Safety of topical sildenafil cream, 3.6% in a randomized, placebo-controlled trial for the treatment of female sexual arousal disorder.

BACKGROUND: There are currently no Food and Drug Administration-approved treatments for female sexual arousal disorder (FSAD), which is physiologically analogous to male erectile dysfunction. AIMS: The study sought to test the systemic and local genital safety of topical sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD and their sexual partners over a 12-week treatment period. METHODS: This was a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream among healthy premenopausal women with FSAD. Safety was assessed by the frequency and incidence of treatment-emergent adverse events (TEAEs) among participants and their sexual partners. Participants recorded the incidence of TEAEs in a daily eDiary (electronic diary). Sexual partners were contacted within 72 hours of each sexual event in which investigational product was used. All participants used placebo cream for 1 month, during a single-blind run-in period, and then if eligible, were randomized 1:1 to sildenafil cream or placebo cream. Participants used their assigned investigational product over a 12-week double-blind dosing period. They attended monthly follow-up visits, in which their eDiary TEAE data were reviewed by the study staff and graded for severity and relationship to study product. OUTCOMES: The frequency and incidence of TEAEs among participants and their sexual partners. RESULTS: During the 12-week double-blind dosing period, there were 78 TEAEs reported by 29 of 99 sildenafil-assigned participants and 65 TEAEs reported by 28 of 94 placebo-assigned participants (P = .76). All TEAEs were mild or moderate in severity. The most common treatment-related TEAE among active and placebo-assigned participants was application site discomfort. There were no differences in the number of treatment-related TEAEs among sildenafil cream vs placebo cream users (P > .99). Four sildenafil cream participants and 3 placebo cream participants discontinued the study due to TEAEs involving application site discomfort (P > .99). There were 9 TEAEs reported by 7 of 91 sexual partners exposed to sildenafil cream vs 4 TEAEs reported by 4 of 84 sexual partners exposed to placebo cream (P = .54). CLINICAL IMPLICATIONS: These data support further clinical development of topical sildenafil cream for the treatment of FSAD. STRENGTHS AND LIMITATIONS: Safety was assessed among participants and their sexual partners after 1357 and 1160 sexual experiences in which sildenafil cream or placebo cream were used, respectively. The phase 2b study was powered for the primary objectives of efficacy, rather than safety. CONCLUSION: These data demonstrate that topically applied sildenafil cream was safe and well tolerated by exposed users and their sexual partners.

Comparisons and correlations of 1-month recall vs 24-hour recall in patient-reported outcomes of an exploratory, phase 2b, randomized, double-blind, placebo-controlled clinical trial of sildenafil cream, 3.6% for the treatment of female sexual arousal disorder.

BACKGROUND: Efficacy assessments in clinical trials of treatments for female sexual arousal disorder (FSAD) and other female sexual dysfunction (FSD) diagnoses rely on various patient-reported outcomes (PROs). AIMS: We sought to compare 1-month recall PRO measures among participants enrolled in a clinical trial who provided these data without (test population) vs with (control population) use of an at-home, 24-hour recall electronic diary (eDiary), capturing similar data. METHODS: Preplanned subset analysis as performed during a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD. Preliminary product efficacy was assessed via 1-month recall and 24-hour recall questionnaires. A subset of the participants, the Evaluation of Recall Subset [ERS] provided PROs via the 1-month recall instruments but did not provide data via the 24-hour recall eDiary. OUTCOMES: Responses to the 1-month recall instruments were compared among ERS (test) vs non-ERS (control) participants. Among the non-ERS population, correlations between 1-month and 24-hour recall endpoints were calculated. RESULTS: There were no significant differences in the study co-primary 1-month recall efficacy endpoints, the Arousal Sensation (AS) domain of the 28-item Sexual Function Questionnaire (SFQ28) and the Female Sexual Distress Scale - Desire, Arousal, Orgasm question 14, among ERS vs non-ERS participants during the initial 1-month no-drug run-in period or the 1-month single-blind placebo run-in period (P values > .47). Scores on these 1-month recall PROs continued to be similar after randomization for sildenafil cream (P values > .30) and placebo cream (P values > .20) assigned ERS and non-ERS participants during the 3-month double-blind dosing period. There were strong correlations between the SFQ28 AS and eDiary AS scores during the no-drug run-in (R = 0.79, P < .01) and the single-blind run-in (R = 0.73 P < .001). During the double-blind dosing period, the SFQ28 AS score continued to be highly correlated with the eDiary AS score among sildenafil cream users (R = 0.83; P < .001) and placebo cream users (R = 0.8; 2 P < .001). CLINICAL IMPLICATIONS: There was no evidence that 1-month recall PRO instruments introduce recall bias; assessing arousal sensations with 24-hour vs 1-month PRO instruments is similar and either method could be used to assess efficacy depending on study objectives. STRENGTHS AND LIMITATIONS: This preplanned subset analysis compared efficacy of PROs based on recall duration. While the subset was preplanned, the study was powered to detect significant differences in the primary efficacy objectives, not among this subset analyses. CONCLUSION: These data will be used in planning future efficacy assessments of sildenafil cream for FSAD. CLINICAL TRIAL REGISTRATION: This clinical trial was registered with ClinicalTrials.gov, NCT04948151.

