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Lifestyle factors and serum androgens among 636 middle aged men from seven countries in the European Prospective Investigation into Cancer and Nutrition (EPIC)

An Erratum to this article was published on 25 April 2009

Abstract

Objective

To evaluate the association between lifestyle and dietary factors and serum concentrations of androgens in middle-aged healthy men.

Methods

We conducted a cross-sectional analysis of the association of lifestyle factors with circulating concentrations of androstenedione (A-dione), 3-α-androstanediol glucuronide (A-diol-g), testosterone (T), SHBG (sex hormone-binding globulin), and free testosterone (FT) among 636 men in the European Prospective Investigation into Cancer and Nutrition.

Results

Compared with the youngest age group (40–49 years), the oldest (70–79 years) had a higher mean concentration of SHBG (by 44%) and lower mean concentrations of A-diol-g (by 29%) FT (19%). Men in the highest BMI group (≥29.83 kg/m2) had a higher mean A-diol-g concentration (by 38%) and lower mean concentration of T (by 20%) SHBG (29%) compared with the lowest (<24.16 kg/m2). Current smokers had higher mean concentrations of T (by 13%), SHBG (14%), and A-dione (15%) compared with never smokers. Physical activity and dietary factors were not associated with androgen concentrations, although men in the highest fifth of alcohol intake had higher mean concentrations of A-dione (by 9%), FT (11%) compared with the lowest.

Conclusion

Our results suggest that age, body weight, smoking, and alcohol intake are associated with circulating androgen concentrations in men.

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Abbreviations

A-dione:

Androstenedione

A-diol-g:

3-α-androstanediol glucuronide

BMI:

Body mass index

CI:

Confidence interval

DHT:

Dihydrotestosterone

FT:

Calculated free testosterone

LH:

Luteinising hormone

SD:

Standard deviation

T:

Testosterone

SHBG:

Sex hormone-binding globulin

References

  1. Allen NE, Appleby PN, Davey GK et al (2002) Lifestyle and nutritional determinants of bioavailable androgens and related hormones in British men. Cancer Causes Control 13:353–363. doi:10.1023/A:1015238102830

    PubMed  Article  Google Scholar 

  2. Khaw KT, Dowsett M, Folkerd E et al (2007) Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 116:2694–2701. doi:10.1161/CIRCULATIONAHA.107.719005

    PubMed  Article  CAS  Google Scholar 

  3. Selvin E, Feinleib M, Zhang L et al (2007) Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care 30:234–238. doi:10.2337/dc06-1579

    PubMed  Article  CAS  Google Scholar 

  4. Kuchuk NO, van Schoor NM, Pluijm SM et al (2007) The association of sex hormone levels with quantitative ultrasound, bone mineral density, bone turnover and osteoporotic fractures in older men and women. Clin Endocrinol (Oxf) 67:295–303. doi:10.1111/j.1365-2265.2007.02882.x

    Article  CAS  Google Scholar 

  5. Stanley HL, Schmitt BP, Poses RM et al (1991) Does hypogonadism contribute to the occurrence of a minimal trauma hip fracture in elderly men? J Am Geriatr Soc 39:766–771

    PubMed  CAS  Google Scholar 

  6. Platz EA, Giovannucci E (2004) The epidemiology of sex steroid hormones and their signaling and metabolic pathways in the etiology of prostate cancer. J Steroid Biochem Mol Biol 92:237–253. doi:10.1016/j.jsbmb.2004.10.002

    PubMed  Article  CAS  Google Scholar 

  7. Roddam AW, Allen NE, Appleby P et al (2008) Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 100:170–183. doi:10.1093/jnci/djm323

    PubMed  Article  CAS  Google Scholar 

  8. Hsing AW, Reichardt JK, Stanczyk FZ (2002) Hormones and prostate cancer: current perspectives and future directions. Prostate 52:213–235. doi:10.1002/pros.10108

    PubMed  Article  CAS  Google Scholar 

  9. 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. doi:10.1079/PHN2002394

    PubMed  Article  CAS  Google Scholar 

  10. Lahmann PH, Friedenreich C, Schuit AJ et al (2007) Physical activity and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev 16:36–42. doi:10.1158/1055-9965.EPI-06-0582

    PubMed  Article  Google Scholar 

  11. Travis RC, Key TJ, Allen NE et al (2007) Serum androgens and prostate cancer among 643 cases and 643 controls in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 121:1331–1338. doi:10.1002/ijc.22814

