BACKGROUND:Systemic therapy with phosphodiesterase type 5 inhibitors (PDE5is) is the standard of care for erectile dysfunction (ED), but these treatments are not effective in all men, and others may prefer non-systemic treatment options. AIM:The goal of this Delphi consensus initiative was to address unmet needs in the treatment of men with ED and the best use of a US Food and Drug Administration (FDA) cleared topical therapy, MED3000 (Eroxon®), that is available without a prescription. METHODS:The iterative Delphi process involved the creation of an initial slate of 38 statements and brief summaries of related evidence (if available), followed by the review from 2 co-chairs and 3 rounds of consensus development by an independent panel. OUTCOMES:The Delphi process reduced the initial set of 38 statements to 31 for which there was ≥80% support (in some cases after revision of the initial statement and revoting) from the panel in the final round of voting. RESULTS:Statements for which consensus was achieved were consistent with current guidelines in recognizing the need for topical ED therapy. They also provided practical expert advice on the best use of this topical therapy. Statements regarding MED3000 (Eroxon®) for which consensus was not achieved identified important clinical considerations that would benefit from further analysis of existing clinical trial results for MED3000 and collection of new real-world data. CLINICAL IMPLICATIONS:This initiative identified multiple unmet needs that may be addressed by a well-tolerated and efficacious topical treatment. It also provided a critical assessment from experienced healthcare professionals of the evidence supporting the use of an over-the-counter topical therapy for ED. STRENGTHS AND LIMITATIONS:The main strength of this Delphi initiative was an expert assessment of unmet needs in ED and the place in therapy for topical medications. The main limitation was that available data for topical treatment leaves some questions unanswered, most notably efficacy in different subpopulations of men with ED. CONCLUSIONS:Overall, the statements supported in this Delphi initiative may provide a framework for more detailed recommendations that could be incorporated into treatment guidelines. In addition, the statements for which unanimous support could not be achieved help to identify evidence gaps that are targets for future research.
INTRODUCTION:Long-term penile length data after inflatable penile prosthesis placement derive largely from small rehabilitation series. We evaluated long-term change in measured penile length and transverse width, potential predictors, and device use after primary implantation without a prescribed rehabilitation protocol. METHODS:This retrospective cohort analysis included 223 returning patients with a preoperative stretched-flaccid length, a fully inflated intraoperative placement-time length, and a fully inflated office length recorded at least 24 months after primary implantation. The primary outcome was the within-state placement-to-follow-up difference. Secondary analyses included the mixed-state difference from preoperative stretched-flaccid length, tape-measured mid-shaft width, exploratory predictors, device use, and prespecified subgroups. RESULTS:The mean follow-up was 49.0 months and the mean age was 74.2 years. Long-term fully inflated length exceeded the fully inflated placement-time length by 1.28 cm (95% CI, 1.12-1.45; P < .0001). Using a pragmatic 0.5-cm descriptive threshold, 70.0% increased, 25.6% were stable, and 4.5% decreased. The 2.04-cm difference from preoperative stretched-flaccid length mixed different measurement states and was not interpreted as biological gain. Mean tape-measured mid-shaft width changed by 0.13 cm (95% CI, 0.08-0.17), but the method did not support mechanistic inference. In the complete 2021-2023 operative registry, 160 of 628 eligible implants (25.5%) were represented. Of 223 patients, 213 (95.5%) reported sexual activity at follow-up. CONCLUSIONS:Among patients who returned for long-term care, the measured fully inflated penile length was greater than the intraoperative placement-time value. The opportunistic and uncontrolled design, incomplete capture, rater-timepoint confounding, measurement limitations, and device-state differences preclude causal or mechanistic conclusions. These findings do not support prosthesis placement as a cosmetic lengthening procedure or use of the exploratory predictor for clinical decisions.
