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Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD.

Purpose of Review : The history of pharmacotherapy to treat sexual desire disorders is fraught with political debate that pits clinical psychologists, sexologists, and sociologists against the sexual medicine and uro-gyn communities. This review highlights events that led to this rift and how it played out politically to influence decisions made by regulatory bodies like the US Food and Drug Administration during and after hearings to consider approving testosterone, flibanserin, and bremelanotide, for the treatment of sexual desire disorders in women. Recent Findings: The current climate for further development of pharmacotherapies is questionable due to a lack of proper marketing and a campaign of misinformation about currently approved drugs as weak, dangerous, and/or unnecessary. Summary: Pharmacotherapies work, and their promise as adjuncts to sex therapy for HSDD will give women far more choice in the kind of treatments that fit their needs. Such treatments may well have efficacy in men and trans persons with HSDD. [ABSTRACT FROM AUTHOR]

Background/aim: Glioblastoma is the most aggressive form of brain tumor and has a dismal prognosis; therefore, novel therapeutic approaches based on the mechanisms underlying its aggressive nature are urgently required. A growing body of evidence suggests that neurotransmitters play a key role in modulating the biology of glioblastoma; however, the role of melanocortins remains unclear., Materials and Methods: The effects of bremelanotide, a melanocortin receptor agonist, alone or in combination with chemotherapeutic agents, on survivin expression and cell viability were investigated in human glioblastoma cell lines., Results: Bremelanotide reduced survivin expression and induced cell death in glioblastoma cells at concentrations that were not toxic to normal human cells, and both of these effects were canceled in the presence of an antagonist of melanocortin receptors 3 and 4. Bremelanotide-induced cell death was prevented by the forced over-expression of survivin in glioblastoma cells, suggesting that bremelanotide induces glioblastoma cell death by inhibiting the expression of survivin. Bremelanotide also promoted cell death induced by chemotherapeutic agents, such as temozolomide and osimertinib., Conclusion: The present results identified melanocortin receptors 3 and 4 as novel and viable therapeutic targets for glioblastoma. Activation of these receptors by bremelanotide may inhibit the expression of survivin, thereby sensitizing glioblastoma cells to cell death., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Abstract Background For the treatment of female sexual dysfunction, the most relevant outcome measures are patient-reported treatment effects and changes in symptoms, underscoring the need for reliable, validated patient-reported outcome (PRO) instruments. The aim of this study was to evaluate the psychometric characteristics (validity and reliability) of the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) PRO measure, which was adapted from the validated FSDS-Revised (FSDS-R) questionnaire and added 2 questions involving arousal and orgasm. Methods Psychometric analyses were based on the data from a multicenter phase 2b dose-finding study that compared the safety and efficacy of bremelanotide versus placebo and were conducted in the evaluable modified intent-to-treat population (N = 325) from that study. Psychometric evaluation of the new items in the FSDS-DAO included confirmatory factor analyses, tests of internal consistency and test–retest reliability, examinations of convergent and discriminant validity, and determination of responsiveness. The validity of the FSDS-DAO was evaluated based on previously developed instruments, including the Female Sexual Function Index (FSFI), General Assessment Questionnaire (GAQ), Women’s Inventory of Treatment Satisfaction (WITS-9), and Female Sexual Encounter Profile-Revised (FSEP-R). Results Confirmatory factor analyses demonstrated that the FSDS-DAO items fit very well (Bentler’s comparative fit index of 0.929). Cronbach’s α for the FSDS-DAO total score was ≥ 0.91 at Visits 1, 2, 5, and 12, demonstrating adequate internal consistency reliability. Test–retest reliability was acceptable with an intra-class coefficient of 0.61 and a Spearman’s correlation coefficient score of 0.62 between Visits 1 and 2 (4 weeks). Acceptable construct validity was demonstrated by significant correlations with related PRO scales in the expected directions and magnitude. For example, participants reporting the worst levels of sexual function on the FSFI also showed the worst FSDS-DAO scores at Visits 5 and 12. The FSDS-DAO total score was responsive to change. Conclusions Evidence supports the validity and reliability of the FSDS-DAO for assessing sexually related distress in women with female sexual arousal disorder and/or hypoactive sexual desire disorder; the addition of the arousal and orgasm items did not impact the validity and reliability of the measure. Clinical Trial Registration ClinicalTrials.gov NCT01382719.

