The safety of postmenopausal testosterone therapy

Women's Health

Volumn 8, Issue 3, 2012, Pages 263-275

  Maclaran, Kate ^a,b   Panay, Nick ^a  

^a QUEEN CHARLOTTE S AND CHELSEA HOSPITAL   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

androgen; HRT; menopause; sexual desire; testosterone

Indexed keywords

ANDROGEN; CONJUGATED ESTROGEN; ESTRADIOL; ESTRATEST; ESTROGEN; GESTAGEN; MEDROXYPROGESTERONE ACETATE; METHYLTESTOSTERONE; PLACEBO; TESTOSTERONE; TESTOSTERONE UNDECANOATE;

ACNE; ANDROGEN DEFICIENCY; ANDROGEN THERAPY; AORTA ATHEROSCLEROSIS; BLOOD CLOTTING; BLOOD PRESSURE; BODY MASS; BONE DENSITY; BREAST; BREAST CANCER; CANCER RISK; CARBOHYDRATE METABOLISM; CARDIOVASCULAR RISK; CLITORIS HYPERTROPHY; DISEASE ASSOCIATION; DISEASE MARKER; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG EXPOSURE; DRUG IMPLANT; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; ENDOMETRIAL THICKNESS; ENDOMETRIUM; ENDOMETRIUM CANCER; ENDOMETRIUM CARCINOMA; ENDOMETRIUM HYPERPLASIA; ENDOMETRIUM PROLIFERATION; FEMALE GENITAL TRACT PARAMETERS; FEMALE SEXUAL DYSFUNCTION; GEL; GLUCOSE METABOLISM; HAIR LOSS; HEMATOLOGY; HIRSUTISM; HORMONE ACTION; HORMONE RESPONSE; HORMONE SUBSTITUTION; HORMONE SYNTHESIS; HUMAN; HYPOACTIVE SEXUAL DESIRE DISORDER; INSULIN RESISTANCE; INTRAABDOMINAL FAT; KIDNEY FUNCTION; LIBIDO DISORDER; LIPID ANALYSIS; LIVER FUNCTION; MENOPAUSAL SYNDROME; MENOPAUSE RELATED DISORDER; NONHUMAN; POSTMENOPAUSE; REVIEW; SIDE EFFECT; TESTOSTERONE BLOOD LEVEL; TRANSDERMAL PATCH; VAGINA BLEEDING; VIRILIZATION; VITAL SIGN; VOICE CHANGE; WEIGHT REDUCTION;

ANDROGENS; ENDOMETRIUM; ESTROGEN REPLACEMENT THERAPY; FEMALE; HUMANS; POSTMENOPAUSE; RISK FACTORS; TESTOSTERONE;

EID: 84860568811     PISSN: 17455057     EISSN: 17455065     Source Type: Journal    
DOI: 10.2217/whe.12.11     Document Type: Review

References (118)

