EFFECTS OF ACUTE ALCOHOL INTOXICATION ON PITUITARY–GONADAL AXIS HORMONES, PITUITARY–ADRENAL AXIS HORMONES, ß-ENDORPHIN AND PROLACTIN IN HUMAN ADULTS OF BOTH SEXES

J. Frias1, J. M. Torres, M. T. Miranda2, E. Ruiz and E. Ortega,*

Department of Biochemistry and Molecular Biology and Institute of Neurosciences, School of Medicine,
1 Trauma Emergency Department, Virgen de las Nieves University Hospital and
2 Department of Biostatistics, School of Medicine, University of Granada, Avda. de Madrid, s/n, 18012, Granada, Spain

Received 9 March 2001; in revised form 16 July 2001; accepted 20 August 2001


    ABSTRACT
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
— The effects of acute alcohol intoxication (AAI) on the pituitary–gonadal axis hormones, and the possible contribution of pituitary–adrenal axis hormones, ß-endorphin and prolactin to alcohol-induced dysfunction of pituitary–gonadal axis hormones were studied in adult men and women. Blood samples were drawn from adults of both sexes who arrived at the emergency department with evident behavioural symptoms of drunkenness (AAI) or from adult volunteers with nil consumption of alcohol (controls). Our results demonstrated that AAI produces a high increase in plasma prolactin, corticotropin (adrenocorticotropic hormone, ACTH), and cortisol in adults of both sexes, a decrease in luteinizing hormone levels only in men, an increase in dehydroepiandrosterone-sulphate (DHEAS) and a contradictory behaviour of testosterone according to gender, with increased plasma testosterone in women and a decrease in men. ACTH and prolactin correlated positively with cortisol, DHEAS and testosterone in women, which suggests that prolactin and ACTH could contribute to stimulated adrenal androgen production. In contrast, the decrease in testosterone and increase in ß-endorphin in men suggests that AAI could have an inhibitory effect on testicular testosterone, perhaps mediated by ß-endorphin. Our results suggest that the effect of alcohol on pituitary–gonadal axis hormones in humans could depend on the gender and degree of sexual maturity of the individual.


    INTRODUCTION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Acute and chronic alcohol misuse have been shown to cause reproductive function derangements in humans and experimental animals (Mendelson et al., 1977Go, 1981Go, 1987Go; Little et al., 1992Go). Studies carried out in our laboratory on adolescent humans revealed that alcohol ingestion produces a decrease in plasma testosterone levels in males, a great increase in testosterone levels in females and no significant changes in either follicle-stimulating hormone (FSH) or luteinizing hormone (LH) levels in males or females (Frias et al., 2000Go). Preliminary studies on rats (Little et al., 1992Go) demonstrated that administration of alcohol to prepubescent males stimulated testosterone secretion with no changes in serum LH, whereas alcohol administration to adult male rats led to decreases in both LH and testosterone levels. These data suggest that the effects of alcohol on pituitary–gonadal axis hormones may depend on gender and sexual maturation of the subjects. Intervention studies have demonstrated that alcohol ingestion elevates pituitary–adrenal axis hormone (Aguirre et al., 1995Go), ß-endorphin (Gianoulakis et al., 1996Go) and prolactin (Ida et al., 1992Go; Sarkola et al., 1999Go), which may disrupt the reproductive function (Yen, 1991Go). The hypersecretion of prolactin, ß-endorphin and pituitary–adrenal axis hormones may also be involved in alcohol-induced dysfunction of the pituitary–gonadal axis hormones in human adults.

The present paper represents a cross-sectional study on the effects of acute alcohol intoxication (AAI) on pituitary–gonadal axis hormones in adult men and women and the possible relationship to changes in ß-endorphin, prolactin and pituitary– adrenal axis hormones.


