Maturitas
Volume 59, Issue 3 , Pages 209-218 , 20 March 2008

Breast cancer risk in postmenopausal women using testosterone in combination with hormone replacement therapy

  • Johannes Bitzer

      Affiliations

    • University-Women's Hospital Basel, Department of Gynecological Social Medicine and Psychosomatic, Spitalstrasse 21, 4031 Basel, Switzerland
    • Corresponding Author InformationCorresponding author. Tel.: +41 61 2659043.
    • ,
  • Peter Kenemans

      Affiliations

    • VU University Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands
    • ,
  • Alfred O. Mueck

      Affiliations

    • University-Women's Hospital Tuebingen, Department of Endocrinology and Menopause, Germany
    • ,
  • for the ’FSDeducation Group

      Affiliations

    • Contributing members of the FSDeducation Group (Female Sexual Dysfunction): Farook Al-Azzawi, Leicester, UK; Johannes Bitzer, Basel, Switzerland; Alessandra Graziottin, Milan, Italy; Peter Kenemans, Amsterdam NL (Chair); Michèle Lachowsky, Paris, France; Sylvain Mimoun, Paris, France; Alfred O. Mueck (external expert); Rossella Nappi, Pavia, Italy; Santiago Palacios, Madrid, Spain; HP Zahradnik, Freiburg, Germany. Further information on www.FSDeducation.eu.

Received 29 October 2007 ,Revised 25 January 2008 ,Accepted 28 January 2008.

