Characteristics of systemic testosterone therapy for female hypoactive sexual desire disorder-a claims database analysis.

BACKGROUND: Testosterone therapy (TTh) is recommended for postmenopausal women with hypoactive sexual desire disorder (HSDD); however, there remain insufficient data to support use of TTh in premenopausal women with sexual dysfunction. AIM: In this study, we used a large national database to evaluate prescribing trends of TTh for women with HSDD. METHODS: We conducted a cohort analysis of information from electronic health records acquired from the data network TriNetX Diamond. The study cohort consisted of women 18-70 years of age with a diagnosis of HSDD. We analyzed trends of testosterone prescriptions, routes of testosterone administration, and coadministration of testosterone with estrogen. OUTCOMES: Despite an increase in rates of testosterone prescriptions for HSDD, there remains a high degree of variability in the duration of treatment, route of administration, and coadministration of estrogen with significant underprescription of testosterone. RESULTS: Our query of the TriNetX database led to the identification of 33 418 women diagnosed with HSDD at a mean age of 44.2 ± 10.8 years, among whom 850 (2.54%) women received a testosterone prescription. The testosterone prescriptions were highly variable with regard to duration and route of administration and coadministration with estrogen. For all patients until 2015, the prevalence of testosterone prescriptions for HSDD showed a positive quadratic relation was observed. Since 2015 a linear increase in prevalence was observed, with the highest rate of increase for patients aged 41-55 years. CLINICAL IMPLICATIONS: The findings of this study reveal a significant need for further research investigating the optimal use of TTh to enhance the sexual health of women with HSDD, and further studies on the long-term effects of testosterone use must be undertaken to ensure that patients have access to safe and effective treatment. STRENGTHS AND LIMITATIONS: Limitations to this study include patient de-identification and lack of availability of testosterone dosage data. However, this study also has many strengths, including being the first, to our knowledge, to characterize the prescribing trends of testosterone for women with HSDD. CONCLUSION: Testosterone therapy should be considered as a potential therapy for premenopausal female patients with HSDD. Further studies on the long-term effects of testosterone use must be undertaken to address disparities in the management of HSDD and to ensure patients can access treatment.

What Women Want? The State of the Art regarding the Treatment of Young Women with Hypoactive Sexual Desire Disorder.

BACKGROUND: Hypoactive sexual desire disorder (HSDD) in premenopausal women involves biological, psychological, and social aspects. In the European Society for Sexual Medicine meeting in Rotterdam in February 2023, several leading experts in the field discussed the multifaceted nature of this disorder and the state of the art regarding treatment at a round table. This review reflects the information discussed at this event and further discusses current controversies. SUMMARY: HSDD is the most prevalent female-estimated sexual disorder reported by 28% of the 40% premenopausal women with sexual dysfunction. Flibanserin and bremelanotide are the only approved medications to treat HSDD in the USA, and none are approved in Europe. Lybrido, Lybridos, and Lorexys are under development. There are several psychological factors with impact in sexual desire, including depression and sexual abuse. Feminine sexual scripts, the pleasure gap, and structural inequalities also affect sexual desire. Evidence strongly supports the value of combining medical and psychological approaches in the treatment of HSDD, but there is ongoing controversy regarding the pharmacological treatment of young women with HSDD. However, some women seem open and would like to have access to drug treatment. KEY MESSAGES: The treatment of HSDD in young women requires a mixed treatment approach that addresses the disorder's complexity. Despite clinicians seeming to be divided between using pharmacological and/or psychosocial approaches, some women might respond better to one type of intervention over the others. This calls for the development of tools that assess the best approach for each person, including their will and informed choice.

[Sexual dysfunction on the background of antidepressant therapy]. / Seksual'nye disfunktsii na fone antidepressivnoi terapii.

