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Study Objective We performed a long-term follow-up to quantify the impairment of sexual quality of life (SQL) and health-related QL (HRQL) in sexually active women after laparoscopic excision of deep infiltrating endometriosis (DIE). Design Prospective case-control study. Setting Hospital Clinic of Barcelona. Patients A total of 193 patients (after dropout and exclusions) were divided into 2 groups: one hundred twenty-nine premenopausal women with DIE (DIE group) and 64 healthy women who underwent tubal ligation (C group). Interventions All patients underwent laparoscopic surgery: laparoscopic endometriosis surgery in the DIE group and laparoscopic tubal ligation in the C group. All women were followed for at least 36 months, and they completed the Medical Outcomes Study 36-item short form questionnaire to assess their HRQL and 3 self-administered questionnaires that evaluate different aspects of SQL: the generic Sexual Quality of Life–Female questionnaire, the Female Sexual Distress Scale to evaluate “sexually related distress,” and the Brief Profile of Female Sexual Function to screen hypoactive sexual desire disorder. The patients with DIE as well as the controls completed the 4 questionnaires before surgery, and the patients with DIE also completed the questionnaires at 6 and 36 months after surgery. Measurements and Main Results A comparison of the patients and controls before surgery showed a statistically significant impairment in SQL and HRQL among the patients with DIE. A statistically significant improvement in SQL and HRQL was observed in the DIE group 6 months after surgery, with scores being similar to those of the C group. An evaluation 36 months after surgery showed that SQL and HRQL were better than presurgical SQL and HRQL in the DIE group, with a slight reduction compared with the 6-month evaluation. Conclusion SQL and HRQL improved in patients with DIE undergoing complete laparoscopic endometriosis resection and were comparable to those of healthy women at 6 months after surgery, showing a slight reduction at 36 months of follow-up.

The US Food and Drug Administration (FDA) has approved two drugs for ‘hypoactive sexual desire disorder’ in women, flibanserin (Addyi) in 2015 and bremelanotide (Vyleesi) in 2019. In this paper we examine the outcome measures and clinical trial data upon which regulatory approval was based. In clinical trials, flibanserin led to an average of only one additional enjoyable sexual experience every two months, bremelanotide to none. Trials for both drugs feature shifts in primary outcomes and a contested indication. A politicised industry-sponsored advocacy campaign and conflicted patient and expert testimony likely influenced flibanserin’s approval at its third attempt. Bremelanotide, with even weaker efficacy, capitalised on the regulatory precedent set by the approval of flibanserin. Reconsideration of regulatory decisions to approve these drugs is in order, as well as a broader examination of how future regulatory decisions can better address conflicts of interest and clinically meaningful benefit.

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.

Flibanserin (FLB) was approved by FDA for the treatment of pre-menopausal female hypoactive sexual desire disorder (HSDD). FLB suffers from low oral bioavailability (33%) which might be due to hepatic first-pass metabolism in addition to its poor aqueous solubility. The sublingual route could be a promising alternative for FLB due to the avoidance of enterohepatic circulation. However, the drug needs to dissolve in the small volume of saliva in order to be absorbed through the sublingual mucosa. Therefore, FLB nanocrystals were prepared by sono-precipitation technique according to 23 full factorial design. FLB-nanocrystals were formulated using two surfactants (PVP K30 and PL F127) in two different amounts (200 and 400 mg) and the volume of ethanol was either 3 or 5 mL. Nanocrystal formulation was optimized according to the desirability function to have a minimum particle size, zeta potential, polydispersity index, and maximum saturated solubility. The optimized formula had a particle size of 443.12 ± 14.91 nm and a saturated solubility of 23.27 ± 4.62 mg/L which is five times the saturated solubility of FLB. Nanocrystal dispersion of the optimized formula was solidified by freeze-drying and used to prepare rapidly disintegrating sublingual tablets containing Pharmaburst® as superdisintegrant. Sublingual tablet formulation with the shortest disintegration time (36 s) was selected for the in vivo study. FLB nanocrystal-based sublingual tablets exhibited a two-fold increase in bioavailability with a faster onset of action compared to the commercially available oral formulation. These findings prove the potential application of FLB nanocrystal-based sublingual tablets in the treatment of HSDD.

Background The Global Consensus Position Statement on the Use of Testosterone Therapy for Women (Global Position Statement) recommended testosterone therapy for postmenopausal women with hypoactive sexual desire disorder (HSDD). Aim To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with HSDD. Methods The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method. Outcomes A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up. Results Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data. Clinical Implications This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring. Strengths & Limitations This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging. Conclusion Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need. Parish SJ, Simon JA, Davis SR, et al. International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women. J Sex Med 2021;18:849–867.

Introduction In 2000, the FDA began issuing advice about treatments for hypoactive sexual desire disorder (HSDD) in women. How its recommendations have evolved has not been reviewed. Its consistent preference for self-rating by patients over evaluation by an examining clinician has not been addressed. Objectives Recount the changes in FDA’s proposals about patient-reported outcomes and diagnostics. Compare the value of patient-reported measures and clinical interviews. Methods Historical review is based on draft guidances, publications, meetings, and prescribing information. Results The FDA has avoided clinician input into diagnosis and evaluation of the severity of HSDD in women. It abandoned its initial (2000) insistence on counts of satisfying sexual events to define efficacy in favor of symptom-related scales to evaluate desire and distress with daily self-ratings. By 2015, the FDA accepted the self-rated Female Sexual Function Index-Desire Domain (FSFI-D) to measure desire and the most relevant item of the Female Sexual Distress Scale-Revised (FSDS-R) to measure distress; retrospection for both is one month. The FDA rejected the one clinician-rated broad measure of HSDD, the Sexual Interest and Desire Inventory (SIDI-F), although well-validated and treatment-sensitive. Since 2005, the FDA has accepted the Decreased Sexual Desire Screener (DSDS) to diagnose HSDD by non-expert clinicians using self-ratings and exploring them in more depth in a clinical interview. Conclusion FDA’s decisions on how to measure HSDD in women may have stabilized on accepting 2 co-primary measures: the FSFI-D and the FSDS-R item on bother about low desire, and on accepting the DSDS for diagnosis. FDA’s rejection of clinician ratings of severity through interviews in clinical trials seems unsound because interviews can give broader assessments than (brief) self-ratings, although the agency’s logic was to avoid diagnostic controversies and help avoid overcommercialization. Semistructured clinical interviews for diagnosis (DSDS) and severity-rating (SIDI-F) are well validated and are recommended for clinical practice. Pyke RE. FDA Decisions on Measures of Hypoactive Sexual Desire Disorder in Women: A History, With Grounds to Consider Clinical Judgment. Sex Med Rev 2021;9:186–193.

