Introduction:Age at first sexual intercourse (AFS) is an indicator of sexual initiation and may reflect broader life-course trajectories, but its relationship with frailty remains unclear. To examine genetic evidence for a potential association between AFS and frailty and to characterize nonlinear, threshold, and sex-specific patterns in population-based observational analyses. Methods:We performed Mendelian randomization (MR) analyses using summary statistics for AFS and frailty. We further analyzed data from the National Health and Nutrition Examination Survey (NHANES; n = 8282) and UK Biobank (UKB; n = 109 449) among participants aged 50 years or older with AFS ≥15 years. Participants reporting AFS <15 years were analyzed separately. Frailty status was defined using a frailty index cutoff of >0.21, and the nonlinear and threshold associations between AFS and frailty. Results:MR analyses showed that genetically predicted earlier AFS was associated with higher frailty risk (β = -0.30; 95% CI, -0.36 to -0.25), with similar estimates in males (β = -0.23; 95% CI, -0.30 to -0.16) and females (β = -0.22; 95% CI, -0.30 to -0.13). In observational analyses, restricted cubic spline models showed significant L-shaped associations between AFS and frailty in both NHANES and UKB. AFS <15 years was not significantly associated with frailty in the overall analyses. Compared with the third quintile of AFS, participants in the first and second quintiles had 61% (OR = 1.61, 95% CI: 1.40-1.85) and 19% (OR = 1.19, 95% CI, 1.05-1.41) higher odds of frailty, respectively, whereas fifth quintiles had 23% (OR = 0.77, 95% CI, 0.64-0.91) lower odds of frailty in NHANES; participants in the first quintile had 34% (OR = 1.34, 95% CI, 1.18-1.52) higher odds of frailty in UKB. Threshold analyses identified integer cut points of 21 years in NHANES and 23 years in UKB. Below these thresholds, later AFS was associated with lower odds of frailty; above them, associations were not statistically significant. Conclusion:MR analyses provided genetic evidence consistent with a potential association between earlier AFS and higher frailty risk, while population-based analyses showed an L-shaped association among middle-aged and older adults. These findings should be interpreted cautiously and not as definitive evidence of causality. Earlier AFS may be relevant to frailty risk later in life, supporting safe, informed, and rights-based sexual development rather than defining an optimal age for sexual debut.
Introduction:Male sexual dysfunction (MSD) can induce or exacerbate depressive symptoms, and MSD caused by antidepressants may further aggravate the depressive symptoms of patients. However, real-world evidence regarding the association between different antidepressants and MSD remains insufficient. This study aims to systematically analyze the differences in the association between antidepressants and MSD, by utilizing the U.S. Food and Drug Administration Adverse Event Reporting System. Methods:Adverse drug events (ADEs) for male patients using antidepressants were retrieved. Adverse drug events were classified using the Standardized MedDRA Query. Disproportionality analysis was performed using reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma-Poisson shrinker, and Bayesian confidence propagation neural network. The time-to-onset of MSD for each drug and the inclusion of MSD information in the drug labels were also analyzed. Results:Among the 28 included drugs, 24 drugs reported MSD, 18 drugs simultaneously satisfied the positive signal criteria of all 4 algorithms. Sertraline had the highest number of MSD (988 cases), accounting for 6.22% of its total 15 875 cases. Escitalopram showed the strongest signal on all 4 algorithms [ROR: 13.67, PRR: 13.19, lower limit of 95% CI of empirical Bayes geometric mean (EBGM05): 12.19, lower limit of 95% CI of the information component (IC025): 3.59]. The time-to-onset of MSD for most antidepressant drugs followed an "Early failure" model. Conclusion:This study employed 4 algorithms to detect and evaluate potential association signals between antidepressants and MSD. Among the 28 antidepressants analyzed, 18 demonstrated significant associations with MSD. Beyond traditional selective serotonin reuptake inhibitors, the signal strength of MSD associated with other classes of antidepressants should not be overlooked.