The review is devoted to the problem of sexual dysfunction caused by taking antidepressants. Sexual dysfunction is widespread, but it is not reported, and its impact on the quality of life and compliance of patients is underestimated. Partly because of its bidirectional association with depression, sexual dysfunction is difficult to diagnose. Possible mechanisms and risk factors associated with sexual dysfunction in patients with depression are considered. The data on the frequency of sexual dysfunction with the use of various antidepressants are given. Therapeutic strategies for sexual dysfunction associated with taking antidepressants are described. The advantages of agomelatin as an antidepressant associated with a low risk of sexual side effects are emphasized.

Sexual Dysfunction in Schizophrenia: A Systematic Review and Meta-Analysis.

Importance: In individuals with schizophrenia, antipsychotic-induced dysfunctions are frequent but often underexplored in clinical practice. Objective: To synthetize the data of observational studies exploring the prevalence of sexual dysfunction in individuals with schizophrenia-spectrum disorders as well as associated factors. Data Sources: A systematic literature search without language or time restrictions was conducted in Google, Google Scholar, PubMed/MEDLINE, Science Direct, and Université Sorbonne Paris Cité for studies published up to June 8, 2022. Study Selection: All observational studies reporting a prevalence of sexual dysfunction in schizophrenia-spectrum disorder were included. Data Extraction and Synthesis: The MOOSE guidelines with independent extraction by 2 observers and random-effects models were used. Main Outcomes and Measures: The prevalence of sexual dysfunction and each specific dysfunction. Results: A total of 72 of 1119 studies from 33 countries on 6 continents published from inception to June 2022 were included with a total of 21 076 participants with schizophrenia. The pooled global prevalence of sexual dysfunctions was 56.4% (95% CI, 50.5-62.2), with a prevalence of 55.7% (95% CI, 48.1-63.1) for men and 60.0% (95% CI, 48.0-70.8) for women. The most frequent sexual dysfunction was erectile dysfunction in men (44%; 95% CI, 33.5-55.2), followed by loss of libido in men (41%; 95% CI, 30.7-51.4), ejaculation dysfunction in men (39%; 95% CI, 26.8-51.8), orgasm dysfunction in women (28%; 95% CI, 18.4-40.2), and amenorrhea in women (25%; 95% CI, 17.3-35.0). Factors associated with heterogeneity were study design, time and location, sociodemographic data, alcohol use disorder, psychiatric diagnosis, illness severity, and the use of antidepressants and anxiolytics. Sexual dysfunctions were more frequent in schizophrenia vs schizoaffective disorders, and erectile disorders were less frequent in individuals with longer illness duration. Antidepressant and mood stabilizer prescriptions were associated with lower rates of erection disorders (ß, -6.30; 95% CI, -10.82 to -1.78); P = .006 and -13.21; 95% CI, -17.59 to -8.83; P < .001, respectively) and ejaculation disorders (ß, -6.10; 95% CI, -10.68 to -1.53; P = .009 and ß, -11.57; 95% CI, -16.34 to -6.80; P < .001, respectively). No obvious improvements in the rates of sexual dysfunction at other times were found, and there were conflicting results regarding antipsychotic classes. Conclusions and Relevance: This systematic review and meta-analysis found a high prevalence of sexual dysfunction among individuals with schizophrenia, with considerable heterogeneity in associated factors. The findings also suggest that some dysfunctions may be explained by schizophrenia. The association between lower rates of dysfunction and antidepressant use suggests that treating comorbid depression could be an effective strategy to improve sexual health. A lack of data on metabolic parameters and physical health in general was also noted, while these issues are frequent in the care of schizophrenia.

Testosterone use for hypoactive sexual desire disorder in postmenopausal women.

Testosterone is an important evidence-based therapy for hypoactive sexual desire disorder (HSDD) in postmenopausal women. Clinical practice guidelines based on the most comprehensive meta-analysis of benefits and risks of testosterone therapy to date state that the sole evidence-based indication for testosterone therapy is HSDD in postmenopausal women. The guidelines also provide recommendations regarding identification of patients, dosing, monitoring, and follow-up. This Practice Pearl will discuss evidence-based testosterone therapy for management of HSDD in postmenopausal women.

Targeting the central melanocortin system for the treatment of metabolic disorders.

