Cancer Causes & Control

, Volume 17, Issue 10, pp 1237–1244 | Cite as

Sex steroid hormones in young manhood and the risk of subsequent prostate cancer: a longitudinal study in African-Americans and Caucasians (United States)

  • Chiaojung J. Tsai
  • Barbara A. Cohn
  • Piera M. Cirillo
  • David Feldman
  • Frank Z. Stanczyk
  • Alice S. WhittemoreEmail author
Original Paper



To investigate the relation of sex hormone levels in young adults to subsequent prostate cancer risk.


From 1959 to 1967, the Child Health and Development Studies collected sera from 10,442 men (median age: 34 years) and followed them for a median of 32 years. In this analysis, we selected 119 African-Americans and 206 Caucasians diagnosed with prostate cancer during the follow-up period. Two prostate cancer-free men were chosen to match each prostate cancer case on race and birth year. We compared the levels of testosterone, estradiol, and sex hormone-binding globulin in cases to those of their matched controls using conditional logistic regression.


There was no significant association between absolute levels of sex hormones in youth and prostate cancer risk in either race. However, among Caucasians, but not African-Americans, prostate cancer risk was positively associated with the ratio of total testosterone to total estradiol (odds ratio relating the fourth to the first quartile: 3.01; 95% confidence interval: 1.42–6.39).


The association between testosterone to estradiol ratio and prostate cancer risk in young Caucasians is consistent with similar findings in older Caucasians. The absence of this association in African-Americans needs confirmation in other data involving larger numbers of African-Americans.


African-American Caucasian Prospective study Prostate cancer Testosterone Estrogen Steroid hormone 



This research was supported by NIH grant CA94069 and the Cancer Research Fund, under Interagency Agreement (97-12013 (University of California contract (98-00924v) with the Department of Health Services Cancer Research Program. The authors acknowledge the efforts of the late Dr. Jacob Yerushalmy who initiated the Child Health and Development Studies (CHDS) and had the vision to include fathers in the cohort; Dr. Barbara J. van den Berg, the second CHDS Director, who preserved the archived serum samples and initiated cancer follow-up; Roberta E. Christianson who updates the cancer linkage and maintains the serum inventory, the late Dr. Frank W. Oechsli who developed methods for vital status follow-up, and Dr. Pentti Siiteri who provided helpful comments on the manuscript. We also acknowledge the National Institute of Child Health and Human Development for support of the maintenance of the CHDS cohort, including the cancer linkage (N0HD13334 and N01HD63258) and William Wright and his staff at the California Tumor Registry, who helped develop the CHDS cohort as a resource for cancer research. The authors also wish to thank Lilly Chang for performing the hormone assays. Mention of trade name, proprietary product or specific equipment does not constitute a guaranty or warranty by the Department of Health Services, nor does it imply approval to the exclusion of other products. The views expressed herein represent those of the authors and do not necessarily represent the position of the State of Californian, Department of Health Services.