Introduction:Diabetes mellitus-induced erectile dysfunction (DMED) is a common complication of diabetes and is often associated with impaired nitric oxide (NO) signaling and increased oxidative stress. Angiotensin (1-7) (Ang (1-7)) has been reported to exert protective effects in cardiovascular and metabolic disorders; however, its role and underlying mechanisms in DMED remain incompletely understood. This study investigated whether Ang (1-7) improves erectile function in DMED through regulation of the caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) signaling pathway. Methods:A type 2 diabetes mellitus rat model was established and divided into control, diabetes mellitus (DM), DMED, DMED treated with Ang (1-7), and DMED treated with saline groups. Erectile function was evaluated by the intracavernous pressure to mean arterial pressure ratio (ICP/MAP). Cav-1, eNOS, and phosphorylated eNOS (p-eNOS Ser1177) expression in corpus cavernosum tissue was assessed by western blot. Plasma NO and peroxynitrite (ONOO-) levels were measured by enzyme-linked immunosorbent assay. Primary rat corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose and treated with Ang (1-7) or methyl-β-cyclodextrin, a caveolae-disrupting agent. Protein expression, oxidative stress markers, and intracellular calcium levels were analyzed. Results:DMED rats exhibited reduced erectile function, decreased Cav-1 expression, reduced eNOS phosphorylation, lower NO levels, and increased ONOO- compared with controls. Ang (1-7) treatment significantly improved erectile responses, restored Cav-1 expression and eNOS phosphorylation, increased NO production, and reduced oxidative stress. In CCSMCs, high glucose suppressed Cav-1 and p-eNOS expression, increased ONOO- production, and disrupted calcium homeostasis. Ang (1-7) reversed these changes. Disruption of caveolae with methyl-β-cyclodextrin diminished the effects of Ang (1-7) on eNOS phosphorylation, oxidative stress, and intracellular calcium regulation. Discussion:Ang (1-7) improves erectile function in DMED rats and protects CCSMCs from high glucose-induced injury. These effects are associated with the restoration of Cav-1/eNOS signaling, enhanced NO bioavailability, reduced oxidative stress, and improved calcium homeostasis. The findings support an important role for caveolae-mediated signaling in DMED and suggest that Ang (1-7) may represent a potential therapeutic strategy for diabetic erectile dysfunction.
Introduction:Energy-based therapies for genitourinary syndrome of menopause (GSM) remain controversial, and evidence for vaginal high-intensity focused ultrasound (HIFU) is limited. The aim of this study was to evaluate the safety and exploratory efficacy of vaginal HIFU in women with GSM. Methods:In this prospective, single-arm, exploratory study, women with GSM underwent vaginal HIFU and were followed for 24 weeks. Women with prior gynecologic surgery or treated malignancy were eligible if ≥6 months had elapsed and clinical stability was confirmed. Patient-reported outcomes included visual analog scale (VAS) scores for GSM symptoms, the Vulvovaginal Symptoms Questionnaire (VSQ), the Female Sexual Function Index (FSFI), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Objective measures included the Vaginal Health Index (VHI), vaginal pressure, pelvic organ prolapse quantification, vaginal pH, and vaginal microbiome profiling. The primary endpoint was the percent change from baseline to 12 weeks in the VAS score of the participant-identified most bothersome GSM symptom. Results:Eighteen women comprised the full analysis set. The primary endpoint showed a reduction in symptom severity (mean percent change -67.7%; 95% confidence interval [CI], -87.6% to -47.7%). Individual VAS scores decreased over time and were generally maintained throughout follow-up. The VSQ improved at 24 weeks (-40.4%; 95% CI, -64.6% to -16.2%), and the ICIQ-SF improved at 12 weeks (-29.0%; 95% CI, -54.6% to -3.4%), although this improvement was not sustained at 24 weeks. Total FSFI scores did not change. Improvements were observed in VHI and vaginal pressure, while vaginal pH and microbiome composition remained stable. No Grade ≥3 adverse events occurred. Discussion:In this exploratory study, vaginal HIFU was associated with improvements in the most bothersome GSM symptom and selected objective measures without serious adverse events. However, given its single-arm design and small sample size, no definitive conclusions regarding its efficacy or safety can be drawn, and further studies are needed to elucidate the mechanisms of action, optimize treatment parameters, characterize the safety profile, and determine the clinical utility of vaginal HIFU.