A large body of preclinical and clinical data shows that the central melanocortin system is a promising therapeutic target for treating various metabolic disorders such as obesity and cachexia, as well as anorexia nervosa. Setmelanotide, which functions by engaging the central melanocortin circuitry, was approved by the FDA in 2020 for use in certain forms of syndromic obesity. Furthermore, the FDA approvals in 2019 of two peptide drugs targeting melanocortin receptors for the treatment of generalized hypoactive sexual desire disorder (bremelanotide) and erythropoietic protoporphyria-associated phototoxicity (afamelanotide) demonstrate the safety of this class of peptides. These approvals have also renewed excitement in the development of therapeutics targeting the melanocortin system. Here, we review the anatomy and function of the melanocortin system, discuss progress and challenges in developing melanocortin receptor-based therapeutics, and outline potential metabolic and behavioural disorders that could be addressed using pharmacological agents targeting these receptors.

Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.

Importance: The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior. Objective: To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD. Design, Setting, and Participants: This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021. Interventions: Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo. Main Outcomes and Measures: Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal. Results: Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02). Conclusions and Relevance: Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire. Trial Registration: isrctn.org Identifier: ISRCTN17271094.

Pharmacotherapy for female sexual dysfunctions (FSDs): what is on the market and where is this field heading?

INTRODUCTION: Female sexual dysfunctions (FSDs) are common in women of any age and have a huge impact on quality of life and relationships. They have a multifaceted etiology limiting the development of pharmacotherapies with a high rate of effectiveness. Safety issues are also a concern. AREAS COVERED: The authors report the most recent advances in pharmacotherapy for premenopausal and postmenopausal women with a main focus on hypoactive sexual desire disorders (HSDD) and associated sexual symptoms. Good levels of evidence have emerged for psychoactive agents, such as flibanserin and bremelanotide, as well as hormonal compounds (transdermal testosterone). The authors also report briefly on intravaginal DHEA (prasterone), local estrogen therapy (LET), and ospemifene to manage effectively vulvovaginal atrophy/genitourinary syndrome of menopause (VVA/GSM). In addition, they discuss promising therapeutic options highlighting the main reasons that hamper the availability of new labeled products. Finally, they include the importance of the multimodal approach to address FSDs. EXPERT OPINION: Approved pharmacotherapies for FSD are limited. Validated multidimensional instruments and adequate objective measures of physical and mental responses to sexual external and internal incentives are mandatory to identify women suitable to chronic or on-demand treatments and to assess their pattern of response in research and practice.

Lamotrigine-Induced Persistent Genital Arousal Disorder and a Potential Treatment.

Persistent Genital Arousal Disorder (PGAD) is a rare disorder characterized by involuntary genital arousal without relief after orgasm or subjective feelings of sexual excitement. There is sparse data for effective treatments of PGAD, which can cause significant distress, anxiety, and depression for patients. We present a case of a patient with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) who was diagnosed with PGAD shortly after she was started on lamotrigine for mood stabilization. Inpatient psychiatric treatment with increasing doses of sertraline resulted in reduction of her symptoms, suggesting its possible role in PGAD treatment and management.

An evaluation of bremelanotide injection for the treatment of hypoactive sexual desire disorder.

INTRODUCTION: Female sexual response implies a deep intertwining between psychosocial and neurobiological mediators. Regulation of central melanocortin signaling may enhance sexual desire. In premenopausal women with hypoactive sexual desire disorder (HSDD), melanocortin receptor agonist bremelanotide (Vyleesi) has been hypothesized to trigger excitatory brain pathways. AREAS COVERED: Hereby we summarize bremelanotide's proposed mechanism of action, pharmacokinetics, efficacy and safety data derived from clinical trials. A literature search of peer-reviewed publications on the current evidence on the pharmacotherapy with bremelanotide was performed using the PubMed database. EXPERT OPINION: Bremelanotide appears to be moderately safe and well-tolerated; the most common adverse reaction is nausea (40%). Although data from clinical trials demonstrated a significant change in validated questionnaires, the overall clinical benefit appears to be modest. However, these results should be interpreted in the light of the dramatic challenges in conducting well-designed clinical trials for female sexual dysfunction, due to the significant placebo effect of pharmacotherapy, and the frequent use of outcome measures that are likely to be highly susceptible to expectation biases, such as long periods of recall of sexual and emotional response.