INTRODUCTION:Vaginoplasty is a high benefit but technically complex procedure that is associated with reduced gender dysphoria, improved quality of life, and high patient satisfaction. Despite increasing utilization of gender-affirming vaginoplasty, national data identifying predictors of perioperative morbidity remain limited. This study evaluates patient risk factors and morbidity following gender-affirming vaginoplasty to inform patient counseling and optimize perioperative care. METHODS:This retrospective cohort study utilizes the American College of Surgeons National Surgical Quality Improvement Program database (2011-2023) to characterize patient profiles, operative factors, and outcomes for vaginoplasty. Patients were identified using ICD-9/10 codes for gender dysphoria and relevant CPT codes. Multivariable analyses were performed to identify factors independently associated with surgical complications, readmissions, and reoperations. RESULTS:A total of 978 vaginoplasty procedures were identified. Procedure volumes increased rapidly from under 15 operations a year through 2015, to a peak of 156 procedures in 2017. Most procedures were performed by plastic surgeons (82.6%), followed by urologists (16.2%).Overall, 16.0% of patients experienced an adverse event within 30 days, including 13.0% with recorded complications, 3.6% with an unplanned readmission, and 4.9% with an unplanned reoperation.On multivariable analysis, Black race (relative risk [RR] 1.59, 95% confidence interval [CI] 1.12-2.27 relative to White patients), obese BMI (RR 1.56, 95% CI 1.04-2.34), and procedures attributed to urology (RR 1.52, 95% CI 1.09-2.11 relative to plastic surgery) were associated with higher recorded risk of adverse events, while hypertension was associated with increased risk of readmission or reoperation (RR 2.04, 95% CI 11.05-3.96). CONCLUSIONS:Vaginoplasty is a complex but rapidly growing surgical procedure with low rates of serious adverse outcomes in the 30-day postoperative period. This study characterizes short-term outcomes and risk factors in one of the largest national cohorts of gender-affirming vaginoplasty to date. Although procedures attributed to urology as the primary specialty were associated with higher recorded adverse event rates, this finding may reflect differences in case complexity or multidisciplinary practice patterns rather than surgeon specialty itself. Observed differences across patient characteristics and operative contexts highlight the importance of preoperative optimization, multidisciplinary collaboration, and standardized perioperative care.
INTRODUCTION:Testosterone therapy is increasingly used to treat individuals assigned female at birth, but its mechanisms of action on sexual functioning are poorly characterized and existing animal models do not integrate genital and behavioral responses. We therefore developed a preclinical mouse model to study testosterone therapy's actions on responsive sexual arousal in female mice. METHODS:Young adult female mice were ovariectomized and treated with testosterone in the male range or vehicle and their genital, behavioral, and neural responses to conditioning with clitoral stimulation (4-6 sessions over the course of 2 weeks) were characterized. Mice were then euthanized following clitoral or sham stimulation and proto-oncogene Fos protein (FOS) immunoreactivity used as a proxy measure of neural activation in brain regions associated with sexual responses and reward. RESULTS:Following repeated experience with clitoral stimulation, testosterone-treated but not vehicle-treated mice exhibited clear signs of sexual arousal, including visible genital vasocongestive arousal and mounting of cage mates. Testosterone-treatment increased FOS immunoreactivity in the nucleus accumbens regardless of stimulation and in the medial preoptic nucleus and the piriform cortex only with clitoral stimulation. Neither effects of stimulation nor testosterone treatment were observed in other examined brain regions (arcuate nucleus, ventromedial nucleus, and suprachiasmatic nucleus). DISCUSSION:This preclinical mouse model allows for study of androgen action on sexual function of individuals assigned female at birth and for integration of endocrine and behavioral approaches to treatment. Limitations include uncertain generalizability to sexual functioning of humans and incomplete mechanistic understanding. Together, results indicate that testosterone treatment activates conditioned sexual arousal to rewarding genital stimulation in female mice, providing a conscious mouse model of androgenized female genital arousal.
