage, low glycosylated hemoglobin A1c and increased common carotid artery intima-media thickness may be more prone to early aging after high dose therapy.

Natural history of 107 cases of fetal aortic stenosis from a European multicenter retrospective study.

OBJECTIVES: Fetal aortic valvuloplasty (FV) aims to prevent fetal aortic valve stenosis progressing into hypoplastic left heart syndrome (HLHS), which results in postnatal univentricular (UV) circulation. Despite increasing numbers of FVs performed worldwide, the natural history of the disease in fetal life remains poorly defined. The primary aim of this study was to describe the natural history of fetal aortic stenosis, and a secondary aim was to test previously published criteria designed to identify cases of emerging HLHS with the potential for a biventricular (BV) outcome after FV. METHODS: From a European multicenter retrospective study of 214 fetuses with aortic stenosis (2005-2012), 107 fetuses in ongoing pregnancies that did not undergo FV were included in this study and their natural history was reported. We examined longitudinal changes in Z-scores of aortic and mitral valve and left ventricular dimensions and documented direction of flow across the foramen ovale and aortic arch, and mitral valve inflow pattern and any gestational changes. Data were used to identify fetuses satisfying the Boston criteria for emerging HLHS and estimate the proportion of these that would have been ideal FV candidates. We applied the threshold score whereby a score of 1 was assigned to fetuses for each Z-score meeting the following criteria: left ventricular length and width > 0; mitral valve diameter > -2; aortic valve diameter > -3.5; and pressure gradient across either the mitral or aortic valve > 20 mmHg. We compared the predicted circulation with known survival and final postnatal circulation (BV, UV or conversion from BV to UV). RESULTS: Among the 107 ongoing pregnancies there were eight spontaneous fetal deaths and 99 livebirths. Five were lost to follow-up, five had comfort care and four had mild aortic stenosis not requiring intervention. There was intention-to-treat in these 85 newborns but five died prior to surgery, before circulation could be determined, and thus 80 underwent postnatal procedures with 44 BV, 29 UV and seven BV-to-UV circulatory outcomes. Of newborns with intention-to-treat, 69/85 (81%) survived ≥ 30 days. Survival at median 6 years was superior in cases with BV circulation (P = 0.041). Those with a postnatal UV circulation showed a trend towards smaller aortic valve diameters at first scan than did the BV cohort (P = 0.076), but aortic valve growth velocities were similar in both cohorts to term. In contrast, the mitral valve diameter was significantly smaller at first scan in those with postnatal UV outcomes (P = 0.004) and its growth velocity (P = 0.008), in common with the left ventricular inlet length (P = 0.004) and width (P = 0.002), were reduced significantly by term in fetuses with UV compared with BV outcome. Fetal data, recorded before 30 completed gestational weeks, from 70 treated neonates were evaluated to identify emerging HLHS. Forty-four had moderate or severe left ventricular depression and 38 of these had retrograde flow in the aortic arch and two had left-to-right flow at atrial level and reversed a-waves in the pulmonary veins. Thus 40 neonates met the criteria for emerging HLHS and BV circulation was documented in 13 (33%). Of these 40 cases, 12 (30%) had a threshold score of 4 or 5, of which five (42%) had BV circulation without fetal intervention. CONCLUSIONS: The natural history in our cohort of fetuses with aortic stenosis and known outcomes shows that a substantial proportion of fetuses meeting the criteria for emerging HLHS, with or without favorable selection criteria for FV, had a sustained BV circulation without fetal intervention. This indicates that further work is needed to refine the selection criteria to offer appropriate therapy to fetuses with aortic stenosis. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Alcohol intake, androgen and glucocorticoid steroids in premenopausal women using oral contraceptives: an interventional study.

Long-term heavy alcohol intake is associated with endocrinological abnormalities the mechanisms of which are still unclear. The objective of the present study was to investigate the effect of alcohol intake on plasma and urine glucocorticoid and androgen steroid levels in healthy premenopausal women using oral contraceptives. In a placebo-controlled interventional study with a cross-over design including nine premenopausal women using oral contraceptives no effect of tolerance was observed with regard to the magnitude of the acute transient alcohol-induced testosterone elevation after a 1-week alcohol drinking period (0.8 g/kg per day). At non-intoxicated time points elevated plasma testosterone and androstenedione levels were found in the afternoon but not in the morning during the alcohol drinking period compared with placebo. An increase in plasma cortisol levels was observed after the discontinuation of alcohol drinking. No effects were observed in total glucocorticoid conjugates in morning urine spot samples. An increase during the alcohol period relative to placebo was, however, observed in the urine etiocholanolone/androsterone, tetrahydrocortisol/allotetrahydrocortisol as well as the 20-hydroxy-/20-ketosteroid ratios. No consistent effect was observed in the urine (tetrahydrocortisol+allotetrahydrocortisol)/tetrahydrocortisone ratio. It is suggested that the alcohol-induced alterations in plasma glucocorticoid and androgen levels during non-intoxicated conditions are due to a change in the hypothalamic-pituitary-adrenal function. The effects observed in the conjugated urine glucocorticoid and androgen ratios are likely to be mediated by a change in the metabolism of these steroids in the liver. The present results may be of relevance in the development of disturbances in the glucocorticoid as well as sex steroid balance among heavy female drinkers.