[Management of sexual side effects of antidepressants]. / Prise en charge des effets secondaires sexuels des antidépresseurs.

Antidepressants are associated with a high risk of sexual dysfunction. Their sexual side effects are greatly underestimated in clinical practice because they are rarely discussed spontaneously by the patient and poorly investigated by clinicians. Nonetheless, they are responsible for a decrease in quality of life as well as a decrease in treatment adherence, leading to a risk of relapse or worsening of the treated mental pathology. This is particularly problematic as antidepressants are often needed on a long-term basis and spontaneous remission of these sexual side effects is low. Prevention, investigation and handling of sexual side effects are therefore important goals in the management of patients treated with antidepressants.

Les antidépresseurs sont associés à un risque élevé de dysfonctions sexuelles. Leurs effets secondaires sexuels sont largement sous-estimés dans la pratique clinique car ils sont rarement abordés spontanément par le patient et peu recherchés par les cliniciens. Ils sont pourtant responsables d'une baisse de la qualité de vie ainsi que d'une diminution de l'observance au traitement, entraînant un risque de rechute ou d'aggravation de la pathologie mentale traitée. Ceci est d'autant plus problématique que les antidépresseurs sont souvent nécessaires à long terme et que la rémission spontanée de ces manifestations indésirables est faible. La prévention, la recherche et la gestion des effets secondaires sexuels sont donc des enjeux importants dans la prise en charge de patients traités par antidépresseurs.

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.

Importance: Despite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown. Objective: To test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD. Design, Setting, and Participants: This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021. Interventions: A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion. Main Outcomes and Measures: Blood oxygen level-dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli. Results: Of the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007). Kisspeptin's enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects. Conclusions and Relevance: These findings lay the foundations for clinical applications for kisspeptin in women with HSDD. Trial Registration: ISRCTN trial registry identifier: ISRCTN17271094.

Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder.

BACKGROUNDHypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem globally, affecting approximately 10% of women, but has limited treatment options. Melanocortin 4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, through unknown mechanisms. Studying the pathways involved is crucial for our understanding of normal and abnormal sexual behavior.METHODSUsing psychometric, functional neuroimaging, and hormonal analyses, we conducted a randomized, double-blinded, placebo-controlled, crossover clinical study to assess the effects of MC4R agonism compared with placebo on sexual brain processing in 31 premenopausal heterosexual women with HSDD.RESULTSMC4R agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity and deactivated the secondary somatosensory cortex, specifically in response to visual erotic stimuli, compared with placebo. In addition, MC4R agonism enhanced functional connectivity between the amygdala and the insula during visual erotic stimuli compared with placebo.CONCLUSIONThese data suggest that MC4R agonism enhanced sexual brain processing by reducing self-consciousness, increasing sexual imagery, and sensitizing women with HSDD to erotic stimuli. These findings provide mechanistic insight into the action of MC4R agonism in sexual behavior and are relevant to the ongoing development of HSDD therapies and MC4R agonist development more widely.TRIAL REGISTRATIONClinicalTrials.gov NCT04179734.FUNDINGThis is an investigator-sponsored study funded by AMAG Pharmaceuticals Inc., the Medical Research Council (MRC) (MR/T006242/1), and the National Institute for Health Research (NIHR) (CS-2018-18-ST2-002 and RP-2014-05-001).

Pharmacologic therapeutic options for sexual dysfunction.

