Fertility and Sterility
Volume 90, Issue 1 , Pages 129-140 , July 2008

Androgen therapy for loss of desire in women: is the benefit worth the breast cancer risk?

  • Leslie R. Schover, Ph.D.

      Affiliations

    • Corresponding Author InformationReprint requests: Leslie R. Schover, Ph.D., Department of Behavioral Science, Unit 1330, UT M. D. Anderson Cancer Center, P. O. Box 301439, Houston, TX 77230-1439 (FAX: 713-745-4286).

Received 13 December 2006 ,Revised 23 May 2007 ,Accepted 23 May 2007.

References 

  1. Laumann EO, Paik A, Rosen RD. Sexual dysfunction in the United States: prevalence and predictors. JAMA. 1999;281:537–544
  2. Avis NE, Zhao X, Johannes CB, Ory M, Brockwell S, Greendale GA. Correlates of sexual function among multi-ethnic middle-aged women: results from the Study of Women's Health Across the Nation (SWAN). Menopause. 2005;2:385–398
  3. Gracia CR, Freeman EW, Sammel MD, Lin H, Mogul M. Hormones and sexuality during transition to menopause. Obstet Gynecol. 2007;109:831–840
  4. Moreira ED, Brock G, Glasser DB, Nicolosi A, Laumann EO, Paik A, et al. Global Study of Sexual Attitudes and Behaviors Study Group Help-seeking behaviour for sexual problems: the Global Study of Sexual Attitudes and Behaviors. Int J Clin Pract. 2005;59:6–16
  5. Spark RF. Intrinsa fails to impress FDA advisory panel. Int J Impot Res. 2005;17:283–284
  6. Wierman ME, Basson R, Davis SR, Khosla S, Miller KK, Rosner W, et al. Androgen therapy in women: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2006;91:3697–3710
  7. European Medicines Agency. European Public Assessment Report (EPAR): Intrinsa®. EPAR Summary for the Public. EMEA/H/C/634, June 2006. Available at: http://www.emea.eu.int/humandocs/PDFs/EPAR/intrinsa/063406en1.pdf. Accessed May 2, 2007.
  8. BioSante Pharmaceuticals Investor Fact Sheet, January 2007. Available at: http://www.biosantepharma.com/pub/factsheet.pdf. Accessed May 15, 2007.
  9. Vivus, Inc. Testosterone metered dose transdermal spray (MDTR®)—for treatment of low sexual desire in women. Available at: http://www.vivus.com/main.taf?p=3,3,3,2. Accessed May 15, 2007.
  10. Advisory Committee Briefing Document. Intrinsa® (testosterone transdermal system), NDA No. 21-769. Procter& Gamble Pharmaceuticals, Inc. Advisory Committee for Reproductive Health Drugs, December 02, 2004, p. 15 Available at: http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4082B1_01_A-P%26G-Intrinsa.pdf. Accessed June 15, 2007.
  11. Freeman MP. Testosterone supplementation in women: prescribing practices in one community. J Womens Health. 2004;13:239–240
  12. Kornblut AE, Wilson D. How one pill escaped place on steroid list. New York Times, April 17, 2005. Available at: http://www.biopsychiatry.com/dhea/legal.html. Accessed May 2, 2007.
  13. Labrie F, Luu-The V, Martel C, Chernomoretz A, Calvo E, Morissette J, et al. Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG). J Steroid Biochem Mol Biol. 2006;100:52–58
  14. Labrie F, Belanger A, Belanger P, Bérubé R, Martel C, Cusan L, et al. Metabolism of DHEA in postmenopausal women following percutaneous administration. J Steroid Biochem Mol Biol. 2007;103:178–188
  15. Schonberg MA, Davis RB, Wee CC. After the Women's Health Initiative: decision making and trust of women taking hormone therapy. Womens Health Issues. 2005;15:187–195
  16. Basson R. Rethinking low sexual desire in women. BJOG. 2002;109:357–363
  17. Basson R, Leiblum S, Brotto L, Derogatis L, Fourcroy J, Fugl-Meyer K, et al. Revised definitions of women's sexual dysfunction. J Sex Med. 2004;1:40–48
  18. Hayes RD, Dennerstein L, Bennett CM, Koochaki PE, Leiblum SR, Graziottin A. Relationship between hypoactive sexual desire disorder and aging. Fertil Steril. 2007;87:107–112
  19. Sands R, Studd J. Exogenous androgens in postmenopausal women. Am J Med. 1995;98:76S–79S
  20. Bachmann G, Bancroft J, Braunstein G, Burger H, Davis S, Dennerstein L, et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril. 2002;77:660–665