Background:Erectile dysfunction (ED) affects millions and is associated with cardiovascular disease, diabetes, and depression-conditions that share risk factors with substance use disorders. Aim:This study investigates the temporal relationship between ED diagnosis and subsequent substance abuse/dependence diagnoses across different age groups. Methods:This retrospective cohort study used the TriNetX database to identify adult males from US hospitals with ED diagnoses (ICD-10: N52) with at least 3 years of follow-up. Controls were propensity-matched 1:1 on age and race. Patients were stratified into three age groups (20-39, 40-64, and ≥ 65 years). Cox proportional hazards models assessed risk over a 3-year follow-up period. Outcomes:Primary outcome was any substance abuse/dependence diagnosis (ICD-10: F10-F19 categories); secondary outcomes examined individual substance categories. Results:The study included 323 838 patients (161 919 with ED, 161919 controls) across three age strata. In men ≥65 years (n = 176 960), ED was associated with elevated risk for multiple substances. Sedative abuse/dependence showed the strongest association (HR 2.28, 95% CI 1.52-3.42, P < .001), followed by other psychoactive substances (HR 1.79, 95% CI 1.43-2.24), opioids (HR 1.58, 95% CI 1.27-1.95), cocaine (HR 1.60, 95% CI 1.26-2.04), and cannabis (HR 1.45, 95% CI 1.10-1.92) (all P < .05). The elderly cohort showed reduced overall risk (HR 0.86, 95% CI 0.82-0.89, P < .001), driven by protection against nicotine dependence (HR 0.71, 95% CI 0.68-0.75, P < .001). In men 40-64 years (n = 133 292), ED was associated with increased risk for cannabis (HR 1.32, P = .013) and other psychoactive substances (HR 1.21, P = .031), with protective effects for nicotine (HR 0.90, P < .001). Men 20-39 years (n = 13 586) showed protective associations for opioid (HR 0.53, P = .020) and stimulant abuse (HR 0.35, P = .003). Clinical Implications:Clinicians should maintain heightened awareness for substance abuse risk, particularly sedative misuse, when evaluating and treating elderly men with ED. Age-specific screening and counseling may be warranted. Strengths and Limitations:Strengths include large sample size and propensity matching. Limitations include potential selection bias, inability to assess treatment adherence, and database-specific coding variations. Conclusion:Elderly men with ED demonstrate significantly elevated risk for sedative, opioid, and cocaine abuse in the 3 years following ED diagnosis, while younger men show protective associations. These findings suggest a bidirectional relationship that warrants further investigation.
Objectives:The nipple, a key erogenous zone in female sexual response, is often insufficiently considered in clinical practice, and scientific studies on nipple stimulation are limited. The aim of this study was to conduct a systematic review and meta-analysis of studies examining the effect of nipple stimulation on sexual response and sexual satisfaction in young women. Methods:For this systematic review and meta-analysis, studies were identified through a search of the PubMed, Cochrane Library, EBSCOhost, Embase, Web of Science, PsycINFO, and Scopus databases without any year restrictions. Results:A total of nine studies (~1276 participants) were included in the systematic review. Of these, six studies (390 intervention, 441 control; n = 831) contributed to the meta-analysis of sexual response/orgasm outcomes, and six studies (655 intervention, 621 control; n = 1276) contributed to the meta-analysis of sexual satisfaction. Nipple stimulation significantly improved sexual response [standardized mean difference (SMD) = 0.51, P < .00001] and sexual satisfaction (SMD = 0.59, P = .005). Discussion:Nipple stimulation may be used as a supportive method to enhance sexual function and sexual satisfaction in young women. It may be considered as a complementary approach to sexual counseling and therapy, particularly for women experiencing sexual aversion, difficulty with arousal, and orgasm problems. This meta-analysis suggests that nipple stimulation may have a moderate positive effect on sexual response and sexual satisfaction in young women; however, the findings should be interpreted with caution due to the limited age range of the included population and the heterogeneity across studies.
Introduction:Recreational ketamine use is rapidly increasing, and ketamine-induced uropathy (KIU) is gaining recognition for its severe impact on quality of life (QoL), including pain, hematuria, lower urinary tract symptoms (LUTS), and potential negative effects on sexual function. This study investigates the prevalence of sexual dysfunction among men with KIU. Methods:Male patients with KIU completed the International Index of Erectile Function (IIEF-5 and/or IIEF-15). Erectile dysfunction (ED) was defined as a score of ≤21 on IIEF-5 or ≤ 25 on domain A of IIEF-15. Patients who had not been sexually active in the previous four weeks (a score of 0 on IIEF-5 or within any domain of IIEF-15) were excluded. The impact of LUTS on sexual life and its perceived severity were assessed using items 10a and 10b of the International Consultation on Incontinence Questionnaire LUTS Quality of Life module (ICIQ-LUTSqol). A score > 5 on item 10b was considered indicative of a (major) problem. Results:A total of 123 men with KIU, mean age 28 years (range: 18-50 years), completed the questionnaire(s): 81 (66%) completed IIEF-5, and 88 (72%) IIEF-15. Only 42% (N = 37) had been sexually active in the preceding four weeks. Mean IIEF-5 score in these patients was 18 (SD 5.7), with 63% meeting the criteria for ED. Mean IIEF-15 domain A score was 50 (SD 16.3), with 51% classified as having ED. Beyond ED, 39% reported reduced or absent ejaculation volume, and 52% reported mild to severe pain during ejaculation. Overall, 58-75% reported that LUTS had at least some negative impact on their sexual life, and 64% perceived this impact as a (major) problem. Discussion:Less than half of men with KIU were sexually active in the past four weeks, with the majority reporting sexual health issues, including frequent erectile dysfunction and ejaculatory dysfunction, which were often perceived as significant problems. Awareness is needed among current and potential recreational ketamine users, as well as their healthcare providers, regarding the detrimental effects of ketamine not only on bladder function but also on sexual health.