    PubMed  Article  CAS  Google Scholar 

  12. Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672. doi:10.1210/jc.84.10.3666

    PubMed  Article  CAS  Google Scholar 

  13. 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 

  14. Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124:17–27

    PubMed  CAS  Google Scholar 

  15. Kipnis V, Freedman LS, Brown CC et al (1993) Interpretation of energy adjustment models for nutritional epidemiology. Am J Epidemiol 137:1376–1380

    PubMed  CAS  Google Scholar 

  16. Harman SM, Metter EJ, Tobin JD et al (2001) Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 86:724–731. doi:10.1210/jc.86.2.724

    PubMed  Article  CAS  Google Scholar 

  17. Muller M, den Tonkelaar I, Thijssen JH et al (2003) Endogenous sex hormones in men aged 40–80 years. Eur J Endocrinol 149:583–589. doi:10.1530/eje.0.1490583

    PubMed  Article  CAS  Google Scholar 

  18. Gray A, Feldman HA, McKinlay JB et al (1991) Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 73:1016–1025

    PubMed  CAS  Google Scholar 

  19. Svartberg J, Midtby M, Bonaa KH et al (2003) The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso Study. Eur J Endocrinol 149:145–152. doi:10.1530/eje.0.1490145

    PubMed  Article  CAS  Google Scholar 

  20. Feldman HA, Longcope C, Derby CA et al (2002) Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 87:589–598. doi:10.1210/jc.87.2.589

    PubMed  Article  CAS  Google Scholar 

  21. Ukkola O, Gagnon J, Rankinen T et al (2001) Age, body mass index, race and other determinants of steroid hormone variability: the HERITAGE Family Study. Eur J Endocrinol 145:1–9. doi:10.1530/eje.0.1450001

    PubMed  Article  CAS  Google Scholar 

  22. Wu AH, Whittemore AS, Kolonel LN et al (2001) Lifestyle determinants of 5alpha-reductase metabolites in older African-American, white, and Asian-American men. Cancer Epidemiol Biomarkers Prev 10:533–538

    PubMed  CAS  Google Scholar 

  23. Sparrow D, Bosse R, Rowe JW (1980) The influence of age, alcohol consumption, and body build on gonadal function in men. J Clin Endocrinol Metab 51:508–512

    PubMed  CAS  Google Scholar 

  24. Mulligan T, Iranmanesh A, Gheorghiu S et al (1995) Amplified nocturnal luteinizing hormone (LH) secretory burst frequency with selective attenuation of pulsatile (but not basal) testosterone secretion in healthy aged men: possible Leydig cell desensitization to endogenous LH signaling—a clinical research center study. J Clin Endocrinol Metab 80:3025–3031. doi:10.1210/jc.80.10.3025

    PubMed  Article  CAS  Google Scholar 

  25. Veldhuis JD, Urban RJ, Lizarralde G et al (1992) Attenuation of luteinizing hormone secretory burst amplitude as a proximate basis for the hypoandrogenism of healthy aging in men. J Clin Endocrinol Metab 75:707–713. doi:10.1210/jc.75.3.707

    PubMed  Article  CAS  Google Scholar 

  26. Mulligan T, Iranmanesh A, Johnson ML et al (1997) Aging alters feed-forward and feedback linkages between LH and testosterone in healthy men. Am J Physiol 273:R1407–R1413

    PubMed  CAS  Google Scholar 

  27. Lecomte P, Lecureuil N, Lecureuil M et al (1998) Sex differences in the control of sex-hormone-binding globulin in the elderly: role of insulin-like growth factor-I and insulin. Eur J Endocrinol 139:178–183. doi:10.1530/eje.0.1390178

    PubMed  Article  CAS  Google Scholar 

  28. Singh A, Hamilton-Fairley D, Koistinen R et al (1990) Effect of insulin-like growth factor-type I (IGF-I) and insulin on the secretion of sex hormone binding globulin and IGF-I binding protein (IBP-I) by human hepatoma cells. J Endocrinol 124:R1–R3. doi:10.1677/joe.0.124R001

    PubMed  Article  CAS  Google Scholar 

  29. Kaaks R, Lukanova A, Sommersberg B (2000) Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review. Prostate Cancer Prostatic Dis 3:157–172. doi:10.1038/sj.pcan.4500421