    SUBJECTS AND METHODS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Subjects
A total of 21 subjects (12 men and nine women) with AAI aged 20–27 years were studied. They arrived at the emergency department with evident behavioural symptoms of drunkenness (slurred speech, unstable gait). We could not determine the exact time period between alcohol ingestion and arrival at the emergency room, although their clinical symptoms suggested that this interval was not very long. According to those who accompanied them, the drinking sessions had commenced 4–6 h earlier and no other drugs had been consumed by the subjects. After symptoms had remitted, all subjects confirmed that they had been drunk on their arrival at the emergency department after drinking for 4–6 h and most admitted to being habitual drinkers, although, on the basis of questionnaire responses and tests (MAST, CAGE and MALT) none could be classified as alcoholics (Selzer, 1971Go; Paton and Saunders, 1981Go; Rueff et al., 1989Go). All subjects confirmed that they had taken no drug other than alcohol.

A total of 27 healthy volunteers (11 men and 16 women) aged 20–27 years whose alcohol consumption was nil were studied as controls. These volunteers were not habitual drinkers and none of them had consumed any alcohol during the 48 h prior to withdrawal of blood samples for assay. The controls arrived at the Emergency Department with mild trauma (contusions, sprains, etc.) in all cases.

All participants gave their informed consent to take part in this study, which was carried out in accordance with the Helsinki Declaration. None of the subjects studied had apparent endocrine disorders and none was taking any medication at the time of the study. None of the women was pregnant. The study design and situation of the AAI women and controls made it difficult to establish the ovarian cycle phase or use of the contraceptive pill.

Biochemical assays
To avoid circadian variations in the hormone study, blood samples were drawn from both AAI and controls at the same time of day, during the 3-h period from 12.00 to 03.00. For hormone assays, the serum was frozen at –20°C until its analysis. For alcohol determinations, the blood was refrigerated at 4°C until the assays were performed. ß-endorphin was measured using Nichols Institute (San Juan Capistrano, CA, USA) radioimmunoassay kits and corticotropin (adrenocorticotropic hormone, ACTH) was measured using immunoradiometric CIS Biointernational (Gif-sur-Yvette, France) kits. Prolactin FSH, LH, testosterone, oestradiol (E2) and progesterone were measured by electrochemiluminescence immunoassay using the Boehringer Mannheim Elecsys 2010 immunoassay analyser (Roche Diagnostics, Mannheim, Germany). Dehydroepiandrosterone-sulphate (DHEAS) and cortisol were measured by chemiluminescent enzyme immunoassay using the Immunolite Automated Analyzer (Diagnostic Products Corporation Los Angeles, CA, USA). Intra-assay and inter-assay coefficients of variation were 4.1 and 7.7% for ß-endorphin; 2.9 and 4.8% for ACTH; 2.8 and 3.8% for prolactin; 1.8 and 5.3% for FSH; 1.8 and 5.1% for LH; 1.4 and 2.2% for testosterone; 2.7 and 5% for E2; 1.5 and 4.1% for progesterone; 6.8 and 8.1% for DHEAS; and 6.8 and 9.9% for cortisol. The detection limits were 10 pg/ml for ß-endorphin, 2 pg/ml for ACTH, 0.47 ng/ml for prolactin, 0.10 mIU/ml for FSH, 0.10 mIU/ml for LH, 0.02 ng/ml for testosterone, 10 pg/ml for E2, 0.03 ng/ml for progesterone, 2 µg/dl for DHEAS and 0.2 µg/dl for cortisol. The blood-alcohol concentrations were determined by the gas-chromatographic head-space method using a Perkin–Elmer Sigma 300 FID chromatograph with Hewlett Packard HP 390A integrator. The limit of detection (LOD) was 0.01 g/l and the limit of quantification (LOQ) 0.1 g/l.

Statistical analysis
Results are expressed as means ± SEM. Student's t-test or Welch's t-test was employed where appropriate to examine statistically significant differences. A linear correlation between all hormones was determined, and P < 0.05 was considered significant. The regression models were constructed with a forward stepwise procedure. A variable was included when P < 0.05.


