Skip to main content

Advertisement

SpringerLink
Log in

Association of serum α-tocopherol with sex steroid hormones and interactions with smoking: implications for prostate cancer risk

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Background

Vitamin E may protect against prostate cancer, possibly only in smokers and, we hypothesize, through altered sex steroid hormones. A controlled trial in smokers showed that sex hormone levels were inversely associated with baseline serum α-tocopherol and decreased in response to vitamin E supplementation. The vitamin E-hormone relation is understudied in non-smokers.

Methods

Serum sex steroid hormones and α-tocopherol were measured for 1,457 men in NHANES III. Multivariable-adjusted geometric mean hormone concentrations by α-tocopherol quintile were estimated.

Results

We observed lower mean testosterone, estradiol, and SHBG concentrations with increasing serum α-tocopherol (Q1 = 5.5 and Q5 = 4.6 ng/ml, p-trend = 0.0007; Q1 = 37.8 and Q5 = 33.1 pg/ml, p-trend = 0.02; Q1 = 38.8 and Q5 = 30.6 pg/ml, p-trend = 0.05, respectively). Interactions between serum α-tocopherol and exposure to cigarette smoke for total testosterone, total estradiol, and SHBG were found with the inverse relation observed only among smokers.

Conclusions

Results from this nationally representative, cross-sectional study indicate an inverse association between serum α-tocopherol and circulating testosterone, estradiol, and SHBG, but only in men who smoked. Our findings support vitamin E selectively influencing sex hormones in smokers and afford possible mechanisms through which vitamin E may impact prostate cancer risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Heinonen OP, Albanes D, Virtamo J et al (1998) Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 90:440–446

    Article  PubMed  CAS  Google Scholar 

  2. Lippman SM, Klein EA, Goodman PJ et al (2009) Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and Vitamin E cancer prevention trial (SELECT). JAMA 301:39–51

    Article  PubMed  CAS  Google Scholar 

  3. Gaziano JM, Glynn RJ, Christen WG et al (2009) Vitamins E and C in the prevention of prostate and total cancer in men: the physicians’ health study II randomized controlled trial. JAMA 301:52–62

    Article  PubMed  CAS  Google Scholar 

  4. Willett WC, Polk BF, Underwood BA et al (1984) Relation of serum vitamins A and E and carotenoids to the risk of cancer. N Engl J Med 310:430–434

    Article  PubMed  CAS  Google Scholar 

  5. Hayes RB, Bogdanovicz JF, Schroeder FH et al (1988) Serum retinol and prostate cancer. Cancer 62:2021–2026

    Article  PubMed  CAS  Google Scholar 

  6. Hsing AW, Comstock GW, Abbey H, Polk BF (1990) Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer. J Natl Cancer Inst 82:941–946

    Article  PubMed  CAS  Google Scholar 

  7. Shibata A, Paganini-Hill A, Ross RK, Henderson BE (1992) Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer 66:673–679

    Article  PubMed  CAS  Google Scholar 

  8. Rohan TE, Howe GR, Burch JD, Jain M (1995) Dietary factors and risk of prostate cancer: a case-control study in Ontario, Canada. Cancer Causes Control 6:145–154

    Article  PubMed  CAS  Google Scholar 

  9. Andersson SO, Wolk A, Bergstrom R et al (1996) Energy, nutrient intake and prostate cancer risk: a population-based case-control study in Sweden. Int J Cancer 68:716–722

    Article  PubMed  CAS  Google Scholar 

  10. Meyer F, Bairati I, Fradet Y, Moore L (1997) Dietary energy and nutrients in relation to preclinical prostate cancer. Nutr Cancer 29:120–126

    Article  PubMed  CAS  Google Scholar 

  11. Nomura AM, Stemmermann GN, Lee J, Craft NE (1997) Serum micronutrients and prostate cancer in Japanese Americans in Hawaii. Cancer Epidemiol Biomarkers Prev 6:487–491

    PubMed  CAS  Google Scholar 

  12. Chan JM, Stampfer MJ, Ma J, Rimm EB, Willett WC, Giovannucci EL (1999) Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev 8:893–899

    PubMed  CAS  Google Scholar 

  13. Jain MG, Hislop GT, Howe GR, Ghadirian P (1999) Plant foods, antioxidants, and prostate cancer risk: findings from case-control studies in Canada. Nutr Cancer 34:173–184

    Article  PubMed  CAS  Google Scholar 

  14. Schuurman AG, Goldbohm RA, Brants HA, van den Brandt PA (2002) A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control CCC 13:573–582