Aims: The melanocortin 4 receptor (MC4R) plays a central role in appetite regulation, and agonistic activity at this receptor promotes satiety. Results from two randomized controlled clinical trials examine the effects of bremelanotide's agonism at MC4R on caloric intake and body weight. Methods: Premenopausal women with a body mass index >30 kg/m2 were studied in two phase 1, single‐centre, randomized, double‐blind, placebo‐controlled trials. Study A matched subjects 1:1 to receive subcutaneous placebo or bremelanotide three times daily for days 1‐15. Study B was a crossover trial with six distinct treatment sequences consisting of three 4‐day treatment periods, investigating once‐a‐day and twice‐a‐day exposure to bremelanotide versus placebo. Subjects received one of the three treatments twice‐daily during each period: 0 mg/0 mg, 2.5 mg/0 mg or 2.5 mg/2.0 mg bremelanotide. Body weight and food intake were recorded in detail daily. Adverse events were recorded throughout both studies. Results: In Study A, 27 of 30 bremelanotide subjects (90.0%) completed the trial and exhibited a significantly greater reduction in body weight after 16 days versus placebo [least squares mean difference (95% CI), −1.3 (−1.9 to −0.8) kg; p <.0001]. Mean caloric intake in bremelanotide subjects was decreased versus placebo, with a magnitude of reduction of approximately 400 kcal/day throughout Study A (p <.01). In Study B, 15 of 27 subjects (55.6%) completed all three phases. Significantly greater reduction of mean body weight occurred in twice‐daily bremelanotide subjects versus placebo (1.7 vs. 0.9 kg, respectively, p <.001). Total caloric intake reduction was significantly greater in the bremelanotide groups versus placebo (mean difference range: 398‐469 kcal; p <.0001). Conclusions: Agonist activity at the MC4R may aid in reducing caloric intake and weight loss in obese women. [ABSTRACT FROM AUTHOR]

Female sexual dysfunction (FSD) in hypertension has been less studied than male sexual dysfunction, and antihypertensive agents' impact on female sexual function is not defined. In this review, randomized double-blind clinical trials and cross-sectional studies related to female sexual function in hypertension were analyzed from 1991 to 2021. FSD appeared to be higher in hypertensive women than in normotensive women. Beta-blockers are the only antihypertensive agents with relatively strong evidence of damaging the female sexual function. Angiotensin receptor blockers (ARB) are relatively beneficial to female sexual function. To treat FSD in the presence of hypertension, controlling blood pressure is key, and the administration of angiotensin receptor blockers is preferred. In addition to controlling blood pressure, for premenopausal women, flibanserin and bremelanotide can be tried, while ospemifene and hormone supplements are preferred for postmenopausal women. [ABSTRACT FROM AUTHOR]

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD. [ABSTRACT FROM AUTHOR]

