Pharmacotherapy for Sexual Dysfunction in Women

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Pharmacotherapy for Sexual Dysfunction in Women (2022)
Jeong Hoo Lee · Jenny E. Lee · Veronica Harsh · Anita H. Clayton




Abstract

Purpose of Review
This review article discusses the controversy in the DSM-5 conceptualization and diagnostic criteria for female sexual dysfunction (FSD). An overview of recent studies on available treatments for hypoactive sexual desire disorder (HSDD), female sexual arousal disorder (FSAD), and genitopelvic pain/penetration disorder (GPPD) is provided.

Recent Findings Include delineation of the process of care for pre-and postmenopausal women with HSDD; release of the global position statement on testosterone therapy in women; updates on efficacy and safety of vaginal estrogen for genitourinary syndrome of menopause and bremelanotide for HSDD; removal of fibanserin alcohol REMS; and development of new technology to enhance bioavailability and brain delivery of treatments.

Summary The DSM-5 revision combining HSDD and FSAD into one diagnostic category is a less accurate characterization of these separate disorders and may hinder access to demonstrated effective treatments for women with these conditions. There is a wide range of pharmacological, other physiological, and psychological treatment options available for women with FSD, which can be offered based on their specific symptoms, potential benefits/risks, and preferences.




Introduction

Sexual function and, thus, dysfunction are impacted by biology (e.g., genetics, neuroendocrine function, health conditions, and substances), intrapsychic factors (e.g., body image, depressive symptoms), and interpersonal (e.g., quality of current/past relationships, partner availability, life stressors) and socio-cultural elements (e.g., religious/ social/cultural expectations and norms) [1]. The interaction of these components manifests in the sexual response and associated emotions and behaviors. The most common sexual model endorsed by women without sexual complaints is the linear model which incorporates the observations of Masters and Johnson of sexual initiation/stimulation leading to excitement/arousal, orgasm, and resolution, with Helen Singer Kaplan adding the concept of sexual desire initiating the sexual response cycle. The non-sequential or circular model of sexual response described by Basson best represents the experience of women with sexual dysfunction as measured by the Female Sexual Function Index (FSFI) [2–4]. Sexual functioning is mediated by excitatory elements which process and respond to sexual stimuli vs. inhibitory factors that are activated normally during sexual refractory periods [5]. Excitatory elements include neurotransmitters (e.g., dopamine norepinephrine, nitric oxide), sex steroids (e.g., estrogen, testosterone), and hormonal neuromodulators (e.g., oxytocin, vasopressin, melanocortins), while inhibitory factors include the neurotransmitter serotonin, the hormone prolactin, hormone modulators like opioids, and neuromodulators such as endocannabinoids. These biological factors may have an impact on the central nervous system (CNS) and/or the periphery/genitals which may be further modulated by psychosocial and cultural factors.




*Prevalence

*Pathophysiology

*Classification Systems and Nomenclature Controversies

*Hypoactive Sexual Desire Disorder—Review From 2017 to Present




*Flibanserin

Flibanserin is a 5-hydroxytryptamine 5-HT1A agonist and 5-HT2A antagonist.

*Bremelanotide
Bremelanotide is a novel cyclic heptapeptide analog of the neuropeptide α-melanocyte-stimulating hormone. It has a high affinity for the melanocortin-4 receptors.

*Testosterone




Female Sexual Arousal Disorder


FSAD is prevalent among women. According to the Prevalence of Female Sexual Problems Associated with Distress and Determinants of Treatment Seeking (PRESIDE) study, the US population's age-adjusted estimate for the prevalence of distressing sexual problems with arousal was 5.1% [7]. There are several treatment options available to address the condition to this date.


*Hormonal Treatments Estrogen
-Estrogen
-Testosterone
-Dehydroepiandrosterone


*Non‑hormonal Treatment
-Phosphodiesterase 5—Inhibitor
-Others





*Genitopelvic Pain–Penetration Disorder

Genitopelvic pain–penetration disorder (GPPD) encompasses the symptoms of dyspareunia and vaginismus [67]. Difficulties in differentiating between acquired vaginismus and dyspareunia have resulted in a proposal to combine these two sexual pain disorders into GPPD disorder for the fifth edition of DSM and ICD-11 [68]. GPPD is difficult to treat because the etiologic cause is usually multifactorial and difficult to isolate [65]. Common causes of pain during intercourse include organic causes such as hypertonic pelvic floor musculature, endometriosis, vaginitis, menopause-related vaginal dryness, malignancy, and infection [67]. Other factors include psychological or environmental conditions, such as depression and past sexual trauma or early childhood abuse [65].


*Non‑hormonal Treatments

*Hormonal Therapies

-Ospemifene
-Prasterone





Conclusions

Female sexual function/dysfunction is related to a complex interaction of biology, intrapsychic factors, interpersonal dynamics, and socio-cultural elements. Modified DSM-IV criteria for FSD have been adopted for the ICD-11 Chapter of Conditions Related to Sexual Health, so as to be more useful in categorizing specific populations responsive to available treatments and allowing for the inclusion of women with known causes of FSD to be managed by addressing modifiable factors. A number of medications, hormonal therapies, and non-hormonal interventions such as lubricants/moisturizers, physical therapy, devices, and cognitive therapy are available for the treatment of FSD with recent publications outlining appropriate populations, effectiveness, and safety for specific interventions, detailed clinical recommendations, and new technologies in development.
 
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Table 1 Comparison of HSDD diagnostic criteria across DSM-IV, DSM-5, and ISSWSH classification systems
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