    Article  PubMed  Google Scholar 

  15. Huang HY, Alberg AJ, Norkus EP, Hoffman SC, Comstock GW, Helzlsouer KJ (2003) Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. Am J Epidemiol 157:335–344

    Article  PubMed  Google Scholar 

  16. Rodriguez C, Jacobs EJ, Mondul AM, Calle EE, McCullough ML, Thun MJ (2004) Vitamin E supplements and risk of prostate cancer in US men. Cancer Epidemiol Biomarkers Prev 13:378–382

    PubMed  CAS  Google Scholar 

  17. Kirsh VA, Hayes RB, Mayne ST et al (2006) Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst 98:245–254

    Article  PubMed  CAS  Google Scholar 

  18. Stram DO, Hankin JH, Wilkens LR et al (2006) Prostate cancer incidence and intake of fruits, vegetables and related micronutrients: the multiethnic cohort study* (United States). Cancer Causes Control 17:1193–1207

    Article  PubMed  Google Scholar 

  19. Key TJ, Appleby PN, Allen NE et al (2007) Plasma carotenoids, retinol, and tocopherols and the risk of prostate cancer in the European prospective investigation into cancer and nutrition study. Am J Clin Nutr 86:672–681

    PubMed  CAS  Google Scholar 

  20. Weinstein SJ, Wright ME, Lawson KA et al (2007) Serum and dietary vitamin E in relation to prostate cancer risk. Cancer Epidemiol Biomarkers Prev 16:1253–1259

    Article  PubMed  CAS  Google Scholar 

  21. Peters U, Littman AJ, Kristal AR, Patterson RE, Potter JD, White E (2008) Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort. Cancer Causes Control 19:75–87

    Article  PubMed  Google Scholar 

  22. Gill JK, Franke AA, Steven Morris J et al (2009) Association of selenium, tocopherols, carotenoids, retinol, and 15-isoprostane F(2t) in serum or urine with prostate cancer risk: the multiethnic cohort. Cancer Causes Control 20:1161–1171

    Article  PubMed  Google Scholar 

  23. Gann PH, Ma J, Giovannucci E et al (1999) Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res 59:1225–1230

    PubMed  CAS  Google Scholar 

  24. Roddam AW, Allen NE, Appleby P, Key TJ (2008) Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 100:170–183

    Article  PubMed  CAS  Google Scholar 

  25. Thompson IM, Goodman PJ, Tangen CM et al (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215–224

    Article  PubMed  CAS  Google Scholar 

  26. Andriole GL, Bostwick DG, Brawley OW et al (2010) Effect of dutasteride on the risk of prostate cancer. N Engl J Med 362: 1192–1202

    Google Scholar 

  27. Barrett-Connor E, Khaw KT (1987) Cigarette smoking and increased endogenous estrogen levels in men. Am J Epidemiol 126:187–192

    PubMed  CAS  Google Scholar 

  28. Attia AM, el-Dakhly MR, Halawa FA, Ragab NF, Mossa MM (1989) Cigarette smoking and male reproduction. Arch Androl 23:45–49

    Article  PubMed  CAS  Google Scholar 

  29. Field AE, Colditz GA, Willett WC, Longcope C, McKinlay JB (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

    Article  PubMed  CAS  Google Scholar 

  30. English KM, Pugh PJ, Parry H, Scutt NE, Channer KS, Jones TH (2001) Effect of cigarette smoking on levels of bioavailable testosterone in healthy men. Clin Sci (Lond) 100:661–665

    Article  CAS  Google Scholar 

  31. Tamimi R, Mucci LA, Spanos E, Lagiou A, Benetou V, Trichopoulos D (2001) Testosterone and oestradiol in relation to tobacco smoking, body mass index, energy consumption and nutrient intake among adult men. Eur J Cancer Prev 10:275–280

    Article  PubMed  CAS  Google Scholar 

  32. Allen NE, Appleby PN, Davey GK, Key TJ (2002) Lifestyle and nutritional determinants of bioavailable androgens and related hormones in British men. Cancer Causes Control 13:353–363

    Article  PubMed  Google Scholar 

  33. Muller M, den Tonkelaar I, Thijssen JH, Grobbee DE, van der Schouw YT (2003) Endogenous sex hormones in men aged 40–80 years. Eur J Endocrinol 149:583–589

    Article  PubMed  CAS  Google Scholar 

  34. Svartberg J, Midtby M, Bonaa KH, Sundsfjord J, Joakimsen RM, Jorde R (2003) The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso study. Eur J Endocrinol 149:145–152