1. Basaria S, Dobs AS. Clinical review: Controversies regarding transdermal androgen therapy in postmenopausal women. J. Clin. Endocrinol. Metab. 91, 4743-4752 (2006)
2. Braunstein GD. The endocrine society clinical practice guideline and the North American menopause society position statement on androgen therapy in women: Another one of Yogi's forks. J. Clin. Endocrinol. Metab. 92(11), 4091-4093 (2007)
3. Wan Y. Testosterone patches for female sexual dysfunction. Drug Ther. Bull. 47(3), 30-34 (2009)
4. Davison SL, Davis SR. Androgenic hormones and aging - The link with female sexual function. Horm. Behav. 59(5), 745-753 (2011)
5. Palacios S. Androgens and female sexual function. Maturitas 57(1), 61-65 (2007)
6. Panay N, Fenton A. The role of testosterone in women. Climacteric 12(3), 185-187 (2009)
7. Dunn JF, Nisula BC, Rodbard D. Transport of steroid hormones: Binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J. Clin. Endocrinol. Metab. 53(1), 58-68 (1981)
8. 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. 80(4), 1429-1430 (1995)
9. Laughlin GA, Barrett-Connor E, Kritz- Silverstein D, von Mühlen D. Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: The Rancho Bernardo Study. J. Clin. Endocrinol. Metab. 85(2), 645-651 (2000)
10. Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: Changes with age, menopause, and oophorectomy. J. Clin. Endocrinol. Metab. 90(7), 3847-3853 (2005)
11. Basson R. Women's sexual function and dysfunction: Current uncertainties, future directions. Int. J. Impot. Res. 20(5), 466-478 (2008)
12. Shifren JL. The role of androgens in female sexual dysfunction. Mayo Clin. Proc. 79(Suppl. 4), S19-S24 (2004)
13. Davis SR, McCloud P, Strauss BJ, Burger H. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Maturitas 21(3), 227-236 (1995)
14. Davis SR, Walker KZ, Strauss BJ. Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women. Menopause 7(6), 395-401 (2000)
15. Sherwin BB. Affective changes with estrogen and androgen replacement therapy in surgically menopausal women. J. Affect Disord. 14(2), 177-187 (1988)
16. Black EF. The use of testosterone propionate in gynaecology. Can. Med. Assoc. J. 47(2), 124-128 (1942)
17. Greenblatt RB, Barfield WE, Garner JF, Calk GL, Harrod JP. Evaluation of an estrogen, androgen, estrogen-Androgen combination, and a placebo in the treatment of the menopause. J. Clin. Endocrinol. Metab. 10(12), 1547-1558 (1950)
18. Lobo RA. Androgens in postmenopausal women: Production, possible role, and replacement options. Obstet. Gynecol. Surv. 56(6), 361-376 (2001)
19. Bachmann G, Bancroft J, Braunstein G et al. Female androgen insufficiency: The Princeton consensus statement on definition, classification, and assessment. Fertil. Steril. 77(4), 660-665 (2002)
20. Sherwin BB, Gelfand MM, Brender W. Androgen enhances sexual motivation in females: A prospective, crossover study of sex steroid administration in the surgical menopause. Psychosom. Med. 47(4), 339-351 (1985)
21. Flöter A, Nathorst-Böös J, Carlström K, von Schoultz B. Addition of testosterone to estrogen replacement therapy in oophorectomized women: Effects on sexuality and well-being. Climacteric 5(4), 357-365 (2002)
22. Lobo RA, Rosen RC, Yang HM, Block B, Van Der Hoop RG. Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire. Fertil. Steril. 79(6), 1341-1352 (2003)
23. Dobs AS, Nguyen T, Pace C, Roberts CP. Differential effects of oral estrogen versus oral estrogen-Androgen replacement therapy on body composition in postmenopausal women. J. Clin. Endocrinol. Metab. 87(4), 1509-1516 (2002)
24. Davis SR, van Der Mooren MJ, van Lunsen RH 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 13(3), 387-396 (2006)
25. Simon J, Braunstein G, Nachtigall L et al. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J. Clin. Endocrinol. Metab. 90(9), 5226-5233 (2005)
26. Shifren JL, Davis SR, Moreau M et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: Results from the INTIMATE NM1 study. Menopause 13(5), 770-779 (2006)
27. Buster JE, Kingsberg SA, Aguirre O et al. Testosterone patch for low sexual desire in surgically menopausal women: A randomized trial. Obstet. Gynecol. 105, 944-952 (2005)