Reference 

  1. Burger HG, Dudley EC, Cui J, Dennerstein L, Hopper JL. A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition. J Clin Endocrinol Metab. 2000;85(August (8)):2832–2838
  2. Zumoff B, Strain GW, Miller LK, Rosner W. Twenty-four-hour mean plasma testosterone concentration declines with age in normal premenopausal women. J Clin Endocrinol Metab. 1995;80(April (4)):1429–1430
  3. Casson PR, Elkind-Hirsch KE, Buster JE, Hornsby PJ, Carson SA, Snabes MC. Effect of postmenopausal estrogen replacement on circulating androgens. Obstet Gynecol. 1997;90(December (6)):995–998
  4. Simon J, Klaiber E, Wiita B, Bowen A, Yang HM. Differential effects of estrogen–androgen and estrogen-only therapy on vasomotor symptoms, gonadotropin secretion, and endogenous androgen bioavailability in postmenopausal women. Menopause. 1999;6(2):138–146
  5. Davis S. Androgen replacement in women: a commentary. J Clin Endocrinol Metab. 1999;84(June (6)):1886–1891
  6. Davis SR. The therapeutic use of androgens in women. J Steroid Biochem Mol Biol. 1999;69(April (1–6)):177–184
  7. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA. 1999;281(February (6)):537–544
  8. Tamimi RM, Hankinson SE, Chen WY, Rosner B, Colditz GA. Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women. Arch Intern Med. 2006;166(July (14)):1483–1489
  9. Hackenberg R, Hofmann J, Holzel F, Schulz KD. Stimulatory effects of androgen and antiandrogen on the in vitro proliferation of human mammary carcinoma cells. J Cancer Res Clin Oncol. 1988;114(6):593–601
  10. Marugo M, Bernasconi D, Miglietta L, et al. Effects of dihydrotestosterone and hydroxyflutamide on androgen receptors in cultured human breast cancer cells (EVSA-T). J Steroid Biochem Mol Biol. 1992;42(June (5)):547–554
  11. Dimitrakakis C, Zhou J, Wang J, et al. A physiologic role for testosterone in limiting estrogenic stimulation of the breast. Menopause. 2003;10(July (4)):292–298
  12. Ortmann J, Prifti S, Bohlmann MK, Rehberger-Schneider S, Strowitzki T, Rabe T. Testosterone and 5 alpha-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines. Gynecol Endocrinol. 2002;16(April (2)):113–120
  13. Poulin R, Baker D, Labrie F. Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line. Breast Cancer Res Treat. 1988;12(October (2)):213–225
  14. Krämer E, Seeger H, Krämer B, Wallwiener D, Mueck AO. The effect of progesterone, testosterone and synthetic progestogens on growth factor- and estradiol-treated human cancerous and benign breast cells. Eur J Obstet Reprod Biol. 2006;129:77–83
  15. Hofling M, Lindén Hirschberg A, Skoog L, Tan IE, Hägerström T, von Schoultz B. Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in post menopausal women. Menopause. 2007;14:183–190
  16. Somboonporn W, Davis SR. Postmenopausal testosterone therapy and breast cancer risk. Maturitas. 2004;49(December (4)):267–275
  17. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996;17:1–12
  18. Brinton LA, Hoover R, Fraumeni JF. Menopausal oestrogens and breast cancer risk: an expanded case–control study. Br J Cancer. 1986;54(November (5)):825–832
  19. Brinton LA. The relationship of exogenous estrogens to cancer risk. Cancer Detect Prev. 1984;7(3):159–171
  20. Ewertz M. Influence of non-contraceptive exogenous and endogenous sex hormones on breast cancer risk in Denmark. Int J Cancer. 1988;42(6):832–838
  21. Colditz GA, Hankinson SE, Hunter DJ, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995;332(24):1589–1593
  22. Dimitrakakis C, Jones RA, Liu A, Bondy CA. Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. Menopause. 2004;11(September (5)):531–535
  23. Conner P, Söderqvist G, Skoog L, et al. Breast cell proliferation in postmenopausal women during HRT evaluated through fine needle aspiration cytology. Breast Cancer Res Treat. 2003;78:159–165
  24. Conner P, Christow A, Kersemaekers W, et al. A comparative study of breast cell proliferation during hormone replacement therapy: effects of tibolone and continuous combined estrogen–progestogen treatment. Climateric. 2004;7:50–58
  25. Isaksson E, von Schoultz E, Odlind V, et al. Effects of oral contraceptives on breast epithelial proliferation. Breast Cancer Res Treat. 2001;65:163–169
  26. Ando S, De AF, Rago V, et al. Breast cancer: from estrogen to androgen receptor. Mol Cell Endocrinol. 2002;193(July (1–2)):121–128
  27. Jayo MJ, Register TC, Hughes CL, et al. Effects of an oral contraceptive combination with or without androgen on mammary tissues: a study in rats. J Soc Gynecol Investig. 2000;7(4):257–265
  28. Kandouz M, Lombet A, Perrot JY, et al. Proapoptotic effects of antiestrogens, progestins and androgen in breast cancer cells. J Steroid Biochem Mol Biol. 1999;69(April (1–6)):463–471
  29. Lapointe J, Fournier A, Richard V, Labrie C. Androgens down-regulate bcl-2 protooncogene expression in ZR-75-1 human breast cancer cells. Endocrinology. 1999;140(January (1)):416–421
  30. Liao DJ, Dickson RB. Roles of androgens in the development, growth, and carcinogenesis of the mammary gland. J Steroid Biochem Mol Biol. 2002;80(February (2)):175–189
  31. Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN. Proportion of breast cancer cases in the United States explained by well-established risk factors. J Natl Cancer Inst. 1995;87(November (22)):1681–1685
  32. American Cancer Society . Cancer facts and figures. 2005;
  33. Kenemans P, Speroff L. Clinical recommendations and practical guidelines. A report of the International Tibolone Consensus Group. Maturitas. 2005;51:21–28
  34. Suzuki T, Miki Y, Moriya T, et al. 5Alpha-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production. Int J Cancer. 2007;120(January (2)):285

PII: S0378-5122(08)00033-9

doi: 10.1016/j.maturitas.2008.01.005

Maturitas
Volume 59, Issue 3 , Pages 209-218 , 20 March 2008

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