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Semin Reprod Med 2006; 24(2): 115-124
DOI: 10.1055/s-2006-939570
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Testosterone Therapy for Postmenopausal Women: Efficacy and Safety

Woraluk Somboonporn1
  • 1Assistant Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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Publication History

Publication Date:
24 April 2006 (online)

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ABSTRACT

The treatment of postmenopausal women with a variety of androgen formulations is increasing, despite the lack of clear guidelines regarding the diagnosis of androgen insufficiency. This review summarizes evidence on the efficacy and safety of adding testosterone to hormone therapy in postmenopausal women. Fair to good evidence exists that the use of testosterone in combination with hormone therapy has both benefits and risks. The benefits are an improvement in sexual function with various regimens of testosterone use (good evidence), an improved sense of well-being with transdermal testosterone (fair evidence), and a reduction in triglyceride levels with methyl testosterone (fair evidence). The most consistent risk is a reduction in high-density lipoprotein (HDL) cholesterol, particularly with methyl testosterone (good evidence). There has been insufficient reporting of other side effects; hence, testosterone therapy should be used with caution. The use of testosterone may be justified in specific clinical circumstances and should be limited to short-term use; long-term studies are not available. Close surveillance for HDL cholesterol and other side effects is necessary.

KEYWORDS

Hormone therapy - postmenopausal women - testosterone

REFERENCES

  • 1 Davis S. Androgen replacement in women: a commentary.  J Clin Endocrinol Metab. 1999;  84 1886-1891
    CrossrefPubMedSearch in Google Scholar
  • 2 Simpson E R. Role of aromatase in sex steroid action.  J Mol Endocrinol. 2000;  25 149-156
    CrossrefPubMedSearch in Google Scholar
  • 3 Bachmann G, Bancroft J, Braunstein G et al.. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment.  Fertil Steril. 2002;  77 660-665
    CrossrefPubMedSearch in Google Scholar
  • 4 Heinonen P K, Koivula T, Rajaniemi H, Pystynen P. Peripheral and ovarian venous concentrations of steroid and gonadotropin hormones in postmenopausal women with epithelial ovarian tumors.  Gynecol Oncol. 1986;  25 1-10
    CrossrefPubMedSearch in Google Scholar
  • 5 Laughlin G A, Barrett-Connor E, Kritz-Silverstein D, von Muhlen D. Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: the Rancho Bernardo Study.  J Clin Endocrinol Metab. 2000;  85 645-651
    PubMedSearch in Google Scholar
  • 6 Hughes Jr C L, Wall L L, Creasman W T. Reproductive hormone levels in gynecologic oncology patients undergoing surgical castration after spontaneous menopause.  Gynecol Oncol. 1991;  40 42-45
    CrossrefPubMedSearch in Google Scholar
  • 7 Judd H L, Lucas W E, Yen S S. Effect of oophorectomy on circulating testosterone and androstenedione levels in patients with endometrial cancer.  Am J Obstet Gynecol. 1974;  118 793-798
    PubMedSearch in Google Scholar
  • 8 Bancroft J, Cawood E H. Androgens and the menopause; a study of 40-60-year-old women.  Clin Endocrinol (Oxf). 1996;  45 577-587
    CrossrefPubMedSearch in Google Scholar
  • 9 Burger H G, Dudley E C, Hopper J L et al.. The endocrinology of the menopausal transition: a cross-sectional study of a population-based sample.  J Clin Endocrinol Metab. 1995;  80 3537-3545
    CrossrefPubMedSearch in Google Scholar
  • 10 Overlie I, Moen M H, Morkrid L, Skjaeraasen J S, Holte A. The endocrine transition around menopause-a five years prospective study with profiles of gonadotropines, estrogens, androgens and SHBG among healthy women.  Acta Obstet Gynecol Scand. 1999;  78 642-647
    CrossrefPubMedSearch in Google Scholar
  • 11 Rannevik G, Jeppsson S, Johnell O et al.. A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density.  Maturitas. 1995;  21 103-113