BACKGROUND:Peyronie's disease (PD) causes debilitating penile curvature. For moderate-to-severe cases failing conservative therapy, plaque incision/excision with graft repair is a surgical option for selected patients, but it carries risks of erectile dysfunction and penile shortening. AIM:To report outcomes of a modified technique combining microscopic plaque grinding with a high-speed micro-burr and graft reconstruction (autologous tunica vaginalis or bovine pericardial patch) in moderate-to-severe PD. METHODS:This was a single-center retrospective cohort study of 45 patients (curvature >60° or compound deformities) treated between January 2021 and December 2025. The median follow-up was 11.5 months (range 6-24 months). Outcomes included penile straightening rate, erectile function (International Index of Erectile Function-5 [IIEF-5]), disease-specific bother, complications, and patient satisfaction. INTRODUCTION:Outcomes: The primary outcome was satisfactory penile straightening (residual curvature ≤10°). Secondary outcomes included IIEF-5 score, bother score, satisfaction, and complication rates. RESULTS:Satisfactory penile straightening (residual curvature ≤10°) was achieved in 91.1% (41/45); 8.9% had residual curvature between 10° and 20°, which was considered acceptable and did not affect sexual function. International Index of Erectile Function-5 remained stable (preoperative: 20.8 ± 2.1 vs. postoperative: 20.4 ± 2.0, P = 0.360). Transient glans hypoesthesia occurred in 75.6% and resolved within a median of 2.0 months (range 0.7-2.8). Subjective penile shortening was reported by 53.3%, whereas objective measurement showed a mean increase of +1.4 cm in stretched penile length. The Peyronie's Disease Questionnaire symptom bother score decreased significantly from a median of 13 to 2 (P < 0.001). The satisfaction rate (score ≥ 4) was 93.3%. No significant differences were observed between graft types (autologous tunica vaginalis n = 34 vs. bovine pericardial patch n = 11). CLINICAL IMPLICATIONS:This technique offers effective curvature correction with preserved erectile function in selected patients with moderate-to-severe PD. STRENGTHS AND LIMITATIONS:Strengths include (1) the use of microsurgical technique and electric plaque grinding, (2) meticulous tunica vaginalis repair and Buck's fascia reconstruction, (3) independent outcome assessment, and (4) complete follow-up exceeding 6 months. Limitations include the single-center retrospective design, small sample size, and non-randomized graft selection. CONCLUSION:Microscopic plaque grinding with graft repair appears to be a preferred surgical approach for curvature correction while maintaining stable erectile function in selected patients. Larger prospective studies are needed to confirm these findings.
INTRODUCTION:Female genital self-image (FGSI) is a critical component of body image and sexual well-being. A comprehensive synthesis of the factors influencing FGSI is essential for both clinical practice and future research. OBJECTIVES:This study examines the factors that predict or are associated with FGSI. METHODS:A methodical search was conducted across several academic databases-PubMed, Web of Science, Scopus, PsycINFO, Embase and Cochrane Library-to identify relevant studies published between January 2000 and June 2025. RESULTS:A total of 47 studies were considered suitable for inclusion in this review, encompassing data from 33 734 individuals. The studies exhibited heterogeneity in design (predominantly cross-sectional) and measurement instruments for FGSI. We found that factors associated with FGSI can be classified into four distinct categories, including demographic factors (eg, age, education, ethnicity, and relationship status), physical and anatomical factors (eg, vulvovaginal morphology, menstrual cycle characteristics, and genital conditions like pelvic floor discomfort symptoms), sexual factors (eg, sexual function, satisfaction, assertiveness, and experiences), and psychological factors (eg, overall body image, self-esteem, and depression). CONCLUSION:FGSI is a multifaceted construct that is influenced by a complex interplay of demographic, physical, sexual, and psychological factors. A clear understanding of these associated and predictive factors is vital for developing effective interventions aimed at promoting positive FGSI and overall sexual health in women. Given the cross-sectional nature of most included studies, causal inferences cannot be made. This review provides a foundational framework for both clinical assessment and future research in this field.
