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Relation of demographic factors, menstrual history, reproduction and medication use to sex hormone levels in postmenopausal women

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Abstract

In postmenopausal women, levels of estrogens, androgens, and perhaps prolactin have been related to risk of breast and other hormonal cancers in women. However, the determinants of these hormone concentrations have not been firmly established. Associations among various demographic, menstrual, and reproductive factors, medication use and endogenous sex hormone concentrations (estradiol, free estradiol, estrone, estrone sulfate, testosterone, free testosterone, sex hormone binding globulin, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), dihydrotestosterone, and prolactin) were evaluated in a cross-sectional analysis from a simple random sample of 274 postmenopausal women selected from the Women’s Health Initiative Dietary Modification Trial. In multiple regression analyses on log-transformed hormones, the concentrations of DHEA, and DHEAS were negatively and statistically significantly associated with age (both β = −0.03, P < 0.001, respectively). Estradiol, estrone, DHEA, and free testosterone concentrations were higher in African-American than in non-Hispanic White women, but after multivariate adjustment the associations were statistically significant only for free testosterone (β = 0.38, P = 0.01). Women who had a history of bilateral oophorectomy had a mean 35% lower testosterone concentration compared with women with at least one ovary remaining (β = −0.43, P = 0.002), and lower free testosterone (β = −0.42, P = 0.04) after multivariate adjustment. Women who reported regular use of NSAIDs had higher DHEA concentrations (β = 0.20, P = 0.04) and lower prolactin concentrations (β = −0.18, P = 0.02) compared with non-users. These results suggest that while age, oophorectomy status, and NSAID use may be associated with selected sex hormone concentrations, few menstrual or reproductive factors affect endogenous sex hormones in the postmenopausal period.

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References

  1. Cook LS, Weiss NS (2000) Endometrial cancer. In: Goldman MB, Hatch MC (eds) Women and health. San Diego, Academic Press, 916–931

  2. Kelsey JL, Gammon MD, John EM (1993) Reproductive factors and breast cancer. Epidemiol Rev 15(1):36–47

    PubMed  CAS  Google Scholar 

  3. Chubak J, Tworoger S, Yasui Y, Ulrich C, Stanczyk F, McTiernan A (2004) Associations between reproductive and menstrual factors and postmenopausal sex hormone concentrations. Cancer Epidemiol Biomarkers Prev 8:1296–1301

    Google Scholar 

  4. Hankinson S, Colditz G, Hunter D, Manson J, Willett W, Stampfer M, Longcope C, Speizer F (1995) Reproductive factors and family history of breast cancer in relation to plasma estrogen and prolactin levels in postmenopausal women in the Nurses’ Health Study (United States). Cancer Causes Control 6:217–224

    Article  PubMed  CAS  Google Scholar 

  5. Garcia Rodriguez L, Gonzalez-Perez A (2004) Risk of breast cancer among users of aspirin and other anti-inflammatory drugs. Br J Cancer 91(3):525–529

    Article  PubMed  CAS  Google Scholar 

  6. Harris R, Chlebowski R, Jackson R, Frid D, Ascenseo J, Anderson G, Loar A, Rodabough R, White E, McTiernan A (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63:6096–6101

    PubMed  CAS  Google Scholar 

  7. Terry M, Gammon M, Zhang F, Tawfik H, Teitelbaum S, Britton J, Subbaramaiah K, Dannenberg A, Neugut A (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 291(20):2433–2440

    Article  PubMed  CAS  Google Scholar 

  8. Cook N, Lee I, Gaziano J, Gordon D, Ridker P, Manson J, Hennekens C, Buring J (2005) Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. JAMA 294(1):47–55

    Article  PubMed  CAS  Google Scholar 

  9. Jacobs E, Thun M, Connell C, Rodriguez C, Henley S, Feigelson H, Patel A, Flanders W, Calle E (2005) Aspirin and Other Nonsteroidal Anti-inflammatory Drugs and Breast Cancer Incidence in a Large U.S. Cohort. Cancer Epidemiol Biomarkers Prev 14:261–264

    Article  PubMed  CAS  Google Scholar 

  10. Marshall S, Bernstein L, Anton-Culver H, Deapen D, Horn-Ross P, Mohrenweiser H, Peel D, Pinder R, Purdie D, Reynolds P, Stram D, West D, Wright W, Ziogas A, Ross R (2005) Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status. J Natl Cancer Inst 97(11):805–812

    Article  PubMed  CAS  Google Scholar 

  11. Endogenous Hormones and Breast Cancer Collaborative Group (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94(8):606–616

    Google Scholar 

  12. Hankinson S, Willett W, Michaud D, Manson J, Colditz G, Longcope C, Rosner B, Speizer F (1999) Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 91(7):629–634

    Article  PubMed  CAS  Google Scholar 

  13. Tworoger S, Eliassen A, Rosner B, Sluss P, Hankinson S (2004) Plasma prolactin concentrations and risk of postmenopausal breast cancer. Cancer Res 64(18):6814–6819