    PubMed  Article  CAS  Google Scholar 

  30. Schneider G, Kirschner MA, Berkowitz R et al (1979) Increased estrogen production in obese men. J Clin Endocrinol Metab 48:633–638

    PubMed  CAS  Google Scholar 

  31. Tchernof A, Despres JP, Belanger A et al (1995) Reduced testosterone and adrenal C19 steroid levels in obese men. Metabolism 44:513–519. doi:10.1016/0026-0495(95)90060-8

    PubMed  Article  CAS  Google Scholar 

  32. Wu AH, Whittemore AS, Kolonel LN et al (1995) Serum androgens and sex hormone-binding globulins in relation to lifestyle factors in older African-American, white, and Asian men in the United States and Canada. Cancer Epidemiol Biomarkers Prev 4:735–741

    PubMed  CAS  Google Scholar 

  33. Couillard C, Gagnon J, Bergeron J et al (2000) Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: the HERITAGE Family Study. J Clin Endocrinol Metab 85:1026–1031. doi:10.1210/jc.85.3.1026

    PubMed  Article  CAS  Google Scholar 

  34. Joseph MA, Wei JT, Harlow SD et al (2002) Relationship of serum sex-steroid hormones and prostate volume in African American men. Prostate 53:322–329. doi:10.1002/pros.10154

    PubMed  Article  CAS  Google Scholar 

  35. Derby CA, Zilber S, Brambilla D et al (2006) Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study. Clin Endocrinol (Oxf) 65:125–131. doi:10.1111/j.1365-2265.2006.02560.x

    Article  CAS  Google Scholar 

  36. Field AE, Colditz GA, Willett WC et al (1994) The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men. J Clin Endocrinol Metab 79:1310–1316. doi:10.1210/jc.79.5.1310

    PubMed  Article  CAS  Google Scholar 

  37. Longcope C, Feldman HA, McKinlay JB et al (2000) Diet and sex hormone-binding globulin. J Clin Endocrinol Metab 85:293–296. doi:10.1210/jc.85.1.293

    PubMed  Article  CAS  Google Scholar 

  38. Vermeulen A, Kaufman JM, Deslypere JP et al (1993) Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab 76:1140–1146. doi:10.1210/jc.76.5.1140

    PubMed  Article  CAS  Google Scholar 

  39. Horton R, Hawks D, Lobo R (1982) 3 alpha, 17 beta-androstanediol glucuronide in plasma. A marker of androgen action in idiopathic hirsutism. J Clin Invest 69:1203–1206. doi:10.1172/JCI110558

    PubMed  Article  CAS  Google Scholar 

  40. Horton R (1992) Dihydrotestosterone is a peripheral paracrine hormone. J Androl 13:23–27

    PubMed  CAS  Google Scholar 

  41. Tchernof A, Labrie F, Belanger A et al (1997) Androstane-3alpha, 17beta-diol glucuronide as a steroid correlate of visceral obesity in men. J Clin Endocrinol Metab 82:1528–1534. doi:10.1210/jc.82.5.1528

    PubMed  Article  CAS  Google Scholar 

  42. Giagulli VA, Giorgino R, Vermeulen A (1993) Origin and significance of plasma androsterone glucuronide levels: a parameter of adrenal androgen secretion and hepatic 5 alpha-reductase activity. J Clin Endocrinol Metab 76:918–923. doi:10.1210/jc.76.4.918

    PubMed  Article  CAS  Google Scholar 

  43. Dai WS, Gutai JP, Kuller LH et al (1988) Cigarette smoking and serum sex hormones in men. Am J Epidemiol 128:796–805

    PubMed  CAS  Google Scholar 

  44. Hautanen A, Manttari M, Kupari M et al (1993) Cigarette smoking is associated with elevated adrenal androgen response to adrenocorticotropin. J Steroid Biochem Mol Biol 46:245–251. doi:10.1016/0960-0760(93)90300-L

    PubMed  Article  CAS  Google Scholar 

  45. Goh VH, Tong TY, Mok HP et al (2007) Interactions among age, adiposity, bodyweight, lifestyle factors and sex steroid hormones in healthy Singaporean Chinese men. Asian J Androl 9:611–621. doi:10.1111/j.1745-7262.2007.00322.x