Validation of the multidimensional model of the subjective orgasm experience in the context of same-sex relationships.

Background/objective: The Multidimensional Model of the Subjective Orgasm Experience (MMSOE) has been validated in the context of heterosexual relationships, with no evidence in the context of same-sex relationships. This study aims to examine the association of its dimensions (Affective, Intimacy, Sensory, and Rewards) with the propensity for sexual excitation, rating of sexual arousal, rating of genital sensations, and genital response. Method: Sixty-eight young adults (34 males and 34 females) who were sexually active with people of the same sex participated in a laboratory task in which they viewed content-neutral and sexually explicit gay films. Regression models were conducted to explain the dimensions of MMSOE from measures of sexual arousal. Results: In males, the rating of sexual arousal explained the Sensory dimension, while the genital response explained the Affective dimension, with sexual arousal as a state gaining more prominence. In females, however, the propensity for sexual excitation explained the Sensory dimension, with more salience of sexual arousal as a trait. Conclusions: The MMSOE is shown to be a valid theoretical framework for the study of orgasmic experience in the context of same-sex relationships, with clear implications for clinical practice.

Female Sexual Health: Screening and Evaluation.

Female sexual dysfunction is highly prevalent, affecting 30% to 50% of cisgender women globally. Low sexual desire, sexual arousal disorder, and orgasm disorder affect 10% to 20%, 6% to 20%, and 4% to 14% of women, respectively. Dyspareunia or pain with intercourse affects 8% to 22% of women. Universal screening is recommended; and a thorough medical history and physical examination are the foundations of evaluation and assessment. Laboratory tests and imaging are sometimes warranted, but referral to a sexual medicine expert is suggested if the practitioner is unfamiliar or uncomfortable with treatment.

Victim Sexual Arousal During Nonconsensual Sex: A Scoping Review.

Sexual arousal in male and female victims during nonconsensual sex is an understudied phenomenon with many potential psychological, clinical, and legal implications for survivors. The aim of this scoping review was to assess the literature to determine whether we could estimate the frequency and circumstances of physiological sexual arousal (e.g., erection, lubrication, ejaculation, orgasm) among victims during nonconsensual sex. Six reference database and hand searches led to the screening of 13,894 articles and other reports. Eight articles and one book published between 1977 and 2019 included relevant data from 136 male survivors and 250 female survivors. Results confirmed that physiological sexual arousal (only genital responses were mentioned) can occur in both male and female victims during nonconsensual sex. The frequency of these responses could not be determined because of the widely different methodologies used. In addition, it was not possible to determine the circumstances in which victim sexual arousal was more likely to occur although some were inferred. The results of the scoping review highlight that physiological sexual arousal during nonconsensual sex does occur for victims but has not been studied systematically. There is a clear need to properly assess the type, circumstances, consequences, and frequency of sexual arousal during nonconsensual sex in large and diverse populations of male and female survivors.

Arousal, interindividual differences and temporal binding a psychophysiological study.