28. Braunstein GD, Sundwall DA, Katz M et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: A randomized, placebo-controlled trial. Arch. Intern. Med. 165(14), 1582-1589 (2005)
29. Davis SR, Moreau M, Kroll R et al. APHRODITE Study Team: Testosterone for low libido in postmenopausal women not taking estrogen. N. Engl. J. Med. 359, 2005-2017 (2008)
30. Panay N, Al-Azzawi F, Bouchard C et al. Testosterone treatment of HSDD in naturally menopausal women: The ADORE study. Climacteric 13(2), 121-131 (2010)
31. Chakravarti S, Collins WP, Newton JR, Oram DH, Studd JW. Endocrine changes and symptomatology after oophorectomy in premenopausal women. Br. J. Obstet. Gynaecol. 84(10), 769-775 (1977)
32. Burger H, Hailes J, Nelson J, Menelaus M. Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women. Br. Med. J. (Clin. Res. Ed.). 294(6577), 936-937 (1987)
33. Nathorst-Böös J, Flöter A, Jarkander-Rolff M, Carlström K, Schoultz B. Treatment with percutanous testosterone gel in postmenopausal women with decreased libido - effects on sexuality and psychological general well-being. Maturitas 53(1), 11-18 (2006)
34. Maclaran K, Panay N. Managing low sexual desire in women. Womens Health 7(5), 571-581 (2011)
35. Al-Azzawi F, Bitzer J, Brandenburg U et al. Therapeutic options for postmenopausal female sexual dysfunction. Climacteric 13(2), 103-120 (2010)
36. Shifren JL, Braunstein GD, Simon JA et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N. Engl. J. Med. 343(10), 682-688 (2000)
37. Glaser R, York AE, Dimitrakakis C. Beneficial effects of testosterone therapy in women measured by the validated menopause rating scale (MRS). Maturitas 68(4), 355-361 (2011)
38. Davison SL, Bell RJ, Gavrilescu M et al. Testosterone improves verbal learning and memory in postmenopausal women: Results from a pilot study. Maturitas 70(3), 307-311 (2011)
39. Watts NB, Notelovitz M, Timmons MC, Addison WA, Wiita B, Downey LJ. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause. Obstet. Gynecol. 85(4), 529-537 (1995)
40. Barrett-Connor E, Young R, Notelovitz M et al. A two-year, double-blind comparison of estrogen-Androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles. J. Reprod. Med. 44(12), 1012-1020 (1999)
41. Garnett T, Studd J, Watson N, Savvas M, Leather A. The effects of plasma estradiol levels on increases in vertebral and femoral bone density following therapy with estradiol and estradiol with testosterone implants. Obstet. Gynecol. 79(6), 968-972 (1992)
42. Wierman ME, Basson R, Davis SR et al. Androgen therapy in women: An Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 91(10), 3697-3710 (2006)
43. Nachtigall L, Casson P, Lucas J, Schofield V, Melson C, Simon JA. Safety and tolerability of testosterone patch therapy for up to 4 years in surgically menopausal women receiving oral or transdermal oestrogen. Gynecol. Endocrinol. 27(1), 39-48 (2011)
44. van Staa TP, Sprafka JM. Study of adverse outcomes in women using testosterone therapy. Maturitas 62(1), 76-80 (2009)
45. Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH, Channer KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart 96(22), 1821-1825 (2010)
46. Rajkhowa M, Neary RH, Kumpatla P et al. Altered composition of high density lipoproteins in women with the polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 82(10), 3389-3394 (1997)
47. Pirwany IR, Fleming R, Greer IA, Packard CJ, Sattar N. Lipids and lipoprotein subfractions in women with PCOS: Relationship to metabolic and endocrine parameters. Clin. Endocrinol. (Oxf.) 54(4), 447-453 (2001)
48. Brand JS, van Der Schouw YT. Testosterone, SHBG and cardiovascular health in postmenopausal women. Int. J. Impot. Res. 22(2), 91-104 (2010)
49. Lambrinoudaki I, Christodoulakos G, Rizos D et al. Endogenous sex hormones and risk factors for atherosclerosis in healthy Greek postmenopausal women. Eur. J. Endocrinol. 154(6), 907-916 (2006)
50. Stork S, Bots ML, Grobbee DE, van Der Schouw YT. Endogenous sex hormones and C-reactive protein in healthy postmenopausal women. J. Intern. Med. 264(3), 245-253 (2008)