Transdermal testosterone therapy, dosed within premenopausal physiologic testosterone ranges, used alone or with menopausal hormone therapy for postmenopausal hypoactive sexual desire disorder, has shown short-term efficacy, with few androgenic side effects. After natural or surgical menopause, meaningful improvements include an additional satisfying sexual episode per month; improvement in desire, arousal, orgasm, pleasure, and responsiveness; and a reduction in distress. Long-term data on cardiovascular, cancer, and cognitive safety are lacking. No approved testosterone preparation is available for women. Compounded testosterone creams or reduced dosing of male-approved therapies represent off-label use. Injections or pellets cause supraphysiological testosterone levels and are not recommended.

Hypoactive sexual desire disorder (HSDD) represents a common condition among transgender women. However, to date no specific guidelines for the management of HSDD in transgender persons are available. The aim of the present narrative Review is to evaluate evidence-based treatment for HSDD and to suggest treatment options for HSDD in transgender women. Clinically relevant publications on the management of HSDD (from 1985 to 2020) were searched in PubMed and Medline databases, using the following terms: "sexual desire", "sexual health", "HSDD", "transgender", "gender-affirming treatment", "sexual therapy", "testosterone treatment", "Central nervous system-active medications", and variants. Since sexual desire could be affected by several factors, a comprehensive assessment of HSDD- exploring biological, psychological, and social domains- is recommended, in order to identify possible predisposing, precipitating and maintaining factors. Among treatment options, transgender women may benefit of different sex therapy strategies and/or central nervous system-active medications-such as flibanserin, bremelanotide, bupropion and buspirone-and transdermal testosterone, bearing in mind that this option could be poorly accepted by patients due to the risk of virilizing effects. The lack of data regarding the efficacy of HSDD treatment options in transgender women emphasize the need for literature to focus more on this topic in the future.

Hypoactive sexual desire disorder (HSDD) is a common female sexual dysfunction and is estimated to affect approximately 10% of women in the United States. It has been suggested that HSDD is associated with an imbalance of hormone and neurotransmitter levels in the brain, resulting in decreased excitation, increased inhibition, or a combination of both. Evidence suggests neurotransmitters, including dopamine (DA), norepinephrine, and serotonin, as well as hormones such as estradiol and testosterone, contribute to female sexual desire and response. Current treatments for HSDD include psychotherapy, and two US Food and Drug Administration-approved medications for premenopausal women: flibanserin, a serotonin mixed agonist and antagonist, and bremelanotide, a melanocortin receptor (MCR) agonist. Melanocortins are endogenous neuropeptides associated with the excitatory pathway of the female sexual response system. MCRs are found throughout the body, including the brain. Bremelanotide is an MCR agonist that nonselectively activates several of the receptor subtypes, of which subtype 4 (MC4R) is the most relevant at therapeutic doses. MC4R is predominantly expressed in the medial preoptic area (mPOA) of the hypothalamus in the brain, and is important for female sexual function. Animal studies suggest that bremelanotide may affect female sexual desire by activating presynaptic MC4Rs on neurons in the mPOA of the hypothalamus, leading to increased release of DA, an excitatory neurotransmitter that increases sexual desire. This review presents what is known about the mechanism of action of bremelanotide in the context of treating HSDD.

Background Research on the relationship between physical activity (PA) and female sexual dysfunction (FSD) is lacking. Aim To investigate the clinical, psychological, and sexual correlates of PA in women with FSD. Methods A non-selected series of n = 322 pre- and post-menopausal patients consulting for FSD was retrospectively studied. Regular involvement in PA and its frequency (6 hours/week: extremely active) were investigated with a specific question. Outcomes FSDs, including HSDD (Hypoactive sexual desire disorder) and FGAD (Female genital arousal disorder), were diagnosed according to a structured and clinical interview. Participants underwent a physical examination and a clitoral Doppler ultrasound, and were asked to complete the Female Sexual Function Index, Female Sexual Distress Scale-Revised, Body Uneasiness Test, and Middlesex Hospital Questionnaire. RESULTS At multivariate analysis, women engaging in PA (67.4%, n = 217) scored significantly higher in several Female Sexual Function Index domains - including desire, arousal and lubrication - and showed lower sexual distress and lower resistance of clitoral arteries, as compared to sedentary women. A significant, inverse association between PA and HSDD was observed. Mediation analysis demonstrated that the negative association between PA and HSDD was partly mediated by body image concerns (Body Uneasiness Test Global severity index), psychopathological symptoms (Middlesex Hospital Questionnaire total score) and sexual distress (Female Sexual Distress Scale-Revised score). These latter 2 factors also partly mediated the association between PA and a reduced risk of FGAD, whilst a lower BMI was a full mediator in the relationship between PA and FGAD. Finally, extreme PA was associated with significantly worse scores in several psychosexual parameters (i,e, sexual satisfaction and histrionic/hysterical symptoms), even compared to a sedentary lifestyle. Clinical Implications Women consulting for FSD may gain benefits on desire, arousal, lubrication and sex-related distress from regular PA; however, physicians should remain alert to the downsides of excessive exercise. Strengths & Limitations The main strength lies in the novelty of the findings. The main limitations are the cross-sectional nature, the clinical setting, the small sample size of the different PA groups, and the use of self-reported instruments for the evaluation of PA. CONCLUSION In women with FSD, PA was associated with better sexual function and clitoral vascularization, lower sexual distress and reduced odds of HSDD and FGAD; the benefits of PA on sexuality were mediated by both psychological and organic determinants; excessive PA was related with a poor overall sexual function and with a low sexual satisfaction.