PURPOSE OF REVIEW: Sexual problems are reported by up to 45% of individuals assigned female at birth. Although sexual function is a complex biopsychosocial construct, there are a number of pharmacologic treatment options aimed at addressing the changing vaginal hormonal milieu in postmenopausal individuals and moderating the excitatory and inhibitory aspects of the central nervous system in those with hypoactive sexual desire disorder. RECENT FINDINGS: The last decade has seen an increase in the number and type of pharmacologic treatment options for dysfunction primarily associated with menopause and hypoactive sexual desire disorder. Recent publications and systematic reviews have strengthened the safety data of existing FDA-approved medications as well as off-label therapies. SUMMARY: Pharmacologic treatment with local estrogen and testosterone replacement in postmenopausal individuals and with centrally-acting therapies such as flibanserin, bremelanotide, and testosterone in premenopausal individuals assigned female at birth are safe and can be used to improve sexual desire and sexual satisfaction.

Pharmacological Treatment for Pedophilic Disorder and Compulsive Sexual Behavior Disorder: A Review.

Guidelines for the pharmacological treatment of paraphilic disorders have historically been based on data from forensic settings and on risk levels for sexual crime. However, emerging treatment options are being evaluated for individuals experiencing distress because of their sexual urges and preferences, targeting both paraphilic disorders such as pedophilic disorder (PeD) and the new diagnosis of compulsive sexual behavior disorder (CSBD) included in the International Classification of Diseases, 11th Revision (ICD-11). As in other mental disorders, this may enable individualized pharmacological treatment plans, taking into account components of sexuality (e.g. high libido, compulsivity, anxiety-driven/sex as coping), medical and psychiatric comorbidity, adverse effects and patient preferences. In order to expand on previous reviews, we conducted a literature search focusing on randomized controlled trials of pharmacological treatment for persons likely to have PeD or CSBD. Our search was not restricted to studies involving forensic or criminal samples. Twelve studies conducted between 1974 and 2021 were identified regardless of setting (outpatient or inpatient), with only one study conducted during the last decade. Of a total of 213 participants included in these studies, 122 (57%) were likely to have PeD, 34 (16%) were likely to have a CSBD, and the remainder had unspecified paraphilias (40, 21%) or sexual offense (17, 8%) as the treatment indication. The diagnostic procedure for PeD and/or CSBD, as well as comorbid psychiatric symptoms, has been described in seven studies. The studies provide some empirical evidence that testosterone-lowering drugs reduce sexual activity for patients with PeD or CSBD, but the body of evidence is meager. There is a need for studies using larger samples, specific criteria for inclusion, longer follow-up periods, and standardized outcome measures with adherence to international reporting guidelines.

Medical Treatment of Female Sexual Dysfunction.

Female sexual dysfunction (FSD) comprises multiple overlapping sexual disorders with a multifaceted cause within the frame of the biopsychosocial model. Health care providers can screen for FSD according to their level of expertise and deliver at least basic counseling before eventually referring to sexual medicine specialists for specific care. The therapeutic algorithm comprises a multidisciplinary approach, including pharmacologic and nonpharmacologic management. Flibanserin and bremelanotide are psychoactive agents indicated for the treatment of generalized acquired hypoactive sexual desire disorder (HSDD) in premenopausal women, whereas transdermal testosterone is effective on HSDD in postmenopausal women. Menopause hormone therapy (systemic and local) is the mainstay for individualized management of women at midlife.

Accidental Flibanserin Ingestion in Children Causing Acute Respiratory and Central Nervous System Depression: What Health Care Professionals Need to Know.

This commentary serves to raise awareness for health care professionals about the potential risks of accidental ingestion of flibanserin tablets by children. Flibanserin was approved by the U.S. Food and Drug Administration (FDA) for the treatment of acquired generalized hypoactive sexual desire disorder in premenopausal women. Since its approval in 2015, the FDA has identified five reports of serious accidental ingestion by toddlers. All five children, boys with ages ranging from 18 months to 2 years, presented with central nervous system and respiratory depression, and two of them required intubation. A combination of hypertension, hyperthermia, and seizure-like activity was also seen in four of the five children. The clinical manifestation resembles serotonin syndrome (eg, tachycardia, hypertension, and muscle stiffness). As flibanserin use increases, greater awareness by health care professionals regarding the risk of accidental pediatric ingestion is needed to facilitate preventative counseling for patients with young children.