  1. 1.
    Smigal C, Jemal A, Ward E, et al. (2006) Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin 56(3):168–183PubMedGoogle Scholar
  2. 2.
    Lucia MS, Bostwick DG, Bosland M, et al. (1998) Workgroup I: rodent models of prostate cancer. Prostate 36(1):49–55PubMedCrossRefGoogle Scholar
  3. 3.
    Zhang Y, Nan B, Yu J, Snabboon T, Andriani F, Marcelli M (2002) From castration-induced apoptosis of prostatic epithelium to the use of apoptotic genes in the treatment of prostate cancer. Ann N Y Acad Sci 963:191–203PubMedCrossRefGoogle Scholar
  4. 4.
    Thompson IM, Goodman PJ, Tangen CM, et al. (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349(3):215–224PubMedCrossRefGoogle Scholar
  5. 5.
    Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ (1996) Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst 88(16):1118–1126PubMedGoogle Scholar
  6. 6.
    Parsons JK, Carter HB, Platz EA, Wright EJ, Landis P, Metter EJ (2005) Serum testosterone and the risk of prostate cancer: potential implications for testosterone therapy. Cancer Epidemiol Biomarkers Prev 14(9):2257–2260PubMedCrossRefGoogle Scholar
  7. 7.
    Chen C, Weiss NS, Stanczyk FZ, et al. (2003) Endogenous sex hormones and prostate cancer risk: a case–control study nested within the Carotene and Retinol Efficacy Trial. Cancer Epidemiol Biomarkers Prev 12(12):1410–1416PubMedGoogle Scholar
  8. 8.
    Dorgan JF, Albanes D, Virtamo J, et al. (1998) Relationships of serum androgens and estrogens to prostate cancer risk: results from a prospective study in Finland. Cancer Epidemiol Biomarkers Prev 7(12):1069–1074PubMedGoogle Scholar
  9. 9.
    Heikkila R, Aho K, Heliovaara M, et al. (1999) Serum testosterone and sex hormone-binding globulin concentrations and the risk of prostate carcinoma: a longitudinal study. Cancer 86(2):312–315PubMedCrossRefGoogle Scholar
  10. 10.
    Hsing AW, Comstock GW (1993) Serological precursors of cancer: serum hormones and risk of subsequent prostate cancer. Cancer Epidemiol Biomarkers Prev 2(1):27–32PubMedGoogle Scholar
  11. 11.
    Nomura AM, Stemmermann GN, Chyou PH, Henderson BE, Stanczyk FZ (1996) Serum androgens and prostate cancer. Cancer Epidemiol Biomarkers Prev 5(8):621–625PubMedGoogle Scholar
  12. 12.
    Stattin P, Lumme S, Tenkanen L, et al. (2004) High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study. Int J Cancer 108(3):418–424PubMedCrossRefGoogle Scholar
  13. 13.
    Vatten LJ, Ursin G, Ross RK, et al. (1997) Androgens in serum and the risk of prostate cancer: a nested case–control study from the Janus serum bank in Norway. Cancer Epidemiol Biomarkers Prev 6(11):967–969PubMedGoogle Scholar
  14. 14.
    Eaton NE, Reeves GK, Appleby PN, Key TJ (1999) Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies. Br J Cancer 80(7):930–934PubMedCrossRefGoogle Scholar
  15. 15.
    Ellis L, Nyborg H (1999) Racial/ethnic variations in male testosterone levels: a probable contributor to group differences in health. Steroids 57(2):72–75CrossRefGoogle Scholar
  16. 16.
    Ghafoor A, Jemal A, Cokkinides V, et al. (2002) Cancer statistics for African Americans. CA Cancer J Clin 52(6):326–341PubMedGoogle Scholar
  17. 17.
    Ross R, Bernstein L, Judd H, Hanisch R, Pike M, Henderson B (1986) Serum testosterone levels in healthy young black and white men. J Natl Cancer Inst 76(1):45–48PubMedGoogle Scholar
  18. 18.
    Winters SJ, Brufsky A, Weissfeld J, Trump DL, Dyky MA, Hadeed V (2001) Testosterone, sex hormone-binding globulin, and body composition in young adult African American and Caucasian men. Metabolism 50(10):1242–1247PubMedCrossRefGoogle Scholar
  19. 19.
    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(7):735–741PubMedGoogle Scholar
  20. 20.
    Eastham JA, May RA, Whatley T, Crow A, Venable DD, Sartor O (1998) Clinical characteristics and biopsy specimen features in African-American and white men without prostate cancer. J Natl Cancer Inst 90(10):756–760PubMedCrossRefGoogle Scholar
  21. 21.
    van den Berg BJ, Christianson RE, Oechsli FW (1988) The California Child Health and Development Studies of the School of Public Health, University of California at Berkeley. Paediatr Perinat Epidemiol 2(3):265–282PubMedCrossRefGoogle Scholar
  22. 22.
    Whittemore AS, Cirillo PM, Feldman D, Cohn BA (2005) Prostate specific antigen levels in young adulthood predict prostate cancer risk: results from a cohort of Black and White Americans. J Urol 174(3):872–876 (discussion 6)PubMedCrossRefGoogle Scholar
  23. 23.
    Goebelsmann U, Bernstein GS, Gale JA, et al. (1979) Serum gonadotropin, testosterone, estradiol and estrone levels prior to and following bilateral vasectomy. In: Lepow IH, Crozier R (eds) Vasectomy: immunologic and pathophysiologic effects in animals and man. Academic Press, New York, p 165 Google Scholar
