1- Myers et al. (3737. Myers LS, Dixen J, Morrissette D, Carmichael M, Davidson JM. Effects of estrogen, androgen, and progestin on sexual psychophysiology and behavior in postmenopausal women. J Clin Endocrinol Metab. 1990;70(4):1124-31, http://dx.doi.org/10.1210/jcem-70-4-1124. http://dx.doi.org/10.1210/jcem-70-4-1124...
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Physiologically menopausal women (n = 40) |
Randomized, double-blind, placebo-controlled trial |
10 weeks |
Group 1: CEEs, 0.625 mg/dayGroup 2: CEEs, 0.625 mg/day + MPA, 5 mg/dayGroup 3: CEEs, 0.625 mg/day + MT, 5 mg/dayGroup 4: placebo |
Increased pleasure from masturbationNo changes in mood, behavior, or sexual arousalNote: Sexual function was normal at the outset, and there was no ERT prior to the beginning of the study |
2- Davis et al. (3838. Davis SR, McCloud P, Strauss BJ, Burger H. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Maturitas. 1995;21(3):227-36, http://dx.doi.org/10.1016/0378-5122(94)00898-H. http://dx.doi.org/10.1016/0378-5122(94)0...
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Physiologically menopausal women (n = 34) |
Randomized, single-blind, trial |
3 months; 2 years |
Group 1: T implants, 50 mg + estradiol implants, 50 mg |
Increased sexual activity, sexual satisfaction, sexual pleasure, and orgasm |
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Group 2: Estradiol implants, 50 mg only |
Increased bone mineral density |
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Progesterone was administered to women who had not undergone hysterectomy |
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3- Shifren et al. (4545. 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(10):682-8.) |
Surgically menopausal women with sexual dysfunction (n = 75) |
Randomized, double-blind, placebo-controlled trial |
12 weeks |
Group 1: CEEs, 0.625 mg/day + transdermal T patch, 150 µg/day |
Increased sexual activity, sexual pleasure, orgasm, sexual fantasy, and well-being in the group of women receiving daily doses of 300 µg of T |
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Group 2: CEEs, 0.625 mg/day orally + transdermal T patch, 300 µg/day |
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Group 3: CEEs, 0.625 mg/day orally + placebo |
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4- Louie K.D. (4646. Louie KD. Transdermal testosterone replacement to improve women's sexual functioning. Can Fam Physician. 2001;47:1571-3.) |
Surgically menopausal women in the 31-56 year age bracket (n = 75) |
Randomized, crossover, double-blind, placebo-controlled trial |
12 weeks |
Group 1: Transdermal T patches, 150 µg/dayGroup 2: Transdermal T patches, 300 µg/dayGroup 3: placebo |
The 300-µg/day dose was found to have significantly increased the frequency of sexual activity, sexual pleasure, and orgasm. However, it did not increase sexual desire, arousal, or receptivity |
5- Dobs et al. (4747. 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. Journal of Clinical Endocrinology and Metabolism. 2002;87:1509-16, http://dx.doi.org/10.1210/jcem.87.4.8362. http://dx.doi.org/10.1210/jcem.87.4.8362...
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Physiologically menopausal women (n = 36) |
Randomized, parallel, double-blind, trial |
16 weeks |
Group 1: EEs, 1.25 mg/day (n = 18) |
Increased sexual activity and pleasure in women receiving EEs (1.25 mg/day) + MT (2.5 mg/day) |
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Group 2: EEs, 1.25 mg/day + MT, 2.5 mg/day (n = 18) |
Increased lean body mass, increased muscle strength, and reduced body fat in women receiving EEs (1.25 mg/day) + MT (2.5 mg/day) |
6- Floter et al. (4949. Floter A, Nathorst-Boos J, Carlstrom K, Schoultz B. Addition of testosterone to estrogen replacement in oophorectomized women: effects on sexuality and well-being, Climacteric. 2002;5(4):357-65.) |
Surgically postmenopausal women (n = 50) |
Randomized, double-blind, placebo-controlled trial |
24 weeks |
Group1: T undecanoate, 40 mg/day + estradiol valerate, 2 mg/dayGroup 2: Placebo + estradiol valerate, 2 mg/day |
The use of estradiol valerate in combination with T undecanoate improved sexual response more significantly than did the use of estradiol valerate alone.The two groups were similar in terms of improved well-being and self-esteem. |
7- Goldstat et al. (3939. Goldstat R, Briganti E, Tran J, Wolfe R, Davis SR. Transdermal testosterone therapy improves wellbeing, mood, and sexual function in premenopausal women. Menopause. 2003;10:390-8, http://dx.doi.org/10.1097/01.GME.0000060256.03945.20. http://dx.doi.org/10.1097/01.GME.0000060...
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Premenopausal women with HSDD |
Randomized, crossover, placebo-controlled trial |
12 weeks |
Group1: T cream, 10 mg/dayGroup 2: Placebo |
Improved sexual function, well-being, and mood |
8- Lobo et al. (4848. 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. 2003;(79):1341-52, http://dx.doi.org/10.1016/S0015-0282(03)00358-3. http://dx.doi.org/10.1016/S0015-0282(03)...