Background: Hypoactive sexual desire disorder (HSDD), the most prevalent female sexual dysfunction, is characterized as persistent diminished desire for sexual activity accompanied by distress. The efficacy and safety of bremelanotide, a melanocortin receptor agonist approved by the U.S. Food and Drug Administration for treatment of acquired generalized HSDD in premenopausal women, were established in the phase 3 RECONNECT studies, two identically designed double-blind randomized placebo-controlled studies with an optional 52-week open-label extension. This report investigates efficacy of bremelanotide versus placebo according to prespecified subgroups (age, weight, body mass index [BMI], and bioavailable testosterone) in the RECONNECT studies. Materials and Methods: Patients self-administered bremelanotide 1.75 mg or placebo subcutaneously using an autoinjector, as needed, before sexual activity for 24 weeks. Efficacy was assessed using change from baseline to end-of-study for Female Sexual Function Index desire domain and Female Sexual Distress Scale-Desire/Arousal/Orgasm Item 13 for bremelanotide versus placebo. Results: Among 1202 patients included in the integrated and subgroup analyses, bremelanotide achieved statistically significant improvements in measures of increased desire and decreased distress associated with low desire across all age, weight, and BMI subgroups, and all baseline bioavailable testosterone quartiles, with few exceptions. Bremelanotide was further associated with statistically significant increases in reported sexual desire (p < 0.05) in patients not taking hormonal contraceptives, and with a numerical advantage in those taking hormonal contraceptives. Patients treated with bremelanotide experienced decreased distress compared with those in the placebo group at levels of statistical significance (p < 0.05) regardless of hormonal contraceptive use. Statistically significant improvements were observed in the presence or absence of decreased arousal, and regardless of HSDD duration. Conclusions: Bremelanotide was associated with statistically significant improvements in sexual desire and reduced distress across several prespecified subgroups, with few exceptions. [ABSTRACT FROM AUTHOR]

Background: Bremelanotide, a melanocortin receptor agonist, is Food and Drug Administration (FDA)-approved for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder. Methods: Review of bremelanotide's safety profile from the clinical development program (phases 1 through 3). Results: The clinical development program comprised 3500 subjects in 43 completed studies. In the phase 3 studies, subjects took bremelanotide for up to 18 months. The most common adverse events (AEs) were nausea (40.0% vs. 1.3%), flushing (20.3% vs. 1.3%), headache (11.3% vs. 1.9%), and injection site reactions (5.4 vs. 0.5), bremelanotide versus placebo groups, respectively, in the integrated double-blind portion of the phase 3 studies (N = 1247). Nausea was the most common reason for bremelanotide discontinuation. There were no deaths; a few subjects experienced serious AEs. Focal hyperpigmentation was rare when bremelanotide was dosed in accordance with label recommendations, but it occurred in more than one-third of subjects following up to 16 consecutive daily dosings. Small and transient but statistically significant blood pressure increases were observed during ambulatory blood pressure monitoring. Most drug–drug interactions were not clinically significant, except for interactions that lowered plasma concentrations of indomethacin and naltrexone. In the double-blind portion of the integrated phase 3 studies, 70% of the bremelanotide group proceeded to the open-label phase of the studies versus 87% of those on placebo. Conclusions: The AEs associated with bremelanotide are mostly mild to moderate. Although not deemed clinically important, bremelanotide should be used with caution in patients at risk of cardiovascular disease, and blood pressure should be well controlled during treatment. Clinical Trial Registration number: NCT02333071 [Study 301] and NCT02338960 [Study 302]. [ABSTRACT FROM AUTHOR]

Abstract Background The Elements of Desire Questionnaire (EDQ) is a patient-reported outcome (PRO) measure developed to evaluate sexual desire and was included in two identically designed phase 3 clinical trials (RECONNECT) as an exploratory endpoint. The EDQ was developed based on a literature review, qualitative research with patients with hypoactive sexual desire disorder (HSDD), and input from clinical experts. This instrument is intended to be used to collect efficacy data in clinical trials evaluating potential treatments for HSDD. The objective of this study was to evaluate the measurement properties of both the monthly and daily recall versions of the EDQ during the RECONNECT trials. Methods Participants completed the EDQ daily version for 7 consecutive days prior to selected monthly clinic visits. The monthly recall version was completed at each monthly clinic visit. The analysis population consisted of all subjects with Female Sexual Function Index (FSFI) data at baseline and ≥ 1 follow-up visit. Results At baseline, 1144 and 676 subjects completed the monthly and daily recall EDQs, respectively. The EDQ scores had good internal consistency and test-retest reliability. Monthly and daily recall EDQ scores were correlated with FSFI-desire domain scores at baseline and month 3. Scores from the monthly and daily recall versions were also correlated. After 6 months, there was a significantly greater improvement for bremelanotide versus placebo in both the monthly and daily recall versions (both P