    RESULTS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Effects of AAI on the pituitary–gonadal axis
Serum testosterone levels were very significantly lower in AAI men versus control men (Table 1Go); in contrast, testosterone levels were significantly higher in AAI women versus control women. Serum LH and FSH levels were not significantly different between AAI women and control women. In AAI men, the serum FSH was not different but LH was significantly decreased versus control men. Serum E2 did not differ but progesterone was higher in AAI men than in control men; in contrast, neither progesterone nor E2 levels differed in AAI women versus control women.


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Table 1. Pituitary–gonadal axis hormones in acute alcohol-intoxicated (AAI) subjects and controls
 
Effects of AAI on the pituitary–adrenal axis
Serum ACTH and cortisol levels were significantly increased in AAI men and women (Table 2Go). The responses of ACTH and cortisol to AAI were higher in women than in men. ACTH and cortisol were 11- and 2.2-fold higher, respectively, in AAI women (versus control women), compared with 6.2- and 1.5-fold higher in AAI men (versus control men). Serum DHEAS levels were significantly higher in AAI females, compared to control females, but were not different between AAI males and control men.


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Table 2. Pituitary–adrenal axis hormones in acute alcohol-intoxicated (AAI) subjects and controls
 
Effects of AAI on other hormones
Serum prolactin levels were significantly increased in AAI men and women, compared to their respective controls (Fig. 1Go). The response of prolactin to AAI was higher in women than in men. Thus, prolactin was 5.8-fold higher in AAI women and 3.5-fold higher in AAI men. Plasma ß-endorphin was significantly increased in AAI men and women, versus their respective controls (Fig. 2Go).



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Fig. 1. Serum prolactin in subjects with acute alcohol intoxication (AAI) and controls (C).

dP < 0.0005.

 


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Fig. 2. Serum ß-endorphin in subjects with acute alcohol intoxication (AAI) and controls (C).

aP < 0.05.

 
Linear regression analysis
The multiple linear regression analysis between the hormones studied showed a positive correlation in females for prolactin–ACTH (r = 0.57), prolactin–DHEAS (r = 0.59), prolactin–testosterone (r = 0.61), prolactin–cortisol (r = 0.56), ACTH–cortisol (r = 0.62), ACTH–DHEAS (r = 0.58), ACTH–testosterone (r = 0.54), testosterone–DHEAS (r = 0.59), testosterone–cortisol (r = 0.57), and cortisol– DHEAS (r = 0.52), and a positive correlation in males for ACTH–progesterone (r = 0.65), ACTH–cortisol (r = 0.61), cortisol–progesterone (r = 0.50), and testosterone–DHEAS (r = 0.49).

Alcohol concentrations
Blood-alcohol concentrations in the AAI subjects were 196 ± 1 mg/dl in the men and 210 ± 14 mg/dl in the women.


    DISCUSSION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Our results clearly demonstrate that AAI produced a large increase in ACTH, ß-endorphin, cortisol and prolactin in our adult men and women, in agreement with the findings of our previous studies on adolescent humans (Frias et al., 2000Go). Our present data are also consistent with those reported by other authors for ACTH (Aguirre et al., 1995Go), ß-endorphin (Gianoulakis et al., 1996Go) and prolactin (Ida et al., 1992Go; Sarkola et al., 1999Go) in spite of the fact that our experimental design, representing a cross-sectional approach, was different from that of the others, which represented intervention studies. Alcohol may modify central levels of corticotropin-releasing hormone (CRH), opioid peptides, catecholamines and gamma aminobutyric acid, substances involved in prolactin, ACTH and ß-endorphin secretion (Widdowson and Homan, 1992Go; Harris et al., 1995Go).

The response of prolactin and pituitary–adrenal axis hormones to AAI was greater in women than in men. Alcohol metabolism is different in women and men (Mishra et al., 1989Go; Ammon et al., 1996Go; Kwo et al., 1998Go); however, this does not explain our results, as there were no significant differences in blood alcohol between men and women with AAI. Our results are, however, consistent with the findings by Ogilvie and Rivier (1997) that alcohol administration results in activation of the pituitary–adrenal axis, with female rats secreting more ACTH and corticosterone than males in response to the same dose of alcohol.