  21. Rivera-Woll LM, Papalia M, Davis SR, Burger HG. Androgen insufficiency in women: diagnostic and therapeutic implications. Hum Reprod Update. 2004;10:421–432
  22. Cawood EH, Bancroft J. Steroid hormones, the menopause, sexuality and well-being of women. Psychol Med. 1996;26:925–936
  23. Gracia CR, Sammel MD, Freeman EW, Liu L, Hollander L, Nelson DB. Predictors of decreased libido in women during the late reproductive years. Menopause. 2004;1:144–150
  24. Dennerstein L, Randolph J, Taffe J, Dudley E, Burger H. Hormones, mood, sexuality, and the menopausal transition. Fertil Steril. 2002;77(Suppl 4):S42–S48
  25. Dennerstein L, Lehert P, Burger H. The relative effects of hormones and relationship factors on sexual function of women though the natural menopausal transition. Fertil Steril. 2005;84:174–180
  26. Davis SR, Davison SL, Donath S, Bell RJ. Circulating androgen levels and self-reported sexual function in women. JAMA. 2005;294:91–96
  27. Santoro N, Torrens J, Crawford S, Allsworth JE, Finkelstein JS, Gold EB, et al. Correlates of circulating androgens in mid-life women: the Study of Women's Health Across the Nation. J Clin Endocrin Metab. 2005;90:4836–4845
  28. Mishra G, Kuh D. Sexual functioning throughout menopause: the perceptions of women in a British cohort. Menopause. 2006;13:880–890
  29. Modelska K, Litwack S, Ewing SK, Yaffe K. Endogenous estrogen levels affect sexual function in elderly post-menopausal women. Maturitas. 2004;49:124–133
  30. Dennerstein L, Koochaki P, Barton I, Graziottin A. Hypoactive sexual desire disorder in menopausal women: a survey of western European women. J Sex Med. 2006;3:212–222
  31. Leiblum SR, Koochaki PE, Rodenberg CA, Barton IP, Rosen RC. Hypoactive sexual desire disorder in postmenopausal women: US results from the Women's International Study of Health and Sexuality (WISHeS). Menopause. 2006;13:46–56
  32. Aziz A, Brännstrom M, Bergquist C, Silfverstolpe G. Perimenopausal androgen decline after oophorectomy does not influence sexuality or psychological well-being. Fertil Steril. 2005;83:1021–1028
  33. Aziz A, Bergquist C, Brännstrom M, Nordholm L, Silfverstolpe G. Differences in aspects of personality and sexuality between perimenopausal women making different choices regarding prophylactic oophorectomy at elective hysterectomy. Act Obstet Gynecol Scand. 2005;85:854–859
  34. Farquhar CM, Harvey SA, Yu Y, Sadler L, Stewart AW. A prospective study of 3 years of outcomes after hysterectomy with and without oophorectomy. Am J Obstet Gynecol. 2006;194:711–717
  35. McKinlay JB, McKinlay SM, Brambilla DJ. Health status and utilization behavior associated with menopause. Am J Epidemiol. 1987;125:110–121
  36. Shifren JL, Avis NE. Surgical menopause: effects on psychological well-being and sexuality. Menopause. 2007;14:586–591
  37. Nicolosi A, Laumann EO, Glasser DB, Moreira ED, Paik A, Gingell C Global Study of Sexual Attitudes and Behaviors Investigators' Group. Sexual behavior and sexual dysfunctions after age 40: the global study of sexual attitudes and behaviors. Urology. 2004;64:991–997
  38. Laumann EO, Paik A, Glasser DB, Kang J-H, Wang T, Levinson B, et al. A cross-national study of subjective sexual well-being among older women and men: finding from the Global Study of Sexual Attitudes and Behaviors. Arch Sex Behav. 2006;35:145–161
  39. Fears TR, Ziegler RG, Donaldson JL, Falk RT, Hoover RN, Stanczyk FZ, et al. Reproducibility studies and interlaboratory concordance for androgen assays in female plasma. Cancer Epid Biomarkers Prev. 2000;9:403–412
  40. Gruschke A, Kuhl H. Validity of radioimmunological methods for determining free testosterone in serum. Fertil Steril. 2001;76:576–582
  41. Sinha-Hikim I, Arver S, Beall G, Shen R, Guerrero M, Sattler F, et al. The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and human immunodeficiency virus-infected women. J Clin Endocrin Metab. 1998;83:1312–1318