The sense of agency varies as a function of arousal in negative emotional contexts. As yet, it is unknown whether the same is true for positive affect, and how inter-individual characteristics might predict these effects. Temporal binding, an implicit measure of the sense of agency, was measured in 59 participants before and after watching either an emotionally neutral film clip or a positive film clip with high or low arousal. Analyses included participants' individual differences in subjective affective ratings, physiological arousal (pupillometry, skin conductance, heart rate), striatal dopamine levels via eye blink rates, and psychopathy. Linear mixed models showed that sexual arousal decreased temporal binding whereas calm pleasure had no facilitation effect on binding. Striatal dopamine levels were positively linked whereas subjective and physiological arousal may be negatively associated with binding towards actions. Psychopathic traits reduced the effect of high arousal on binding towards actions. These results provide evidence that individual differences influence the extent to which the temporal binding is affected by high arousing states with positive valence.

"One a Day Keeps the Prison Away": Understanding the Experiences of Individuals Convicted of Sexual Offences Receiving Anti-Androgens for the Treatment of Problematic Sexual Arousal.

Problematic sexual arousal (PSA) is an umbrella term to describe a range of clinical presentations related to excessive sexual thinking (e.g., sexual preoccupation) and sexual behavior (e.g., hypersexuality). Although such concepts are known to affect sexual recidivism among individuals convicted of sexual offences, PSA is not routinely or directly targeted in offending behavior programs in England and Wales. However, in recent years, there have been moves to incorporate pharmacological interventions for addressing this among people with sexual offence histories. Although some work to understand the experiences of those taking SSRI medication for this purpose has emerged, little is known about the experiences of service users taking anti-androgen medication. In this study, we interviewed all individuals in prison taking anti-androgens for the treatment of problematic sexual arousal following convictions for sexual offences in England at the time of data collection (N = 10). Using a phenomenologically oriented thematic analysis, we established themes pertaining to "Differing needs: Motivations for treatment," "Medication as a risk management strategy," and how the medication helped the men in their pursuit of "Discovering a 'new me'." This work contributes important knowledge to inform the development of ethical and effective prescribing of anti-androgen medication with this population and offer recommendations for both future research and the development of clinical practice.

'Staying Hot': Investigating the influence of overnight conditions on the penile skin temperature during male sexual arousal-A novel methodology for nocturnal erection detection.

Objective: The objective of this study is to assess the impact of overnight environmental conditions on erectile penile temperature within a controlled setting, with the aim of investigating the feasibility of using temperature measurements for nocturnal erection detection in erectile dysfunction diagnostics. Subjects/patients and methods: We conducted a proof-of-concept study involving 10 healthy male participants aged 20 to 25. The study was carried out at the Department of Urology, St. Antonius Ziekenhuis, the Netherlands. Penile temperature thermistor measurements were taken during visually aroused erections of participants in naked state and in simulated overnight condition (underwear and blankets). Main outcome variables were peak and baseline temperature during erectile periods. To minimize the impact of differences in erectile strength and duration between consecutive measurements, we applied randomization to the order of the environmental conditions. Results: We observed a significant increase in penile temperature during erection in both the naked (p < 0.01) and simulated overnight condition (p < 0.01). The mean temperature increase was 1.70 and 0.67°C, respectively. While penile temperature returned to baseline immediately after naked erections, the 'Staying Hot effect' was noted in the simulated overnight condition measurements, where the temperature remained elevated at peak temperature for the entire 30-min period following the erection. Conclusions: The findings from this study indicate that the penile temperature not only significantly increases during naked sexual arousal but is also detectable under simulated overnight conditions. This underscores the potential of using temperature measurements for nocturnal erection detection, representing a crucial initial step in developing a modernized, non-invasive sensor system for ambulatory erectile dysfunction diagnostics. Further research, including an overnight study, is needed to gain insights into the feasibility of utilizing penile temperature measurements for nocturnal erection detection and to assess the impact of the 'Staying Hot effect' on subsequent erection detection.

Genital arousal and responsive desire among women with and without sexual interest/arousal disorder symptoms.