Background: For the treatment of female sexual dysfunction, the most relevant outcome measures are patient-reported treatment effects and changes in symptoms, underscoring the need for reliable, validated patient-reported outcome (PRO) instruments. The aim of this study was to evaluate the psychometric characteristics (validity and reliability) of the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) PRO measure, which was adapted from the validated FSDS-Revised (FSDS-R) questionnaire and added 2 questions involving arousal and orgasm. Methods: Psychometric analyses were based on the data from a multicenter phase 2b dose-finding study that compared the safety and efficacy of bremelanotide versus placebo and were conducted in the evaluable modified intent-to-treat population (N = 325) from that study. Psychometric evaluation of the new items in the FSDS-DAO included confirmatory factor analyses, tests of internal consistency and test–retest reliability, examinations of convergent and discriminant validity, and determination of responsiveness. The validity of the FSDS-DAO was evaluated based on previously developed instruments, including the Female Sexual Function Index (FSFI), General Assessment Questionnaire (GAQ), Women's Inventory of Treatment Satisfaction (WITS-9), and Female Sexual Encounter Profile-Revised (FSEP-R). Results: Confirmatory factor analyses demonstrated that the FSDS-DAO items fit very well (Bentler's comparative fit index of 0.929). Cronbach's α for the FSDS-DAO total score was ≥ 0.91 at Visits 1, 2, 5, and 12, demonstrating adequate internal consistency reliability. Test–retest reliability was acceptable with an intra-class coefficient of 0.61 and a Spearman's correlation coefficient score of 0.62 between Visits 1 and 2 (4 weeks). Acceptable construct validity was demonstrated by significant correlations with related PRO scales in the expected directions and magnitude. For example, participants reporting the worst levels of sexual function on the FSFI also showed the worst FSDS-DAO scores at Visits 5 and 12. The FSDS-DAO total score was responsive to change. Conclusions: Evidence supports the validity and reliability of the FSDS-DAO for assessing sexually related distress in women with female sexual arousal disorder and/or hypoactive sexual desire disorder; the addition of the arousal and orgasm items did not impact the validity and reliability of the measure. Clinical Trial Registration ClinicalTrials.gov NCT01382719. [ABSTRACT FROM AUTHOR]

Background: Hypoactive sexual desire disorder (HSDD) has a significant negative impact on women's overall health and relationships with their partners. Primary analyses from the RECONNECT clinical trials demonstrated statistically significant and clinically meaningful improvements in sexual desire and related distress with bremelanotide relative to placebo in premenopausal women with HSDD. Exit surveys and patient interviews were conducted to evaluate the impact of HSDD and bremelanotide treatment from the patient's perspective. Materials and Methods: Upon completion of the double-blind study but before participation in the open-label extension, up to 250 participants were recruited to complete the quantitative exit survey (17 questions). A subset of up to 90 patients was invited to participate in the telephone interview (17 questions). Patients who volunteered to participate remained blinded to study drug until the survey and interviews were completed. Results: Quantitative exit surveys were completed by 242 RECONNECT participants; 80 of these women also completed qualitative telephone exit interviews. Participants who received bremelanotide described increased feelings of sexual desire, physical arousal, and improvements in overall quality of their sexual activities in their partner relationship. In comparison, women taking placebo reported benefits that did not include the physiological responses described by women receiving bremelanotide, such as positive experiences of seeking HSDD treatment and improved communication with their partner. Conclusions: Exit surveys and patient interviews support the primary findings from RECONNECT and provide quantitative and qualitative assessments of the impact of HSDD on patients' quality of life and the patients' perspectives on the impact of bremelanotide. Clinical trial numbers NCT02333071, NCT02338960. [ABSTRACT FROM AUTHOR]

