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
-
2
Simpson E R.
Role of aromatase in sex steroid action.
J Mol Endocrinol.
2000;
25
149-156
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
14
Judd H L, Yen S S.
Serum androstenedione and testosterone levels during the menstrual cycle.
J Clin Endocrinol Metab.
1973;
36
475-481
-
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
-
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
-
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
-
18
Davis S R.
Androgens and female sexuality.
J Gend Specif Med.
2000;
3
36-40
-
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
-
20
Lobo R A.
Androgens in postmenopausal women: production, possible role, and replacement options.
Obstet Gynecol Surv.
2001;
56
361-376
-
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
-
22
Simerly R B.
Distribution and regulation of steroid hormone receptor gene expression in the central nervous system.
Adv Neurol.
1993;
59
207-226
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
32
Cameron D R, Braunstein G D.
Androgen replacement therapy in women.
Fertil Steril.
2004;
82
273-289
-
33
Davis S, Davison S, Donath S, Bell R.
Circulating androgen levels and self-reported sexual function in women.
JAMA.
2005;
294
91-96
-
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;
-
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;
-
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
-
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
-
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
-
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
-
40 Shepanek M. A study of estrogen androgen replacement therapy (EART) versus estrogen replacement therapy [dissertation]. Washington, DC; Georgetown University 1999
-
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
-
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
-
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;
-
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
-
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
-
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
-
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.
-
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
-
49
Vanderschueren D, Vandenput L, Boonen S et al..
Androgens and bone.
Endocr Rev.
2004;
25
389-425
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
58
Sherwin B B.
Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women.
Psychoneuroendocrinology.
1988;
13
345-357
-
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
-
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
-
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
-
62
Christiansen K.
Behavioural effects of androgen in men and women.
J Endocrinol.
2001;
170
39-48
-
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
-
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
-
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
-
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;
-
67
Somboonporn W, Davis S R.
Postmenopausal testosterone therapy and breast cancer risk.
Maturitas.
2004;
49
267-275
-
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
-
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
-
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
-
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
-
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