BACKGROUND: Models depicting sexual desire as responsive to sexual arousal may be particularly apt for women experiencing arousal or desire difficulties, and the degree to which arousal triggers desire may depend on the relationship context and desire target and timing-yet, these associations have not been directly tested among women with and without sexual interest/arousal disorder (SIAD). AIM: To assess the role of SIAD status and relationship satisfaction in the associations between genital arousal and 4 types of responsive desire. METHODS: One hundred women (n = 27 meeting diagnostic criteria for SIAD) in romantic relationships with men viewed a sexual film (pleasurable intimate depiction of oral sex and penile-vaginal intercourse) while their genital arousal was recorded via vaginal photoplethysmography (n = 63) or thermal imaging of the labia (n = 37). Partner and solitary desire was assessed immediately before and after the film (immediate desire) and 3 days later (delayed desire). OUTCOMES: Outcomes consisted of genital response (z scored by method) and associations between genital response and responsive sexual desire. RESULTS: The key difference between women with and without SIAD was not in their ability to experience genital arousal but in how their genital responses translated to responsive sexual desire. Women with SIAD actually exhibited greater genital arousal than unaffected women. Associations between genital arousal and desire were significant only for women with SIAD and depended on relationship satisfaction and desire type. For women with SIAD with low relationship satisfaction, higher arousal predicted lower immediate desire for a partner; for those with high relationship satisfaction, arousal was either positively related (vaginal photoplethysmography) or unrelated (thermal imaging of the labia) to immediate desire for a partner. Associations with other desire types were not significant. CLINICAL IMPLICATIONS: Patterns of genital arousal and partner-specific responsive desire among women affected with SIAD were indicative of an avoidance model in response to heightened genital arousal, unless relationship satisfaction was high; attending to genital arousal sensations could be a means of triggering sexual desire for women with SIAD who are satisfied in their relationships. STRENGTHS AND LIMITATIONS: This is one of the first sexual psychophysiologic studies to connect relationship factors to patterns of sexual response. The differing arousal assessment procedures and lack of official diagnosis may have attenuated results. The homogeneous sample and in-person session requirement limit generalizability. CONCLUSION: When compared with unaffected women, women affected by SIAD may exhibit stronger arousal responses with sufficiently incentivized sexual stimuli, and the connection between their genital arousal and responsive desire for their partners may be stronger and more dependent on relationship context.

A non-latex condom has no influence on male physiological sexual arousal / Un condón sin látex no influye en la excitación sexual fisiológica masculina

Background/Objective: Men do not use external condoms for several reasons, which can result in public health problems. One of these is related to Condom-Associated Erectile Problems. This study aimed to examine the sexual arousal response of heterosexual men when using an external condom made of synthetic resin type AT-10. Method: A total of 82 Colombian young men (Mage = 23.17 years, SD = 3.04, age range = 18–30) participated in this experimental study. Two random groups (experimental and control; n = 41 each) were compared. The experimental group used condoms, whereas the control group did not. Fit and feel condom perceptions, initial erectile scores, age, and substance use were controlled for. Erection was measured while viewing a sexual video by using penile plethysmography and subjective arousal. Results: The results, obtained from comparing the experimental group (using pre-erection condoms) with the control group (not using condoms), revealed no significant difference in both subjective and physiological sexual arousal. This suggests that pre-erection condoms do not have an effect on the erectile response. Discussion: More research is needed in this area to provide treatment and clinical interventions or sexual and reproductive education to mitigate the occurrence of sexual dysfunction, unplanned pregnancies, or sexually transmitted infections. Also, research addresses public health issues related to the prevention and/or intervention of sexual risk behaviors and sexual dysfunctions, highlighting their significance in sexual education and clinical practice.(AU)

Pudendal nerve blockade for persistent genital arousal disorder (PGAD): A clinical review and case report.