    Article  PubMed  CAS  Google Scholar 

  14. Manjer J, Johansson R, Berglund G, Janzon L, Kaaks R, Agren A, Lenner P (2003) Postmenopausal breast cancer risk in relation to sex steroid hormones, prolactin and SHBG (Sweden). Cancer Causes Control 14(7):599–607

    Article  PubMed  Google Scholar 

  15. Lukanova A, Lundin E, Micheli A, Arslan A, Ferrari P, Rinaldi S, Krogh V, Lenner P, Shore R, Biessy C, Muti P, Riboli E, Koenig K, Levitz M, Stattin P, Berrino F, Hallmans G, Kaaks R, Toniolo P, Zeleniuch-Jacquotte A (2004) Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer 108(3):425–432

    Article  PubMed  CAS  Google Scholar 

  16. Boyapati S, Shu X, Gao Y, Dai Q, Yu H, Cheng J, Jin F, Zheng W (2004) Correlation of blood sex steroid hormones with body size, body fat distribution, and other known risk factors for breast cancer in post-menopausal Chinese women. Cancer Causes Control 15(3):305–311

    Article  PubMed  Google Scholar 

  17. McTiernan A, Rajan KB, Tworoger SS, Irwin M, Bernstein L, Baumgartner R, Gilliland F, Stanczyk FZ, Yasui Y, Ballard-Barbash R (2003) Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol 21(10):1961–1966

    Article  PubMed  CAS  Google Scholar 

  18. 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(1):47–59

    Article  PubMed  CAS  Google Scholar 

  19. McTiernan A, Wu L, Chen C, Chlebowski R, Mossavar-Rahmani Y, Modugno F, Perri MG, Stanczyk FZ, Van Horn L, Wang CY (2006) Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring) 14(9):1662–1677

    Article  CAS  Google Scholar 

  20. Meldrum D, Davidson D, Tateryn I, Judd H (1981) Changes in circulating steroids with aging in postmenopausal women. Obstet Gynecol 57:624–628

    PubMed  CAS  Google Scholar 

  21. Siiteri PK (1987) Adipose tissue as a source of hormones. Am J Clin Nutr 45(1 Suppl):277–282

    PubMed  CAS  Google Scholar 

  22. Judd HL, Shamonki IM, Frumar AM, Lagasse LD (1982) Origin of serum estradiol in postmenopausal women. Obstet Gynecol 59(6):680–686

    PubMed  CAS  Google Scholar 

  23. Siiteri PK, Murai JT, Hammond GL, Nisker JA, Raymoure WJ, Kuhn RW (1982) The serum transport of steroid hormones. Recent Prog Horm Res 38:457–510

    PubMed  CAS  Google Scholar 

  24. Ritenbaugh C, Patterson R, Chlebowski R, Caan B, Fels-Tinker L, Howard B, Ockene J (2003) The women’s health initiative dietary modification trial: overview and baseline characteristics of participants. Ann Epidemiol 13:S87-S97

    Article  PubMed  Google Scholar 

  25. The Women’s Health Initiative Study Group (1998) Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials 19(1):61–109

    Article  Google Scholar 

  26. Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, Margolis KL, Limacher MC, Manson JE, Parker LM, Paskett E, Phillips L, Robbins J, Rossouw JE, Sarto GE, Shikany JM, Stefanick ML, Thomson CA, Van Horn L, Vitolins MZ, Wactawski-Wende J, Wallace RB, Wassertheil-Smoller S, Whitlock E, Yano K, Adams-Campbell L, Anderson GL, Assaf AR, Beresford SA, Black HR, Brunner RL, Brzyski RG, Ford L, Gass M, Hays J, Heber D, Heiss G, Hendrix SL, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Kotchen JM, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Henderson MM (2006) Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295(6):629–642

    Article  PubMed  CAS  Google Scholar 

  27. Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T (1999) Measurement characteristics of the Women’s Health Initiative food frequency questionnaire. Ann Epidemiol 9(3):178–187

    Article  PubMed  CAS  Google Scholar 

  28. Langer R, White E, Lewis C, Kotchen J, Hendrix S, Trevisan M (2003) The Women’s Health Initiative observational study: baseline characteristics of participants and reliability of baseline measures. Ann Epidemiol 13:S107-S121

    Article  PubMed  Google Scholar 

  29. McTiernan A, Kooperberg C, White E, Wilcox S, Coates R, Adams-Campbell LL, Woods N, Ockene J (2003) Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women’s Health Initiative Cohort Study. JAMA 290(10):1331–1336

    Article  PubMed  CAS  Google Scholar 

  30. 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

    Article  PubMed  CAS  Google Scholar 

  31. Rinaldi S, Geay A, Dechaud H, Biessy C, Zeleniuch-Jacquotte A, Akhmedkhanov A, Shore RE, Riboli E, Toniolo P, Kaaks R (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 

  32. DiLuigi L, Guidetti L, Romanelli F, Baldari C, Conte D (2001) Acetylsalicylic acid inhibits the pituitary response to exercise-related stress in humans. Med Sci Sports Exerc 33(12):2029–2035