Mental health disorders are among the top leading causes of disease burden worldwide and many patients have high levels of treatment resistance. Even though medications offer improvement to some patients, antidepressants are only effective in about half of those treated, and schizophrenia is treatment-refractory in about one-third of patients. One way to combat this disparity is to improve medication development and discovery for psychiatric disorders through evidence-based research. Recently, most psychiatric medications approved by the United States Food and Drug Administration (FDA) are for increased tolerability or extended release. Because of the slow, incremental progress, there is a pressing need to explore novel medications with new indications or mechanisms of action to treat the expanding population with mental disorders, especially in those who are fully or partially recalcitrant to first-line medication options. This review aims to present the newest FDA medications with new indications, establish the clinical need for each, and discuss future directions in drug development. We searched and reviewed novel psychiatric medications approved by the FDA from 2018 to 2022. We then analyzed each medication in the United States Clinical Trials Registry and gathered updated results for efficacy and safety information. We also searched PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, Web of Science, Elsevier, and Google Scholar to understand how these new indications met current clinical needs. Finally, we inquired about related technological implications that will lead the field of psychopharmacology now and in the years to come. We found 12 novel psychiatric medications approved by the FDA from 2018 to 2022, representing a very small percentage of the total FDA approvals during that period. These psychiatric medications with novel mechanisms or improved efficacy and safety  are expected to provide further options for treating mental health disorders; promising results will lead to new patterns of research., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Giliberto et al.)

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 similarity 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 well-being 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. [ABSTRACT FROM AUTHOR]

Objective: To review data regarding bremelanotide, a recently approved therapy for hypoactive sexual desire disorder (HSDD). Data Sources: Literature search of Medline, SCOPUS, and EMBASE was performed using the search terms bremelanotide, bremelanotide injection, Vyleesi, and melanocortin 4 receptor agonist between January 1, 1996, and December 15, 2019. Reference lists from included articles were also reviewed for pertinent citations. Study Selection/Data Extraction: We included phase 2 and 3 trials of bremelanotide. There were 2 reports of phase 3 trials and 2 reports of phase 2 trials. Additional information from supplementary analyses was also referenced. Data Synthesis: Bremelanotide demonstrates significant improvement in desire and a significant decrease in distress related to lack of desire. The most common adverse effects include nausea (39.9%), facial flushing (20.4%), and headache (11%). Relevance to Patient Care and Clinical Practice: Bremelanotide is the second Food and Drug Administration-approved medication for the treatment of HSDD. Bremelanotide's place in therapy is unknown, as the HSDD guidelines were last updated in 2017. Although the trials met statistical significance for change in sexual desire elements and distress related to sexual desire, the clinical benefit may only be modest. Conclusion: Bremelanotide is a subcutaneous injection that can be administered as needed approximately 45 minutes prior to sexual activity. Bremelanotide is safe and has limited drug-drug interactions, including no clinically significant interactions with ethanol. Prescribing guidelines recommend no more than 1 dose in 24 hours and no more than 8 doses per month. Individuals should discontinue use after 8 weeks without benefit. [ABSTRACT FROM AUTHOR]

This article reviews seven drugs recently approved by the FDA, including indications, precautions, adverse reactions, and nursing considerations. [ABSTRACT FROM AUTHOR]

