Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition (original) (raw)

Abstract

Objective

Women with a moderate intake of alcohol have higher concentrations of sex steroids in serum, and higher risk of developing breast cancer, compared to non-drinkers. In the present study, we investigate the relationships between alcohol consumption and serum levels of sex steroids and sex-hormone binding globulin (SHBG) in 790 pre- and 1,291 post-menopausal women, who were part of the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods

Serum levels of testosterone (T), androstenedione (Δ4), dehydroepiandrosterone sulphate (DHEAS), estrone (E1), estradiol (E2) and SHBG were measured by direct immunoassays. Free T (fT) and free E2 (fE2) were calculated according to mass action laws. Current alcohol intake exposure to alcohol was assessed from dietary questionnaires.

Results

Pre-menopausal women who consumed more than 25 g/day of alcohol had about 30% higher DHEAS, T and fT, 20% higher Δ4 and about 40% higher E1, concentrations compared to women who were non-consumers. E2, fE2 and SHBG concentrations showed no association with current alcohol intake. In post-menopausal women, DHEAS, fT, T, Δ4, and E1 concentrations were between 10% and 20% higher in women who consumed more than 25 g/day of alcohol compared to non-consumers. E2 or fE2 were not associated with alcohol intake at all. SHBG levels were about 15% lower in alcohol consumers compared to non-consumers.

Conclusion

This study supports the hypothesis of an influence of alcohol intake on sex hormone concentrations in blood.

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Abbreviations

EPIC:

European Prospective Investigation into Cancer and Nutrition

T:

Testosterone

Δ4 :

Androstenedione

DHEAS:

Dehydroepiandrosterone sulphate

E1 :

Estrone

E2 :

Estradiol

SHBG:

Sex-hormone binding globulin

BMI:

Body mass index

OR:

Odds ratio

CI:

Confidence interval

References

  1. Smith-Warner SA, Spiegelman D, Yaun SS, et al (1998) Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA 279:535–540
    Article PubMed CAS Google Scholar
  2. Hamajima N, Hirose K, Tajima K, et al (2002) Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 87:1234–1245
    Article PubMed CAS Google Scholar
  3. Ellison RC, Zhang Y, McLennan CE, Rothman KJ (2001) Exploring the relation of alcohol consumption to risk of breast cancer. Am J Epidemiol 154:740–747
    Article PubMed CAS Google Scholar
  4. Horn-Ross PL, Canchola AJ, West DW, et al (2004) Patterns of alcohol consumption and breast cancer risk in the California Teachers Study cohort. Cancer Epidemiol Biomarkers Prev 13:405–411
    PubMed Google Scholar
  5. Garland M, Hunter DJ, Colditz GA, et al (1999) Alcohol consumption in relation to breast cancer risk in a cohort of United States women 25–42 years of age. Cancer Epidemiol Biomarkers Prev 8:1017–1021
    PubMed CAS Google Scholar
  6. Mahabir S, Baer DJ, Johnson LL, et al (2004) The effects of moderate alcohol supplementation on estrone sulfate and DHEAS in postmenopausal women in a controlled feeding study. Nutr J 3:11
    Article PubMed CAS Google Scholar
  7. Dorgan JF, Baer DJ, Albert PS, et al (2001) Serum hormones and the alcohol-breast cancer association in postmenopausal women. J Natl Cancer Inst 93:710–715
    Article PubMed CAS Google Scholar
  8. Sarkola T, Adlercreutz H, Heinonen S, von Der PB, Eriksson CJ (2001) The role of the liver in the acute effect of alcohol on androgens in women. J Clin Endocrinol Metab 86:1981–1985
    Google Scholar
  9. Reichman ME, Judd JT, Longcope C, et al (1993) Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women. J Natl Cancer Inst 85:722–727
    PubMed CAS Google Scholar
  10. Garcia-Closas M, Herbstman J, Schiffman M, Glass A, Dorgan JF (2002) Relationship between serum hormone concentrations, reproductive history, alcohol consumption and genetic polymorphisms in pre-menopausal women. Int J Cancer 102:172–178
    Article PubMed CAS Google Scholar
  11. Hankinson SE, Willett WC, Manson JE, et al (1995) Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. J Natl Cancer Inst 87:1297–1302
    PubMed CAS Google Scholar
  12. Onland-Moret NC, Peeters PH, van der Schouw YT, Grobbee DE, van Gils CH (2005) Alcohol and endogenous sex steroid levels in postmenopausal women: a cross-sectional study. J Clin Endocrinol Metab 90:1414–1419
    Article PubMed CAS Google Scholar
  13. Verkasalo PK, Thomas HV, Appleby PN, Davey GK, Key TJ (2001) Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre-and postmenopausal women (United Kingdom). Cancer Causes Control 12:47–59
    Article PubMed CAS Google Scholar
  14. Wu F, Ames R, Evans MC, France JT, Reid IR (2001) Determinants of sex hormone-binding globulin in normal postmenopausal women. Clin Endocrinol (Oxf) 54:81–87
    Article CAS Google Scholar
  15. Cauley JA, Gutai JP, Kuller LH, LeDonne D, Powell JG (1989) The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol 129:1120–1131
    PubMed CAS Google Scholar
  16. Madigan MP, Troisi R, Potischman N, Dorgan JF, Brinton LA, Hoover RN (1998) Serum hormone levels in relation to reproductive and lifestyle factors in postmenopausal women (United States). Cancer Causes Control 9:199–207
    Article PubMed CAS Google Scholar
  17. Cigolini M, Targher G, Bergamo Andreis IA, et al (1996) Moderate alcohol consumption and its relation to visceral fat and plasma androgens in healthy women. Int J Obes Relat Metab Disord 20:206–212
    PubMed CAS Google Scholar
  18. Muti P, Trevisan M, Micheli A, et al (1998) Alcohol consumption and total estradiol in premenopausal women. Cancer Epidemiol Biomarkers Prev 7:189–193
    PubMed CAS Google Scholar
  19. Dorgan JF, Reichman ME, Judd JT, et al (1994) The relation of reported alcohol ingestion to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States). Cancer Causes Control 5:53–60
    Article PubMed CAS Google Scholar
  20. Kaaks R, Rinaldi S, Key TJ, et al (2005) Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12:1071–1082
    Article PubMed CAS Google Scholar
  21. Kaaks R, Berrino F, Key T, et al (2005) Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 97:755–765
    Article PubMed CAS Google Scholar
  22. Bingham S, Riboli E (2004) Diet and cancer – the European Prospective Investigation into Cancer and Nutrition. Nat Rev Cancer 4:206–215
    Article PubMed CAS Google Scholar
  23. Haftenberger M, Lahmann PH, Panico S, et al (2002) Overweight, obesity and fat distribution in 50- to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Public Health Nutr 5:1147–1162
    Article PubMed CAS Google Scholar
  24. Riboli E, Hunt KJ, Slimani N, et al (2002) European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 5:1113–1124
    Article PubMed CAS Google Scholar
  25. Rinaldi S, Dechaud H, Biessy C, et al (2001) Reliability and validity of commercially available, direct radioimmunoassays for measurement of blood androgens and estrogens in postmenopausal women. Cancer Epidemiol Biomarkers Prev 10:757–765