In the present study, we found reduced LH in AAI men versus controls. In our previous studies on adolescents, we found no significant differences in LH between AAI males and controls (Frias et al., 2000Go). One explanation for these discrepancies could be the varied sexual maturity of the adolescent. Another possibility is that in the fully sexually mature male, alcohol affects both the testes and the central component of the hypothalamic–pituitary–gonadal axis, i.e. the release of luteinizing hormone-releasing hormone (LHRH)/LH, as has been described in rats (Little et al., 1992Go). Alcohol increases CRH at the central level, and this elevated CRH may decrease serum LH by a mechanism probably mediated by LHRH (Rivier et al., 1986Go; Barbarino et al., 1990Go; Frias et al., 1990Go, 1997Go). In accordance with previous reports (Mendelson et al., 1981Go; Välimäki et al., 1983Go), we found no significant differences in LH levels among AAI and control women. Earlier studies (Sarkola et al., 1999Go) found no significant alcohol effects on LH levels among subjects not using oral contraceptives, and observed a decline among subjects using oral contraceptives at mid-cycle. The lack of a significant difference in LH, E2 and progesterone among the women we studied could be attributed to differences in the ovarian cycle phase or contraceptive pill. Unfortunately, in the present study, neither the ovarian cycle phase nor use of the contraceptive pill was assessed.

We found an increase in circulating testosterone among the AAI females, in accordance with an earlier report (Sarkola et al., 2000Go). The higher values of testosterone in women were not associated with significant changes in LH or FSH. Although the effects of alcohol on the hepatic metabolism of testosterone should be borne in mind (Karila et al., 1996Go), the high levels of ACTH and prolactin and the correlations of prolactin and ACTH with cortisol, DHEA-S and testosterone in the women we studied suggest that prolactin and ACTH could have contributed to stimulated adrenal androgen production in our AAI women. The role of prolactin has been earlier suggested (Higuchi et al., 1984Go; Glasow et al., 1996Go). The increase in DHEAS in blood and perhaps in the brain of our women (Corpechot et al., 1981Go) could be of physiological significance. In fact, neurosteroids influence sexual behaviour, mood, memory and aggressiveness (Robel et al., 1995Go).

In contrast to the findings in women, serum testosterone levels were very significantly decreased in our AAI men, in agreement with earlier findings that demonstrated the inhibitory effect of alcohol on testosterone in adult males (Mendelson et al., 1977Go). A comparison between the testosterone values obtained in the present study (AAI adult men) and those in our earlier study (AAI adolescent males) (Frias et al., 2000Go) shows that the decrease in testosterone levels was greater in AAI adults (44.5%) than in AAI adolescents (20%). Several hypotheses can be proposed to account for this finding: (1) testosterone values are higher in adult controls versus prepubertal controls (6.3 ± 0.1 vs 4.7 ± 0.39), and the decrease in testosterone values could be more evident at high values than at low values of testosterone; (2) the adolescents studied (both AAI and controls) could have varied degrees of sexual maturity, which could mask the effects of alcohol on testosterone levels in these subjects; (3) the amount of alcohol consumed by the adults was greater than that taken by the adolescents (Frias et al., 2000Go); (4) another possible explanation could be differences in adrenal/testicular contribution to circulating testosterone. In fact, alcohol could increase circulating testosterone in prepubertal males (as in females), since testicular contribution to circulating testosterone could be minimal (at least in cases of less sexual development). In contrast, in sexually mature adult men, the adrenal contribution to circulating testosterone is minimal compared with the testicular contribution. With respect to the effects of ethanol on the testes, it has been well established that alcohol decreases testicular testosterone production through modifications in the [NAD+]/[NADH] ratio (Emanuele et al., 1993Go), the arginine– NO synthase (Adams et al., 1993Go), the opioid system (Cicero et al., 1989Go; Emanuele et al., 1998Go), and a neural adrenergic-dependent pathway between the brain and the testes (Rivier, 1999Go).