Hipoaktif cinsel istek bozukluğu kadınlarda en sık görülen cinsel istek bozukluğudur. Bu derlemede cinsel fonksiyon bozukluğu olan kadınlarda azalmış cinsel arzuya yönelik olarak tarama yapılması ve hangi durumlarda kişinin tedaviye ihtiyacı olduğunun belirlenmesi amaçlanmaktadır. Ayrıntılı tıbbi ve seksüel öykü tedavinin yönlendirilmesinde en önemli basamaktır. Laboratuvar testleri ayırıcı tanıda önem kazanmaktadır. Tedavi basamaklarında öncelikli olarak hastaya eğitim ve danışmanlık verilmesi ve davranışsal terapi uygulaması ile başlanmalıdır. Etki eden faktörlerin modifikasyonu önemlidir. Bu basamaklardan sonra yanıt alınamazsa medikal tedavi uygulanmalıdır.

Introduction Previous studies have shown a strong association between diabetes mellitus (DM) and the frequency and severity of some aspects of male sexual dysfunction (SD). The same relationship with prediabetes (preDM) has been less well investigated. Aim To systematically review the current literature on the association between preDM and SD, focusing on erectile dysfunction (ED), sex steroid hormone alterations, and premature ejaculation (PE). Methods The present review was conducted in accordance with the PRISMA declaration standards for systematic reviews. A systematic search for the terms “male sexual dysfunction,” “prediabetes,” “IFG or IGT,” “glycemia,” “ED,” “ejaculation,” and “hypoactive sexual desire disorder” was carried out in the PubMed and Embase databases. Main Outcome Measure Prevalence of SD in men with preDM and severity of ED, PE, and hormone alterations in men with preDM compared with controls. Results 12 studies reporting data on the association between SD and preDM were found in the literature. According to these studies, ED is more prevalent in men with preDM compared with controls, the severity of ED increases progressively as a function of impaired glucose metabolism, testosterone values and preDM are strongly correlated, men with preDM are at increased risk of testosterone deficiency and hypogonadism, men with hypogonadism have a higher prevalence of preDM, and the association between PE and preDM is controversial. Conclusion PreDM is a common and underdiagnosed clinical condition that is strongly associated with male SD. A detailed glucose metabolism investigation should be performed in every patient with SD to screen for glucose abnormalities and eventually to implement prevention program to decrease their chances of developing life-changing chronic illnesses. Boeri L, Capogrosso P, Ventimiglia E, et al. Sexual Dysfunction in Men with Prediabetes. Sex Med Rev 2019;8:622–634.

Female sexual dysfunction (FSD) is a serious health problem because of its high prevalence and deleterious effects on women's quality of life. Practitioners of women's health must care able to detect FSD in its early stage so that timely treatment could be offered. Also, the clinicians have lack understanding about the approach for identification and evaluation of the sexual problem. The study aimed to investigate the effect of guided psychosexual health instructions on changes in sexual activity among women with reduced sexual dysfunctions (hypoactive). Methods: A quasi- experimental design was used (pre and posttest one group) Setting: The study was conducted at Kebly and Bahary Maternal& Child Health Care Centers at Shibin Elkom Sample 100 participants of women were selected according to their responses in two-scale of sexual dysfunctions and elicited as hypoactive sexual dysfunctions from MCH Tools of the study: 1- Structured interview questionnaire classified into two parts, the first part deal with a biosocial data as age, level of education, and the employment status as well as complaining from physical or gynecological problems hindering them for conducting healthy marital relationship with their partner. The second part was: The Female Sexual Function Index (FSFI), A Multidimensional Self-Report Instrument for the Assessment of Female Sexual Function in a 19-item questionnaire, It was developed by Rosen, et al. (2010) as a brief instrument for assessing the key dimensions of sexual function in women. 2-Sexual Dysfunction Questionnaire It was developed by Infrasca et, al (2011) to assess women's readiness and preparation for sexual functions disorders Introduced as a brief self-report inventory. Results showed that there was a highly statistically significant difference P well as vaginal lubrication, orgasm, and degree of satisfaction during sexual activity. It was concluded that the use of guided psychosexual intervention was effective in managing sexual dysfunctions problems and enhancing satisfaction to reach orgasm. Recommendations. All health care providers should include screening questions regarding sexual well-being as a standard of practice. Treating medical, psychosexual, relationship problems, and addressing sociocultural issues, which can be effective in helping women and their partners dealing with hypoactive sexual desire disorder. Health care providers should involve the woman’s partner in the assessment and treatment of sexual health concerns when it is appropriate and safe to do so. Also, health guidelines protocol of care for (SD) should be providers to involve the woman’s partner in addressing sexual issues

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.

To compare sexual function and quality of life (QoL) in breast cancer survivors with and without a history of bilateral salpingo-oophorectomy (BSO). A cross-sectional study of breast cancer survivors treated at a tertiary referral hospital in Western Australia. The Female Sexual Function Index was used to determine rates of female sexual dysfunction (FSD) and hypoactive sexual desire disorder (HSDD). Participants also completed the Relationship Assessment Scale, Menopause-specific quality of life questionnaire and Short Form Health Survey-36. A total of 427 women were invited to participate: 119 had undergone BSO and 308 were controls with at least one ovary remaining. A total of 172 women participated (overall response rate 40.3%), consisting of 76 women in the BSO group (response rate 63.9%) and 96 women with at least one ovary remaining (response rate 31.2%). There was no difference in FSD between the two groups: 63/76 (82.9%) women who had undergone BSO had FSD compared to 75/96 (78.1%) controls (p = 0.458). No difference in HSDD was observed (p = 0.084) between the BSO group 70/76 (96.0%) and the controls 96/96 (100%). Women who had undergone BSO had lower general health scores compared to the control group (p = 0.034). Both groups had similar energy levels, emotional well-being, pain scores, physical functioning levels and social functioning levels. In this study, women with prior treatment for breast cancer had high levels of FSD and HSDD, irrespective of whether they had undergone BSO. Both groups reported similar sexual function scores and QoL.