Functional relevance of human adh polymorphism.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were C. J. Peter Eriksson and Tatsushige Fukunaga. The presentations were (1) 4-Methylpyrazole as a tool in the investigation of the role of ADH in the actions of alcohol in humans, by Taisto Sarkola and C. J. Peter Eriksson; (2) ADH2 polymorphism and flushing in Asian populations, by Wei J. Chen, C. C. Chen, J. M. Ju, and Andrew T. A. Cheng; (3) Role of ADH3 genotypes in the acute effects of alcohol in a Finnish population, by Hidetaka Yamamoto, Kathrin Kohlenberg-Müller, and C. J. Peter Eriksson; (4) Clinical characteristics and disease course of alcoholics with different ADH2 genotypes, by Mitsuru Kimura, Masanobu Murayama, Sachio Matsushita, Haruo Kashima, and Susumu Higuchi; (5) ADH2 polymorphism, alcohol drinking, and birth defects, by Lucinda Carr, D. Viljoen, L. Brooke, T. Stewart, T. Foroud, J. Su, and Ting-Kai Li; and (6) ADH genotypes and alcohol use in Europeans, by John B. Whitfield.

The role of the liver in the acute effect of alcohol on androgens in women.

The hypothalamic-pituitary-gonadal and -adrenal axes are regarded as the main sites of the actions of alcohol on steroids. In the present study the effect of alcohol (0.4-0.5 g/kg, orally) on venous plasma and urinary androgens was investigated in 21 premenopausal women using oral contraceptives as well as in 10 premenopausal nonusers. After intake of alcohol, an acute elevation in plasma testosterone, a decline in androstenedione levels, and an elevation in the ratio of testosterone to androstenedione were observed in both groups. The effects lasted throughout the period of ethanol elimination and were abolished during pretreatment with 4-methylpyrazole (10-15 mg/kg, orally). The acute effects were higher in the group using oral contraceptives than in the nonusers. The testosterone effect in plasma was reflected in the free testosterone fraction. A decline in urinary androsterone and etiocholanolone levels, the principal catabolic products of androgens, was observed during alcohol intoxication. In conclusion, the present acute effects on plasma and urinary steroid hormones seem to be explained by an inhibited catabolism mediated by the alcohol-induced change in the redox state in the liver. Our results suggests that the liver should be included as a major site in the acute endocrinological effects of alcohol on steroid hormones in women.

Effect of 4-methylpyrazole on endogenous plasma ethanol and methanol levels in humans.

BACKGROUND: Endogenous methanol and ethanol levels are found in human blood. It is assumed that these compounds are derived mainly from microflora in the gastrointestinal tract and that the small amounts formed are consequently eliminated, mainly in the liver, by the alcohol dehydrogenase (ADH) pathway. The objective of the present study was to investigate the effect of 4-methylpyrazole (4-MP), a specific ADH inhibitor, on endogenous plasma methanol and ethanol levels in healthy women and men. METHODS: A double-blind placebo-controlled interventional study was carried out. RESULTS: A significant elevation in plasma endogenous ethanol and methanol levels was observed after intake of 4-MP (10-15 mg/kg p.o.). For methanol levels, a linear increase from 20 +/- 14 micromol/l before intake to 39 +/- 22 micromol/l at 420 min from intake of 4-MP (levels 20 +/- 14 micromol/l and 14 +/- 9 micromol/l during the corresponding placebo time points) was found. For ethanol, concentrations increased from levels below detection limit (i.e., < 5 micromol/l, determined by headspace gas chromatography) before intake to 30 +/- 20 micromol/l at 195 min from intake of 4-MP. A small increase in ethanol levels, to 13 +/- 8 micromol/l, but not in methanol levels, was observed after the intake of lingonberry juice containing no ethanol or methanol. No sex differences in the ethanol and methanol levels before or after the intake of 4-MP were found. CONCLUSIONS: The present study provides conclusive evidence for a constant endogenous production as well as clearance of ethanol and methanol in humans. In addition, the study shows that the ethanol and methanol produced are, at least in part, eliminated by the ADH pathway.

Lack of effect of alcohol on ethinylestradiol in premenopausal women.