BACKGROUND: Persistent genital arousal disorder (PGAD) is a condition characterized by unwanted and potentially painful genital sensations or spontaneous orgasms without stimulation. We present a case of a 55-year-old woman with refractory genital arousal disorder that was treated with serial pudendal nerve blocks. CASE: RW is a 55-year-old woman with chronic pelvic pain, pudendal neuralgia, MDD, SI, GAD, CRPS, and persistent genital arousal disorder for 11 years. Her PGAD was refractory to conservative management, physical therapy, and bilateral clitoral artery embolization. We performed bilateral pudendal nerve blocks with Kenalog and Bupivacaine, which provided almost complete relief for 2-3 months. We performed a bilateral pudendal nerve radiofrequency ablation; however, there was minimal benefit. RW continues to have significant relief with serial pudendal nerve blocks. SUMMARY AND CONCLUSION: Persistent genital arousal disorder is often refractory to medication and physical therapy requiring significant intervention such as entrapment surgery or artery embolization. Our case demonstrates pudendal nerve blocks as a potential treatment modality with minimal side effects.

Combined estrogen-progestin oral contraceptives and female sexuality: an updated review.

INTRODUCTION: Sexual side effects of combined oral contraceptives (COCs) have not been fully understood, but increasing evidence prompts broader risk/benefit evaluation and merits inclusion in counseling on contraceptive options. OBJECTIVES: The study sought to explore the impact of combined estrogens-progestin oral contraceptives on components of female sexuality, including sexual desire, anatomic genitourinary changes, lubrication, orgasm, provoked vestibulodynia, well-being, body image, partner preference, and relationship stability. METHODS: A literature review was performed between April 2023 and January 2024 exploring the association between combined oral contraceptive pills and sexual health. RESULTS: Although COCs decrease free testosterone, it is unclear if COCs affect sexual function, including desire. Antiandrogenic COCs do seem to have a negative effect on sexual arousal, lubrication, and orgasm. Provoked vestibulodynia may be related to early onset of COC use, low-estrogen pills, and antiandrogenic progestins. Emotional and sexual side effects are strong predictors of COC discontinuation. Longitudinal data indicate that using COCs when meeting and selecting a partner has implications on sexual satisfaction and relationship length. Analysis of data is complicated by various doses and forms of estrogen and progestin in COCs, which have changed over time. CONCLUSION: Lack of randomized placebo-controlled studies and heterogenicity in study design hampers generalized statements about the effects of COCs on sexual function. Despite these challenges, consideration of sexual dysfunction when presenting and prescribing hormonal contraception is essential for informed consent, shared decision making, and ensuring reliable contraceptive choices.

A Dress Is Not a Yes: Towards an Indirect Mouse-Tracking Measure of Men's Overreliance on Global Cues in the Context of Sexual Flirting.

Assessing another person's intention to flirt and, relatedly, their sexual interest is based on the interpretation and weighting of global (e.g., clothing style) and specific (e.g., facial expression) cues. Since cue incongruency increases the risk of erroneous judgments and thus can entail undesirable outcomes for both parties involved, detection of an individual propensity for overly relying on global (sexual) rather than specific (affective) cues is of social and clinical-forensic importance. Using a purpose-designed and pre-validated stimulus set, we developed a mouse-tracking task as an indirect behavioral measure for males' overreliance on global cues (OGC) in the context of sexual flirting. In a convenience sample of heterosexual cisgender men (N = 79), experimentally induced sexual arousal was shown to increase the probability of OGC as a function of task difficulty (i.e., congruent or incongruent combinations of global and specific cues displayed by a potential female flirting partner). While error rate and reaction time proved to be indicators of OGC, the spatial measures maximum deviation and area under the curve provided less consistent results. In addition, error rate suggested sex drive and sexual objectification to act as moderators of the relationship between sexual arousal and OGC. Exploratory analysis further revealed a theoretically meaningful pattern of correlations between mouse-tracking measures and self-report measures of problematic (e.g., disinhibited, exploitative) sexuality. Implications of the results are discussed and a framework for differentiating potential causes of OGC (i.e., misperception, lack of self-control, and egocentric hedonism) is proposed.

Blame and Severity Attributions in Vignette-Based Female-On-Male Rape: The Case of the Victim's Prior Sexual Victimization, Resistance, and Sexual Arousal.