Introduction Sexual performance anxiety (SPA) is one of the most prevalent sexual complaints; yet, no diagnosis is recognized for either gender. Thus, research into treatment has been minimal. Aim Review the prevalence of SPA and its relation to sexual dysfunctions and anxiety disorders. Compare SPA to (non-sexual) performance anxiety and social anxiety (PA/SA). Apply pharmacologic principles to the known properties of drugs and phytotherapies to hypothesize treatments for SPA. Methods Review SPA and PA/SA through PubMed searches for relevant literature from 2000 to 2018. Main Outcome Measure Prevalence was estimated using population-representative surveys. For treatment results, controlled clinical trial results were prioritized over open-label trial results. Results SPA affects 9–25% of men and contributes to premature ejaculation and psychogenic erectile dysfunction (ED). SPA affects 6–16% of women and severely inhibits sexual desire. Cognitive behavior therapy and mindfulness meditation training have been proven effective for PA/SA and are recommended for SPA, but controlled studies are lacking. Phosphodiesterase type 5 inhibitors are effective for psychogenic ED and premature ejaculation, both of which include SPA as a major element. Drugs proven for PA/SA have adverse sexual and sedative effects, but serotonergic anxiolytics with prosexual effects (buspirone ± testosterone, trazodone ± bupropion) may have potential, and sage, passionflower, l -theanine, and bitter orange are anxiolytic. Nitric oxide boosters ( l -citrulline, l -arginine, Panax ginseng) have the potential for increasing genital tumescence and lubrication, and plant-based alpha-adrenergic antagonists may aid sexual arousal (yohimbine/yohimbe, Citrus aurantium/p-synephrine). Conclusion SPA causes or maintains most common sexual dysfunction. No treatments are well proven, although cognitive behavior therapy, mindfulness meditation training, and serotonergic anxiolytics (buspirone, trazodone, gepirone) have potential, and phosphodiesterase type 5 inhibitors are effective for psychogenic ED and premature ejaculation. Several phytotherapies also appear to have potential. Pyke RE. Sexual Performance Anxiety. J Sex Med 2020;8:183–190.

Introduction Treatment of hypoactive sexual desire disorder (HSDD) remains unfulfilled. The only approved medication, flibanserin (FLI), is highly underused owing to concerns about central nervous system (CNS) depression and interactions. Trazodone (TRZ), which is not often used for sexual problems, has evidence suggesting efficacy but similar concerns. Aim To explore whether the pharmacologic similarities between TRZ and FLI could allow treatment of HSDD without CNS depression. Methods A literature search on TRZ was performed for clinical effects and to facilitate pharmacologic considerations relating to doses for HSDD and CNS depression. Main Outcome Measure The main measures were threshold doses for sedative-hypnotic effects, and calculated doses for occupy 20% of agonist receptors and 70% of antagonist receptors, considering 5HT1A, 5HT2A, 5HT2C, and α1 receptors for sexual benefits and 5HT2A, α1, and histamine type 1 receptors for CNS depression. Results 3.5–19.2-mg extended-release (XR) TRZ daily (bioequivalent to 1.2–6.4-mg immediate-release [IR] TRZ 3 times a day) is estimated to be the minimum effective dose for improving sexual desire and arousal; 75 mg (25-mg IR) appears to be the threshold dose for CNS depression. Conclusion Although tested only in much larger dose strengths, the optimal dose of XR TRZ for HSDD according to receptor and PK data appears to be about 4–20 mg. HSDD or arousal problems might be treated without over-sedation with XR 150-mg TRZ matrix tablets quartered to 37.5 mg daily or 50-mg IR TRZ tablets quartered to 12.5 mg given 2–3 times daily or as needed for arousal problems. Interindividual sensitivity might require varying the dose. Mechanistically rational adjuncts (eg, bupropion or dopaminergics) might augment response. Pyke RE. Trazodone in Sexual Medicine: Underused and Overdosed? Sex Med Rev 2020;8:206–216.

Research suggests that posttraumatic stress disorder (PTSD) is associated with sexual dysfunction; however, there is a paucity of research examining the relations among trauma exposure, PTSD, and low sexual desire, specifically. Thus, the goal of the present study was to investigate whether women with hypoactive sexual desire disorder (HSDD; n = 132) were more likely to meet criteria for a diagnosis of current or lifetime PTSD relative to women with no sexual desire concerns (n = 137). We also sought to compare the type, frequency, and intensity of PTSD symptoms between the two groups. Finally, we examined whether women in the two groups were exposed to more, or different types of, potentially traumatic events. Compared to women with no sexual health concerns, women with HSDD were more likely to meet criteria for current PTSD, odds ratio (OR) = 5.50, 95% CI [1.18, 25.61]; and lifetime PTSD, OR = 2.78, 95% CI [1.56, 4.94]. Women in the HSDD group also had higher odds of meeting criteria for avoidance (5.10 times) and hyperarousal symptoms (4.48 times) and scored higher on measures of past-month PTSD symptom frequency, d = 0.62, and intensity, d = 0.57. No group differences were observed regarding reexperiencing symptoms, the associated features of PTSD, or type or frequency of exposure to potentially traumatic events. The findings indicate PTSD symptomatology may be a predisposing or perpetuating contributor to low sexual desire, and low sexual desire and PTSD may be related through an alteration in stress adaptability.

About 40% of postmenopausal women have decreased sexual desire, causing distress. Estrogen therapy attenuates vaginal complaints but has no effect on sexual desire. Although sexual function has been linked to testosterone, there is no clear relation between sexual desire and circulating levels of testosterone. Nevertheless, treatment with transdermal (patch) testosterone improved sexual function in several randomized controlled trials. Women with hypoactive sexual desire disorder who were treated with testosterone reported more satisfying sexual episodes and sexual desire compared with the placebo group. Adverse effects were mild. However, there is no testosterone drug designed for women available on the European market. Consequently, women who opt for testosterone treatment have to use preparations made for men with a high drug concentration. Adequate dosage for women is therefore challenging. A trial of 5 mg transdermal testosterone (gel or cream) daily or less has been suggested, followed by close monitoring of side effects and hormone level.