  24. 24.
    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(6):801–810PubMedCrossRefGoogle Scholar
  25. 25.
    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(10):3666–3672PubMedCrossRefGoogle Scholar
  26. 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(10 Pt 1):1065–1071PubMedGoogle Scholar
  27. 27.
    Mohr BA, Feldman HA, Kalish LA, Longcope C, McKinlay JB (2001) Are serum hormones associated with the risk of prostate cancer? Prospective results from the Massachusetts Male Aging Study. Urology 57(5):930–935PubMedCrossRefGoogle Scholar
  28. 28.
    Hsing AW, Reichardt JK, Stanczyk FZ (2002) Hormones and prostate cancer: current perspectives and future directions. Prostate 52(3):213–235PubMedCrossRefGoogle Scholar
  29. 29.
    Bianco JJ, Handelsman DJ, Pedersen JS, Risbridger GP (2002) Direct response of the murine prostate gland and seminal vesicles to estradiol. Endocrinology 143(12):4922–4933PubMedCrossRefGoogle Scholar
  30. 30.
    McPherson SJ, Wang H, Jones ME, et al. (2001) Elevated androgens and prolactin in aromatase-deficient mice cause enlargement, but not malignancy, of the prostate gland. Endocrinology 142(6):2458–2467PubMedCrossRefGoogle Scholar
  31. 31.
    Ho SM, Leav I, Merk FB, Yu M, Kwan PW, Ziar J (1995) Induction of atypical hyperplasia, apoptosis, and type II estrogen-binding sites in the ventral prostates of Noble rats treated with testosterone and pharmacologic doses of estradiol-17 beta. Lab Invest 73(3):356–365PubMedGoogle Scholar
  32. 32.
    Leav I, Ho SM, Ofner P, Merk FB, Kwan PW, Damassa D (1988) Biochemical alterations in sex hormone-induced hyperplasia and dysplasia of the dorsolateral prostates of Noble rats. J Natl Cancer Inst 80(13):1045–1053PubMedGoogle Scholar
  33. 33.
    Wang Y, Hayward SW, Donjacour AA, et al. (2000) Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue. Cancer Res 60(21):6008–6017PubMedGoogle Scholar
  34. 34.
    Harkonen PL, Makela SI (2004) Role of estrogens in development of prostate cancer. J Steroid Biochem Mol Biol 92(4):297–305PubMedCrossRefGoogle Scholar
  35. 35.
    Gapstur SM, Gann PH, Kopp P, Colangelo L, Longcope C, Liu K (2002) Serum androgen concentrations in young men: a longitudinal analysis of associations with age, obesity, and race. The CARDIA male hormone study. Cancer Epidemiol Biomarkers Prev 11(10 Pt 1):1041–1047PubMedGoogle Scholar
  36. 36.
    Srinivasan SR, Freedman DS, Sundaram GS, Webber LS, Berenson GS (1986) Racial (black-white) comparisons of the relationship of levels of endogenous sex hormones to serum lipoproteins during male adolescence: the Bogalusa Heart Study. Circulation 74(6):1226–1234PubMedGoogle Scholar
  37. 37.
    Lunn RM, Bell DA, Mohler JL, Taylor JA (1999) Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2). Carcinogenesis 20(9):1727–1731PubMedCrossRefGoogle Scholar
  38. 38.
    Panz VR, Joffe BI, Spitz I, Lindenberg T, Farkas A, Haffejee M (2001) Tandem CAG repeats of the androgen receptor gene and prostate cancer risk in black and white men. Endocrine 15(2):213–216PubMedCrossRefGoogle Scholar
  39. 39.
    Sartor O, Zheng Q, Eastham JA (1999) Androgen receptor gene CAG repeat length varies in a race-specific fashion in men without prostate cancer. Urology 53(2):378–380PubMedCrossRefGoogle Scholar
  40. 40.
    Hamalainen EK, Adlercreutz H, Puska P, Pietinen P (1983) Decrease of serum total and free testosterone during a low-fat high-fibre diet. Journal of Steroid Biochemistry 18(3):369–370PubMedCrossRefGoogle Scholar
  41. 41.
    Dorgan JF, Judd JT, Longcope C, et al. (1996) Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study. Am J Clin Nutr 64(6):850–855PubMedGoogle Scholar
  42. 42.
    Udry JR, Morris NM, Kovenock J (1995) Androgen effects on women’s gendered behaviour. J Biosoc Sci 27(3):359–368PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Chiaojung J. Tsai
    • 1
  • Barbara A. Cohn
    • 2
  • Piera M. Cirillo
    • 2
  • David Feldman
    • 3
  • Frank Z. Stanczyk
    • 4
  • Alice S. Whittemore
    • 1
    Email author
  1. 1.Department of Health Research and PolicyStanford University School of MedicineStanfordUSA
  2. 2.Center for Research on Women’s and Children’s HealthChild Health and Development Studies, Public Health InstituteBerkeleyUSA
  3. 3.Department of Medicine, Division of Endocrinology, Gerontology and MetabolismStanford University School of MedicineStanfordUSA
  4. 4.Department of Medicine, Division of Reproductive Endocrinology and InfertilityUniversity of Southern CaliforniaLos AngelesUSA

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