Female Hypoactive Sexual Desire Disorder

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Female Hypoactive Sexual Desire Disorder: A Practical Guide to Causes, Clinical Diagnosis, and Treatment
Sheryl A. Kingsberg, Ph.D., and James A. Simon, MD




Abstract

Hypoactive sexual desire disorder (HSDD) in women is defined as the persistent or recurrent absence of sexual thoughts or fantasies and/or lack of desire for sexual activity that is associated with marked personal distress and/or interpersonal difficulties, and cannot be better attributed to another primary disorder, medication, or general medical condition. Notably, HSDD shares some similarities with depression, as its etiology can be explained using a biopsychosocial model that includes biological, psychological, and sociocultural factors, as well as interpersonal influences. Due to its high prevalence and negative impact on the overall health and wellbeing of women, primary care health professionals and women’s health practitioners need to be actively aware of HSDD, particularly because patients may be reluctant or unwilling to initiate a discussion about their sexual concerns during routine visits. HSDD is well established as a valid and treatable clinical entity. Even for those inexperienced in treating sexual problems, there are simple and validated screening tools such as the Decreased Sexual Desire Screener that can help identify HSDD and a need for further evaluation and treatment. There have been few established pharmacologic treatments for HSDD. Flibanserin was the first drug approved for the treatment of HSDD by the U.S. Food and Drug Administration (FDA). Bremelanotide, a novel melanocortin receptor agonist, was recently approved by the FDA for the treatment of acquired, generalized HSDD in premenopausal women. Increased awareness and recognition of HSDD as a medical condition should provide an incentive for further clinical development of effective treatments for HSDD.





Introduction

Female sexual dysfunctions (FSDs) refer to problems of low sexual desire, diminished arousal, orgasmic difficulties, and pain with sexual activity. There is evidence that sexual concerns among women in the United States are highly prevalent. One study showed that over 40% of U.S. women reported some type of sexual problem, and 11.5% of these women considered these problems distressing.1 Similar incidence of sexual problems and associated distress have also been reported in European populations.2–5

Hypoactive sexual desire disorder, or HSDD, is one of the most prevalent FSDs and has been estimated to occur in *7 million women in the United States.2,6 HSDD has been defined by the International Society for the Study of Women’s Sexual Health (ISSWSH) as a medical condition characterized by decreased or absent spontaneous or responsive sexual desire (i.e., sexual thoughts or fantasies) associated with negative emotional states and personal distress.7 FSDs, including HSDD, can have a profound effect on women’s quality of life, overall health, and well-being.8–10

With almost 50% of women reporting some type of sexual concern, it is important that health care professionals (HCPs) most likely to encounter women with FSDs, namely, family practitioners, obstetricians/gynecologists, primary care physicians, physician assistants, and nurse practitioners, understand FSDs, including HSDD.
FSDs may be infrequently addressed due to poor mastery of discussions involving sexual health, inadequate medical training/education, evolving definitions of FSD, and limited knowledge of available diagnostic tools.2,11 With ongoing research, expanded educational efforts, and public advocacy and awareness, there is increasing recognition that female (and male) sexual dysfunctions are best understood from a biopsychosocial perspective. Despite the biological component of HSDD, there have been few effective pharmacologic treatment options for this condition, although some are currently under development.

In this article, we focus specifically on HSDD, as low desire with associated distress is the most widely reported sexual complaint among women.1,12 Until as recently as 2015, treatment for HSDD was limited to psychotherapy, homeopathic remedies, over-the-counter therapies, and off-label prescription medications; even now, there remains a significant unmet need for safe and effective pharmacologic treatments. There has, however, been some recent progress in the diagnosis and the treatment of this condition.9,12 This review will highlight the causes, diagnosis, and treatment of HSDD.




