Dr. Ron’s Research Review – November 23, 2011

This week’s research review: DHEA or Testostosterone for hypoactive sexual desire disorder (HSDD) in women.

Hypoactive sexual desire disorder (HSDD) is a common multi-factorial condition that is characterized by a decrease in sexual desire that causes marked personal distress and/or interpersonal difficulty. (Nappi, Martini et al. 2010)

An article published in Menopause described a study on the effects of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women. (Labrie, Archer et al. 2009)

In the same issue, Buster challenges that assumptions that intravaginal DHEA is transformed into estrogen within vaginal epithelium cells and that there is no detectable increase in circulating estradiol. (Buster 2009)

Buster states that the impairments in sexual desire are a tougher sell if you believe that female sexual desire is a perception residing in the female brain. Transvaginal DHEA would have little impact the central nervous system when there is little to no change in circulating sex steroids. The enhancements of improved sexual performance are persuasive - but not quite so convincing. (Buster 2009)

Buster states that the effects of systemic testosterone on female sexual desire are dramatic and have been documented repeatedly, particularly in the last decade. (Buster 2009)

In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 microg of testosterone per day resulted in a modest but meaningful improvement in sexual function. (Davis, Moreau et al. 2008)

Transdermal patches and topical gels avoid the hepatic first-pass metabolism and are the preferred formulations. Testosterone therapy is usually administered concomitantly with estrogen therapy due to a lack of adequate safety and efficacy data on testosterone alone. (Hubayter and Simon 2008)

Transdermal testosterone is approved in Europe for postmenopausal women who experience HSDD as a result of a bilateral oophorectomy. (Nappi, Martini et al. 2010)

Dr. Ron


Articles

Transvaginal dehydroepiandrosterone: an unconventional proposal to deliver a mysterious androgen that has no receptor or target tissue using a strategy with a new name: hormone precursor replacement therapy (HPRT)

         (Buster 2009) Download

Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women

         (Labrie, Archer et al. 2009) Download

OBJECTIVE: The objective of this study was to provide evidence that the transformation of DHEA into both androgens and/or estrogens locally in cells of the three layers of the vagina (epithelium, lamina propria, and muscularis) would have effects of greater impact, including effects on sexual function, than only effects on superficial epithelial cells as achieved with estrogens. METHODS: This prospective, randomized, double-blind, and placebo-controlled phase III clinical trial has evaluated the effect of daily local intravaginal application of Prasterone (dehydroepiandrosterone; DHEA) for 12 weeks on the domains of sexual dysfunction, namely, desire/interest, arousal, orgasm, and pain at sexual activity, in 216 postmenopausal women with moderate to severe symptoms of vaginal atrophy. RESULTS: A time- and dose-dependent improvement of the four domains of sexual function was observed. At the 12-week time interval, the 1.0% DHEA dose led, compared with placebo, to 49% (P = 0.0061) and 23% (P = 0.0257) improvements of the desire domains in the Menopause Specific Quality of Life and Abbreviated Sex Function questionnaires, respectively. Compared with placebo, the Abbreviated Sex Function arousal/sensation domain was improved by 68% (P = 0.006), the arousal/lubrication domain by 39% (P = 0.0014), orgasm by 75% (P = 0.047), and dryness during intercourse by 57% (P = 0.0001). CONCLUSIONS: By a local action in the vagina, DHEA applied daily at doses at which serum steroids remain well within normal postmenopausal values exerts relatively potent beneficial effects on all four aspects of sexual dysfunction. Such data indicate that combined androgenic/estrogenic stimulation in the three layers of the vagina exerts important beneficial effects on sexual function in women without systemic action on the brain and other extravaginal tissues.