An acute elevation in estradiol during alcohol intake has been reported in postmenopausal women on estrogen replacement therapy. The objective of the present study was to investigate the acute and long-term effect of alcohol on ethinylestradiol, the estrogen component found in most oral contraceptives. Nine healthy premenopausal women with regular use of an oral contraceptive containing 30 microg ethinylestradiol and 75 microg gestodene were challenged with alcohol (0.4 g/kg p.o., approximately 2-3 standard drinks) 2 h after intake of the oral contraceptive pill at menstrual cycle day 14. Blood samples were taken at 0, 2, 3, 4, 5, and 6 h from intake of alcohol. The challenge was repeated after a 7-day period of controlled alcohol intake (0.8 g/kg/day) at cycle day 21. The same experiments were carried out during placebo conditions. At day 21 an increase in the alcohol elimination rate was observed compared with day 14. No significant acute or long-term effect of alcohol on ethinylestradiol was found. The lack of an acute effect comparable to that reported for estradiol may be due to the protection of the ethinyl group at the 17-position of ethinylestradiol.

Mean cell volume and gamma-glutamyl transferase are superior to carbohydrate-deficient transferrin and hemoglobin-acetaldehyde adducts in the follow-up of pregnant women with alcohol abuse.

BACKGROUND AND OBJECTIVE: To compare the usefulness of carbohydrate-deficient transferrin (CDT), the ratio of CDT to total transferrin, and hemoglobin-acetaldehyde adducts with mean cell volume (MCV) and gamma-glutamyl transferase (GGT) in the follow-up of alcohol abuse during pregnancy. METHODS: Forty-four pregnant drug and alcohol abusing female patients attending a special outpatient clinic were followed from the 8th to 24th gestational week onwards. A population of sixty-two healthy pregnant women was recruited to assess the effect of gestation on the markers. RESULTS: Eight of thirteen heavy drinking (> or =8 drinks/week) patients delivered infants with fetal alcohol effects (FAE). MCV and GGT were higher among heavy drinking patients than in moderately drinking (<8 drinks/week) patients (92+/-4 vs 90+/-3 fl and 31+/-34 vs 16+/-10 U/ L, respectively), and in patients delivering infants with FAE compared with patients delivering healthy infants (95+/-3 vs 90+/-3 fl and 34+/-26 vs 15+/-10 U/L, respectively). Hemoglobin-acetaldehyde adducts, CDT, and the ratio of CDT to total transferrin were neither associated with the reported level of alcohol consumption nor with the occurrence of FAE. In the receiver operating characteristics analysis MCV was found to be superior to CDT and the adducts, and GGT superior to the adducts, in identifying heavy drinking and in predicting FAE. In the control population, both CDT and total transferrin were found to rise during pregnancy, whereas the ratio of CDT to total transferrin was found to decline. The upper reference range of 33 U/L for CDT was considerably higher than that of non-pregnant women (26 U/L). CONCLUSION: MCV and GGT appear to be the most efficient laboratory markers for detecting excessive alcohol consumption and the adverse effects of alcohol on the fetus.

Acute effect of alcohol on androgens in premenopausal women.

The aim of the present study was to investigate the effect of alcohol on androgen levels among premenopausal women. Eighty-seven women in the mid-cycle phase of the menstrual cycle, 47 of whom used oral contraceptives (OC+), were included in the study. The range for reported alcohol consumption was 0-4 drinks/day. The total testosterone levels were significantly higher after alcohol intake (0.5 g/kg) than after placebo at 45 min and 90 min from the start of drinking among both OC- and OC+ subjects. This effect was also seen in the free testosterone fraction. The effect on testosterone was more prominent among OC+ subjects. Androstenedione levels were significantly lowered and the testosterone:androstenedione ratio significantly elevated by alcohol among both OC- and OC+ subjects. No effect of alcohol on dehydroepiandrosterone or dihydrotestosterone levels was observed. A positive correlation was observed between the change in testosterone levels and the change in androstenedione levels during placebo conditions. The correlation was significantly reduced during alcohol conditions among OC+ subjects, indicating an increased androstenedione to testosterone conversion. No significant dose (0.34, 0.68 and 1.02 g/kg) or time (45, 90 and 150 min) effects on total testosterone were observed in a substudy involving 10 OC+ subjects. The present results suggest that the testosterone effect is related to the zero-order mechanism of ethanol oxidation. The observed testosterone and androstenedione effects are suggested to be the result of an increased androstenedione to testosterone conversion in the liver caused by the alcohol-mediated elevation in the [NADH]:[NAD(+)] ratio. The present findings may be relevant in the development of hyperandrogenism and loss of female sexual characteristics associated with heavy alcohol consumption.

Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol, and luteinizing hormone in premenopausal women.

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.

Estrogen-related acetaldehyde elevation in women during alcohol intoxication.

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.