    PubMed CAS Google Scholar
  26. Rinaldi S, Geay A, Dechaud H, et al (2002) Validity of free testosterone and free estradiol determinations in serum samples from postmenopausal women by theoretical calculations. Cancer Epidemiol Biomarkers Prev 11:1065–1071
    PubMed CAS Google Scholar
  27. Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem 16:801–810
    Article PubMed CAS Google Scholar
  28. Belgorosky A, Escobar ME, Rivarola MA (1987) Validity of the calculation of non-sex hormone-binding globulin-bound estradiol from total testosterone, total estradiol and sex hormone-binding globulin concentrations in human serum. J Steroid Biochem 28:429–432
    Article PubMed CAS Google Scholar
  29. Tjonneland A, Thomsen BL, Stripp C, et al (2003) Alcohol intake, drinking patterns and risk of postmenopausal breast cancer in Denmark: a prospective cohort study. Cancer Causes Control 14:277–284
    Article PubMed Google Scholar
  30. Kaaks R, Slimani N, Riboli E (1997) Pilot phase studies on the accuracy of dietary intake measurements in the EPIC project: overall evaluation of results. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol 26(Suppl 1):S26–S36
    Article PubMed Google Scholar
  31. Sieri S, Agudo A, Kesse E, et al (2002) Patterns of alcohol consumption in 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) project. Public Health Nutr 5:1287–1296
    Article PubMed CAS Google Scholar
  32. Sowers MF, Beebe JL, McConnell D, Randolph J, Jannausch M (2001) Testosterone concentrations in women aged 25–50 years: associations with lifestyle, body composition, and ovarian status. Am J Epidemiol 153:256–264
    Article PubMed CAS Google Scholar
  33. Rivier C (1996) Alcohol stimulates ACTH secretion in the rat: mechanisms of action and interactions with other stimuli. Alcohol Clin Exp Res 20:240–254
    Article PubMed CAS Google Scholar
  34. Sarkola T, Fukunaga T, Makisalo H, Peter Eriksson CJ (2000) Acute effect of alcohol on androgens in premenopausal women. Alcohol Alcohol 35:84–90
    PubMed CAS Google Scholar
  35. Sierksma A, Sarkola T, Eriksson CJ, van der Gaag MS, Grobbee DE, Hendriks HF (2004) Effect of moderate alcohol consumption on plasma dehydroepiandrosterone sulfate, testosterone, and estradiol levels in middle-aged men and postmenopausal women: a diet-controlled intervention study. Alcohol Clin Exp Res 28:780–785
    PubMed CAS Google Scholar
  36. Sarkola T, Makisalo H, Fukunaga T, Eriksson CJ (1999) Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol, and luteinizing hormone in premenopausal women. Alcohol Clin Exp Res 23:976–982
    Article PubMed CAS Google Scholar
  37. Nagata C, Kabuto M, Takatsuka N, Shimizu H (1997) Associations of alcohol, height, and reproductive factors with serum hormone concentrations in postmenopausal Japanese women. Steroid hormones in Japanese postmenopausal women. Breast Cancer Res Treat 44:235–241
    Article PubMed CAS Google Scholar
  38. Newcomb PA, Klein R, Klein BE, et al (1995) Association of dietary and life-style factors with sex hormones in postmenopausal women. Epidemiology 6:318–321
    PubMed CAS Google Scholar
  39. Gavaler JS, Love K, Van Thiel D, et al (1991) An international study of the relationship between alcohol consumption and postmenopausal estradiol levels. Alcohol Alcohol Suppl 1:327–330
    Google Scholar
  40. Gavaler JS, Love K (1992) Detection of the relationship between moderate alcoholic beverage consumption and serum levels of estradiol in normal postmenopausal women: effects of alcohol consumption quantitation methods and sample size adequacy. J Stud Alcohol 53:389–394
    PubMed CAS Google Scholar
  41. Ginsburg ES, Mello NK, Mendelson JH, et al (1996) Effects of alcohol ingestion on estrogens in postmenopausal women. JAMA 276:1747–1751
    Article PubMed CAS Google Scholar
  42. Cobb CF, Van Thiel DH (1982) Mechanism of ethanol-induced adrenal stimulation. Alcohol Clin Exp Res 6:202–206
    PubMed CAS Google Scholar
  43. Valimaki M, Harkonen M, Ylikahri R (1983) Acute effects of alcohol on female sex hormones. Alcohol Clin Exp Res 7:289–293
    PubMed CAS Google Scholar
  44. Mendelson JH, Lukas SE, Mello NK, Amass L, Ellingboe J, Skupny A (1988) Acute alcohol effects on plasma estradiol levels in women. Psychopharmacology (Berl.) 94:464–467
    Article CAS Google Scholar
  45. Lukanova A, Lundin E, Micheli A, et al (2004) Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer 108:425–432
    Article PubMed CAS Google Scholar
  46. Micheli A, Muti P, Pisani P, et al (1991) Repeated serum and urinary androgen measurements in premenopausal and postmenopausal women. J Clin Epidemiol 44:1055–1061
    Article PubMed CAS Google Scholar
  47. Zeleniuch-Jacquotte A, Gu Y, Shore RE, et al (2005) Postmenopausal levels of sex hormones and risk of breast carcinoma in situ: results of a prospective study. Int J Cancer 114:323–327
    Article PubMed CAS Google Scholar