Introduction:Peyronie's disease (PD) and erectile dysfunction (ED) are prevalent and frequently coexisting male sexual disorders that share endothelial dysfunction, oxidative stress, and tunical fibrosis as common pathophysiologic pathways. Recognizing their interconnected nature has reframed both conditions within a unified model of penile vascular-fibrotic disease. Objectives:To synthesize recent advances in the mechanistic, diagnostic, and therapeutic understanding of PD and ED, and to propose an integrated framework for comprehensive sexual medicine care. Methods:A integrative narrative review of contemporary clinical studies, translational studies, molecular studies and guideline recommendations was conducted to evaluate epidemiologic trends, shared molecular mechanisms, and evolving therapeutic modalities addressing both PD and ED. Results:Up to 60% of PD patients experience concomitant ED. Both disorders are linked by endothelial nitric oxide synthase dysregulation, oxidative stress, and transforming growth factor-β1-mediated fibrosis. Diagnostic evaluation now integrates penile duplex Doppler ultrasonography, elastography, and psychometric tools to assess vascular, structural, and psychosexual domains. Therapeutic strategies increasingly adopt multimodal approaches: phosphodiesterase-5 inhibitors improve hemodynamics and may attenuate early fibrotic activity; intralesional therapy remains central to nonsurgical management, with collagenase Clostridium histolyticum as the established standard for plaque remodeling and adjunct injectables such as verapamil, interferon-α2b, and hyaluronic acid providing additional anti-inflammatory or antifibrotic benefits, particularly in the active phase; and low-intensity shockwave therapy promotes angiogenesis and tissue recovery. Regenerative therapies-including stem cell, exosome, and gene-targeted interventions-offer promising disease-modifying potential. Surgery (plication, grafting, or prosthesis implantation) remains definitive for refractory cases, complemented by psychosexual rehabilitation. Conclusions:PD and ED represent a shared vascular-fibrotic spectrum requiring integrated, mechanism-driven management. Emerging regenerative and molecular therapies, supported by artificial intelligence-assisted diagnostics and digital health tools, signal a paradigm shift toward personalized, holistic restoration of structure, function, and intimacy.
Introduction:Hymen anatomy and physiology remain poorly understood, even among health-care providers. Misconceptions about virginity testing, virginity certification, and hymenoplasty can lead to harmful practices and place women who are unable to prove their virginity at risk of violence or even death. The aim of this study is to investigate the knowledge, attitudes, and practices of gynecologists and pediatricians in Switzerland regarding virginity testing, virginity certification, and hymenoplasty, and to identify gaps to inform future training and professional guidelines. Methods:Gynecologists, pediatricians, and medical students completed a 22-question survey. Group differences were assessed using chi-square or Fisher's exact tests, with significance set at 5%. Results:A total of 542 participants completed the survey. Overall, 97.5% believed that the absence of bleeding during the first vaginal penetration does not mean that someone is not a "virgin." However, for 13.3% of respondents, hymenal rupture does define the loss of virginity, and 24.5% believed that a gynecologist can determine virginity status, with a significant association with medical practice settings (P < .001), university hospitals (P = .01), private clinics (P = .009), and public institutions (P < .001). Hymenoplasty was considered effective by 16.2% of the participants in ensuring bleeding at subsequent penetration. The right of patients or family to request a virginity check was acknowledged by 18.9% of participants, even if most respondents (85.9%) believed that practicing hymenal reconstruction reinforces gender inequalities. In addition, 68% of participants agreed that a virginity certificate should be issued in life-threatening situations.A little over one-third (39.3%) of the responding physicians had received at least one request for virginity testing, certification, or hymenal reconstructive surgery; 30.4% of them accepted the request, but only 28.8% of all requests offered multidisciplinary management. Discussion:Women may encounter different approaches depending on the health-care professional they consult, reflecting a lack of standardized care. This national survey highlights substantial knowledge gaps and variability in practice among Swiss health-care professionals, underscores the absence of official guidelines and a coordinated support network, and calls on Swiss medical societies to establish clear, evidence-based recommendations that prioritize patient information, safety, and support while integrating these topics into education, residency training, and medical school curricula.