Testosterone therapy for sexual dysfunction in postmenopausal women

            (Hubayter and Simon 2008) Download

BACKGROUND: After menopause, both surgical and natural, increases occur in the number of women experiencing sexual dysfunction. Although a direct link between sexual dysfunction and endogenous testosterone levels has not been clearly established, testosterone therapy is known to improve the signs and symptoms related to hypoactive sexual desire. However, testosterone supplementation is not approved in the United States for these clinical indications, primarily because of a lack of data evaluating the possible side-effects of these drugs. METHOD: A MEDLINE search was performed, with a priority for well-designed studies (randomized, controlled trials, meta-analysis), for published data related to the efficacy and safety of testosterone therapy in postmenopausal women. RESULTS: Randomized trials have demonstrated an improvement in sexual function with testosterone in postmenopausal women with hypoactive sexual desire disorder, particularly after oophorectomies. Side-effects have been well tolerated and reversible upon discontinuation. CONCLUSION: Exogenous testosterone treatment provides a rational therapeutic alternative to consider in women whose hypoactive sexual desire disorder negatively affects their quality of life and who have no biologic or psychosocial causes not related to decreased androgen levels for their sexual disorder. Women receiving testosterone should be monitored for clinical improvement and for adverse reactions. Transdermal patches and topical gels avoid the hepatic first-pass metabolism and are the preferred formulations. Testosterone therapy is usually administered concomitantly with estrogen therapy due to a lack of adequate safety and efficacy data on testosterone alone.


 

Testosterone for low libido in postmenopausal women not taking estrogen

         (Davis, Moreau et al. 2008) Download

BACKGROUND: The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown. METHODS: We conducted a double-blind, placebo-controlled, 52-week trial in which 814 women with hypoactive sexual desire disorder were randomly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo. Efficacy was measured to week 24; safety was evaluated over a period of 52 weeks, with a subgroup of participants followed for an additional year. The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes. RESULTS: At 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs. 0.7, P<0.001) but not in the group receiving 150 microg per day (1.2 episodes, P=0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 microg per day, P<0.001; 150 microg per day, P=0.04) and decreases in distress (300 microg per day, P<0.001; 150 microg per day, P=0.04). The rate of androgenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group (30.0% vs. 23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization. CONCLUSIONS: In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 microg of testosterone per day resulted in a modest but meaningful improvement in sexual function. The long-term effects of testosterone, including effects on the breast, remain uncertain. (ClinicalTrials.gov number, NCT00131495.)


Management of hypoactive sexual desire disorder in women: current and emerging therapies

            (Nappi, Martini et al. 2010)  Download

Hypoactive sexual desire disorder (HSDD) is a common multifactorial condition which is characterized by a decrease in sexual desire that causes marked personal distress and/or interpersonal difficulty. The general idea that HSDD is a sexual dysfunction difficult to treat is due to the large number of potential causes and contributing factors. Indeed, a balanced approach comprising both biological and psycho-relational factors is mandatory for accurate diagnosis and tailored management in clinical practice. There are currently no approved pharmacological treatments for premenopausal women with HSDD, while transdermal testosterone is approved in Europe for postmenopausal women who experience HSDD as a result of a bilateral oophorectomy. Even though the role of sex hormones in modulating the sexual response during the entire reproductive life span of women is crucial, a better understanding of the neurobiological basis of sexual desire supports the idea that selective psychoactive agents may be proposed as nonhormonal treatments to restore the balance between excitatory and inhibitory stimuli leading to a normal sexual response cycle. We conclude that the ideal clinical approach to HSDD remains to be established in term of efficacy and safety, and further research is needed to develop specific hormonal and nonhormonal pharmacotherapies for individualized care in women.


References

Buster, J. E. (2009). "Transvaginal dehydroepiandrosterone: an unconventional proposal to deliver a mysterious androgen that has no receptor or target tissue using a strategy with a new name: hormone precursor replacement therapy (HPRT)." Menopause 16(5): 858-9.

Davis, S. R., M. Moreau, et al. (2008). "Testosterone for low libido in postmenopausal women not taking estrogen." N Engl J Med 359(19): 2005-17.

Hubayter, Z. and J. A. Simon (2008). "Testosterone therapy for sexual dysfunction in postmenopausal women." Climacteric 11(3): 181-91.

Labrie, F., D. Archer, et al. (2009). "Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women." Menopause 16(5): 923-31.

Nappi, R. E., E. Martini, et al. (2010). "Management of hypoactive sexual desire disorder in women: current and emerging therapies." Int J Womens Health 2: 167-75.