As we mentioned in the introduction, Little et al. (1992) studied the effects of alcohol on the pituitary–gonadal axis in sexually mature and immature rats, controlling for age and dose of alcohol consumed. Alcohol reduced testosterone levels in the sexually mature rats and increased testosterone levels in the sexually immature ones. This finding would support hypothesis 4 above.

To summarize, we have demonstrated that AAI produces an increase in ß-endorphin, prolactin and pituitary–adrenal axis hormones among human adults of both sexes. AAI produces a decrease in LH in men, but not in women, and an opposite change of pattern in testosterone according to gender, with an increase in plasma testosterone in women and a decrease in plasma testosterone in men. This opposite behaviour of testosterone could explain, as other authors have suggested (Eriksson et al., 1994Go), the opposite effects of acute alcohol ingestion on the subjective feeling of sexual arousal, excitement and desire in men and women. Finally, DHEAS increased significantly in women, but not in the men, after alcohol ingestion. DHEA, a neurosteroid, may also increase sexual excitement in women. Neurosteroids are thought to influence cerebral functions that control mood, memory and sexual behaviour in animals. Based on our previous and present data, we believe that the gender and the age of the individual may modify the response of pituitary–gonadal axis hormones to alcohol consumption, at least in part through modifications in the testicular/adrenal contribution to the circulating testosterone. Our study suggests a possible additional biochemical mechanism to explain the opposing effects of acute alcohol ingestion on plasma testosterone levels in men and women. In one gender, there is the hyper-response of pituitary–adrenal axis hormones, including DHEA, and, in the other, there is a direct effect on the testes.


    ACKNOWLEDGEMENTS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
We thank R. Davies for revising the English text and M. Quintana and R. Arcas for technical assistance. This work was funded in part by DGICYT PM-97-0177 and by the ‘Junta de Andalucia’ through their ‘Endocrinologia y Metabolismo’ group.


    FOOTNOTES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
* Author to whom correspondence should be addressed. Back


    REFERENCES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Adams, M. L., Forman, J. B., Kalicki, J. M., Meyer, E. R., Sewing, B. and Cicero, T. J. (1993) Antagonism of alcohol induced suppresion of rat testosterone secretion by an inhibitor of nitric oxidase synthesis. Alcoholism: Clinical and Experimental Research 17, 660–664.[ISI][Medline]

Aguirre, J. C., Del-Arbol, J. L., Rico, J., Raya, J. and Ruiz, E. (1995) Effect of acute alcohol intoxication on the opioid system in humans. Alcohol 12, 559–562.[ISI][Medline]

Ammon, E., Schafer, C., Hoffman, U. and Klotz, U. (1996) Disposition and first-pass metabolism of ethanol in humans: is it gastric or gender? Clinical Pharmacology and Therapy 59, 503–513.

Barbarino, A., Marinis, L., Tofani, A., Della-Casa, S., D'amico, C., Mancini, A., Corsello, S. M., Sciuto, R. and Barini, B. (1990) Corticotropin-releasing hormone inhibition of gonadotropin release and the effects of opioids blockade. Journal of Clinical Endocrinology and Metabolism 68, 523–528.[Abstract]

Cicero, T. J., Adams, M. L., O'Connor, L. and Nock, B. (1989) In vivo evidence for a direct effect of naloxone in testicular steroidogenesis in the male rat. Endocrinology 125, 957–963.[Abstract]

Corpechot, C., Robel, P., Axelson, M., Sjövall, J. and Baulien, E. E. (1981) Characterization and measurement of dehydroepiandrosterone sulfate in rat brain. Proceedings of the National Academy of Sciences of the USA 78, 4704–4707.[Abstract]

Emanuele, M. A., Halloran, M. M., Uddin, S., Tentler, J. J., Emanuele, N. V., Lawrence, A. M. and Kelly, M. R. (1993) The effects of alcohol on the neuroendocrine control of reproduction. In Alcohol and the Endocrine System, Zakhari, S. ed., pp. 89–116. National Institute of Health Publications, Bethesda, MD.