Introduction Testosterone has been studied for its benefits on sexual health for decades. The research regarding testosterone in women has produced evidence that this is a potential treatment for women suffering from female sexual dysfunction. There are several limitations of the testosterone trials that can affect their interpretation and challenges posed by some regulatory agencies that have prevented approval of any testosterone treatment for women in several countries. Aim To summarize the challenges of testosterone trials in terms of study populations, patient-reported outcomes, validated instruments in research, confounders, and regulatory barriers. Methods A thorough review of published data on testosterone for the treatment of women's sexual health problems was undertaken. A detailed evaluation of the limitations of these trials was conducted and incorporated with the published evidence on the regulatory processes involved in moving testosterone from clinical research to drug approval. Main Outcome Measure Main outcome measures are assessment of clinical trial populations, survey tools, confounders, and regulatory barriers. Results There is some heterogeneity of study populations included in testosterone trials in women. Similarly, there have been differences in instruments used to assess patient-reported outcomes and often minimal control for potential confounders. The regulatory agency had posed a challenge to approve any testosterone treatment for women based on unproven concerns and a lack of regulatory guidance for drug developers. Clinical Implications There is strong evidence that shows testosterone is effective for treating sexual health concerns in the women included in clinical trials. Strength & Limitations Strengths include thorough review of published literature and trial design for sexual health concerns. Limitations include being restricted to English Language publications and not having access to unpublished clinical trial data. Conclusions Testosterone trials in women have been limited by homogeneity in the study populations and outcomes measured. Drug development has been hampered by inconsistent regulatory barriers.

Background Androgens are essential hormones in women. Yet, androgen therapy is understudied and underutilized despite showing improvement in postmenopausal hypoactive sexual desire disorder (HSDD) and the genitourinary syndrome of menopause (GSM). Additionally, regulatory concerns have left a significant gap in commercially available testosterone preparations, formulated specifically for women, in most countries. This has led to off-label use of male formulations and compounded therapies which are under-regulated. Beyond HSDD and GSM, testosterone likely influences the brain, breast, cardiovascular and musculoskeletal systems. These effects are not well studied, and therefore it is difficult to counsel patients on testosterone therapy when used for these endpoints. Ultimately, further study is needed to elucidate these effects, create a fuller picture of the risks and benefits, and encourage product development specifically designed for women.

A multitude of biopsychosocial factors influences sexual health at midlife, a common concern in daily practice along with vaginal and pelvic health. Health-care providers (HCPs) need to be proactive in dealing with possible symptoms because in most cases early management prevents distress and improves quality of life. Female sexual dysfunctions (FSDs) may have a complex etiology but sexual history is not difficult implementing basic knowledge of risk factors and some skills helping women to cope with hormonal and age-related changes. This work summarizes key points to approach sexual symptoms in midlife women, providing principles to diagnose and manage hypoactive sexual desire disorder (HSDD) and genitourinary syndrome of menopause (GSM)/vulvovaginal atrophy (VVA), as well as manage contraceptive needs.

Hypoactive sexual desire disorder (HSDD) is a persistent or recurrent absence of sexual fantasies and desire for sexual activity, causing marked personal distress or interpersonal difficulties. HSDD affects 10% of U.S. women and is associated with depression and other negative emotional states. It is imperative that psychiatrists are competent to make this diagnosis and are aware of available treatment options. A full psychiatric and medical history are necessary to identify potential causes or contributing factors that may need to be addressed first. The authors discuss the diagnostic tools available as well as general diagnostic considerations for psychiatrists. Given its importance in the understanding of the available treatments for this disorder, the pathophysiology behind HSDD is reviewed. The authors emphasize the treatment of HSDD, including general treatment considerations, treatment in the context of depression, and psychotherapy and medications that have been approved by the U.S. Food and Drug Administration.

An informed consent discussion for a patient with Hypoactive Sexual Desire Disorder.

Nearly half of women in the United States report problems with sexual function. Many health care providers do not ask about sexual concerns during routine clinical encounters because of personal discomfort, lack of familiarity with treatment, or the belief that they lack adequate time to address this complex issue. This may be especially true for hypoactive sexual desire disorder (HSDD), the most commonly identified sexual problem among women. HSDD is characterized by a deficiency of sexual thoughts, feelings, or receptiveness to sexual stimulation that has been present for at least 6 months, causes personal distress, and is not due to another medical condition. This is an up-to-date overview of HSDD for clinicians, discussing its physiology, assessment, diagnosis, and treatment strategies. Although a definitive physiology of HSDD is still unknown, multiple hormones and neurotransmitters likely participate in a dual-control model to balance excitation and inhibition of sexual desire. For assessment and diagnosis, validated screening tools are discussed, and the importance of a biopsychosocial assessment is emphasized, with guidance on how this can be implemented in clinical encounters. The 2 recently approved medications for HSDD, flibanserin and bremelanotide, are reviewed as well as off-label treatments. Overall, HSDD represents a common yet likely underrecognized disorder that midwives and other health care providers who care for women across the life span are in a unique position to address.

Introduction: Hypoactive sexual desire disorder (HSDD) is the most prevalent sexual dysfunction in women, previously managed with off-label therapies. Indicated for premenopausal women, flibanserin is the first FDA-approved medication to treat HSDD.Areas covered: This review summarizes flibanserin's pharmacokinetics, proposed mechanism of action, and safety data in clinical trials with a focus on sedation- and hypotension-related adverse events, and drug interactions with alcohol and antidepressants. Sources included peer-reviewed publications and internal data from the manufacturer.Expert opinion: Flibanserin is a well-tolerated and effective treatment that decreases distress and restores sexual desire to a level that is normative for the individual patient with HSDD. Simplification of a risk mitigation program for flibanserin in the US is likely to increase the number of prescribing clinicians if accompanied with educational efforts to clarify flibanserin's risk-benefit profile. As flibanserin is dosed daily and may be used for a decade or more in the typical premenopausal patient, long-term pharmacovigilance data will be essential. Over time, HSDD will be treated by more nonspecialist health care professionals and flibanserin will likely become established as a significant treatment option along with other medications approved for this indication in the context of a holistic biopsychosocial treatment paradigm.