    Article  CAS  Google Scholar 

  33. Brueggemeier R, Quinn A, Parrett M, Joarder F, Harris R, Robertson F (1999) Correlation of aromatase and cyclooxygenase gene expression in human breast cancer specimens. Cancer Lett 140:27–35

    Article  PubMed  CAS  Google Scholar 

  34. Zhao Y, Agarwal V, Mendelson C, Simpson E (1996) Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology 137:5739–5742

    Article  PubMed  CAS  Google Scholar 

  35. Toniolo P, Koenig K, Pasternack B, Banerjee S, Rosenberg C, Shore R, Strax P, Levitz M (1994) Reliability of measurements of total, protein-bound, and unbound estradiol in serum. Cancer Epidemiol Biomarkers Prev 3(1):47–50

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The WHI program is funded by the National Heart, Lung and Blood Institute, U.S. Department of Health and Human Services.

Author information

Authors and Affiliations

  1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

    Anne McTiernan, LieLing Wu & C. Y. Wang

  2. Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98125, USA

    Chu Chen

  3. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, 98195, USA

    Anne McTiernan

  4. Department of Medicine, School of Medicine, University of Washington, Seattle, WA, 98195, USA

    Anne McTiernan

  5. Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Vanessa M. Barnabei

  6. Department of Obstetric and Gynecology, Wayne State University, Detroit, MI, USA

    Susan Hendrix

  7. University of Pittsburgh Graduate School of Public Health, Pittsburg, PA, USA

    Francesmary Modugno

  8. University of Pittsburgh Cancer Institute, Pittsburg, PA, USA

    Francesmary Modugno

  9. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Thomas Rohan

  10. University of Southern California, Los Angeles, CA, USA

    Frank Z. Stanczyk

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  1. Anne McTiernan
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  4. Chu Chen
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Corresponding author

Correspondence to Anne McTiernan.

Appendix: Short list of WHI investigators

Appendix: Short list of WHI investigators

Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Elizabeth Nabel, Jacques Rossouw, Shari Ludlam, Linda Pottern, Joan McGowan, Leslie Ford, and Nancy Geller.

Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles L. Kooperberg, Ruth E. Patterson, Anne McTiernan; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker; (Medical Research Labs, Highland Heights, KY) Evan Stein; (University of California at San Francisco, San Francisco, CA) Steven Cummings.

Clinical Centers: (Albert Einstein College of Medicine, Bronx, NY) Sylvia Wassertheil-Smoller; (Baylor College of Medicine, Houston, TX) Jennifer Hays; (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA) JoAnn Manson; (Brown University, Providence, RI) Annlouise R. Assaf; (Emory University, Atlanta, GA) Lawrence Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA) Shirley Beresford; (George Washington University Medical Center, Washington, DC) Judith Hsia; (Los Angeles Biomedical Research Institute at Harbor- UCLA Medical Center, Torrance, CA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR) Evelyn Whitlock; (Kaiser Permanente Division of Research, Oakland, CA) Bette Caan; (Medical College of Wisconsin, Milwaukee, WI) Jane Morley Kotchen; (MedStar Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Northwestern University, Chicago/Evanston, IL) Linda Van Horn; (Rush Medical Center, Chicago, IL) Henry Black; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (State University of New York at Stony Brook, Stony Brook, NY) Dorothy Lane; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Alabama at Birmingham, Birmingham, AL) Cora E. Lewis; (University of Arizona, Tucson/Phoenix, AZ) Tamsen Bassford; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of California at Davis, Sacramento, CA) John Robbins; (University of California at Irvine, CA) F. Allan Hubbell; (University of California at Los Angeles, Los Angeles, CA) Howard Judd; (University of California at San Diego, LaJolla/Chula Vista, CA) Robert D. Langer; (University of Cincinnati, Cincinnati, OH) Margery Gass; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Hawaii, Honolulu, HI) David Curb; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Massachusetts/Fallon Clinic, Worcester, MA) Judith Ockene; (University of Medicine and Dentistry of New Jersey, Newark, NJ) Norman Lasser; (University of Miami, Miami, FL) Mary Jo O’Sullivan; (University of Minnesota, Minneapolis, MN) Karen Margolis; (University of Nevada, Reno, NV) Robert Brunner; (University of North Carolina, Chapel Hill, NC) Gerardo Heiss; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (University of Tennessee, Memphis, TN) Karen C. Johnson; (University of Texas Health Science Center, San Antonio, TX) Robert Brzyski; (University of Wisconsin, Madison, WI) Gloria E. Sarto; (Wake Forest University School of Medicine, Winston-Salem, NC) Denise Bonds; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI) Susan Hendrix.

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McTiernan, A., Wu, L., Barnabei, V.M. et al. Relation of demographic factors, menstrual history, reproduction and medication use to sex hormone levels in postmenopausal women. Breast Cancer Res Treat 108, 217–231 (2008). https://doi.org/10.1007/s10549-007-9588-6

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