Dr. Ron’s Research Review – December 28, 2011

This week’s research review focuses on testosterone for female hypoactive sexual desire disorder (HSDD).

At least 16 million women over the age of 50 currently experience low sexual desire, with approximately 4 million women exhibiting hypoactive sexual desire disorder (HSDD). Large randomized, double-blinded placebo-controlled studies demonstrate that transdermal testosterone improves sexual function and activity in postmenopausal women with HSDD. Large multi-center Phase III trials further confirm the positive effects of the testosterone patch in the treatment of HSDD. More recent studies are exploring the utility of testosterone gels. Based upon data from two recent clinical relevance studies, physicians can be reassured that postmenopausal women with HSDD report a meaningful benefit with testosterone therapy, and further, women will only continue therapy if they experience a meaningful benefit. (Krapf and Simon 2009)

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. 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. (Nappi, Martini et al. 2010)

Hypoactive sexual desire disorder (HSDD) is a common clinical problem in women, especially those who have experienced surgical menopause. Surgically menopausal women receiving testosterone experience significant increases in total satisfying sexual activity vs. women receiving placebo, significant improvement in all domains of sexual function, and decreases in personal distress, with a favorable safety profile. (Kingsberg, Simon et al. 2008)

Testosterone administration to postmenopausal women that result in physiological to slightly supraphysiological serum-free testosterone levels is safe for at least 2 years. (Braunstein 2007)

Dr. Ron


Abstracts

Management of female sexual dysfunction in postmenopausal women by testosterone administration: safety issues and controversies

            (Braunstein 2007) Download

INTRODUCTION: A Food and Drug Administration advisory group has questioned the long-term safety of testosterone administration to postmenopausal women. Although only short-term data exist on safety from the double-blind, placebo-controlled trials, testosterone has been used for more than 50 years. Therefore, some data concerning the long-term safety issues must exist in the literature. AIM: To review the published data concerning the safety of administration of testosterone to women. METHODS: Review of published articles identified by a search of the Ovid databases and bibliographies from articles identified as dealing with the topics of testosterone or androgen treatment of women. RESULTS: The major adverse reactions to exogenous androgens are the expected androgenic side effects of hirsutism and acne. High-density lipoprotein levels may be decreased with oral androgens. There are insufficient long-term safety data regarding breast, endometrium, or heart safety to draw strong conclusions, although the data available to date are reassuring. CONCLUSIONS: Testosterone administration to postmenopausal women that result in physiological to slightly supraphysiological serum-free testosterone levels is safe for at least 2 years.

The current outlook for testosterone in the management of hypoactive sexual desire disorder in postmenopausal women

            (Kingsberg, Simon et al. 2008) Download

INTRODUCTION: Hypoactive sexual desire disorder (HSDD) is a common clinical problem in women, especially those who have experienced surgical menopause. Because androgen levels decline with age and drop dramatically following bilateral oophorectomy, it has been hypothesized that reduced levels of testosterone are related to diminished desire. AIM: As presented at a continuing medical education satellite symposium during the 2008 annual meeting of the International Society for the Study of Women's Sexual Health, to review the current state of knowledge about the physiologic effects of testosterone in postmenopausal women, the effects of transdermal testosterone delivery in surgically menopausal women with HSDD, and ongoing studies of a transdermal testosterone gel. METHODS: A review of the pertinent literature, including recent presentations. MAIN OUTCOME MEASURES: Results from the Women's International Study of Health and Sexuality; and studies utilizing the Brief Index of Sexual Functioning for Women, the Psychological General Well-Being Index, and validated instruments that assess female sexual function: the Sexual Activity Log, the Profile of Female Sexual Function, and the Personal Distress Scale. RESULTS: Surgically menopausal women receiving testosterone experience significant increases in total satisfying sexual activity vs. women receiving placebo, significant improvement in all domains of sexual function, and decreases in personal distress, with a favorable safety profile. CONCLUSIONS: Testosterone deficiency may be considered among the underlying causes of HSDD. Currently, testosterone is available to women in the United States only via off-label prescribing or by unregulated compounding of testosterone preparations. New safety trials will examine the long-term safety of testosterone gel in surgically menopausal women with HSDD who are at high risk of cardiovascular disease or breast cancer.

The role of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women

            (Krapf and Simon 2009) Download

At least 16 million women over the age of 50 currently experience low sexual desire, with approximately 4 million women exhibiting hypoactive sexual desire disorder (HSDD). Although early research established that testosterone therapy improves sexual desire in postmenopausal women, safer and more efficacious administration routes were explored. Large randomized, double-blinded placebo-controlled studies demonstrate that transdermal testosterone improves sexual function and activity in postmenopausal women with HSDD. Large multi-center Phase III trials further confirm the positive effects of the testosterone patch in the treatment of HSDD. More recent studies are exploring the utility of testosterone gels. Based upon data from two recent clinical relevance studies, physicians can be reassured that postmenopausal women with HSDD report a meaningful benefit with testosterone therapy, and further, women will only continue therapy if they experience a meaningful benefit. Although most trials combined testosterone with estrogen/progesterone therapy, the recent APHRODITE trial examined testosterone alone, showing increased sexual desire with mild adverse events. Concerns regarding the long-term safety profile of transdermal testosterone must be addressed before the FDA will approve a testosterone product for women. Although some fear an increased risk of breast cancer with exogenous testosterone administration, recent studies support the idea that androgens can play a role in suppressing the proliferative effects of estrogen and progesterone. Long-term safety data is now being collected and analyzed and Phase III trials focusing on long-term risks are underway. In the meantime, transdermal testosterone appears to be a safe and effective therapy for postmenopausal women with HSDD [Swanson S, DeRogatis L, Snabes M, Simes S, Zborowski J. Treatment of HSDD in surgically menopausal women: a newly initiated Phase III, randomized, double-blind, placebo-controlled, multi-center study of the safety and efficacy of LibiGel. Presented at the Annual Meeting of the International Society for the Study of Women's Sexual Health, February 22-25, Orlando, FL; 2007].

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

Braunstein, G. D. (2007). "Management of female sexual dysfunction in postmenopausal women by testosterone administration: safety issues and controversies." J Sex Med 4(4 Pt 1): 859-66.

Kingsberg, S. A., J. A. Simon, et al. (2008). "The current outlook for testosterone in the management of hypoactive sexual desire disorder in postmenopausal women." J Sex Med 5 Suppl 4: 182-93; quiz 193.

Krapf, J. M. and J. A. Simon (2009). "The role of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women." Maturitas 63(3): 213-9.

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.