Objetivo: evaluar la eficacia y seguridad de dos terapias hormonales sustitutivas, combinadas con testosterona, en el tratamiento del trastorno del deseo sexual hipoactivo en mujeres en climaterio. Materiales y métodos: ensayo clínico, aleatorizado, controlado, no enmascarado. Se incluyeron mujeres mayores o igual a 40 años y menores de 60 años, con útero, con actividad sexual en las últimas seis semanas, aquejadas por síntomas vasomotores, cuyo motivo de consulta consistió en bajo deseo sexual. Se utilizó como instrumento el cuestionario Índice de Función Sexual Femenina (IFSF). Se asignaron dos grupos aleatorizados: grupo «A» (51 recibieron estrógenos conjugados de equinos y medroxiprogesterona más testosterona) y grupo «B» (54 tibolona más testosterona). El estudio fue realizado entre julio de 2015 y diciembre de 2016, en Armenia, Quindío, Colombia. Resultados: se analizó una población de 105 mujeres. La media de edad fue de 55,8 (DS±9,38) años. En la población total, al inicio del estudio, la mediana fue de 3 encuentros sexuales por mes. Al final la mediana fue de 5 encuentros sexuales por mes, (grupo «A» 4 encuentros y grupo «B» 7 encuentros, p=0,0036). Al finalizar la investigación se observó que las mujeres del grupo «B», mostraron puntuaciones promedias significativamente más altas en el IFSF (28,56 DS±4,63 puntos), al compararlas con las mujeres del grupo «A» (27,57 DS±4,32) (p

The 52-week open-label extension of the RECONNECT studies demonstrates bremelanotide's favorable safety profile, with sustained efficacy in treating hypoactive sexual desire disorder in premenopausal women., OBJECTIVE: To evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women. METHODS: Women who completed the 24-week double-blind core phase of RECONNECT, composed of two parallel phase 3 trials (301 and 302) examining the safety and efficacy of bremelanotide compared with placebo in premenopausal women with hypoactive sexual desire disorder, could enroll in the 52-week open-label extension, provided they had not experienced serious adverse events during the core phase. Efficacy was assessed using the coprimary endpoints from the core phase, and all adverse events were collected during the open-label extension. All statistical analyses were descriptive. RESULTS: The study 301 open-label extension began on July 17, 2015, and concluded on July 13, 2017; the study 302 open-label extension began on October 5, 2015, and concluded on June 29, 2017. Of the 856 eligible patients who completed the core phase, 684 elected to participate in the open-label extension, and 272 completed it. The most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), and the only severe treatment-emergent adverse event experienced by more than one participant in both studies was nausea during the open-label extension. The change in Female Sexual Function Index–desire domain score and Female Sexual Distress Scale–Desire/Arousal/Orgasm item 13 from baseline to end of the open-label extension ranged from 1.25 to 1.30 and −1.4 to −1.7, respectively, for patients who received bremelanotide during the core phase, and 0.70–0.77 and −0.9, respectively, for patients who received placebo during the core phase. CONCLUSION: During the 52-week open-label extension of RECONNECT, no new safety signals were observed, and premenopausal women treated with bremelanotide exhibited sustained improvements in hypoactive sexual desire disorder symptoms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302). FUNDING SOURCE: Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.

Introduction Prior medication treatment for hypoactive sexual desire disorder (HSDD) in women has left about half the subjects without benefit. Lorexys (LOR), a proprietary combination of the stimulating/excitatory dopamine-norepinephrine reuptake inhibitor bupropion (BUP) and the sedating/inhibitory serotonergic agonist-antagonist trazodone (TRZ), was developed as a multifunctional solution for this problem. Aim Test efficacy, safety, and tolerability of LOR in a range of doses in a combined phase IB/IIA study in premenopausal outpatients with HSDD. Methods Otherwise healthy premenopausal women from 25–50 years of age with HSDD were tested in an open-label, active-control, one-way crossover study, with three 4-week treatments of extended-release TRZ and/or sustained-release BUP. Evaluations were made before and after each treatment. A washout of at least a week followed each treatment. The order of treatments was a standard dose of BUP; a subtherapeutic dose of BUP and TRZ (LOR-low); and a threshold-therapeutic dose of BUP and TRZ (LOR-mod). A midpoint interim analysis was planned to consider adapting doses for efficacy or safety. Main Outcome Measure The primary efficacy measure was the Female Sexual Function Index, Desire domain; the main secondary efficacy measures included the Female Sexual Distress Scale-Revised 13th item, on bother about low desire, and a Patient’s Global Impression of Change. The main outcome comparison was the proportions of responders. Safety measures were elicited adverse events, Epworth Sleepiness Scale, Columbia Suicide Severity Rating Scale 6-item SCREEN version, vital signs, electrocardiograms, and standard laboratory tests. Results Interim analysis did not require altering doses. Most evaluable subjects responded to LOR-mod (at the standard thresholds for response based on minimum clinically relevant difference from baseline, 79% on Female Sexual Function Index, Desire domain, 87% on Female Sexual Distress Scale-Revised Item 13, and 79% on Patient’s Global Impression of Change; each P < .05 vs BUP). As expected, close to half responded to BUP (38%, 45%, and 52%, respectively). Response to LOR-low was intermediate (not significant vs BUP). Sensitivity analyses to compensate for carryover effects supported the efficacy of LOR-mod. Elicited adverse events showed the expected profile of TRZ, but led to no sedative-type dropouts or worsening on the Epworth Sleepiness Scale. Clinical Implications The open-label 1-way crossover design of this phase IB/IIA study limits conclusions, but the consistency of responder analyses showing superiority of LOR-mod dose over control, and the lack of central depressant dropouts, favor further development in double-blind placebo-control trials. Strength & Limitations Strengths include large margins of efficacy over control agent, rapid onset of action, and rigorous safety assessment. Limitations are open-label, cross-over design/lack of placebo control and 1-month duration of exposure. Conclusion Moderate-dose LOR was generally well-tolerated and was significantly more effective than BUP (active control). The results seem highly favorable compared to previously tested agents.

This review attempts to explain female hypoactive sexual desire disorder (HSDD) from a functional evolutionary perspective. Can theory and data regarding the evolved functions of female sexual motivation help explain cases of low sexual desire in women? If so, might some such cases be the product of brain mechanisms operating in ways that promoted reproductive success during human evolution, rather than low desire resulting from pathology? A functional theory of women’s sexual motivation is first summarized, which posits that sexual desire is modulated by both conception probability and social variables related to the initiation and maintenance of pair bonds. Recent evidence consistent with this theory is reviewed, followed by review of evidence showing that variables predicting sexual desire in most women may also explain cases of HSDD. Women’s sexual desire varies in functionally patterned ways. Discovering the evolved design of brain mechanisms that generate those patterns is crucial for understanding HSDD.