51. Bernini GP, Moretti A, Sgró M et al. Influence of endogenous androgens on carotid wall in postmenopausal women. Menopause 8(1), 43-50 (2001)
52. Karim R, Hodis HN, Stanczyk FZ, Lobo RA, Mack WJ. Relationship between serum levels of sex hormones and progression of subclinical atherosclerosis in postmenopausal women. J. Clin. Endocrinol. Metab. 93(1), 131-138 (2008)
53. Golden SH, Maguire A, Ding J et al. Endogenous postmenopausal hormones and carotid atherosclerosis: A case-control study of the atherosclerosis risk in communities cohort. Am. J. Epidemiol. 155(5), 437-445 (2002)
54. Debing E, Peeters E, Duquet W, Poppe K, Velkeniers B, Van den Brande P. Endogenous sex hormone levels in postmenopausal women undergoing carotid artery endarterectomy. Eur. J. Endocrinol. 156(6), 687-693 (2007)
55. Creatsa M, Armeni E, Stamatelopoulos K et al. Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women. Metabolism 61(2), 193-201 (2012)
56. Ouyang P, Vaidya D, Dobs A et al. Sex hormone levels and subclinical atherosclerosis in postmenopausal women: The multi-ethnic study of atherosclerosis. Atherosclerosis 204(1), 255-261 (2009)
57. Patel SM, Ratcliffe SJ, Reilly MP et al. Higher serum testosterone concentration in older women is associated with insulin resistance, metabolic syndrome, and cardiovascular disease. J. Clin. Endocrinol. Metab. 94(12), 4776-4784 (2009)
58. Rexrode KM, Manson JE, Lee IM et al. Sex hormone levels and risk of cardiovascular events in postmenopausal women. Circulation 108(14), 1688-1693 (2003)
59. Laughlin GA, Goodell V, Barrett-Connor E. Extremes of endogenous testosterone are associated with increased risk of incident coronary events in older women. J. Clin. Endocrinol. Metab. 95(2), 740-747 (2010)
60. Ellison KE, Ingelfinger JR, Pivor M, Dzau VJ. Androgen regulation of rat renal angiotensinogen messenger RNA expression. J. Clin. Invest. 83(6), 1941-1945 (1989)
61. Chen YF, Naftilan AJ, Oparil S. Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension 19(5), 456-463 (1992)
62. Adams MR, Williams JK, Kaplan JR. Effects of androgens on coronary artery atherosclerosis and atherosclerosis-related impairment of vascular responsiveness. Arterioscler. Thromb. Vasc. Biol. 15(5), 562-570 (1995)
63. Hutchison SJ, Sudhir K, Chou TM et al. Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta. J. Am. Coll. Cardiol. 29(4), 800-807 (1997)
64. Yue P, Chatterjee K, Beale C, Poole-Wilson PA, Collins P. Testosterone relaxes rabbit coronary arteries and aorta. Circulation 91(4), 1154-1160 (1995)
65. Bruck B, Brehme U, Gugel N et al. Gender-specific differences in the effects of testosterone and estrogen on the development of atherosclerosis in rabbits. Arterioscler. Thromb. Vasc. Biol. 17(10), 2192-2199 (1997)
66. Cooper BC, Gokina NI, Osol G. Testosterone replacement increases vasodilatory reserve in androgen-deficient female rats. Fertil. Steril. 87(2), 422-425 (2007)
67. Elbers JM, Giltay EJ, Teerlink T et al. Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Clin. Endocrinol. (Oxf.) 58(5), 562-571 (2003)
68. Elbers JM, Asscheman H, Seidell JC, Gooren LJ. Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals. Am. J. Physiol. 276, E317-E325 (1999)
69. Elbers JM, Asscheman H, Seidell JC, Megens JA, Gooren LJ. Long-term testosterone administration increases visceral fat in female to male transsexuals. J. Clin. Endocrinol. Metab. 82(7), 2044-2047 (1997)
70. Zang H, Carlström K, Arner P, Hirschberg AL. Effects of treatment with testosterone alone or in combination with estrogen on insulin sensitivity in postmenopausal women. Fertil. Steril. 86, 136-144 (2006)
71. Leão LM, Duarte MP, Silva DM, Bahia PR, Coeli CM, De Farias ML. Influence of methyltestosterone postmenopausal therapy on plasma lipids, inflammatory factors, glucose metabolism and visceral fat: A randomized study. Eur. J. Endocrinol. 154(1), 131-139 (2006)
72. Gruber DM, Sator MO, Kirchengast S, Joura EA, Huber JC. Effect of percutaneous androgen replacement therapy on body composition and body weight in postmenopausal women. Maturitas 29(3), 253-259 (1998)
73. Hickok LR, Toomey C, Speroff L. A comparison of esterified estrogens with and without methyltestosterone: Effects on endometrial histology and serum lipoproteins in postmenopausal women. Obstet. Gynecol. 82(6), 919-924 (1993)
