human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 r and omly 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 dehydroepi and rosterone 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 premenopausal women . IMPLICATION This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation 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 sub study 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 , result ing 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 The reproducibility and validity of self-reported menopausal status were evaluated among the 121,700 female US registered nurses aged 30 - 55 years in 1976 who are participants in the Nurses ' Health Study , a prospect i ve cohort study of diseases in women . When question ed in 1978 , 6,591 of the women who were premenopausal in 1976 reported that their menses had ceased and provided their age at menopause . Two years later , in 1980 , 98.8 per cent of the 6,591 women again reported that they were postmenopausal and again gave the reasons for menopause ( natural or surgical ) . Among those women who reported surgical menopause during the 1976 - 1978 follow-up interval , age at menopause was reported to within one year on both the 1978 and 1980 question naires by 95 per cent of women . Among those reporting natural menopause during the 1976 - 1978 period , 82 per cent of women reported their age at menopause to within one year on the two follow-up question naires . A r and om sample of 255 women reporting surgical menopause between 1982 and 1984 was identified and medical records were obtained for 200 . For all but two women , there was complete agreement between self-report and medical record for details of hysterectomy and extent of ovarian surgery . The reproducibility of self-reported age at menopause was assessed among 31,405 women who were menopausal in 1976 . Reported age at menopause on consecutive question naires showed increasing within-person variance with increasing duration since menopause . ( ABSTRACT TRUNCATED AT 250 WORDS Plasma luteinizing hormone ( LH ) , estradiol , prolactin and progesterone levels were measured in nine normal adult women prior to and following administration of naloxone and oral ingestion of ethanol or placebo-control solution .  Each subject served as her own control in a double-blind study carried out during the midluteal phase of the menstrual cycle . The mean ( + /- SD ) progesterone level was 13.9 + /- 1.3 during control conditions and 13.9 + /- 1.7 during alcohol conditions . The mean peak blood alcohol level was 100 + /- 13 mg/dl within 45 - 60 min after initiation of drinking . Under placebo-control conditions , naloxone stimulated a significant increase in plasma LH and prolactin but did not increase estradiol or progesterone . Alcohol did not attenuate the significant naloxone stimulation of LH , and progesterone levels were equivalent under alcohol and control conditions . Alcohol significantly enhanced naloxone stimulation of prolactin and estradiol . Alcohol administration significantly augmented the naloxone-induced increase in plasma prolactin levels . After alcohol administration , naloxone also induced a significant increase in plasma estradiol levels , which was sustained throughout the 180-min sampling period . The mechanisms underlying alcohol 's enhancement of naloxone-stimulated prolactin and estradiol remain to be determined . The alcohol-related increase in naloxone-stimulated prolactin secretion may reflect increased hypothalamic and /or pituitary sensitivity to alcohol following endogenous opioid blockade by naloxone or an effect of increased estrogen levels . The significant increase in plasma estradiol levels following concurrent naloxone and alcohol administration may occur as a consequence of alterations in steroid biotransformation associated with intrahepatic ethanol catabolism Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study . Design Combination of prospect i ve cohort study with representative population based data on alcohol exposure . Setting Eight countries ( France , Italy , Spain , United Kingdom , the Netherl and s , Greece , Germany , Denmark ) participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Participants 109 118 men and 254 870 women , mainly aged 37 - 70 . Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants . Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex . Partial alcohol attributable fractions for consumption higher than the recommended upper limit ( two drinks a day for men with about 24 g alcohol , one for women with about 12 g alcohol ) and the estimated total annual number of cases of alcohol attributable cancer . Results If we assume causality , among men and women , 10 % ( 95 % confidence interval 7 to 13 % ) and 3 % ( 1 to 5 % ) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries . For selected cancers the figures were 44 % ( 31 to 56 % ) and 25 % ( 5 to 46 % ) for upper aerodigestive tract , 33 % ( 11 to 54 % ) and 18 % ( −3 to 38 % ) for liver , 17 % ( 10 to 25 % ) and 4 % ( −1 to 10 % ) for colorectal cancer for men and women , respectively , and 5.0 % ( 2 to 8 % ) for female breast cancer . A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit : 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women . Conclusions In western Europe , an important proportion of cases of cancer can be attributable to