BACKGROUND:Sleep-related painful erections (SRPE) are a rare parasomnia featuring recurrent nocturnal awakenings from painful penile erections, with daytime erections remaining painless; their central neural mechanisms remain poorly characterized. AIM:To delineate the structural and functional neuroimaging signatures of SRPE using multimodal cerebral magnetic resonance imaging (MRI). METHODS:Twenty-two men with SRPE and 23 age-matched healthy men (HCs) underwent structural and resting-state functional MRI. Grey matter volume (GMV) was compared using voxel-based morphometry (VBM), and regional spontaneous activity using the fractional amplitude of low-frequency fluctuations (fALFF). VBM and fALFF clusters served as seeds for whole-brain seed-to-voxel and region-of-interest-to-region-of-interest (ROI-to-ROI) functional connectivity (FC). All imaging analyses were corrected for multiple comparisons at P < .05 (peak-level family-wise-error for VBM; cluster-level false-discovery-rate for fALFF and seed-to-voxel FC; threshold-free cluster enhancement for ROI-to-ROI FC). Sensitivity analyses adjusted each finding individually for erectile function, premature ejaculation, anxiety, and depression. OUTCOMES:Primary outcomes were between-group differences in GMV, fALFF, and FC; secondary outcomes were correlations between altered imaging metrics and clinical features. RESULTS:Relative to HCs, SRPE patients showed reduced GMV in the bilateral putamen, right posterior orbitofrontal cortex, and bilateral superior temporal gyri (STG). fALFF was decreased in the right inferior temporal gyrus and the left middle occipital gyrus and increased in the left orbital superior frontal gyrus; this increase correlated negatively with the Pittsburgh Sleep Quality Index (r = -0.499, P < .001) and SRPE frequency (r = -0.616, P = .002) but did not survive adjustment for erectile function. Seed-to-voxel FC was increased between the bilateral STG and the anterior cingulate cortex (ACC), the left putamen and left middle temporal gyrus, and the left middle and superior occipital gyri. ROI-to-ROI analysis showed increased connectivity of the bilateral ACC and right midcingulate cortex with the left central operculum, left Heschl's gyrus, and bilateral STG. The right-hemisphere structural findings, the reduced-fALFF findings, and the bilateral STG-ACC hyperconnectivity were robust to all covariates; left-hemisphere and intra-occipital effects were not. CLINICAL IMPLICATIONS:These findings offer preliminary evidence of central nervous system involvement in SRPE that may eventually inform neuromodulation-based approaches. STRENGTHS AND LIMITATIONS:This is the first multimodal cerebral MRI study of SRPE. Limitations include the modest sample, cross-sectional design, absence of sleep-state recording, and comorbidities that preclude causal and fully specific inference. CONCLUSION:Multimodal MRI identified associative structural and functional alterations in regions implicated in pain processing, sleep regulation, and affective-cognitive integration in SRPE.