74. Basaria S, Nguyen T, Rosenson RS, Dobs AS. Effect of methyl testosterone administration on plasma viscosity in postmenopausal women. Clin. Endocrinol. (Oxf.) 57(2), 209-214 (2002)
75. Warnock JK, Swanson SG, Borel RW et al. ESTRATEST clinical study group: Combined esterified estrogens and methyltestosterone versus esterified estrogens alone in the treatment of loss of sexual interest in surgically menopausal women. Menopause 12(4), 374-384 (2005)
76. Raisz LG, Wiita B, Artis A et al. Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. J. Clin. Endocrinol. Metab. 81(1), 37-43 (1996)
77. Worboys S, Kotsopoulos D, Teede H, McGrath B, Davis SR. Evidence that parenteral testosterone therapy may improve endothelium-dependent and -independent vasodilation in postmenopausal women already receiving estrogen. J. Clin. Endocrinol. Metab. 86(1), 158-161 (2001)
78. Hak AE, Westendorp IC, Pols HA, Hofman A, Witteman JC. High-dose testosterone is associated with atherosclerosis in postmenopausal women. Maturitas 56(2), 153-160 (2007)
79. Penotti M, Sironi L, Cannata L et al. Effects of androgen supplementation of hormone replacement therapy on the vascular reactivity of cerebral arteries. Fertil. Steril. 76(2), 235-240 (2001)
80. van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin. Endocrinol. (Oxf.) 47(3), 337-342 (1997)
81. White WB, Grady D, Giudice LC, Berry SM, Zborowski J, Snabes MC. A cardiovascular safety study of LibiGel (testosterone gel) in postmenopausal women with elevated cardiovascular risk and hypoactive sexual desire disorder. Am. Heart J. 163(1), 27-32 (2012)
82. Corbould A. Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. J. Endocrinol. 192(3), 585-594 (2007)
83. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for Type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: A prospective, controlled study in 254 affected women. J. Clin. Endocrinol. Metab. 84(1), 165-169 (1999)
84. Weinberg ME, Manson JE, Buring JE et al. Low sex hormone-binding globulin is associated with the metabolic syndrome in postmenopausal women. Metabolism 55(11), 1473-1480 (2006)
85. Golden SH, Ding J, Szklo M, Schmidt MI, Duncan BB, Dobs A. Glucose and insulin components of the metabolic syndrome are associated with hyperandrogenism in postmenopausal women: The atherosclerosis risk in communities study. Am. J. Epidemiol. 160(6), 540-548 (2004)
86. Oh JY, Barrett-Connor E, Wedick NM et al. Rancho Bernardo study: Endogenous sex hormones and the development of Type 2 diabetes in older men and women: The Rancho Bernardo study. Diabetes Care 25(1), 55-60 (2002)
87. Lovejoy JC, Bray GA, Greeson CS et al. Oral anabolic steroid treatment, but not parenteral androgen treatment, decreases abdominal fat in obese, older men. Int. J. Obes. Relat. Metab. Disord. 19, 614-624 (1995)
88. Iellamo F, Volterrani M, Caminiti G et al. Testosterone therapy in women with chronic heart failure: A pilot double-blind, randomized, placebo-controlled study. J. Am. Coll. Cardiol. 56(16), 1310-1316 (2010)
89. Tuckerman EM, Okon MA, Li T, Laird SM. Do androgens have a direct effect on endometrial function? An in vitro study. Fertil. Steril. 74(4), 771-779 (2000)
90. Yamaki J, Yamamoto T, Okada H. Aromatization of androstenedione by normal and neoplastic endometrium of the uterus. J. Steroid Biochem. 22(1), 63-66 (1985)
91. Legro RS, Kunselman AR, Miller SA, Satyaswaroop PG. Role of androgens in the growth of endometrial carcinoma: An in vivo animal model. Am. J. Obstet. Gynecol. 184(3), 303-308 (2001)
92. Zang H, Sahlin L, Masironi B, Eriksson E, Lindén Hirschberg A. Effects of testosterone treatment on endometrial proliferation in postmenopausal women. J. Clin. Endocrinol. Metab. 92(6), 2169-2175 (2007)
93. Perrone AM, Cerpolini S, Maria Salfi NC et al. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J. Sex Med. 6(11), 3193-3200 (2009)
94. Hackenberg R, Hofmann J, Hölzel F, Schulz KD. Stimulatory effects of androgen and antiandrogen on the in vitro proliferation of human mammary carcinoma cells. J. Cancer Res. Clin. Oncol. 114(6), 593-601 (1988)
