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Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women

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Abstract

Purpose

Mammographic breast and bone mineral densities (BMD) have been associated with luteal phase hormone concentrations in premenopausal women. We assessed the associations of breast and bone densities with follicular phase hormones and sex hormone binding globulin (SHBG) in premenopausal women, given that follicular phase hormones have been shown to be positively associated with premenopausal breast cancer risk.

Methods

One hundred and ninety-two 40–45-year-old women provided a spot urine and/or blood sample during the follicular phase. Hormone and SHBG concentrations, and bone density were measured and routine mammograms were accessed and digitized to obtain breast density measures. Regression models were fit to assess the associations between hormones and SHBG, and breast and bone densities.

Results

Positive associations were observed between percent breast density and SHBG (p trend = 0.02), as well as estradiol (p trend = 0.08), after controlling for body mass index (BMI), number of pregnancies, and breast feeding history. In addition, a statistically significant inverse association was observed between total testosterone and head BMD (p trend = 0.01), after controlling for BMI.

Conclusions

Associations were observed between breast and bone densities, and serum hormone concentrations during the follicular phase of the menstrual cycle.

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References

  1. Henderson BE, Feigelson HS (2000) Hormonal carcinogenesis. Carcinogenesis 21(3):427–433. doi:10.1093/carcin/21.3.427

    Article  PubMed  CAS  Google Scholar 

  2. Compston JE (2001) Sex steroids and bone. Physiol Rev 81(1):419–447

    PubMed  CAS  Google Scholar 

  3. Holt VL, Jenkins J (2000) Endometriosis. In Goldman M, Hatch M (eds) Women and health. Academic Press, San Diego, CA, pp 226–235

  4. Scarpitta AM, Sinagra D (2000) Polycystic ovary syndrome: an endocrine and metabolic disease. Gynecol Endocrinol 14(5):392–395

    Article  PubMed  CAS  Google Scholar 

  5. Pike MC, Krailo MD, Henderson BE, Casagrande JT, Hoel DG (1983) ‘Hormonal’ risk factors, ‘breast tissue age’ and the age-incidence of breast cancer. Nature 303:767–770. doi:10.1038/303767a0

    Article  PubMed  CAS  Google Scholar 

  6. Missmer SA, Spiegelman D, Bertone-Johnson ER, Barbieri RL, Pollak MN, Hankinson SE (2006) Reproducibility of plasma steroid hormones, prolactin, and insulin-like growth factor levels among premenopausal women over a 2- to 3-year period. Cancer Epidemiol Biomarkers Prev 15(5):972–978. doi:10.1158/1055-9965.EPI-05-0848

    Article  PubMed  CAS  Google Scholar 

  7. Boyd NF, Lockwood GA, Martin LJ, Byng JW, Yaffe MJ, Tritchler DL (2001) Mammographic density as a marker of susceptibility to breast cancer: a hypothesis. IARC Sci Publ 154:163–169

    PubMed  CAS  Google Scholar 

  8. Meyer F, Brisson J, Morrison AS, Brown JB (1986) Endogenous sex hormones, prolactin, and mammographic features of breast tissue in premenopausal women. J Natl Cancer Inst 77(3):617–620

    PubMed  CAS  Google Scholar 

  9. Cauley JA, Lucas FL, Kuller LH, Vogt MT, Browner WS, Cummings SR et al (1996) Bone mineral density and risk of breast cancer in older women: the study of osteoporotic fractures. JAMA 276:1404–1408. doi:10.1001/jama.276.17.1404

    Article  PubMed  CAS  Google Scholar 

  10. Nguyen TV, Center JR, Eisman JA (2000) Association between breast cancer and bone mineral density: the Dubbo Osteoporosis Epidemiology Study. Maturitas 36:27–34. doi:10.1016/S0378-5122(00)00133-X

    Article  PubMed  CAS  Google Scholar 

  11. Zhang Y, Kiel DP, Kreger BE, Cupples LA, Ellison C, Dorgan JF et al (1997) Bone mass and the risk of breast cancer among postmenopausal women. N Engl J Med 336:611–617. doi:10.1056/NEJM199702273360903

    Article  PubMed  CAS  Google Scholar 

  12. Atkinson C, Newton KM, Bowles EJ, Yong M, Lampe JW (2008) Demographic, anthropometric, and lifestyle factors and dietary intakes in relation to daidzein-metabolizing phenotypes among premenopausal women in the United States. Am J Clin Nutr 87(3):679–687