INTRODUCTION:Patient-reported outcomes following gender affirming vaginoplasty remain understudied. The aim of this study was to evaluate patient-reported outcomes during the first postoperative year following penile inversion vaginoplasty. METHODS:This retrospective cohort study included n = 76 consecutive patients undergoing penile inversion vaginoplasty (March 2021-January 2024) who completed questionnaires pre-op, and at 1, 3-, 6-, 9-, and 12-months post-op (n = 59, 78%). Patient-reported satisfaction with functional and anatomic outcomes including improvements in gender dysphoria were compared with logistic regression, cumulative link mixed models, and Mann-Whitney U tests. RESULTS:Vaginoplasty reliably improved patient reports of matching gender identity (P < .0001), comfort in clothes (P < .0001), and reduced feelings of embarrassment (P < .0001) and distress when looking at or touching the genitals (each P < .0001). Fifty percent of respondents reached the #4 dilator by 6 months. At 1 year, the reported average vaginal depth was 12.7 cm (min 8.9 cm, max 14.0 cm), and 60% of patients had no issues with dilation. Slight or moderate difficulty was reported by 54% of respondents during the first 3 months, while 20% progressed to severe difficulty or complete cessation, beginning at 6 months and peaking at 9 months post-op. Three patients reported inability to dilate (6-12 months), all with preceding difficulties. Respondents were more likely to endorse ability to engage in their preferred sexual activity after vaginoplasty (P < .0001). Return of genital sensation was gradual, with 100% of patients having at least partial sensation at 6 months and 61% describing full sensation by 1 year (P < .001). Of those who had attempted to achieve orgasm, all were able at 9 months (P < .001). Respondents reported greater satisfaction with urinary function post-operatively (P < .001), despite 25% having diverted stream. All but 1 participant, who had a complicated post-op course, agreed with the statement "I am now happier after my surgery than before my surgery" at 1-year. Mental health concern prevalence remained stable over the course of 1 year (time effect P = .64). CONCLUSION:During the first year after penile inversion vaginoplasty, we found high patient satisfaction for functional outcomes and alleviation of gender dysphoria. Results may assist in pre-operative counseling surrounding goals and expectations, increasing patient involvement, preparedness, and thereby outcomes and satisfaction.
BACKGROUND:Lifelong premature ejaculation (LPE) is a prevalent male sexual dysfunction with unclear neurobiological mechanisms. Despite its high prevalence, the etiology of LPE remains debated, often attributed to psychological or biological factors. Recent neuroimaging studies have highlighted the role of central nervous system dysregulation in sexual behavior. AIM:This study investigates abnormal brain functions and altered network connectivity in LPE patients after visual sexual stimuli (VSS) using functional magnetic resonance imaging. METHODS:Twenty-five LPE patients and 31 healthy controls (HCs) underwent resting-state and task-state functional magnetic resonance imaging (fMRI). Clinical data, including sexual history, self-reported intravaginal ejaculatory latency time, International Index of Erectile Function-5, the Chinese Index of Premature Ejaculation, anxiety/depression scores, and serum testosterone levels, were collected. Neuroimaging preprocessing and analysis focused on amplitude of low-frequency fluctuation, fractional ALFF, and regional homogeneity. Task-state fMRI compared brain activation patterns after VSS. Statistical analyses included voxel-based comparisons and network connectivity assessments using SPM12 and DPABI v3.0. OUTCOMES:LPE patients demonstrate distinct neurofunctional abnormalities after VSS, particularly hyperactivation in the precuneus. RESULTS:Clinical Data: LPE patients exhibited significantly lower International Index of Erectile Function-5 scores and higher depression rates compared to HCs, with no differences in age, BMI, or testosterone levels. Brain Activation: During VSS, LPE patients showed relative signal decrease in the middle cingulate cortex and left precentral gyrus compared to HCs. Regional homogeneity analysis revealed hyperactivation in the precuneus and fusiform gyrus post-stimulus. Network Connectivity: Altered connectivity in premature ejaculation patients involved the fusiform gyrus (linked to posterior cingulate, hippocampus, parahippocampus, and supplementary motor areas) and the superior parietal lobule (connected to the angular gyrus). CLINICAL IMPLICATIONS:These findings suggest that aberrant central nervous system processing of sexual stimuli contributes to premature ejaculation pathophysiology, offering potential targets for neuromodulatory therapies. STRENGTHS AND LIMITATIONS:The study focuses on the different activation patterns of patients with LPE from the perspective of sexual arousal. The methodological aspects of research, such as the use of images or videos in sexual stimulation, remain controversial. The findings of our network analysis only demonstrated a limited number of altered functional connections, and no established network metrics were provided to substantiate the claim of extensive network disruption. These factors collectively represent important limitations of the present study. CONCLUSION:The hyperactivity in this brain region observed in patients could represent a unique response to VSS among those with LPE, ultimately leading to alterations in their ejaculatory behavior..