  42. Guay A, Munarriz R, Jacobson J, Talakoub L, Traish A, Quirk F, et al. Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part A. Serum androgen levels in women aged 20–49 years with no complaints of sexual dysfunction. Int J Impot Res. 2004;16:112–120
  43. Davison S, Bell R, Donath S, Montalto J, Davis S. Androgen levels in adult females: changes with age, menopause and oophorectomy. J Clin Endocrinol Metab. 2005;90:3847–3853
  44. 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 Endocrin Metab. 2000;85:2832–2838
  45. Labrie F, Belanger A, Belanger P, Bérubé R, Martel C, Cusan L, et al. Androgen glucuronides, instead of testosterone, as the new markers of androgenic activity in women. J Steroid Biochem Mol Biol. 2006;99:182–188
  46. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2002;87:587–598
  47. Sowers MF, Beebe JL, McConnell JR, Jannausch M. Testosterone concentrations in women aged 25–50 years: associations with lifestyle, body composition, and ovarian status. Am J Epidemiol. 2001;153:256–264
  48. Tufano A, Marzo P, Enrini R, Morricone L, Caviezel F, Ambrosi B. Anthropometric, hormonal and biochemical differences in lean and obese women before and after menopause. J Endocrin Invest. 2004;27:648–653
  49. McTiernan A, Wu L, Chen C, Chlebowski R, Mossavar-Rahmani Y, Modugno F, et al. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity. 2006;14:1662–1677
  50. McTiernan A, Tworoger SS, Rajan KB, Yasui Y, Sorenson B, Ulrich CM, et al. Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol Biomarkers Prev. 2004;13:1099–1105
  51. Braunstein GD, Sundwall DA, Katz M, Shifren JL, Buster JE, Simon JA, et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women. Arch Intern Med. 2005;165:1582–1589
  52. Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343:682–688
  53. Buster JE, Kingsberg SA, Aguirre O, Brown C, Breaux JG, Buch A, et al. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Obstet Gynecol. 2005;105:944–952
  54. Shifren JL, Davis SR, Moreau M, Waldbaum A, Bouchard C, Derogatis L, et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 Study. Menopause. 2006;13:770–779
  55. Davis SR, van der Mooren MJ, van Lunsen RH, Lopes P, Ribot J, Rees M, et al. Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Menopause. 2006;13:387–396
  56. Bancroft J. Androgens and sexual function in men and women. In:  Bagatell C,  Bremner WJ editor. Contemporary endocrinology: androgens in health and disease. Totowa, NJ: Humana Press; 2003;p. 259–290
  57. Gaudiano BA, Herbert JD. Methodological issues in clinical trials of antidepressant medications: perspectives from psychotherapy outcome research. Psychother Psychosom. 2005;74:17–25
  58. Bausell RB, Lao L, Bergman S, Lee WL, Berman BM. Is acupuncture analgesia an expectancy effect? Preliminary evidence based on participants' perceived assignments in two placebo-controlled trials. Eval Health Prof. 2005;28:9–26
  59. Ganz PA, Desmond KA, Leedham B, Rowland JH, Meyerowitz BE, Belin TR. Quality of life in long-term, disease-free survivors of breast cancer: a follow-up study. J Natl Cancer Inst. 2002;94:39–49
  60. Andersen BL, Anderson B, deProsse C. Controlled prospective longitudinal study of women with cancer: I. sexual functioning outcomes. J Consult Clin Psychol. 1989;57:683–691
  61. Hendren SK, O'Connor BL, Liu M, Asano T, Cohen Z, Swallow CH, et al. Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer. Ann Surg. 2005;242:212–223
  62. Syrjala KL, Schroeder TC, Abrams JR, Atkins TZ, Brown WS, Sanders JE, et al. Sexual function measurement and outcomes in cancer survivors and matched controls. J Sex Res. 2000;37:213–225
  63. Kaplan HS. A neglected issue: the sexual side effects of current treatments for breast cancer. J Sex Marital Ther. 1992;18:3–19
  64. Kaplan HS, Owett T. The female androgen deficiency syndrome. J Sex Marital Ther. 1993;19:3–24
  65. Greendale GA, Peterson L, Zibecchi L, Ganz PA. Factors related to sexual function in postmenopausal women with a history of breast cancer. Menopause. 2001;8:111–119