Introduction:Peyronie's disease (PD) is an acquired fibrotic disorder of the tunica albuginea that can cause pain, curvature, deformity, erectile dysfunction, and substantial psychosexual burden. Management is usually guided by disease phase, yet active disease remains inconsistently defined, and no oral regimen has shown high-certainty disease-modifying efficacy. We synthesize clinical, mechanistic, guideline, outcome-measure, traction, and public-data evidence relevant to active or progressive PD as a target for early antifibrotic trials. Methods:We conducted a targeted narrative translational review of full-text sources on active-phase definitions, PDE5 inhibitor/selective estrogen receptor modulator (SERM) pharmacology, tadalafil-based clinical studies, placebo-controlled tamoxifen evidence, current recommendations, non-surgical evidence reviews, patient-reported outcome measures, traction therapy, and PD transcriptomic or single-cell studies. We selected sources through targeted database searching, citation chasing, and full-text evidence audit; no protocol-registered systematic review was performed. Clinical studies were heterogeneous and largely non-randomized; therefore, we did not attempt a pooled efficacy estimate. Results:Active and stable PD remain clinically useful categories, although their operational definitions vary across studies. Experimental PD models identify fibroblast-to-myofibroblast transformation as a pharmacologically accessible process, with PDE5 inhibitors and SERMs showing timing-dependent antifibrotic effects. Retrospective PDE5 inhibitor studies and clinical audits of PDE5 inhibitor plus tamoxifen therapy report mixed observations on progression and pain, but interpretation is constrained by non-randomized design, small or imbalanced controls, confounding, and heterogeneous endpoints. Placebo-controlled monotherapy evidence remains negative or neutral for tamoxifen, especially when disease duration is broad or not stratified by active inflammatory features. Guidelines and evidence reviews support individualized conservative care without endorsing PDE5 inhibitor/SERM therapy as standard practice. Conclusion:Active/progressive PD is a defensible setting for early antifibrotic trials. PDE5 inhibitor/SERM therapy is among the best-developed mechanistic candidates, but remains investigational. Clinical adoption requires prospective, randomized, stage-defined studies with standardized curvature assessment, plaque imaging, erectile-function measurement, pain assessment, co-intervention documentation, adverse-event capture, and PD-specific patient-reported outcomes.
Introduction:The influence of patient age on treatment outcomes of extracorporeal shock wave therapy (ESWT) for mild-to-moderate erectile dysfunction remains uncertain. This study aimed to evaluate the efficacy of extracorporeal shock wave therapy according to the patient's age. Methods:Patients with mild-to-moderate erectile dysfunction (ED, International Index of Erectile Function [IIEF] score 11-25) who were not receiving any medical or intracavernosal therapy were prospectively included in the study. The patients were divided into 2 age groups: <50 years and ≥ 50 years. All patients underwent the same ESWT protocol. No additional treatments were given to patients during the ESWT period or during follow-up. International Index of Erectile Function and erection hardness score (EHS) were recorded at baseline and at 1, 3, and 6 months. The effectiveness of ESWT was compared between the groups. Results:A total of 52 individuals were included in the study, with a mean age of 49.6 ± 13.6 years. There were no statistically significant differences in baseline IIEF scores and EHSs between the 2 groups (P > .05). In the < 50 years group, the IIEF scores at 1, 3, and 6 months post-ESWT were 21.9, 22.1, and 21.9, respectively. In the ≥ 50 years group, the corresponding scores were 13.3, 17.6, and 19, respectively. At 1, 3, and 6 months after ESWT, the IIEF scores of the group aged ≥ 50 years were significantly lower than that of the group aged < 50 years (P < .05). Erection hardness scores increased in both groups at 1, 3, and 6 months after ESWT; however, the magnitude of this increase was similar between the groups (P > .05). Conclusion:The findings of this study indicate that ESWT demonstrates higher clinical success rates in the younger patient group with mild-to-moderate ED compared with the older patient group. Extracorporeal shock wave therapy may be considered an effective and sufficient standalone treatment option in young patients with ED.