Responder analyses are used to determine whether changes that occur during a clinical trial are clinically meaningful; for subjective endpoints such as those based on patient-reported outcomes (PROs), responder analyses are particularly useful. To identify the minimal clinically important difference (MCID) for selected scores on questionnaires assessing female sexual functioning and to use these differences to analyze the response in a large, controlled, phase 2b, dose-finding study of bremelanotide in premenopausal women with hypoactive sexual desire disorder (HSDD) and mixed HSDD/female sexual arousal disorder (FSAD). The responder analyses were performed for the change from baseline to end of study for a total of 7 endpoints. Each PRO endpoint was assessed using at least 1 of 4 types of responder analyses: a planned analysis anchored to MCIDs based on expert estimates (historical anchors); post hoc analyses based on self-reported global benefit; receiver operating characteristic (ROC) curves; and cumulative distribution function. The prespecified analysis groups were all female sexual dysfunction (FSD)-based diagnoses (all study participants), those with HSDD alone, and a combined group of those with FSAD alone plus those with mixed HSDD/FSAD. Post hoc analyses were also performed for subjects with mixed HSDD/FSAD with a primary diagnosis of HSDD. MCIDs based on the ROC curves for changes in Female Sexual Function Index–desire domain, Female Sexual Distress Scale–Desire/Arousal/Orgasm (FSDS-DAO) total score, FSDS-DAO item 13 and 14 scores, and number of satisfying sexual events. Outcomes matched those based on input from clinical experts. For all 7 endpoints, responder rates at the 1.75 mg dose in the overall modified intention-to-treat population achieved statistical significance compared with placebo (P ≤.03). These responder definitions were subsequently used in the bremelanotide phase 3 registration studies (RECONNECT) that evaluated the safety and efficacy of the bremelanotide 1.75 mg subcutaneous dose in premenopausal women with HSDD. MCIDs for this study were based on changes from a single-blind phase to account for changes due to the placebo effect. These analyses were restricted to a study population composed only of premenopausal women with a clinical diagnosis of HSDD and/or FSAD and were based on data from the same clinical trial. Bremelanotide was safe and well tolerated and demonstrated significant improvement in efficacy vs placebo in the phase 2b trial. The multiple responder analyses offer a valuable approach for determining clinically important effects of bremelanotide for HSDD and FSAD. Althof S, Derogatis LR, Greenberg S, et al. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide. J Sex Med 2019;16:1226–1235. [ABSTRACT FROM AUTHOR]

2019 has been an excellent year in terms of peptides and oligonucleotides (TIDES) approved by the FDA. Despite the drop in the number of total drugs approved by the FDA in 2019 in comparison with 2018 (48 vs. 59), the total number of TIDES authorized increased (seven vs. three). Year after year, TIDES are increasingly present in therapy, as imaging agents, theragnostic and constituent moieties of other complex drugs, such as antibody drug conjugates. This means a consolidation of these kinds of drugs in the pharmaceutical arena, paving the way in the coming years for the approval of others for diverse medical indications. Here the TIDES approved in 2019 are analyzed in terms of chemical structure, medical target, mode of action, and adverse effects.

Aim: Evaluate efficacy/safety of bremelanotide (BMT), a melanocortin-receptor-4 agonist, to treat female sexual dysfunctions in premenopausal women. Methods: Patients randomized to receive placebo or BMT 0.75, 1.25 or 1.75 mg self-administered subcutaneously, as desired, over 12 weeks. Primary end point was change in satisfying sexual events/month. Secondary end points included total score changes on female sexual function index and female sexual distress scale-desire/arousal/orgasm. Results: Efficacy data, n = 327. For 1.25/1.75-mg pooled versus placebo, mean changes from baseline to study end were +0.7 versus +0.2 satisfying sexual events/month (p = 0.0180), +3.6 versus +1.9 female sexual function index total score (p = 0.0017), -11.1 versus -6.8 female sexual distress scale-desire/arousal/orgasm total score (p = 0.0014). Adverse events: nausea, flushing, headache. Conclusion: In premenopausal women with female sexual dysfunctions, self-administered, as desired, subcutaneous BMT was safe, effective, and well tolerated (NCT01382719). [ABSTRACT FROM AUTHOR]

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.

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.