    Article  PubMed  CAS  Google Scholar 

  35. Svartberg J, Jorde R (2007) Endogenous testosterone levels and smoking in men. The fifth Tromso study. Int J Androl 30:137–143

    Article  PubMed  CAS  Google Scholar 

  36. Shiels MS, Rohrmann S, Menke A et al (2009) Association of cigarette smoking, alcohol consumption, and physical activity with sex steroid hormone levels in US men. Cancer Causes Control 20:877–886

    Article  PubMed  Google Scholar 

  37. Hartman TJ, Dorgan JF, Virtamo J, Tangrea JA, Taylor PR, Albanes D (1999) Association between serum alpha-tocopherol and serum androgens and estrogens in older men. Nutr Cancer 35:10–15

    Article  PubMed  CAS  Google Scholar 

  38. Hartman TJ, Dorgan JF, Woodson K et al (2001) Effects of long-term alpha-tocopherol supplementation on serum hormones in older men. Prostate 46:33–38

    Article  PubMed  CAS  Google Scholar 

  39. Hernaandez J, Syed S, Weiss G et al (2005) The modulation of prostate cancer risk with alpha-tocopherol: a pilot randomized, controlled clinical trial. J Urol 174:519–522

    Article  PubMed  Google Scholar 

  40. Beers MH, Berkow R, Merck Research L (1999) The Merck manual of diagnosis and therapy. Merck Research Laboratories, Whitehouse Station

    Google Scholar 

  41. Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. Journal Clin Endocrinol Metabol 84:3666–3672

    Article  CAS  Google Scholar 

  42. 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 epidemiology, biomarkers and prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 11: 1065–1071

  43. Gunter EW, Lewis BG, Koncikowski SM (1996) Laboratory procedures used for the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994. Report. Centers for Disease Control and Prevention, Hyattsville

    Google Scholar 

  44. Chumlea WC, Guo SS, Kuczmarski RJ et al (2002) Body composition estimates from NHANES III bioelectrical impedance data. Int J Obes Relat Metabol Disord J Int Assoc Study Obes 26:1596–1609

    Article  CAS  Google Scholar 

  45. Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B (2008) Fruit, vegetable, vitamin A intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis 11:61–66

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  47. Barella L, Rota C, Stocklin E, Rimbach G (2004) Alpha-tocopherol affects androgen metabolism in male rat. Ann NY Acad Sci 1031:334–336

    Article  PubMed  CAS  Google Scholar 

  48. Barella L, Muller PY, Schlachter M et al (2004) Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats. Biochim Biophys Acta 1689:66–74

    PubMed  CAS  Google Scholar 

  49. Gorber SC, Schofield-Hurwitz S, Hardt J, Levasseur G, Tremblay M (2009) The accuracy of self-reported smoking: a systematic review of the relationship between self-reported and cotinine-assessed smoking status. Nicotine Tob Res 11:12–24

    Article  PubMed  Google Scholar 

  50. Machlin LJ (1991) Handbook of vitamins, 2nd edn. M. Dekker, New York

    Google Scholar 

Download references

Acknowledgment

Funding: This is the 26th paper from the Hormone Demonstration Program funded by the Maryland Cigarette Restitution Fund at Johns Hopkins.

Author information

Authors and Affiliations

  1. Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD, USA

    Alison M. Mondul & Demetrius Albanes

  2. 6120 Executive Blvd Ste 320, Rockville, MD, 20852, USA

    Alison M. Mondul

  3. Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland

    Sabine Rohrmann

  4. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Andy Menke, Manning Feinleib & Elizabeth A. Platz

  5. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA

    Andy Menke

  6. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    William G. Nelson

  7. Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    William G. Nelson

  8. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    William G. Nelson

  9. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    William G. Nelson & Elizabeth A. Platz

  10. The Brady Urological Research Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    William G. Nelson & Elizabeth A. Platz

Authors
  1. Alison M. Mondul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sabine Rohrmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andy Menke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manning Feinleib
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William G. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elizabeth A. Platz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Demetrius Albanes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alison M. Mondul.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mondul, A.M., Rohrmann, S., Menke, A. et al. Association of serum α-tocopherol with sex steroid hormones and interactions with smoking: implications for prostate cancer risk. Cancer Causes Control 22, 827–836 (2011). https://doi.org/10.1007/s10552-011-9753-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-011-9753-4

Keywords

Search

Navigation