Introduction:Pump-related complications remain a significant cause of dissatisfaction and reoperation following inflatable penile prosthesis (IPP) implantation. Despite their clinical importance, scrotal anatomy is currently assessed subjectively, without a standardized method to guide pump placement and surgical decision-making. This study aimed to develop a simple, objective classification system for scrotal morphology and to evaluate its association with intraoperative surgical decisions and pump-related outcomes following IPP surgery. Methods:A retrospective cohort study was conducted including patients who underwent primary 3-piece IPP implantation via a penoscrotal approach between 2018 and 2024. Dependent scrotal length was measured intraoperatively using a ruler from the penoscrotal junction to the most dependent point of the empty scrotum and recorded for all patients. Based on these measurements, patients were categorized according to the proposed Scrotal Size Index (SSI). Associations between SSI categories, intraoperative surgical variables, and pump-related outcomes were analyzed. Primary outcomes included the relationship between SSI categories and operative variables, including cylinder length, rear tip extender (RTE) utilization, and the need for intraoperative pump- or tubing-related adjustments. Secondary outcomes included pump-related complications within 12 months, including malposition, migration, patient-reported accessibility difficulties, and revision surgery. Results:A total of 210 patients were included. The mean dependent scrotal length was 7.25 ± 1.56 cm. Distribution analysis demonstrated distinct clustering of measurements (P < .001), supporting categorization into 3 anatomical groups: Small (<6 cm), medium (6-9 cm), and large (>9 cm), corresponding to the proposed SSI. The distribution of patients across these categories was 26.2%, 57.1%, and 16.7%, respectively. Significant differences in IPP-related variables were observed among SSI categories. Mean cylinder length increased from 16.2 ± 1.6 cm in the small group to 18.1 ± 1.7 cm in the medium group and 21.9 ± 1.9 cm in the large group (P < .001). Mean RTE length similarly increased from 0.9 ± 1.0 cm to 2.1 ± 1.1 cm and 3.0 ± 1.2 cm, respectively (P < .001), with corresponding increases in RTE utilization (32.7%, 65.0%, and 82.9%; P < .001). Conclusion:Scrotal morphology appears to be associated with prosthesis-related operative variables during IPP implantation. The proposed SSI offers a simple and reproducible framework for objective anatomical assessment and may assist intraoperative planning. Further prospective studies are required to determine its utility in predicting pump-related outcomes and to establish its clinical validity.
Introduction:Breast cancer survivors frequently experience sexual dysfunction and impaired partner relationships after treatment, but the effectiveness of nursing interventions in improving these post-treatment outcomes remains uncertain. To evaluate the efficacy of sexual health, nursing interventions on sexual dysfunction and quality of life in breast cancer survivors through a systematic review and meta-analysis of randomized controlled trials. Methods:We searched PubMed, Embase, and Web of Science for randomized controlled trials published from database inception to January 31, 2026. Two reviewers independently screened the studies, extracted the relevant data, and assessed methodological quality. Meta-analysis was conducted using RevMan 5.4, with standardized mean difference (SMD) or mean difference (MD) and 95% CIs used according to the type of outcome measure. Outcomes:The primary outcomes were sexual dysfunction, Female Sexual Function Index (FSFI) scores, and Sexual Quality of Life (SQOL) scores. Results:Sixteen randomized controlled trials involving 1929 patients were included. Compared with usual care, sexual health nursing interventions significantly improved sexual dysfunction (SMD = 0.92, 95% CI: 0.60-1.24, P < .001), FSFI scores (MD = 3.97, 95% CI: 3.07-4.86, P < .001), and SQOL scores (MD = 7.05, 95% CI: 5.94-8.15, P < .001). Subgroup analyses further confirmed the efficacy of sexual health nursing interventions across different intervention types. Sensitivity analysis showed that the pooled results were robust, and no evidence of publication bias was detected by Egger's test (P > .05). Discussion:These findings support the integration of sexual health nursing interventions into routine rehabilitation care for breast cancer survivors, as such interventions may help to alleviate post-treatment sexual dysfunction and improve SQOL. The strengths of this study include a comprehensive database search, rigorous methodology with independent reviewers, and robust sensitivity analysis. The limitations include potential heterogeneity across intervention contents and outcome measures, as well as the inclusion of studies conducted only in high-income countries, which may limit the generalizability of the findings. Sexual health nursing interventions effectively alleviate sexual dysfunction and improve SQOL in breast cancer survivors.
Introduction:This study was conducted to investigate the relationship between sexual health literacy (SHL) and reproductive health and family planning (RHFP) attitudes among university students and to identify the sociodemographic and informational predictors influencing these variables. Methods:A descriptive, cross-sectional design was employed with a sample of 867 university students aged 18-35 in Türkiye between May and September 2024. Data were collected using a Sociodemographic Questionnaire, the Sexual Health Literacy Scale (SHLS), and the Reproductive Health and Family Planning Attitude Scale (RHFPAS). Data analysis included Pearson correlation and multiple linear regression models to determine predictors and relationships. Results:The findings revealed a strong positive correlation between SHL and RHFP attitudes (r = 0.880, P < .05). Multiple linear regression analysis showed that total SHLS scores and students' conceptual definitions of sexual health were significant predictors of RHFP attitudes. In particular, the knowledge and attitude subscales of the SHLS were identified as key determinants. Furthermore, residence type, sexual activity status, and information sources were found to significantly influence both SHL levels and RHFP attitudes. Discussion:SHL is a critical determinant in shaping the RHFP attitudes of young adults. Higher literacy levels directly correlate with more positive attitudes toward reproductive health services, suggesting that targeted educational interventions are necessary to improve health outcomes in this population.