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Postmenopausal women (n = 218) |
Randomized, double-blind, trial |
16 weeks |
Group 1: EEs, 0.625 mg/day (n = 111) |
Improved libido and increased sexual frequency in women receiving EEs + MT |
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Group 2: EEs, 0.625 mg/day + MT, 1.25 mg/day (n = 107) |
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9- Buster et al. (2727. 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(5 Pt 1):944-52, http://dx.doi.org/10.1097/01.AOG.0000158103.27672.0d. http://dx.doi.org/10.1097/01.AOG.0000158...
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Surgically menopausal women (n = 533) |
Multicenter randomized, parallel, double-blind, placebo-controlled trial |
24 weeks |
Group 1: daily ERT + transdermal T patches, 300 µg/day, applied twice weeklyGroup 2: daily ERT+ placebo, applied twice weekly |
Significantly increased sexual desire and frequency of sexual activityImprovement in moodLow incidence of androgenic side effects on the skin |
10- Simon et al. (2626. Simon J, Braunstein G, Nachtigall L, Utian W, Katz M, Miller S, et al. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab. 2005;90(9):5226-33, http://dx.doi.org/10.1210/jc.2004-1747. http://dx.doi.org/10.1210/jc.2004-1747...
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Surgically menopausal women (n = 562) |
Multicenter randomized, parallel, double-blind, placebo-controlled trial |
24 weeks |
Group 1: daily ERT + Transdermal T patches, 300 µg/day, applied twice weekly (n = 283)Group 2: daily ERT+ placebo, applied twice weekly (n = 279) |
Slightly increased sexual desire and frequency of sexual activityImprovement in moodLow incidence of androgenic side effects on the skin |
11- Braunstein et al. (4040. 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: A randomized, placebo controlled trial. Arch Intern Med. 2005;165(14):1582-9, http://dx.doi.org/10.1001/archinte.165.14.1582. http://dx.doi.org/10.1001/archinte.165.1...
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Surgically menopausal women (n = 447) |
Multicenter randomized, parallel, double-blind, placebo controlled trial |
24 weeks |
Group 1: daily ERT + Transdermal T patches, 150 µg/day, applied twice weekly (n = 107)Group 2: daily ERT + Transdermal T patches, 300 µg/day, applied twice weekly (n = 110)Group 3: daily ERT + Transdermal T patches 450 µg/day, applied twice weekly (n = 111)Group 4: daily ERT + placebo, applied twice weekly (n = 119) |
At a dose of 300 µg, T was well tolerated and produced increases in libido and sexual frequencyIncreased androgenic (cutaneous) side effects in the women receiving T at a dose of 450 µg |
12- Davis et al. (2828. Davis SR, van der Mooren MJ, van Lunsen RH, Lopes P, Ribot C, 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(3):387-96, http://dx.doi.org/10.1097/01.gme.0000179049.08371.c7. http://dx.doi.org/10.1097/01.gme.0000179...
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Women with HSDD submitted to oophorectomy and receiving transdermal estrogen (n = 77) |
Randomized, double-blind, placebo-controlled trial |
24 weeks |
The women receiving transdermal estrogen started to receive 300 µg/day of T (n = 37) or placebo (n = 40) |
There was an increase in sexual desire, sexual arousal, and orgasm. |
13- Paula et al. (4141. Paula FJ, Soares JM Jr, Haidar MA, Lima GR, Baracat EC. The benefits of androgens combined with hormone replacement therapy regarding to patients with postmenopausal sexual symptoms. Maturitas. 2007;56(1):69-77, http://dx.doi.org/10.1016/j.maturitas.2006.06.005. http://dx.doi.org/10.1016/j.maturitas.20...
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Postmenopausal women with sexual dysfunction (n = 85) |
Randomized, crossover, double-blind, placebo-controlled trial |
4 months |
Group 1: HRT + placebo (4 months)Group 2: HRT + MT, 2.5 mg/day (4 months)Group 3: HRT + placebo (2 months), followed by HRT in combination with MT, 2.5 mg/day (2 months)Group 4: HRT + MT, 2.5 mg/day (2 months), followed by discontinuation of MT and initiation of HRT + placebo (2 months) |
When receiving MT, the patients in groups 2, 3, and 4 showed improvement in sexual dysfunction, principally in sexual satisfaction and desire. However, in group 3, the results were similar in the two time periods.The use of HRT in combination with MT did not change hepatic enzyme levels or increase cardiovascular risk. |
14- Kingsberg et al. (4242. Kingsberg S, Shifren J, Wekselman K, Rodenberg C, Koochaki P, Derogatis L. Evaluation of the clinical relevance of benefits associated with transdermal testosterone treatment in postmenopausal women with hypoactive sexual desire disorder. J Sex Med. 2007;4(4 Pt 1):1001-8.) |
Surgically postmenopausal women with HSDD (n = 132) |
Randomized, placebo-controlled trial |
6 months |
Group 1: Transdermal T patches, 300 µg/day |
There was an increase in sexual satisfaction and desire. |
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Group 2: placebo |
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15- El Hage et al. (4343. El-Hage G, Eden JA, Manga RZA. A double-blind, randomized, placebo-controlled trial of the effect of testosterone cream on the sexual motivation of menopausal hysterectomized women with hypoactive sexual desire disorder. Climacteric. 2007;10(4):335-43, http://dx.doi.org/10.1080/13697130701364644. http://dx.doi.org/10.1080/13697130701364...