  66. Speer JJ, Hillenberg B, Sugrue DP, Blacker C, Kresge CL, Decker VB, et al. Study of sexual functioning determinants in breast cancer survivors. Breast J. 2005;11:440–447
  67. Franco B. Androgens and breast cancer. Int J Gynecol Cancer. 2006;16(Suppl 2):493
  68. Lillie EO, Bernstein L, Ursin G. Review: The role of androgens and polymorphisms in the androgen receptor in the epidemiology of breast cancer. Breast Cancer Res. 2003;5:164–173
  69. Moe RE, Anderson BO. Guest editorial. Androgens and androgen receptors: a clinically neglected sector in breast cancer biology. J Surg Oncol. 2007;95:437–439
  70. Key T, Appleby P, Barnes I, Reeves , G . Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 2002;94:606–616
  71. Missmer SA, Eliaasen H, Baribieri RL, et al. Endogenous estrogen, androgen and progesterone concentrations and breast cancer risk among postmenopausal women. J Natl Cancer Inst. 2004;96:1856–1865
  72. Zeleniuch-Jacquotte A, Shore RE, Akhmedkhanov A, Afanasyeva Y, Kim MY, et al. Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study. Br J Cancer. 2004;90:153–159
  73. Kahan Z, Gardi J, Nyari T, Foldesi I, Hajnal-Papp R, Ormandi K, et al. Elevated levels of circulating insulin-like growth factor-1, IGF-binding globulin-3 and testosterone predict hormone-dependent breast cancer in postmenopausal women: a case control study. Int J Oncol. 2006;29:193–200
  74. Micheli A, Muti P, Secreto G, Krogh V, Meneghini E, Venturelli E, et al. Endogenous sex hormones and subsequent breast cancer in premenopausal women. Int J Cancer. 2004;112:312–318
  75. Kaaks R, Berrino F, Key T, Rinaldi S, Dossus L, Biessy C, et al. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst. 2005;97:755–765
  76. Eliassen AH, Missmer SA, Tworoger SS, Spiegelman D, Barbieri RL, Dowsett M, et al. Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst. 2006;98:1406–1415
  77. Berrino F, Pasanisi P, Bellati C, Venturelli E, Krogh V, Mastroianni A, et al. Serum testosterone levels and breast cancer recurrence. Int J Cancer. 2005;113:499–502
  78. Col NF, Kim JA, Chlebowski RT. Menopausal hormone therapy after breast cancer: a meta-analysis and critical appraisal of the evidence. Breast Cancer Res. 2005;7:R535–R540
  79. Colditz GA. Menopausal hormone therapy after breast cancer. Breast Cancer Res. 2005;7:168–170
  80. Dimitrakakis C, Jones RA, Liu A, Bondy CA. Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. Menopause. 2004;11:531–535
  81. Stahlberg C, Pedersen AT, Lynge E, Andersen ZJ, Keiding N, Hundrup YA, et al. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe. Int J Cancer. 2004;109:721–727
  82. Tibolone: cancers of the breast and endometrium. Prescrire Int. 2006;15:107
  83. Tworoger SS, Missmer SA, Barbieri RL, Willett WC, Colditz GA, Hankinson SE. Plasma sex hormone concentrations and subsequent risk of breast cancer among women using postmenopausal hormones. J Natl Cancer Inst. 2005;97:595–602
  84. 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;166:1483–1489
  85. American Cancer Society . Cancer facts and figures, 2005. Atlanta: American Cancer Society; 2005;14
  86. Horwich A, Swerdlow AJ. Second primary breast cancer after Hodgkin's disease. Br J Cancer. 2004;90:294–298
  87. Kenney LB, Yasui Y, Inskip PD, Hammond S, Neglia JP, Mertens AC, et al. Breast cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Intern Med. 2004;141:590–597
  88. Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in brca1 and brca2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2005;23:7804–7810
  89. Hartmann U, Heiser K, Ruffer-Hesse C, Kloth G. Female sexual desire disorders: subtypes, classification, personality factors and new directions for treatment. World J Urol. 2002;20:79–88
  90. North American Menopause Society . The role of testosterone therapy in postmenopausal women: position statement of the North American Menopause Society. Menopause. 2005;12:496–511

PII: S0015-0282(07)01229-0

doi: 10.1016/j.fertnstert.2007.05.057

Fertility and Sterility
Volume 90, Issue 1 , Pages 129-140 , July 2008