Modeling Female Sexual Desire

Modeling Female Sexual Desire: An Overview and Commentary. Abigail L. Kohut-Jackson, Johnathan M. Borland and Robert L. Meisel. In Sexual Disorders and Dysfunctions, Ed. Dhastagir Sultan Sheriff, October 25th, 2022. https://www.intechopen.com/online-first/84390

Abstract: Hypoactive sexual desire disorder (HSDD) in women is a condition of low sexual desire that develops over time. Sexual desire normally diminishes over long-term relationships, but is also negatively affected by a demanding lifestyle, poor self-esteem and body image, and loss of intimacy in a relationship. HSDD elevates to a disorder when it is a concern for the woman, arising from conflict with a partner who is interested in a greater frequency of sexual interaction. Two drugs have been marketed (Addyi and Vyleesi) to treat HSDD. Neither drug was originally developed for this purpose, nor is either drug particularly effective. The lack of rational development of drugs to treat sexual disorders in women is due to the mistaken belief that components of female sexuality, such as sexual desire, cannot be effectively modeled in animals. To the contrary, sexual interest, desire, arousal, and reward are measurable aspects of sexual behavior in female rodents. Going forward, basic research using these pre-clinical models should be the starting point for drug development. At the same time, it is not clear that drug development represents the primary therapeutic approach to the problem, with behavioral therapies providing good options for first line of treatments for HSDD.

Keywords: sexual arousalsexual interestsexual rewardhypoactive sexual desire disorderAddyiVyleesianimal modelsmesolimbic systemnucleus accumbensdopamineglutamatemelanocortin receptors

6. Commentary

Nappi [7] presented an expert opinion on the relative lack of drugs to treat female sexual dysfunction. She highlighted the wide range of causes for sexual dysfunction in women, as opposed to simply erectile dysfunction in men. She noted that we still have an incomplete understanding of a woman’s sexuality, which is a prerequisite to developing treatments. She also pointed out that female sexual dysfunction is not a life-threatening clinical problem, so that it is important to balance the clinical effectiveness of drugs with the drug’s safety for the women taking them. Finally, Nappi [7] was concerned with drugs that needed to be taken chronically (e.g., Addyi), and hoped that on-demand medications (e.g., Vyleesi) could be developed. Nappi’s commentary is still very current and meaningful, and rational drug development (in her view) will only be achieved through the cooperative partnership of sexual experts, pharmaceutical companies and medical agencies [7].

6.1 A rational approach to drug development

In Section 4 we described how Addyi and Vyleesi went to clinical trials with remarkably little preclinical data supporting their effects on sexual behavior in animal models. If developing drugs to treat sexual dysfunction in women is an important endeavor, the starting point has to be investment in basic research in both the public and pharmaceutical sectors. This research should be designed to take advantage of current animal models (and develop new animal models [81]) to identify potential molecular targets for therapeutics. This is how drug development begins for essentially all diseases and is only emphasized here because this message clearly was lost in the development and marketing of drugs for HSDD in women.

6.2 Pathologizing the normal

Basson et al. [9] developed a comprehensive model of female sexuality that emphasized the complexity of a woman’s sexual response. At the same time that this model is a valuable contribution to understanding female sexuality, it also highlights the individual variability in sexual responses among women, making it difficult to define what a normal response pattern is. If we cannot define a normal sexual response, then how do we define sexual dysfunction in women [82, 83, 84]. Basson et al. [82] disagree with DSM criteria that quantify numbers of sexual fantasies or whether a woman initiates sexual activity as determinants of sexual dysfunction. They assert that few or no sexual fantasies are not a pathology, nor is it pathological if a woman does not initiate sexual activity.

Based on earlier arguments, Meixel et al. [84] lay out a historical account of the many examples of the drug industry’s marketing strategy of “condition branding”. With condition branding, the drug company creates a medical condition to support the development of a drug. In the example of Addyi, HSDD was elevated in significance as a treatable source of distress as part of the rebranding of the drug to address the disparity in the treatment of sexual dysfunction in men and women. It is disturbing that drug-company supported continuing medical education (CME) modules were developed to “educate” clinicians about this disorder. Meixel et al. [84] note (p. 860):

“Specific marketing messages that we identified within the CME modules included the following:

Hypoactive sexual desire disorder is very common and underdiagnosed.

Hypoactive sexual desire disorder can have a profound effect on quality of life.

Women may not be aware that they are sick or distressed.

Hypoactive sexual desire disorder and distress can have other names.

Clinicians should initiate conversation with their patients about their sexual health.

Clinicians find it difficult to discuss their patients’ sexual concerns and lack training and confidence in the diagnosis of sexual problems.

Clinicians need tools and resources to help them diagnose hypoactive sexual desire disorder.

Simple tools, including the decreased sexual desire screener (DSDS) and Female Sexual Function Index (FSFI) can assist clinicians in diagnosing hypoactive sexual desire disorder.

A major barrier to clinicians talking about hypoactive sexual desire disorder/female sexual dysfunction is the lack of medications.

It is problematic that there are medicines available to treat sexual problems for men but not women.”

Key elements in the continuing education modules to be noted here are that the lack (at the time) of medications for HSDD was an impediment for physicians to have discussions about sexual desire with their patients and that women may have HSDD even if they are unaware of it.

6.3 Therapeutic approaches

A starting point for therapy may lie in reassuring women that their sexual feelings are not abnormal and are shared by many other women [82]. This does not alleviate tensions and conflict in a relationship, but can more effectively set the stage for other therapeutic approaches. For example, changing a women’s view of herself can aid in communication with her partner about her sexuality to alleviate interpersonal conflicts [82]. Knowing that her feelings are normal and shared will boost self-esteem and relieve personal insecurities, both of which are barriers to promoting relationship satisfaction and feeling sexually desirable. This is clearly a simplistic approach that in isolation will not be sufficient for most women [85]. Still, this is an important component of any therapeutic plan.

Given that fatigue is a key factor underlying low sexual desire in women, approaches to reduce lifestyle stress and fatigue may be helpful. Mindfulness strategies can be helpful in this regard [86, 87, 88, 89] and have the advantage of being easy to apply and are inexpensive. Presumably other lifestyle approaches may also be beneficial when HSDD results from these types of life events.

Cognitive processes impact HSDD when women view their own behavior, rather than relationship issues, as central to their levels of sexual desire. A rather thorough review [90] supports a role of cognitive behavioral therapies in treating women with HSDD. The goals of these approaches are straightforward, aiming to increasing the rewarding experiences for women and improve relationships through cognitive restructuring and communication. As with mindfulness strategies, cognitive behavioral therapy can be conducted through online training as well as in person.

Drugs should be a last line of treatment [2, 91], and used perhaps in conjunction with behavioral therapies. The worry with drug therapies is that they necessarily carry side effects that vary in severity. This is unavoidable with any compound that affects neurotransmission, as there will be direct and indirect effects on chemical transmission that are spread throughout the central nervous system, beyond the specific circuits targeting the behaviors in question [36].