alcohol consumption , especially consumption higher than the recommended upper limits . These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer BACKGROUND Growth hormone (GH)-insulin-like growth factor-1 ( IGF-1 ) axis and gonadal hormones demonstrate extensively associated regulation ; however , little is known about the effects of acute alcohol exposure on these hormones . This study examined the effects of intravenous alcohol on the GH-IGF-1 axis and gonadal hormone concentrations , and the influence of age and sex on their regulation . METHODS Forty-eight healthy volunteers ( 24 men and 24 women each in the 21 to 25 and 55 to 65 year age groups ) underwent a 2-session single-blinded study . Subjects received in r and omized counter-balanced order , alcohol infusions , individually computed based on a physiologically based pharmacokinetic model , to maintain a steady-state ( " clamped " ) exposure of 50 mg% or saline for 3 hours in separate sessions . Blood sample s collected at baseline and postinfusion in each session were assayed for levels of GH , IGF-1 , free testosterone , and estradiol . RESULTS Acute alcohol administration result ed in changes in gonadal hormones that differed by sex . Change in free testosterone showed a significant treatment × baseline interaction ( p < 0.001 ) , indicating that alcohol-induced suppression of testosterone occurred predominantly in men . On the other h and , change in estradiol showed a significant treatment × sex interaction ( p = 0.028 ) , indicating that alcohol-induced increases in estradiol occurred predominantly in women . There was a trend for alcohol-induced decreases in IGF-1 levels . Change in GH showed a significant main effect of baseline ( p < 0.001 ) and a trend for treatment by baseline interaction , suggesting an alcohol-induced decrease in individuals with high baseline GH values . There was also a significant main effect of sex ( p = 0.046 ) indicating that men had greater changes in GH across treatment compared with women . CONCLUSIONS Alcohol induced a complex pattern of hormonal responses that varied between younger and older men and women . Some of the observed sex-based differences may help improve our underst and ing of the greater susceptibility to alcohol-related hepatic damage seen in women OBJECTIVES The aim of the study was to explore the influence of reproductive and dietary factors on the age at menopause . METHODS During follow-up of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort in Heidelberg ( median duration 5.8 years ) , 1009 women 
    Output:
    
agent
WIDER IMPLICATION S The findings of this review indicate that alcohol consumption , particularly low and moderate alcohol intake , might be associated with later onset of menopause although the magnitude of the association is low .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 r and omly 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 dehydroepi and rosterone 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 premenopausal women . IMPLICATION This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation 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 sub study 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 , result ing 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 The reproducibility and validity of self-reported menopausal status were evaluated among the 121,700 female US registered nurses aged 30 - 55 years in 1976 who are participants in the Nurses ' Health Study , a prospect i ve cohort study of diseases in women . When question ed in 1978 , 6,591 of the women who were premenopausal in 1976 reported that their menses had ceased and provided their age at menopause . Two years later , in 1980 , 98.8 per cent of the 6,591 women again reported that they were postmenopausal and again gave the reasons for menopause ( natural or surgical ) . Among those women who reported surgical menopause during the 1976 - 1978 follow-up interval , age at menopause was reported to within one year on both the 1978 and 1980 question naires by 95 per cent of women . Among those reporting natural menopause during the 1976 - 1978 period , 82 per cent of women reported their age at menopause to within one year on the two follow-up question naires . A r and om sample of 255 women reporting surgical menopause between 1982 and 1984 was identified and medical records were obtained for 200 . For all but two women , there was complete agreement between self-report and medical record for details of hysterectomy and extent of ovarian surgery . The reproducibility of self-reported age at menopause was assessed among 31,405 women who were menopausal in 1976 . Reported age at menopause on consecutive question naires showed increasing within-person variance with increasing duration since menopause . ( ABSTRACT TRUNCATED AT 250 WORDS Plasma luteinizing hormone ( LH ) , estradiol , prolactin and progesterone levels were measured in nine normal adult women prior to and following administration of naloxone and oral ingestion of ethanol or placebo-control solution .  