Emanuele, M. A., La Paglia, N., Steiner, J., Jabamoni, K., Hansen, M., Kirsteins, L. and Emanuele, N. V. (1998) Reversal of chronic ethanol-induced testosterone suppression in peripubertal male rats by opiate blockade. Alcoholism: Clinical and Experimental Research 22, 1199–1204.[ISI][Medline]

Eriksson, C. J. P., Fukunaga, T. and Lindman, R. (1994) Sex hormone response to alcohol. Nature 369, 711.[ISI][Medline]

Frias, J., Ruiz, E., Rodriguez, E. and Ortega, E. (1990) Effect of CRF in the median eminence on gonadotropin levels in conscious female rats. Neurochemistry International 17, 605–608.[ISI]

Frias, J., Puertas, A., Ruiz, E. and Ortega, E. (1997) Effect of corticotropin releasing factor (CRF) injected in the median eminence on LH secretion in male rats. Neurochemical Research 22, 171–174.[ISI][Medline]

Frias, J., Rodriguez, R., Torres, J. M., Ruiz, E. and Ortega, E. (2000) Effects of acute alcohol intoxication on pituitary gonadal axis hormones, pituitary adrenal axis hormones, beta-endorphin and prolactin in human adolescents of both sexes. Life Sciences 67, 1081–1086.[ISI][Medline]

Gianoulakis, C., Krishnan, B. and Thavundayil, J. (1996) Enhanced sensitivity of pituitary ß-endorphin to ethanol in subjects at high risk of alcoholism. Archives of General Psychiatry 45/12, 1097–1109.

Glasow, A., Breidert, M., Haidan, A., Anderegg, U., Kelly, P. A. and Bornstein, S. R. (1996) Functional aspect of the effect of prolactin (PRL) on adrenal steroidogenesis and distribution of the PRL receptor in the human adrenal gland. Journal of Clinical Endocrinology and Metabolism 81, 3103–3111.[Abstract]

Harris, R. A., Proctor, W. R., McQuilkin, S. J., Klein, R. L., Mascia, M. P., Whatley, V., Whiting, P. J. and Dunwiddie, T. V. (1995) Ethanol increases GABA-A response in cells stably transfected with receptor subunits. Alcoholism: Clinical and Experimental Research 19, 226–232.[ISI][Medline]

Higuchi, K., Nawata, H., Toshio, M., Higashizima, M., Kato, K. I. and Ibayashi, H. (1984) Prolactin has a direct effect on adrenal androgen secretion. Journal of Clinical Endocrinology and Metabolism 59, 714–718.[Abstract]

Ida, Y., Tsujimaru, S., Nakamura, K., Shirao, I., Mukara, H., Egami, H. and Nakazawa, Y. (1992) Effects of acute and repeated alcohol ingestion on HPG and HPA function in normal men. Drug and Alcohol Dependence 31, 57–64.[ISI][Medline]

Karila, T., Kosunen, V., Leinonen, A., Tahtela, R. and Seppala, T. (1996) High doses of alcohol increase urinary testosterone/epitestosterone ratio in female. Journal of Chromatography B 687, 109–116.[ISI][Medline]

Kwo, P. Y., Ramchandani, V. A., O'Connor, S., Amann, D., Carr, L. G., Sandrasegaran, K., Kopecky, K. K. and Li, T.-K. (1998) Gender differences in alcohol metabolism: relationship to liver volume and effect of adjusting for body mass. Gastroenterology 115, 1552–1557.[ISI][Medline]

Little, P. J., Adams, M. L. and Cicero, T. J. (1992) Effect of alcohol on the hypothalamic pituitary gonadal axis in the developing male rat. Journal of Pharmacology and Experimental Therapeutics 263, 1056–1061.[Abstract]