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Acknowledgments

The Authors would like to thank Mr Achaintre, Mrs Bouzac and Mrs Robinot for their valuable and meticulous work in performing all the laboratory analyses, and Mrs Louled for her precious secretarial help.

Author information

Authors and Affiliations

  1. International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex, France
    S. Rinaldi, I. D. Bezemer, L. Dossus, C. Biessy, P. Ferrari, N. Slimani, R. Saracci & R. Kaaks
  2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
    P. H. M. Peeters & D. E. Grobbee
  3. Department of Biomedical Science and Human Oncology CPO-Piemonte, Torino, Italy
    C. Sacerdote
  4. National Cancer Institute, Milan, Italy
    F. Berrino
  5. Dipartimento di Medicina Clinica e Sperimentale, Universita’ Federico II, Naples, Italy
    S. Panico
  6. Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy
    D. Palli
  7. Cancer Registry, Azienda Ospedaliera ‘‘Civile M.P.Arezzo”, Ragusa, Italy
    R. Tumino
  8. University of Cambridge School of Clinical Medicine, Cambridge, UK
    K. T. Khaw
  9. MCR Dunn Human Nutrition Unit, Welcome Trust/MCR building, Cambridge, UK
    S. Bingham
  10. Cancer Research UK, Epidemiology Unit, University of Oxford, Richard Doll Building, Oxford, UK
    N. E. Allen & T. Key
  11. Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark
    M. K. Jensen & K. Overvad
  12. Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
    A. Olsen & A. Tjonneland
  13. Public Health Division of Gipuzkoa, Health Department of the Basque Country, Donostia-San Sebastian, Spain
    P. Amiano
  14. Public Health Institute of Navarra, Pamplona, Spain
    E. Ardanaz
  15. Unit of Epidemiology, Catalan Institute of Oncology (ICO), Barcelona, Spain
    A. Agudo
  16. Andalusian School of Public Health, Granada, Spain
    C. Martinez-García
  17. Public Health & Health Planning Directorate, Asturias, Spain
    J. Ramón Quirós
  18. Conserejía de Sanida, Murcia, Spain
    M. J. Tormo
  19. German Cancer Research Centre, Clinical Epidemiology, Nutritional Epidemiology, Heidelberg, Germany
    G. Nagel & J. Linseisen
  20. Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany
    H. Boeing & M. Schulz
  21. Centre for Nutrition and Health, National Institute of Public Health and the Environment, Bilthoven, The Netherlands
    H. B. Bueno-de-Mesquita
  22. Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Athens, Greece
    M. Koliva, G. Kyriazi & A. Thrichopoulou
  23. INSERM, Institut Gustave Roussy, Villejuif, France
    M. C. Boutron-Ruault & F. Clavel-Chapelon
  24. Department of Epidemiology & Public Health, Faculty of Medicine, Imperial College London, London, UK
    E. Riboli

Authors

  1. S. Rinaldi
  2. P. H. M. Peeters
  3. I. D. Bezemer
  4. L. Dossus
  5. C. Biessy
  6. C. Sacerdote
  7. F. Berrino
  8. S. Panico
  9. D. Palli
  10. R. Tumino
  11. K. T. Khaw
  12. S. Bingham
  13. N. E. Allen
  14. T. Key
  15. M. K. Jensen
  16. K. Overvad
  17. A. Olsen
  18. A. Tjonneland
  19. P. Amiano
  20. E. Ardanaz
  21. A. Agudo
  22. C. Martinez-García
  23. J. Ramón Quirós
  24. M. J. Tormo
  25. G. Nagel
  26. J. Linseisen
  27. H. Boeing
  28. M. Schulz
  29. D. E. Grobbee
  30. H. B. Bueno-de-Mesquita
  31. M. Koliva
  32. G. Kyriazi
  33. A. Thrichopoulou
  34. M. C. Boutron-Ruault
  35. F. Clavel-Chapelon
  36. P. Ferrari
  37. N. Slimani
  38. R. Saracci
  39. E. Riboli
  40. R. Kaaks

Corresponding author

Correspondence toS. Rinaldi.

Additional information

The EPIC study was funded by ‘‘Europe Against Cancer’’ Programme of the European Commission (SANCO); Ligue contre le Cancer (France); Société 3M (France); Mutuelle Générale de I’Éducation Nationale; Institut National de la Santé et de la Recherche Médicale (INSERM); German Cancer Aid; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health (RCESP-C03/09); the participating regional governments and institutions of Spain; Cancer Research UK; Medical Research Council, UK; the Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; the Wellcome Trust, UK; Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer (AIRC); Dutch Ministry of Public Health, Welfare and Sports; Dutch Ministry of Health; Dutch Prevention Funds; LK Research Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Norwegian Cancer Society; Specific study results of this case-control study nested within EPIC, presented in this paper, were obtained with financial support from the National Cancer Institute (USA) [grant nr1U01CA98216-01].

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Rinaldi, S., Peeters, P., Bezemer, I. et al. Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition.Cancer Causes Control 17, 1033–1043 (2006). https://doi.org/10.1007/s10552-006-0041-7

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