Introduction Flibanserin, a treatment for hypoactive sexual desire disorder, carries warnings for increased risk of severe hypotension and syncope when used with alcohol. However, these warnings are not informed by studies that used flibanserin’s recommended bedtime dosing because previous alcohol studies assessed flibanserin’s safety during the day. Aim The aim of this study was to assess the effects of ethanol in a real-world context in premenopausal women taking flibanserin at bedtime. Methods In a randomized, placebo-controlled, double-blind study, 24 healthy premenopausal women (mean age = 34.5 ± 9.9 years; mean body mass index = 25.2 ± 3.4 kg/m2) were dosed with flibanserin or placebo for 3 days to achieve steady-state plasma levels. In a clinical research unit, subjects (n = 22) were provided 2 units of wine (150 mL/unit; 12% ethanol content) or a nonalcoholic beverage with a standardized 3-course evening meal. Flibanserin 100 mg or placebo was administered at bedtime 2.5 hours after the end of the evening meal. On a separate day, subjects were provided the alternative beverage (± alcohol) with the same evening meal and dosed with the same treatment (flibanserin or placebo) at bedtime. After a 5-day washout period, subjects crossed over to the other treatment arm and the protocol was repeated. Main Outcome Measure Adverse events (AEs) and vital signs were monitored. Results In the absence of ethanol, headaches and hypotension were the only AEs that occurred in ≥2 subjects after flibanserin dosing (placebo corrected rates were 17.4% and 8.7%, respectively). After ethanol consumption, the rate of hypotension after flibanserin dosing was no greater than with flibanserin or placebo after nonalcoholic beverage consumption. There were no instances of orthostatic hypotension or syncope and no serious AEs or AEs leading to study discontinuation. Conclusion Flibanserin dosed at bedtime after moderate amounts of alcohol with an evening meal was well-tolerated with no evidence of clinically significant hypotension or syncope.

Bremelanotide (Vyleesi™) is a melanocortin receptor agonist recently approved in the USA for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty. It is a self-administered, on-demand subcutaneous therapy. Initially developed by Palatin Technologies who sponsored the Phase 3 clinical trials, bremelanotide was subsequently out-licensed to AMAG Pharmaceuticals Inc. for exclusive North American rights to develop and commercialize the drug, including submitting the New Drug Application to the US FDA. Bremelanotide is a synthetic peptide analogue of the neuropeptide hormone alpha melanocyte-stimulating hormone (α-MSH) with high affinity for the melanocortin type 4 receptor (thought to be important for sexual function), giving it the potential to modulate brain pathways involved in sexual response. This article summarizes the milestones in the development of bremelanotide leading to this first regulatory approval.

Background 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. Aim 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). Methods 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. Outcomes 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. Results 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). Clinical Implications 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. Strengths & Limitations 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. Conclusion 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.

Introduction Flibanserin, a multifunctional serotonin agonist and antagonist, is approved by the U.S. Food and Drug Administration (FDA) for treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women. During the FDA’s review of flibanserin, concerns were raised about the risks of hypotension, syncope, and sedation-related adverse events, which increase with alcohol use. Based on the results of an alcohol challenge study, the FDA required a boxed warning and alcohol contraindication in the flibanserin prescribing information, as part of a risk evaluation and mitigation strategy program. Aim To evaluate the adverse event profile of flibanserin in the context of that seen with other medications that affect serotonin in the brain and are commonly prescribed for women. Methods This was a review of data provided in the product prescribing information for flibanserin, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, other serotonergic antidepressants, and triptans. Main Outcome Measures The incidence of adverse events was assessed. Results The incidences of hypotension, syncope, and sedation-related adverse events (eg, dizziness, somnolence, fatigue) in studies of flibanserin were within the ranges observed for serotonergic antidepressants; the rates of these adverse events were generally lower with triptan medications. Other flibanserin-associated adverse events (eg, nausea, insomnia, dry mouth) occurred more commonly in patients taking antidepressant medications. Conclusion Although medications that affect the serotonin system have varying adverse event profiles (likely mediated by differences in serotonin-related mechanisms of action, specific brain structures affected, and effects on other neurotransmitter systems), the occurrence of central nervous system–related adverse events was not dissimilar between flibanserin and serotonergic antidepressants. Kingsberg SA, McElroy SL, Clayton AH. Evaluation of Flibanserin Safety: Comparison with Other Serotonergic Medications. Sex Med Rev 2019;7:380–392.

Background: Sexual dysfunction refers to a problem that occurs during the sexual response cycle that prevents the individual from experiencing satisfaction from sexual activity. The assessment of sexual function in women is frequently confounded by many factors, including depressed mood and other comorbid medical and psychiatric disorders. Sildenafil is selective type 5 phosphodiesterase (PDE5) inhibitors, taken orally and effective for men with erectile dysfunction. Previous studies suggested that sildenafil, which acts by inhibiting cyclic GMP specific PDE5 may improve the sexual health of women affected by sexual difficulties such as arousal disorders and may indirectly improve other aspects of sexual life. Sildenafil was effective and well-tolerated in postmenopausal women with sexual arousal disorder without concomitant hypoactive sexual desire disorder or contributory emotional relationship or historical abuse issues.Objective: This study aims to evaluate the effect of sildenafil citrate on female sexual dysfunction.Patients and Methods: The study was conducted in Dermatology, Venereology, and Andrology Department, Faculty of Medicine, Zagazig University Hospitals during the period from April 2017 to August 2018. Fifty-two married female patients were included in this study. Patients were divided into two groups. Group 1 contains twenty-six patients took 50mg sildenafil on-demand and group 2 contains twenty-six patients took a placebo.Results: There were no significant differences between the studied groups regarding the demographic data and FSFI. There were significant differences between pre and post-treatment of sexual dysfunction regarding group І. There were no significant differences in post-treatment results between the two studied groups as regard sexual dysfunction except in orgasm.Conclusion: Sildenafil citrate may be effective in women who could not achieve orgasm

Introduction The literature showed the need for a better understanding of the male sexual response, which has historically been considered as simpler and more mechanistic compared with that in women. Aim To examine the literature on biopsychosocial factors associated with the level of sexual desire in men and discuss some interesting directions for future research. Methods A systematic literature review was conducted. Main outcome measures 169 articles published in Google Scholar, Web of Science, Scopus, EBSCO, and Cochrane Library about male sexual desire and related biopsychosocial factors. Results We found a lack of multidimensional studies on male sexual desire. Most existing research has focused on hypoactive sexual desire disorder in coupled heterosexual men. Biological factors play important roles in the level of sexual desire, but they are insufficient to explain the male sexual response. Psychological, relational, and sexual factors (eg depression, anxiety, emotions, attraction, conflicts, communication, sexual functioning, distress, satisfaction) are involved in the development/maintenance of lack of sexual interest in men. Cultural influence is also relevant, with cognitive factors linked to gender roles and sexual scripts of masculinity identified as important predictors of low sexual desire. Conclusion Male sexual desire is characterized by an interplay among biological, psychological, sexual, relational, and cultural elements. This interplay merits further study to better understand how sexual desire works and how treatments for low sexual interest could be improved.