*Characterization of HSDD

*Prevalence and Impact of HSDD

*Etiology of HSDD

*Screening for HSDD


*Treating HSDD

Testosterone
Testosterone is known to positively impact sexual desire and has been prescribed as an off-label treatment primarily in postmenopausal women with low sexual desire.56 Efficacy and safety of transdermal testosterone at a dose of 300 μg /day has been studied in surgically postmenopausal women.57,58
Generally, testosterone therapy significantly improved sexual activity and desire, while decreasing personal distress although with mostly mild androgenic adverse events (AEs).57,58 A 2015 report based on eight studies (n = 2,820) indicated that there was moderate evidence for testosterone improving satisfying sexual activity over 4 weeks relative to placebo.59 Long-term AEs occurring across the INTIMATE SM1 and SM2 trials, which evaluated the efficacy and safety of the transdermal testosterone patch (TTP) for up to 6 months in surgically postmenopausal women with HSDD on estrogen therapy, have been previously reviewed. Overall, there were no long-term significant safety signals with TTP use over 4 years of treatment; application site reactions and androgenic effects such as acne, alopecia, and unwanted hair growth were the most prevalent AEs.57,58,60,61

A recent systematic review and meta-analysis of randomized controlled trial data on testosterone in women confirmed its efficacy in postmenopausal women with HSDD. Non-oral preparations (e.g., transdermal) are preferred to reduce liver effects.62 A recent consensus recommendation published by a multidisciplinary task force of clinicians from leading societies that reviewed the safety and efficacy of testosterone in women concluded that data support the use of physiologic testosterone for postmenopausal women with HSDD.63 This group recommended only physiologic dosing, based on the efficacy and safety results of meta-analyses.62–64
Owing to concerns over long-term safety, testosterone patch therapy currently lacks the U.S. Food and Drug Administration (FDA) approval for HSDD. Although the treatment had been approved in Europe for postmenopausal women, it was withdrawn in 2012.63,65


*FDA-Approved Therapies
Flibanserin
Bremelanotide


*ISSWSH process of care

*Treatment affordability






Conclusions

HSDD continues to be an underrecognized and undertreated condition. However, the situation is improving with increased awareness of its impact on patients’ health, wellbeing, and quality of life, as well as with the emergence of effective treatments. While its etiology is not entirely clear, we now have a fundamental understanding of the biological component of HSDD and the availability of effective pharmacologic treatments (e.g., flibanserin and bremelanotide). In the past, HCPs and patients may have been reluctant to discuss sexual issues, but as HSDD has become established as a detectable, diagnosable, and treatable entity, this hesitancy should be overcome. HCPs should increase awareness of this condition and its impact, identify women who may be experiencing HSDD through simple tools, such as the DSDS, and move toward referrals or treatments that address the biological, psychological, and social aspects of the condition (Fig. 5). It is crucial to understand that the causes of HSDD are multifactorial; management should be viewed from an integrative perspective,35 with an emphasis on issues that are most bothersome to the patient. It should be recognized that simple screening tools as well as effective treatments for HSDD are currently available, and there is no longer a reason for HSDD to be ignored.
 

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Table 1. The proportion of Women with Low Sexual Desire and Hypoactive Sexual Desire Disorder by Age and Menopausal Status (Women’s International Study of Health and Sexuality)
Screenshot (2419).png
 
FIG. 1. Hormones, neurotransmitters, and HSDD: what you need to know. HSDD, hypoactive sexual desire disorder.
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FIG. 2. The DSDS: a simple and effective tool to identify HSDD. Table (on left) from Clayton et al.38 ª 2009 International Society for Sexual Medicine, with permission from Elsevier. DSDS, Decreased Sexual Desire Screener.
Screenshot (2415).png
 
FIG. 4. RECONNECT trials: study design and results for co-primary endpoints: (A) study design.76–78 (B) Change from baseline to EOS in the Female Sexual Function Index–desire domain score.77 (C) Change from baseline to EOS in the score for feeling bothered by low sexual desire.77 BMT, bremelanotide; EOS, end-of-study.
Screenshot (2417).png
 
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