Each subject served as her own control in a double-blind study carried out during the midluteal phase of the menstrual cycle . The mean ( + /- SD ) progesterone level was 13.9 + /- 1.3 during control conditions and 13.9 + /- 1.7 during alcohol conditions . The mean peak blood alcohol level was 100 + /- 13 mg/dl within 45 - 60 min after initiation of drinking . Under placebo-control conditions , naloxone stimulated a significant increase in plasma LH and prolactin but did not increase estradiol or progesterone . Alcohol did not attenuate the significant naloxone stimulation of LH , and progesterone levels were equivalent under alcohol and control conditions . Alcohol significantly enhanced naloxone stimulation of prolactin and estradiol . Alcohol administration significantly augmented the naloxone-induced increase in plasma prolactin levels . After alcohol administration , naloxone also induced a significant increase in plasma estradiol levels , which was sustained throughout the 180-min sampling period . The mechanisms underlying alcohol 's enhancement of naloxone-stimulated prolactin and estradiol remain to be determined . The alcohol-related increase in naloxone-stimulated prolactin secretion may reflect increased hypothalamic and /or pituitary sensitivity to alcohol following endogenous opioid blockade by naloxone or an effect of increased estrogen levels . The significant increase in plasma estradiol levels following concurrent naloxone and alcohol administration may occur as a consequence of alterations in steroid biotransformation associated with intrahepatic ethanol catabolism Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study . Design Combination of prospect i ve cohort study with representative population based data on alcohol exposure . Setting Eight countries ( France , Italy , Spain , United Kingdom , the Netherl and s , Greece , Germany , Denmark ) participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Participants 109 118 men and 254 870 women , mainly aged 37 - 70 . Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants . Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex . Partial alcohol attributable fractions for consumption higher than the recommended upper limit ( two drinks a day for men with about 24 g alcohol , one for women with about 12 g alcohol ) and the estimated total annual number of cases of alcohol attributable cancer . Results If we assume causality , among men and women , 10 % ( 95 % confidence interval 7 to 13 % ) and 3 % ( 1 to 5 % ) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries . For selected cancers the figures were 44 % ( 31 to 56 % ) and 25 % ( 5 to 46 % ) for upper aerodigestive tract , 33 % ( 11 to 54 % ) and 18 % ( −3 to 38 % ) for liver , 17 % ( 10 to 25 % ) and 4 % ( −1 to 10 % ) for colorectal cancer for men and women , respectively , and 5.0 % ( 2 to 8 % ) for female breast cancer . A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit : 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women . Conclusions In western Europe , an important proportion of cases of cancer can be attributable to alcohol consumption , especially consumption higher than the recommended upper limits . These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer BACKGROUND Growth hormone (GH)-insulin-like growth factor-1 ( IGF-1 ) axis and gonadal hormones demonstrate extensively associated regulation ; however , little is known about the effects of acute alcohol exposure on these hormones . This study examined the effects of intravenous alcohol on the GH-IGF-1 axis and gonadal hormone concentrations , and the influence of age and sex on their regulation . METHODS Forty-eight healthy volunteers ( 24 men and 24 women each in the 21 to 25 and 55 to 65 year age groups ) underwent a 2-session single-blinded study . Subjects received in r and omized counter-balanced order , alcohol infusions , individually computed based on a physiologically based pharmacokinetic model , to maintain a steady-state ( " clamped " ) exposure of 50 mg% or saline for 3 hours in separate sessions . Blood sample s collected at baseline and postinfusion in each session were assayed for levels of GH , IGF-1 , free testosterone , and estradiol . RESULTS Acute alcohol administration result ed in changes in gonadal hormones that differed by sex . Change in free testosterone showed a significant treatment × baseline interaction ( p < 0.001 ) , indicating that alcohol-induced suppression of testosterone occurred predominantly in men . On the other h and , change in estradiol showed a significant treatment × sex interaction ( p = 0.028 ) , indicating that alcohol-induced increases in estradiol occurred predominantly in women . There was a trend for alcohol-induced decreases in IGF-1 levels . Change in GH showed a significant main effect of baseline ( p < 0.001 ) and a trend for treatment by baseline interaction , suggesting an alcohol-induced decrease in individuals with high baseline GH values . There was also a significant main effect of sex ( p = 0.046 ) indicating that men had greater changes in GH across treatment compared with women . CONCLUSIONS Alcohol induced a complex pattern of hormonal responses that varied between younger and older men and women . Some of the observed sex-based differences may help improve our underst and ing of the greater susceptibility to alcohol-related hepatic damage seen in women OBJECTIVES The aim of the study was to explore the influence of reproductive and dietary factors on the age at menopause . METHODS During follow-up of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort in Heidelberg ( median duration 5.8 years ) , 1009 women 
    Output:
    