Background:Sexual distress and sexual pleasure are two clinically distinct parameters used to evaluate sexual dysfunction, alongside psychological distress. Various psychological processes and problems have been implicated in the etiology and maintenance of sexual dysfunction. Two transdiagnostic processes, Early Maladaptive Schemas (EMS) and Psychological Inflexibility (PI), have been associated with psychopathology. However, knowledge about their effects on sexual health outcomes, namely distress and pleasure, is lacking. Aim:This cross-sectional study investigates whether different profiles related to sexual dysfunction-defined by distress related to sexual function, sexual pleasure, and psychological distress-show distinct patterns of EMS and PI and how these patterns may inform targeted interventions. Methods:Data from 612 participants [M age = 37.95 years, 77.0% identified as women (n = 471)] were included in our analysis. A latent profile analysis (LPA) was conducted to identify distinct profiles of distress related to sexual function, sexual pleasure, and psychological distress. Later, Bolck-Croon-Hagenaars procedures were employed to identify in-between profile differences across EMS and PI. Outcomes:The outcomes of our study were EMS and PI scores across profiles. Results:Our analysis yielded 3 distinct profiles: Low Distress/High Pleasure, High Distress/Low Pleasure, and Deeply Affected Pleasure profiles, with the latter presenting with greater symptom severity. Sexual pleasure is the indicator that best discriminates the latter profile from the former two. There is a significant increase in various EMS from the Low Distress/High Pleasure to the High Distress/Low Pleasure profile, specifically in those belonging to the domains of Disconnection and Rejection and Impaired Autonomy and Performance. The early maladaptive schema that differs in the Deeply Affected Pleasure profile (when comparing with the High Distress/Low Pleasure profile) is Emotional Deprivation. Psychological Inflexibility differs in these profiles and is more significant in the Deeply Affected Pleasure cluster. Clinical Implications:Sexual pleasure emerges as a relevant factor to consider in clinical evaluation and intervention. Also, targeting EMS and PI might prove beneficial in patients presenting with increased distress related to sexual function and/or diminished sexual pleasure. Strengths and Limitations:This article incorporates both negative (ie, sexual distress) and positive (ie, sexual pleasure) sexual outcomes as components of a sexual dysfunction and our results put sexual pleasure at the center of clinical conceptualization. Various limitations restrict our findings, namely, the characteristics of the sample (mostly highly educated women), the study design (cross-sectional), the non-inclusion of gender, sexual orientation and relational configuration diversity, and the non-inclusion of other determinants of sexual health (eg, relational factors, chronic disease). Conclusion:EMS and PI are associated with distress related to sexual function, sexual pleasure, and psychological distress, as per the profiles presented. Specifically, the Emotional Deprivation schema might be of importance in patients with diminished sexual pleasure.
Background:Oxidative stress, mitochondrial dysfunction, and endothelial injury are important mechanisms in erectile dysfunction (ED). Methylmalonic acid (MMA) is related to vitamin B12 metabolism, mitochondrial dysfunction, and oxidative stress, but its relationship with ED and endothelial activation remains unclear. Aim:To investigate the associations of MMA and Endothelial Activation and Stress Index (EASIX) with ED and to evaluate whether EASIX mediates the association between MMA and ED. Methods:This cross-sectional study analyzed data from 2 National Health and Nutrition Examination Survey cycles (2001-2002 and 2003-2004; overall period, 2001-2004). A total of 3306 men aged 20 years or older were included. Survey-weighted logistic regression models were used to examine the associations of continuous MMA and EASIX with ED; exploratory categorical analyses based on data-derived cutoffs were treated as sensitivity analyses. The mediating effect of EASIX on the association between MMA and ED was assessed using the distribution-of-product method. Outcomes:The primary outcome was ED, defined using NHANES item KIQ400. The primary exposures were serum MMA and EASIX, both analyzed primarily as continuous variables. Results:Higher MMA was associated with greater odds of ED after adjustment for confounding factors (OR 1.031, 95% CI, 1.008-1.056). Higher EASIX was also associated with increased odds of ED (OR 2.284, 95% CI, 1.278-4.080). In the primary continuous-variable mediation analysis, EASIX significantly mediated the association between MMA and ED, with an indirect-effect OR of 1.0022 (95% CI, 1.0004-1.0049), and the proportion mediated was 7.18%. Exploratory categorical analyses based on restricted cubic spline-derived cutoffs showed similar directions of association. Clinical Implications:Methylmalonic acid and EASIX may serve as population-level markers associated with ED risk and may help inform future studies on metabolic-endothelial pathways in male sexual dysfunction. Strengths and Limitations:Strengths of this study include the use of a nationally representative sample and survey-weighted analyses. Limitations include the cross-sectional design, self-reported assessment of ED, and the historical nature of the NHANES cycles used. Conclusion:Higher MMA and higher EASIX were associated with increased odds of ED, and EASIX partly mediated the association in continuous-variable primary analyses. These findings should be interpreted as hypothesis-generating because of the cross-sectional design.