    PubMed  CAS  Google Scholar 

  13. Taplin SH, Ichikawa L, Buist DS, Seger D, White E (2004) Evaluating organized breast cancer screening implementation: the prevention of late-stage disease? Cancer Epidemiol Biomarkers Prev 13(2):225–234. doi:10.1158/1055-9965.EPI-03-0206

    Article  PubMed  Google Scholar 

  14. Liberman L, Menell JH (2002) Breast imaging reporting and data system (BI-RADS). Radiol Clin North Am 40(3):409–430. doi:10.1016/S0033-8389(01)00017-3

    Article  PubMed  Google Scholar 

  15. Boyd NF, Lockwood GA, Byng JW, Tritchler DL, Yaffe MJ (1998) Mammographic densities and breast cancer risk. Cancer Epidemiol Biomarkers Prev 7(12):1133–1144

    PubMed  CAS  Google Scholar 

  16. Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB et al (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst 87(9):670–675. doi:10.1093/jnci/87.9.670

    Article  PubMed  CAS  Google Scholar 

  17. Atkinson C, Newton KM, Stanczyk FZ, Westerlind KC, Li L, Lampe JW (2008) Daidzein-metabolizing phenotypes in relation to serum hormones and sex hormone binding globulin, and urinary estrogen metabolites in premenopausal women in the United States. Cancer Causes Control 19(10):1085–1093. doi:10.1007/s10552-008-9172-3

    Article  PubMed  Google Scholar 

  18. Goebelsmann U, Bernstein GS, Gale JA, Kletzky OA, Nakamura RM, Coulson AH et al (1979) Serum gonadotropin, testosterone, estradiol, estrone levels prior to, 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 

  19. Probst-Hensch NM, Ingles SA, Diep AT, Haile RW, Stanczyk FZ, Kolonel LN et al (1999) Aromatase and breast cancer susceptibility. Endocr Relat Cancer 6(2):165–173. doi:10.1677/erc.0.0060165

    Article  PubMed  CAS  Google Scholar 

  20. 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):3666–3672. doi:10.1210/jc.84.10.3666

    Article  PubMed  CAS  Google Scholar 

  21. 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):801–810. doi:10.1016/0022-4731(82)90038-3

    Article  PubMed  CAS  Google Scholar 

  22. Rinaldi S, Geay A, Dechaud H, Biessy C, Zeleniuch-Jacquotte A, Akhmedkhanov A 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):1065–1071

    PubMed  CAS  Google Scholar 

  23. Greenland S (1989) Modeling and variable selection in epidemiologic analysis. Am J Public Health 79(3):340–349. doi:10.2105/AJPH.79.3.340

    Article  PubMed  CAS  Google Scholar 

  24. Qin L, Chen J, Ge C, Ma H, Zhang W, Xiao Y et al. (1999) Analysis of bone mineral density and relevant factors in 781 healthy people aged 15 to 50. Zhonghua Yu Fang Yi Xue Za Zhi 33:282–285

    Google Scholar 

  25. Finkelstein JS, Lee ML, Sowers M, Ettinger B, Neer RM, Kelsey JL et al (2002) Ethnic variation in bone density in premenopausal and early perimenopausal women: effects of anthropometric and lifestyle factors. J Clin Endocrinol Metab 87(7):3057–3067. doi:10.1210/jc.87.7.3057

    Article  PubMed  CAS  Google Scholar 

  26. Boyd NF, Stone J, Martin LJ, Jong R, Fishell E, Yaffe M et al (2002) The association of breast mitogens with mammographic densities. Br J Cancer 87(8):876–882. doi:10.1038/sj.bjc.6600537

    Article  PubMed  CAS  Google Scholar 

  27. Noh JJ, Maskarinec G, Pagano I, Cheung LW, Stanczyk FZ (2006) Mammographic densities and circulating hormones: a cross-sectional study in premenopausal women. Breast 15(1):20–28. doi:10.1016/j.breast.2005.04.014

    Article  PubMed  Google Scholar 

  28. Fortunati N, Fissore F, Fazzari A, Piovano F, Catalano MG, Becchis M et al (1999) Induction of camp in breast cancer cells is mediated by foetal calf serum (fcs) and sex hormone-binding globulin (SHBG). J Steroid Biochem Mol Biol 70:73–80. doi:10.1016/S0960-0760(99)00092-8

    Article  PubMed  CAS  Google Scholar 

  29. Riza E, dos Santos Silva I, De Stavola B, Bradlow HL, Sepkovic DW, Linos D et al (2001) Urinary estrogen metabolites and mammographic parenchymal patterns in postmenopausal women. Cancer Epidemiol Biomarkers Prev 10(6):627–634