Introduction Hypoactive Sexual Desire Disorder (HSDD) / Female Sexual Interest/Arousal Disorder (FSIAD) impacts health-related quality of life (HRQoL) of women and their partners, yet existing measures fail to adequately capture relevant concepts (ie, what is essential to measure including symptoms/impacts) important to women with HSDD/FSIAD. Objectives To identify HRQoL tools used to assess women with HSDD/FSIAD, and to evaluate their psychometric properties (ie, reliability, validity, and responsiveness). Methods We conducted searches in PubMed, Embase and PsychINFO from June 5, 1989 to September 30, 2020 for studies in women with HSDD/FSIAD and psychometric analyses (English only). Principles of the Preferred Reporting Items for Systematic reviews and Meta-Analyses, the COnsensus-based Standards for the selection of health Measurement INstruments Risk of Bias Checklist and other psychometric criteria were applied. Based on this search, 56 papers were evaluated including 15 randomized-controlled trials, 11 observational/single arm/open label studies, and 30 psychometric studies. Results Of the 18 measures identified, the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) were included in most studies (> 50%). General HRQoL instruments were not used in any of the clinical trials; the SF-12, SF-36 and EQ-5D-5L were reported in two observational studies. No instruments achieved positive quality ratings across all psychometric criteria. The FSFI, FSDS-R, Sexual Event Diary (SED) and the Sexual Desire Relationship Distress Scale (SDRDS), were the only measures to receive a positive rating for content validity. Conclusion Reliable and valid HRQoL measures that include sexual desire and distress are needed to provide a more systematic and comprehensive assessment of HRQoL and treatment benefits in women with HSDD/FSIAD. While inferences about HRQoL are limited due to the lack of uniformity in concepts assessed and limited psychometric evaluation of these measures in women with HSDD/FSIAD, opportunities exist for the development of reliable and validated tools that comprehensively measure the most relevant and important concepts in women with HSDD/FSIAD. Lim-Watson MZ, Hays RD, Kingsberg S, et al. A systematic literature review of health-related quality of life measures for women with Hypoactive Sexual Desire Disorder and Female Sexual Interest/Arousal Disorder. Sex Med Rev 2021;XX:XXX–XXX.

Kingsberg et al. described results from two 24-week Phase III trials of bremelanotide for treating hypoactive sexual desire disorder (HSDD) in women. 72.72% of protocol-listed outcomes were not reported by Kingsberg et al., who provided results of 15 secondary measures which were not listed in the study protocols. None of their efficacy outcomes were reported in line with CONSORT data reporting standards and no secondary outcome had a stated rationale or cited evidence of validity. My meta-analysis of the trials' data, based on the FDA New Drug Application, found similar results to Kingsberg et al. However, Kingsberg et al. did not report that a) adverse event-induced study discontinuation was substantially higher on bremelanotide: OR = 11.98, 95% CI = 3.74-38.37, NNH: 6 or b) participants preferred placebo, measured by the combination of both 1) completing a clinical trial and 2) electing to participate in the follow-up open-label study (OR = 0.30, 95% CI = .24-.38, NNH: 4). Bremelanotide's modest benefits on incompletely reported post-hoc measures of questionable validity in combination with participants substantially preferring to take placebo suggest that the drug is generally not useful. Kingsberg et al.'s data reporting and measurement practices were incomplete and lacked transparency.

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.

Despite a common misperception that sex decreases with age, the majority of women aged 65 to 74 have sexual encounters two or three times per month. Female sexual dysfunction (FSD) is characterized by personal distress regarding arousal, desire, orgasm or pain, and is especially common during the menopausal transition. FSD often presents with a combination of physical, psychological, and interpersonal components, and co-occurs with medical conditions such as depression, anxiety, incontinence, and thyroid disease. To provide comprehensive care for menopausal and older women, it is important to incorporate questions about sexual health into your routine history, with an eye toward identifying potential factors that could lead to sexual dysfunction and are amenable to intervention. Simply having educational materials displayed in your clinic or administering relevant screening tools, perhaps at annual well woman exams, can encourage discussion of sexual concerns. While there are unique diagnoses, such as hypoactive sexual desire disorder, female sexual interest/arousal disorder (FSAD), and female orgasmic disorder, these diagnoses often co-occur and recommended therapies often overlap. Treatment is almost always multifactorial. Treatment may include medical comorbidity management, psychological and behavioral interventions, medications, devices, sexual aids, and pelvic floor physical therapy. With appropriate treatment, most patients will have significant improvement in sexual function.

Although testosterone (T) is known for being the major sex hormone in males, androgens circulate at relatively high levels also in women throughout their lifespan, playing an important role in maintaining bone metabolism, cognition, and sexual function. To date, the diagnosis of androgen deficiency in women poses considerable controversies, principally due to the lack of both a well-defined clinical syndrome with specific signs and symptoms and female, age-based, standardized reference ranges for serum T and free T concentrations. However, there are many identifiable causes leading to a clinical condition characterized by a lack of androgen action in women. Particularly relevant is its manifestation as reduced sexual motivation and desire, which is related to aging-related androgen decline in natural menopause and abrupt cessation of androgen production in surgical menopause. A 2019 Global Position Statement recommends the use of T therapy – with or without concurrent estrogen therapy – in natural or surgical postmenopausal women diagnosed with hypoactive sexual desire disorder (HSDD), when all biopsychosocial modifiable factors have been addressed. Despite the need of adequately powered randomized clinical trials to further assess the long-term safety of T treatment and its pleiotropic effects, available evidence suggests a new role of T as a fundamental hormone in women sexual well-being.