    CrossrefPubMedSearch in Google Scholar
  • 12 Rozenberg S, Bosson D, Peretz A, Caufriez A, Robyn C. Serum levels of gonadotrophins and steroid hormones in the post-menopause and later life.  Maturitas. 1988;  10 215-224
    CrossrefPubMedSearch in Google Scholar
  • 13 Burger H G, Dudley E C, Cui J, Dennerstein L, Hopper J L. 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 2832-2838
    CrossrefPubMedSearch in Google Scholar
  • 14 Judd H L, Yen S S. Serum androstenedione and testosterone levels during the menstrual cycle.  J Clin Endocrinol Metab. 1973;  36 475-481
    PubMedSearch in Google Scholar
  • 15 Massafra C, De F C, Agnusdei D P, Gioia D, Bagnoli F. Androgens and osteocalcin during the menstrual cycle.  J Clin Endocrinol Metab. 1999;  84 971-974
    CrossrefPubMedSearch in Google Scholar
  • 16 Mushayandebvu T, Castracane V D, Gimpel T, Adel T, Santoro N. Evidence for diminished midcycle ovarian androgen production in older reproductive aged women.  Fertil Steril. 1996;  65 721-723
    PubMedSearch in Google Scholar
  • 17 Hormone therapy for the prevention of chronic conditions in postmenopausal women: recommendations from the U.S. Preventive Services Task Force.  Ann Intern Med. 2005;  142 855-860
    PubMedSearch in Google Scholar
  • 18 Davis S R. Androgens and female sexuality.  J Gend Specif Med. 2000;  3 36-40
    PubMedSearch in Google Scholar
  • 19 Davis S R. Rationale for treating hypoandrogenism in women. In: Bagatell C, Bremner W Androgens in Health and Disease. Totowa, NJ; Humana Press 2003: 365-379
    Search in Google Scholar
  • 20 Lobo R A. Androgens in postmenopausal women: production, possible role, and replacement options.  Obstet Gynecol Surv. 2001;  56 361-376
    CrossrefPubMedSearch in Google Scholar
  • 21 Wang C, Swerdloff R. Androgen pharmacology and delivery systems. In: Bagatell C, Bremner W Androgens in Health and Disease. Totowa, NJ; Humana Press 2003: 141-153
    Search in Google Scholar
  • 22 Simerly R B. Distribution and regulation of steroid hormone receptor gene expression in the central nervous system.  Adv Neurol. 1993;  59 207-226
    PubMedSearch in Google Scholar
  • 23 Celotti F, Negri-Cesi P, Poletti A. Steroid metabolism in the mammalian brain: 5alpha-reduction and aromatization.  Brain Res Bull. 1997;  44 365-375
    CrossrefPubMedSearch in Google Scholar
  • 24 Maes M, Meltzer H Y. The serotonin hypothesis of major depression. In: Bloom FE, Kupfer DJ Psychopharmacology. The Fourth Generation of Progress. New York; Raven Press 1995: 933-944
    Search in Google Scholar
  • 25 Shifren J L, Braunstein G D, Simon J A et al.. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy.  N Engl J Med. 2000;  343 682-688
    CrossrefPubMedSearch in Google Scholar
  • 26 Buster J E, Kingsberg S A, Aguirre O et al.. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial.  Obstet Gynecol. 2005;  105 944-952
    CrossrefPubMedSearch in Google Scholar
  • 27 Montgomery J C, Appleby L, Brincat M et al.. Effect of oestrogen and testosterone implants on psychological disorders in the climacteric.  Lancet. 1987;  1 297-299
    PubMedSearch in Google Scholar
  • 28 Sherwin B B, Gelfand M M. Differential symptom response to parenteral estrogen and/or androgen administration in the surgical menopause.  Am J Obstet Gynecol. 1985;  151 153-160
    PubMedSearch in Google Scholar
  • 29 Floter A, Nathorst-Boos J, Carlstrom K, von Schoultz B. Addition of testosterone to estrogen replacement therapy in oophorectomized women: effects on sexuality and well-being.  Climacteric. 2002;  5 357-365
    PubMedSearch in Google Scholar
  • 30 Regestein Q R, Friebely J, Shifren J, Schiff I. Neuropsychological effects of methyltestosterone in women using menopausal hormone replacement.  J Womens Health Gend Based Med. 2001;  10 671-676
    CrossrefPubMedSearch in Google Scholar
  • 31 Bancroft J. Androgens and sexual function in men and women. In: Bagatell C, Bremner W Androgens in Health and Disease. Totowa, NJ; Humana Press 2003: 259-290
    Search in Google Scholar