95. Dimitrakakis C, Zhou J, Wang J et al. A physiologic role for testosterone in limiting estrogenic stimulation of the breast. Menopause 10(4), 292-298 (2003)
96. Poulin R, Baker D, Poirier D, Labrie F. Androgen and glucocorticoid receptor-mediated inhibition of cell proliferation by medroxyprogesterone acetate in ZR-75-1 human breast cancer cells. Breast Cancer Res. Treat. 13(2), 161-172 (1989)
97. Ortmann J, Prifti S, Bohlmann MK, Rehberger-Schneider S, Strowitzki T, Rabe T. Testosterone and 5a-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines. Gynecol. Endocrinol. 16(2), 113-120 (2002)
98. Lapointe J, Fournier A, Richard V, Labrie C. Androgens down-regulate bcl-2 protooncogene expression in ZR-75-1 human breast cancer cells. Endocrinology 140(1), 416-421 (1999)
99. Kandouz M, Lombet A, Perrot JY et al. Proapoptotic effects of antiestrogens, progestins and androgen in breast cancer cells. J. Steroid Biochem. Mol. Biol. 69(1-6), 463-471 (1999)
100. Dimitrakakis C, Zhou J, Bondy CA. Androgens and mammary growth and neoplasia. Fertil. Steril. 77(Suppl. 4), S26-S33 (2002)
101. Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA. Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB J. 14(12), 1725-1730 (2000)
102. Somboonporn W, Davis SR. National Health and Medical Research Council. Testosterone effects on the breast: Implications for testosterone therapy for women. Endocr. Rev. 25(3), 374-388 (2004)
103. Key T, Appleby P, Barnes I et al. 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. 94(8), 606-616 (2002)
104. Tworoger SS, Rosner BA, Willett WC, Hankinson SE. The combined influence of multiple sex and growth hormones on risk of postmenopausal breast cancer: A nested case-control study. Breast Cancer Res. 13(5), R99 (2011)
105. Beattie MS, Costantino JP, Cummings SR et al. Endogenous sex hormones, breast cancer risk, and tamoxifen response: An ancillary study in the NSABP breast cancer prevention trial (P-1). J. Natl Cancer Inst. 98(2), 110-115 (2006)
106. Danforth KN, Eliassen AH, Tworoger SS et al. The association of plasma androgen levels with breast, ovarian and endometrial cancer risk factors among postmenopausal women. Int. J. Cancer. 126(1), 199-207 (2010)
107. De França Neto AH, Rogatto S, Do Amorim MM, Tamanaha S, Aoki T, Aldrighi JM. Oncological repercussions of polycystic ovary syndrome. Gynecol. Endocrinol. 26(10), 708-711 (2010)
108. Ewertz M. Influence of non-contraceptive exogenous and endogenous sex hormones on breast cancer risk in Denmark. Int. J. Cancer 42(6), 832-838 (1988)
109. 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. 166(14), 1483-1489 (2006)
110. Ness RB, Albano JD, McTiernan A, Cauley JA. Influence of estrogen plus testosterone supplementation on breast cancer. Arch. Intern. Med. 169(1), 41-46 (2009)
111. Brinton LA, Hoover R, Fraumeni JF. Menopausal oestrogens and breast cancer risk: An expanded case-control study. Br. J. Cancer 54(5), 825-832 (1986)
112. Dimitrakakis C, Jones RA, Liu A, Bondy CA. Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. Menopause 11(5), 531-535 (2004)
113. 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. 332(24), 1589-1593 (1995)
114. Jick SS, Hagberg KW, Kaye JA, Jick H. Postmenopausal estrogen-containing hormone therapy and the risk of breast cancer. Obstet. Gynecol. 113(1), 74-80 (2009)
115. Davis SR, Wolfe R, Farrugia H, Ferdinand A, Bell RJ. The incidence of invasive breast cancer among women prescribed testosterone for low libido. J. Sex Med. 6(7), 1850-1856 (2009)
116. Hofling M, Hirschberg AL, Skoog L, Tani E, Hägerström T, von Schoultz B. Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women. Menopause 14(2), 183-190 (2007)
117. Hofling M, Lundström E, Azavedo E, Svane G, Hirschberg AL, von Schoultz B. Testosterone addition during menopausal hormone therapy: Effects on mammographic breast density. Climacteric 10(2), 155-163 (2007)
118. Davis SR, Hirschberg AL, Wagner LK, Lodhi I, von Schoultz B. The effect of transdermal testosterone on mammographic density in postmenopausal women not receiving systemic estrogen therapy. J. Clin. Endocrinol. Metab. 94(12), 4907-4913 (2009)