This study examines blame attributions of victims and perpetrators in female-on-male rape cases and event severity attributions as affected by three victim-related variables: prior sexual victimization, resistance during the rape, and sexual arousal during the rape. It assesses the relative weight of each of these variables in determining the attribution of blame to the victim and perpetrator and the attribution of severity to the event. The study found that sexual arousal and absence of resistance correlated with higher victim blame attribution, lower perpetrator blame, and lower event severity attributions, while prior sexual victimization had the opposite correlations. We therefore conclude that blame and severity attributions are affected by the victim's behavior prior to the rape and during the rape.

A non-latex condom has no influence on male physiological sexual arousal.

Background/Objective: Men do not use external condoms for several reasons, which can result in public health problems. One of these is related to Condom-Associated Erectile Problems. This study aimed to examine the sexual arousal response of heterosexual men when using an external condom made of synthetic resin type AT-10. Method: A total of 82 Colombian young men (Mage = 23.17 years, SD = 3.04, age range = 18-30) participated in this experimental study. Two random groups (experimental and control; n = 41 each) were compared. The experimental group used condoms, whereas the control group did not. Fit and feel condom perceptions, initial erectile scores, age, and substance use were controlled for. Erection was measured while viewing a sexual video by using penile plethysmography and subjective arousal. Results: The results, obtained from comparing the experimental group (using pre-erection condoms) with the control group (not using condoms), revealed no significant difference in both subjective and physiological sexual arousal. This suggests that pre-erection condoms do not have an effect on the erectile response. Discussion: More research is needed in this area to provide treatment and clinical interventions or sexual and reproductive education to mitigate the occurrence of sexual dysfunction, unplanned pregnancies, or sexually transmitted infections. Also, research addresses public health issues related to the prevention and/or intervention of sexual risk behaviors and sexual dysfunctions, highlighting their significance in sexual education and clinical practice.

Auditory Cues Alter the Magnitude and Valence of Subjective Sexual Arousal and Desire Induced by an Erotic Video.

Although women and men rate their subjective arousal similarly in response to "female-centric" erotic videos, women rate their subjective arousal lower than men in response to "male-centric" videos, which often end with the male's ejaculation. This study asked whether ratings of subjective sexual arousal and desire using the Sexual Arousal and Desire Inventory (SADI) would be altered if this ending was present or absent, and whether including or excluding the accompanying soundtrack would influence the magnitude and direction of the responses. A total of 119 cis-gendered heterosexual undergraduates (59 women and 60 men) viewed an 11-min sexually explicit heterosexual video that ended with a 15-s ejaculation scene. Two versions of the video were created, one with the ejaculatory ending (E+) and one without (E-). Participants were assigned randomly to view one of the two versions with (S+) or without (S-) the accompanying soundtrack, after which they completed the state version of the SADI. Women and men found both sequences without sound less arousing on the Evaluative, Motivational, and Physiological subscales of the SADI relative to the S+ sequences. However, on the Negative/Aversive subscale, women found the E + S- sequence more negative than did men, whereas this difference was not found with sound. Thus, women and men were sensitive to the auditory content of sexually explicit videos, and scenes of sexual intercourse ending with explicit ejaculation increased the Evaluative and Motivational properties of subjective sexual arousal and desire. However, this occurred in women only when the auditory cues signaled a clear and gratifying sexual interaction.

Real is the new sexy: the influence of perceived realness on self-reported arousal to sexual visual stimuli.

As state-of-art technology can create artificial images that are indistinguishable from real ones, it is urgent to understand whether believing that a picture is real or not has some import over affective phenomena such as sexual arousal. Thus, in two pre-registered online studies, we tested whether 60 images depicting models in underwear elicited higher self-reported sexual arousal when believed to be (N = 57) or presented as (N = 108) real photographs as opposed to artificially generated. In both cases, Realness correlated with significantly higher scores on self-reported sexual arousal. Consistently with the literature on downregulation of emotional response to fictional works, our result indicates that sexual images that are perceived to be fake are less arousing than those believed to portray real people.