  • 32 Cameron D R, Braunstein G D. Androgen replacement therapy in women.  Fertil Steril. 2004;  82 273-289
    CrossrefPubMedSearch in Google Scholar
  • 33 Davis S, Davison S, Donath S, Bell R. Circulating androgen levels and self-reported sexual function in women.  JAMA. 2005;  294 91-96
    CrossrefPubMedSearch in Google Scholar
  • 34 Braunstein G, Shifren J, Simon J et al.. Testosterone patches for the treatment of low sexual desire in surgically menopausal women. Paper presented at the NAMS 2003, 14th Annual Meeting May 17-21, 2003 Jackson Hole, WY;
    Search in Google Scholar
  • 35 Davis S, Lucas J, Moufarege A, Braunstein G. Testosterone patches for treatment of low sexual desire in surgically menopausal women. Paper presented at: 7th Australian Menopause Society Congress November 13-15, 2003 Tasmania, Australia;
    Search in Google Scholar
  • 36 Davis S R, McCloud P, Strauss B J, Burger H. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality.  Maturitas. 1995;  21 227-236
    CrossrefPubMedSearch in Google Scholar
  • 37 Lobo R A, Rosen R C, Yang H M, Block B, Van Der Hoop R G. 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. 2003;  79 1341-1352
    CrossrefPubMedSearch in Google Scholar
  • 38 Sarrel P, Dobay B, Wiita B. Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses.  J Reprod Med. 1998;  43 847-856
    PubMedSearch in Google Scholar
  • 39 Dobs A S, Nguyen T, Pace C, Roberts C P. Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women.  J Clin Endocrinol Metab. 2002;  87 1509-1516
    CrossrefPubMedSearch in Google Scholar
  • 40 Shepanek M. A study of estrogen androgen replacement therapy (EART) versus estrogen replacement therapy [dissertation]. Washington, DC; Georgetown University 1999
    Search in Google Scholar
  • 41 Sherwin B B, Gelfand M M, Brender W. Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause.  Psychosom Med. 1985;  47 339-351
    PubMedSearch in Google Scholar
  • 42 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). 1987;  294 936-937
    PubMedSearch in Google Scholar
  • 43 Luciano A, Miller B, Sequenzia L et al.. The effect of sublingual micronized estradiol, progesterone and testosterone on menopausal symptoms and sexual health. Paper presented at: the 9th International Menopause Society World Congress on the Menopause October 17-20, 1999 Yokohama, Japan;
    Search in Google Scholar
  • 44 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. 2001;  76 235-240
    CrossrefPubMedSearch in Google Scholar
  • 45 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. 1999;  44 1012-1020
    PubMedSearch in Google Scholar
  • 46 Dow M G, Hart D M, Forrest C A. Hormonal treatments of sexual unresponsiveness in postmenopausal women: a comparative study.  Br J Obstet Gynaecol. 1983;  90 361-366
    PubMedSearch in Google Scholar
  • 47 Somboonporn W, Davis S, Seif M, Bell R. Testosterone for peri- and postmenopausal women. The Cochrane Database of Systematic Reviews 2005; issue 4. Article No: CD004509. 
    PubMed
  • 48 Kenny A M, Raisz L G. Androgens and bone. In: Bagatell C, Bremner W Androgens in Health and Disease. Totowa, NJ; Humana Press 2003: 221-232
    Search in Google Scholar
  • 49 Vanderschueren D, Vandenput L, Boonen S et al.. Androgens and bone.  Endocr Rev. 2004;  25 389-425
    CrossrefPubMedSearch in Google Scholar
  • 50 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. 1992;  79 968-972
    PubMedSearch in Google Scholar
  • 51 Watts N B, Notelovitz M, Timmons M C et al.. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause.  Obstet Gynecol. 1995;  85 529-537
    CrossrefPubMedSearch in Google Scholar
  • 52 Miller J, Chan B K, Nelson H D. Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the U.S. Preventive Services Task Force.  Ann Intern Med. 2002;  136 680-690
    PubMedSearch in Google Scholar
  • 53 Raisz L G, 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. 1996;  81 37-43
    CrossrefPubMedSearch in Google Scholar
  • 54 Davis S R, Walker K Z, Strauss B J. Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women.  Menopause. 2000;  7 395-401
    CrossrefPubMedSearch in Google Scholar