Mendelson, J. H., Mello, N. K. and Ellingboe, J. (1977) Effect of acute alcohol intake and pituitary gonadal hormones in normal human males. Journal of Pharmacology and Experimental Therapeutics 202, 676–682.[Abstract]

Mendelson, J. H., Mello, N. K. and Ellingboe, J. (1981) Acute alcohol intake and pituitary gonadal hormones in normal human females. Journal of Pharmacology and Experimental Therapeutics 218, 23–26.[Abstract]

Mendelson, J. H., Mello, N. K., Cristofano, P., Ellingboe, J., Skupny, A., Palmieri, S. L., Benedikt, R. and Schiff, I. (1987) Alcohol effects on naloxone-stimulated luteinizing hormone, prolactin and estradiol in women. Journal of Studies on Alcohol 48, 287–294.[ISI][Medline]

Mishra, L., Sharma, S., Potter, J. J. and Mezey, E. (1989) More rapid elimination of alcohol in women as compared to their male siblings. Alcoholism: Clinical and Experimental Research 13, 752–754.[ISI][Medline]

Ogilvie, K. M. and Rivier, C. (1997) Prenatal alcohol exposure results in hyperactivity of the hypothalamic pituitary adrenal axis of the offspring: modulation by fostering at birth and postnatal handling. Alcoholism: Clinical and Experimental Research 21, 424–429.[ISI][Medline]

Paton, A. and Saunders, J. B. (1981) Asking the right questions. British Medical Journal 283, 1458–1459.[ISI][Medline]

Rivier, C. (1999) Alcohol rapidly lowers plasma testosterone levels in the rat: evidence that a neural brain–gonadal pathway may be important for decreased testicular responsiveness to gonadotropin. Alcoholism: Clinical and Experimental Research 23, 38–45.[ISI][Medline]

Rivier, C., Rivier, J. and Vale, W. (1986) Stress-induced inhibition of reproductive functions, role of endogenous corticotropin-releasing factor. Science 231, 607–609.[ISI][Medline]

Robel, P., Young, J., Corpechot, C., Mayo, W., Perché, F., Han, M., Simon, H. and Baulien, E. E. (1995) Biosynthesis and assay of neurosteroids in rats and mice: functional correlates. Journal of Steroid Biochemistry and Molecular Biology 53, 355–360.[ISI][Medline]

Rueff, B., Crnac, J. and Darne, B. (1989) Detection of alcoholic patients with CAGE questionnaries in 200 patients. La Presse Medicale 18, 1654–1656.[Medline]

Sarkola, T., Mäkisalo, H., Fukunaga, T. and Eriksson, C. J. P. (1999) Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol, and luteinizing hormone in premenopausal women. Alcoholism: Clinical and Experimental Research 23, 976–982.[ISI][Medline]

Sarkola, T., Fukunaga, T., Mäkisalo, H. and Eriksson, C. J. P. (2000) Acute effect of alcohol on androgens in premenopausal women. Alcohol and Alcoholism 35, 84–90.[Abstract/Free Full Text]

Selzer, M. (1971) The Michigan Alcoholism Screening Test: the quest for a new diagnostic instrument. American Journal of Psychiatry 127, 1653–1658.[ISI][Medline]

Välimäki, M., Härkönen, M. and Ylikahri, R. (1983) Acute effects of alcohol on female sex hormones. Alcoholism: Clinical and Experimental Research 7, 289–293.[ISI][Medline]

Widdowson, P. S. and Homan, R. B. (1992) Ethanol induced increase of endogenous dopamine release may involve endogenous opiates. Journal of Neurochemistry 59, 157–163.[ISI][Medline]

Yen, S. S. C. (1991) Prolactin in human reproduction. In Reproductive Endocrinology, Yen, S. S. C. and Jaffe, R. B. eds, pp. 631–638. W. B. Saunders, Philadelphia.