Sexual function in women with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common and distressing endocrine disorder associated with lower quality of life, subfertility, diabetes, cardiovascular disease, depression, anxiety, and eating disorders. PCOS characteristics, its comorbidities, and its treatment can potentially influence sexual function. However, studies on sexual function in women with PCOS are limited and contradictory. OBJECTIVE AND RATIONALE: The aim was to perform a systematic review of the published literature on sexual function in women with PCOS and assess the quality of the research and certainty of outcomes, to inform the 2023 International Guidelines for the Assessment and Management of PCOS. SEARCH METHODS: Eight electronic databases were searched until 1 June 2023. Studies reporting on sexual function using validated sexuality questionnaires or visual analogue scales (VAS) in PCOS populations were included. Random-effects models were used for meta-analysis comparing PCOS and non-PCOS groups with Hedges' g as the standardized mean difference. Study quality and certainty of outcomes were assessed by risk of bias assessments and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method according to Cochrane. Funnel plots were visually inspected for publication bias. OUTCOMES: There were 32 articles included, of which 28 used validated questionnaires and four used VAS. Pooled Female Sexual Function Index (FSFI) scores in random-effects models showed worse sexual function across most subdomains in women with PCOS, including arousal (Hedges's g [Hg] [95% CI] = -0.35 [-0.53, -0.17], I2 = 82%, P < 0.001), lubrication (Hg [95% CI] = -0.54 [-0.79, -0.30], I2 = 90%, P < 0.001), orgasm (Hg [95% CI] = -0.37 [-0.56, -0.19], I2 = 83%, P < 0.001), and pain (Hg [95% CI] = -0.36 [-0.59, -0.13] I2 = 90%, P < 0.001), as well as total sexual function (Hg [95% CI] = -0.75 [-1.37, -0.12], I2 = 98%, P = 0.02) and sexual satisfaction (Hg [95% CI] = -0.31 [-0.45, -0.18], I2 = 68%, P < 0.001). Sensitivity and subgroup analyses based on fertility status and body mass index (BMI) did not alter the direction or significance of the results. Meta-analysis on the VAS studies demonstrated the negative impact of excess body hair on sexuality, lower sexual attractiveness, and lower sexual satisfaction in women with PCOS compared to controls, with no differences in the perceived importance of a satisfying sex life. No studies assessed sexual distress. GRADE assessments showed low certainty across all outcomes. WIDER IMPLICATIONS: Psychosexual function appears to be impaired in those with PCOS, but there is a lack of evidence on the related distress scores, which are required to meet the criteria for psychosexual dysfunction. Health care professionals should discuss sexual function and distress and be aware of the multifactorial influences on sexual function in PCOS. Future research needs to assess both psychosexual function and distress to aid in understanding the degree of psychosexual dysfunction in PCOS. Finally, more diverse populations (e.g. non-heterosexual and more ethnically diverse groups) should be included in future studies and the efficacy of treatments for sexual dysfunction should also be assessed (e.g. lifestyle and pharmacological interventions).

Gender Dysphoria and Sexual Euphoria: A Bayesian Perspective on the Influence of Gender-Affirming Hormone Therapy on Sexual Arousal.

Self-reported sexual orientation of transgender individuals occasionally changes over transition. Using functional magnetic resonance imaging, we tested the hypothesis that neural and behavioral patterns of sexual arousal in transgender individuals would shift from the assigned to the experienced gender (e.g., trans women's responses becoming more dissimilar to those of cis men and more similar to those of cis women). To this aim, trans women (N = 12) and trans men (N = 20) as well as cisgender women (N = 24) and cisgender men (N = 14) rated visual stimuli showing male-female, female-female or male-male intercourse for sexual arousal before and after four months of gender-affirming hormone therapy. A Bayesian framework allowed us to incorporate previous behavioral findings. The hypothesized changes could indeed be observed in the behavioral responses with the strongest results for trans men and female-female scenes. Activation of the ventral striatum supported our hypothesis only for female-female scenes in trans women. The respective application or depletion of androgens in trans men and trans women might partly explain this observation. The prominent role of female-female stimuli might be based on the differential responses they elicit in cis women and men or, in theory, the controversial concept of autogynephilia. We show that correlates of sexual arousal in transgender individuals might change in the direction of the experienced gender. Future investigations should elucidate the mechanistic role of sex hormones and the cause of the differential neural and behavioral findings.The study was registered at ClinicalTrials.gov (NCT02715232), March 22, 2016.