  • 55 Bates K A, Harvey A R, Carruthers M, Martins R N. Androgens, andropause and neurodegeneration: exploring the link between steroidogenesis, androgens and Alzheimer's disease.  Cell Mol Life Sci. 2005;  62 281-292
    CrossrefPubMedSearch in Google Scholar
  • 56 Rupprecht R, di Michele F, Hermann B et al.. Neuroactive steroids: molecular mechanisms of action and implications for neuropsychopharmacology.  Brain Res Brain Res Rev. 2001;  37 59-67
    CrossrefPubMedSearch in Google Scholar
  • 57 Wisniewski A B, Nguyen T T, Dobs A S. Evaluation of high-dose estrogen and high-dose estrogen plus methyltestosterone treatment on cognitive task performance in postmenopausal women.  Horm Res. 2002;  58 150-155
    CrossrefPubMedSearch in Google Scholar
  • 58 Sherwin B B. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women.  Psychoneuroendocrinology. 1988;  13 345-357
    CrossrefPubMedSearch in Google Scholar
  • 59 Hickok L R, 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. 1993;  82 919-924
    PubMedSearch in Google Scholar
  • 60 Simon J, Klaiber E, Wiita B, Bowen A, Yang H M. Differential effects of estrogen-androgen and estrogen-only therapy on vasomotor symptoms, gonadotropin secretion, and endogenous androgen bioavailability in postmenopausal women.  Menopause. 1999;  6 138-146
    PubMedSearch in Google Scholar
  • 61 Sherwin B B, Gelfand M M. Effects of parenteral administration of estrogen and androgen on plasma hormone levels and hot flushes in the surgical menopause.  Am J Obstet Gynecol. 1984;  148 552-557
    PubMedSearch in Google Scholar
  • 62 Christiansen K. Behavioural effects of androgen in men and women.  J Endocrinol. 2001;  170 39-48
    CrossrefPubMedSearch in Google Scholar
  • 63 Sherwin B B, Gelfand M M. Sex steroids and affect in the surgical menopause: a double-blind, cross-over study.  Psychoneuroendocrinology. 1985;  10 325-335
    CrossrefPubMedSearch in Google Scholar
  • 64 Wu F CW, von Eckardstein A. Androgens and coronary artery disease. In: Bagatell C, Bremner W Androgens in Health and Disease. Totowa, NJ; Humana Press 2003: 191-220
    Search in Google Scholar
  • 65 Farish E, Fletcher C, Hart D et al.. The effects of hormone implants on serum lipoproteins and steroid hormones in bilaterally oophorectomised women.  Acta Endocrinol (Copenh). 1984;  106 116-120
    PubMedSearch in Google Scholar
  • 66 Luciano A, Miller B, Sequenzia L et al.. The effect of sublingual micronized estradiol, progesterone and testosterone on serum lipids and apolipoproteins. Paper presented at: the 9th Annual Meeting of the North American Menopause Society September 17-19, 1998 Toronto, Canada;
    Search in Google Scholar
  • 67 Somboonporn W, Davis S R. Postmenopausal testosterone therapy and breast cancer risk.  Maturitas. 2004;  49 267-275
    CrossrefPubMedSearch in Google Scholar
  • 68 Brinton L A, Hoover R, Fraumeni Jr J F. Menopausal oestrogens and breast cancer risk: an expanded case-control study.  Br J Cancer. 1986;  54 825-832
    PubMedSearch in Google Scholar
  • 69 Ewertz M. Influence of non-contraceptive exogenous and endogenous sex hormones on breast cancer risk in Denmark.  Int J Cancer. 1988;  42 832-838
    PubMedSearch in Google Scholar
  • 70 Dimitrakakis C, Jones R, Liu A, Bondy C. Breast cancer incidence in Australian women using testosterone in addition to estrogen replacement. Proceedings of the 85th Annual Meeting of the Endocrine Society. Philadelphia; The Endocrine Society Press 2003
    Search in Google Scholar
  • 71 van Kesteren P J, Asscheman H, Megens J A, Gooren L J. Mortality and morbidity in transsexual subjects treated with cross-sex hormones.  Clin Endocrinol (Oxf). 1997;  47 337-342
    CrossrefPubMedSearch in Google Scholar
  • 72 Canadian Task Force for Periodic Health Care .Evidence-based clinical prevention. Available at: http://www.ctfphc.org Accessed June 27, 2005

 Dr.
Woraluk SomboonpornM.D. FRTCOG 

Department of Obstetrics and Gynecology, Faculty of Medicine

Khon Kaen University, Khon Kaen, 40002, Thailand

Email: wsomboonporn@yahoo.com