    PubMed  CAS  Google Scholar 

  30. Muti P, Bradlow HL, Micheli A, Krogh V, Freudenheim JL, Schünemann HJ et al (2000) Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16 alpha-hydroxyestrone ratio in premenopausal and postmenopausal women. Epidemiology 11:635–640. doi:10.1097/00001648-200011000-00004

    Article  PubMed  CAS  Google Scholar 

  31. Pacifici R (1998) Cytokines, estrogen, and postmenopausal osteoporosis—the second decade. Endocrinology 139(6):2659–2661. doi:10.1210/en.139.6.2659

    Article  PubMed  CAS  Google Scholar 

  32. Sowers MR, Finkelstein JS, Ettinger B, Bondarenko I, Neer RM, Cauley JA et al (2003) The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN. Osteoporos Int 14:44–52. doi:10.1007/s00198-002-1307-x

    Article  PubMed  CAS  Google Scholar 

  33. Slemenda C, Longcope C, Peacock M, Hui S, Johnston CC (1996) Sex steroids, bone mass, and bone loss: a prospective study of pre-, peri-, and postmenopausal women. J Clin Invest 97:14–21. doi:10.1172/JCI118382

    Article  PubMed  CAS  Google Scholar 

  34. Leelawattana R, Ziambaras K, Roodman-Weiss J, Lyss C, Wagner D, Klug T et al (2000) The oxidative metabolism of estradiol conditions postmenopausal bone density and bone loss. J Bone Miner Res 15(12):2513–2520. doi:10.1359/jbmr.2000.15.12.2513

    Article  PubMed  CAS  Google Scholar 

  35. Bernstein L, Ross RK (1993) Endogenous hormones and breast cancer risk. Epidemiol Rev 15(1):48–65

    PubMed  CAS  Google Scholar 

  36. Turner AS, Maillet JM, Mallinckrodt C, Cordain L (1997) Bone mineral density of the skull in premenopausal women. Calcif Tissue Int 61(2):110–113. doi:10.1007/s002239900305

    Article  PubMed  CAS  Google Scholar 

  37. Ahmad N, Pollard TM, Unwin N (2002) The optimal timing of blood collection during the menstrual cycle for the assessment of endogenous sex hormones: can interindividual differences in levels over the whole cycle be assessed on a single day? Cancer Epidemiol Biomarkers Prev 11(1):147–151

    PubMed  CAS  Google Scholar 

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Acknowledgments

We wish to thank Kelly Ehrlich, Kathy Plant, and the GH Center for Health Studies for screening interviews, clinic visits, and study coordination and all the study participants. This work was supported by the National Institute of Health (R01CA97366) and the FHCRC Center Interdisciplinary Funds.

Author information

Authors and Affiliations

  1. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, P.O. Box 19024, M4-B402, Seattle, WA, 98109, USA

    Mellissa Yong & Johanna W. Lampe

  2. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Mellissa Yong, Victoria L. Holt, Stephen M. Schwartz & Johanna W. Lampe

  3. Department of Oral and Dental Science, University of Bristol, Bristol, UK

    Charlotte Atkinson

  4. Group Health Center for Health Studies, Seattle, WA, USA

    Katherine M. Newton & Erin J. Aiello Bowles

  5. Keck School of Medicine of USC, Los Angeles, CA, USA

    Frank Z. Stanczyk

  6. AMC Cancer Research Center, Denver, CO, USA

    Kim C. Westerlind

  7. Epidemiology Research Unit, Fred Hutchinson Cancer Research Center, P.O. Box 19024, M4-B874, Seattle, WA, 98109, USA

    Victoria L. Holt

  8. Cancer Epidemiology Research Cooperative, Fred Hutchinson Cancer Research Center, P.O. Box 19024, M4-C308, Seattle, WA, 98109, USA

    Stephen M. Schwartz

  9. Clinical Statistics/Clinical Research, Fred Hutchinson Cancer Research Center, P.O. Box 19024, M4-B402, Seattle, WA, 98109, USA

    Wendy M. Leisenring

Authors
  1. Mellissa Yong
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  2. Charlotte Atkinson
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  7. Victoria L. Holt
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  10. Johanna W. Lampe
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Corresponding author

Correspondence to Johanna W. Lampe.

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Yong, M., Atkinson, C., Newton, K.M. et al. Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women. Cancer Causes Control 20, 1039–1053 (2009). https://doi.org/10.1007/s10552-009-9321-3

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  • DOI: https://doi.org/10.1007/s10552-009-9321-3

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