    PubMed  Article  CAS  Google Scholar 

  46. English KM, Pugh PJ, Parry H et al (2001) Effect of cigarette smoking on levels of bioavailable testosterone in healthy men. Clin Sci (Lond) 100:661–665. doi:10.1042/CS20010011

    CAS  Article  Google Scholar 

  47. Isik B, Ceylan A, Isik R (2007) Oxidative stress in smokers and non-smokers. Inhal Toxicol 19:767–769. doi:10.1080/08958370701401418

    PubMed  Article  CAS  Google Scholar 

  48. Dai WS, Kuller LH, LaPorte RE et al (1981) The epidemiology of plasma testosterone levels in middle-aged men. Am J Epidemiol 114:804–816

    PubMed  CAS  Google Scholar 

  49. Mantzoros CS, Georgiadis EI (1995) Body mass and physical activity are important predictors of serum androgen concentrations in young healthy men. Epidemiology 6:432–435. doi:10.1097/00001648-199507000-00020

    PubMed  Article  CAS  Google Scholar 

  50. White LJ, Dressendorfer RH, Ferguson MA et al (2002) Maintenance of testosterone status in fitness joggers after increased training mileage. Eur J Appl Physiol 86:498–502. doi:10.1007/s00421-001-0575-z

    PubMed  Article  CAS  Google Scholar 

  51. Hall HL, Flynn MG, Carroll KK et al (1999) Effects of intensified training and detraining on testicular function. Clin J Sport Med 9:203–208. doi:10.1097/00042752-199910000-00004

    PubMed  Article  CAS  Google Scholar 

  52. Hawkins VN, Foster-Schubert K, Chubak J et al (2008) Effect of exercise on serum sex hormones in men: a 12-month randomized clinical trial. Med Sci Sports Exerc 40:223–233. doi:10.1249/01.mss.0000321026.68454.ad

    PubMed  Article  CAS  Google Scholar 

  53. Eriksson CJ, Fukunaga T, Lindman R (1994) Sex hormone response to alcohol. Nature 369:711. doi:10.1038/369711a0

    PubMed  Article  CAS  Google Scholar 

  54. Mendelson JH, Mello NK, Ellingboe J (1977) Effects of acute alcohol intake on pituitary-gonadal hormones in normal human males. J Pharmacol Exp Ther 202:676–682

    PubMed  CAS  Google Scholar 

  55. Sierksma A, Sarkola T, Eriksson CJ et al (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. doi:10.1097/01.ALC.0000125356.70824.81

    PubMed  Article  CAS  Google Scholar 

  56. Key TJ, Roe L, Thorogood M et al (1990) Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores. Br J Nutr 64:111–119. doi:10.1079/BJN19900014

    PubMed  Article  CAS  Google Scholar 

  57. Wang C, Catlin DH, Starcevic B et al (2005) Low-fat high-fiber diet decreased serum and urine androgens in men. J Clin Endocrinol Metab 90:3550–3559. doi:10.1210/jc.2004-1530

    PubMed  Article  CAS  Google Scholar 

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Acknowledgment

We thank all the participants in EPIC for their invaluable contribution to the study, as well as Bertrand Hémon and colleagues at IARC for their expertise in data handling. We would also like to thank Dr. Shoichiro Tsugane, Division of Epidemiology and Prevention, Research Center for Cancer Prevention and Screening, National Cancer Center, Japan.

Financial Support

This study was funded by research grants from Cancer Research UK; Europe Against Cancer Programme of the European Commission (SANCO); 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; CIBER Epidemiología y Salud Pública (CIBERESP), Spain; the participating regional governments and institutions of Spain; Medical Research Council, UK; the Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; Greek Ministry of Education; Greek Ministry of Health and Social Solidarity; Hellenic Health Foundation; Stavros Niarchos Foundation, Greek; Italian Association for Research on Cancer; Italian National Research Council; 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).

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Correspondence to Reiko Suzuki.

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An erratum to this article is available at http://dx.doi.org/10.1007/s10552-009-9349-4.

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Suzuki, R., Allen, N.E., Appleby, P.N. et al. Lifestyle factors and serum androgens among 636 middle aged men from seven countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control 20, 811–821 (2009). https://doi.org/10.1007/s10552-009-9326-y

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Keywords

  • Androstenedione
  • Androstanediol glucuronide
  • Testosterone
  • Sex hormone-binding globulin
  • Lifestyle factors
  • Diet