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Postmenopausal women submitted to hysterectomy and receiving transdermal estrogen (n = 36) |
Randomized, crossover, double-blind, placebo-controlled trial |
3 months |
Group 1:10 mg/day of topical T (AndroFeme® 1; Lawley Pharmaceuticals, Perth, Australia)Group 2: placebo |
There was an increase in sexual desire, receptivity, and satisfaction.There was no improvement in energy or mood.There were no changes in the lipid profile. |
16- Penteado et al. (4444. Penteado SR, Fonseca AM, Bagnoli VR, Abdo CH, Júnior JM, Baracat EC. Effects of the addition of methyltestosterone to combined hormone therapy with estrogens and progestogens on sexual energy and on orgasm in postmenopausal women. Climacteric. 2008;11(1):17-25, http://dx.doi.org/10.1080/13697130701741932. http://dx.doi.org/10.1080/13697130701741...
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Physiologically postmenopausal women with sexual dysfunction (n = 60) |
Randomized, double-blind, placebo-controlled trial |
6 months |
Group 1: CEEs, 0.625 mg/day + MPA, 2.5 mg/day + placebo (n = 29)Group 2: CEEs, 0.625 mg/day + MPA, 2.5 mg/day + MT, 2.0 mg/day (n = 31) |
The women who received MT experienced increased sexual desire in comparison with those who received placebo. However, there was no difference between the two groups in terms of the ability to achieve orgasm. |
17- Davis et al. (5656. Davis SR, Papalia MA, Norman RJ, O′Neill S, Redelman M, Williamson M, et al. Safety and efficacy of a testosterone metered-dose transdermal spray for treating decreased sexual satisfaction in premenopausal women: a randomized trial. Ann Intern Med. 2008;148(8):569-77, http://dx.doi.org/10.7326/0003-4819-148-8-200804150-00001. http://dx.doi.org/10.7326/0003-4819-148-...
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Postmenopausal women with HSDD and a serum level of free T < 3.8 pmol/L (n = 261) |
Randomized Double-blind, placebo-controlled trial |
16 weeks |
Group 1: transdermal T spray, 56 µl/dayGroup 2: transdermal T spray, 90 µl/dayGroup 3: two 90 µl applications of transdermal T spray per dayGroup 4: placebo |
At a dose of 90 µl/day, transdermal T spray increased libidoThe adverse effect most often reported was hypertrichosis, which correlated with the dose and site of application |
18- Blümel et al. (5050. Blümel JE, Del Pino M, Aprikian D, Vallejo S, Sarrá S, Castelo-Branco C. Effect of androgens combined with hormone therapy on quality of life in post-menopausal women with sexual dysfunction. Gynecol. Endocrinol. 2008;24(12):691-5.) |
Physiologically postmenopausal women with sexual dysfunction (n = 40) |
Randomized, double-blind, double-dummy trial with two parallel treatment arms |
3 months |
Group1: CEEs, 0.625 mg/day+ micronized progesterone,100 mg/day + MT, 1.25 mg/day (n = 20)Group 2: placebo (n = 20) |
The addition of MT to the therapeutic regimen improved the quality of life and sexuality of the postmenopausal women with sexual dysfunction. |
19- Panay et al. (5151. Panay N, Al-Azzawi F, Bouchard C, Davis SR, Eden J, Lodhi I, et al. Testosterone treatment of HSDD in naturally menopausal women: the ADORE study. Climacteric. 2010;13(2):121-31, http://dx.doi.org/10.3109/13697131003675922. http://dx.doi.org/10.3109/13697131003675...
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Naturally postmenopausal women (n = 272) |
Randomized, multicenter, placebo-controlled trial |
6 months |
Group 1: transdermal T patch, 300 µg/day |
There was improvement of sexual dysfunction in the group of women receiving transdermal T. |
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Group 2: placebo |
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20- White et al. (5252. 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. 2012;163(1):27-32, http://dx.doi.org/10.1016/j.ahj.2011.09.021. http://dx.doi.org/10.1016/j.ahj.2011.09....
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Naturally or surgically postmenopausal women with HSDD (n = 2,500, initially) |
Randomized, double-blind, placebo-controlled clinical trial |
The trial began in 2008, and the expected trial duration is 5 years. |
Group 1: 0.22 g/day of 1% hydroalcoholic T gel (LibiGel; Biosante Pharmaceuticals, Inc., Lincolnshire, IL, USA)Group 2: placebo gel |
The trial is still under way. |