Introduction:Erectile dysfunction (ED) associated with long-term high-fat diet (HFD) intake is increasingly recognized as a manifestation of systemic metabolic and vascular dysfunction. This study aimed to evaluate the therapeutic effects of the classical Uyghur medicine formula Bakh Formula (BAKHF) on HFD-induced ED in rats and elucidate its underlying mechanisms. Methods:Male rats with HFD-induced ED were randomly assigned to model, Yimusake (YMSK, positive control), and BAKHF groups. YMSK served as a pharmacological benchmark to validate the model and evaluate BAKHF's effects on erectile function, histology, and hematology. Erectile function was evaluated by maximal intracavernosal pressure to mean arterial pressure (ICP/MAP), sexual behavior tests, and biochemical assays. The primary outcome was erectile function assessed by ICP/MAP, with secondary outcomes including metabolic, endocrine, molecular, and histopathological parameters. The potential mechanisms of BAKHF were elucidated using integrated transcriptomic, proteomic, and network pharmacology analyses, combined with chemical profiling of serum-absorbed compounds, molecular docking, RT-qPCR, and Western blot. Results:Both BAKHF and YMSK improved erectile function, characterized by elevated ICP/MAP ratios and improved sexual behavior parameters. Histologically, both formulas restored penile cavernous structure, reduced collagen deposition, and increased smooth muscle content, confirming YMSK's role as a reliable phenotypic benchmark for the model. However, BAKHF exhibited superior efficacy in restoring systemic metabolic and endocrine homeostasis, including normalization of food intake and serum lipid profiles. Subsequent mechanistic analyses focused on BAKHF and identified its regulatory role in AMPK-associated metabolic and cytoskeletal pathways. Five serum-absorbed compounds, including rosmarinic acid and ferulic acid, were identified as potential bioactive constituents targeting key nodes like GAPDH, PPARγ, and ESR1. Discussion:These findings suggest that BAKHF acts through multi-component, multi-target, and multi-pathway synergy, potentially involving AMPK signaling to regulate metabolic and tissue homeostasis in HFD-induced ED. The integration of multi-omics analyses with experimentally confirmed serum-absorbed compounds and mechanistic validation strengthens the biological plausibility of the findings. However, limitations include the lack of pathway-specific genetic or pharmacological interventions and unresolved contributions of individual constituents. Targeting systemic metabolic and tissue homeostasis through multi-component herbal formulas may represent a complementary therapeutic strategy for metabolism-related ED.
Introduction:Prolactin (PRL) abnormalities can negatively affect sexual function, yet their relationship with subjective female sexual distress remains insufficiently characterized. The primary aim of this study was to examine the association between serum PRL levels and female sexual distress. As a secondary exploratory aim, we assessed whether sexual knowledge and selected sexual health behaviors were independently associated with sexual distress. Methods:This cross-sectional study included 200 sexually active women aged ≥18 years attending a gynecology outpatient clinic. Participants completed the Female Sexual Distress Scale-Revised (FSDS-R) and a structured questionnaire evaluating sexual knowledge and sexual health behaviors, including Kegel exercise knowledge and practice. Morning fasting serum PRL levels were measured between 08:00 and 10:00. Participants were categorized as having normal serum PRL (≤25 ng/mL) or elevated serum PRL (>25 ng/mL). Secondary exploratory analyses stratified PRL into sample-based quartiles. Between-group comparisons and analysis of covariance models were used to examine associations with FSDS-R total scores. Results:Sixty-five participants (32.5%) had elevated PRL. Women with elevated PRL had higher FSDS-R total scores than those with normal PRL (26.1 ± 12.5 vs 22.2 ± 9.4; P = .029). In adjusted analyses, elevated PRL remained independently associated with higher sexual distress (Model 1: F = 5.40, P = .021; Model 2: F = 5.17, P = .024). In secondary exploratory analyses, FSDS-R total scores differed significantly across PRL quartiles (Kruskal-Wallis H[3] = 8.833, P = .032), and PRL quartile remained significant in the fully adjusted model (F[3189] = 4.579, P = .004). Higher Sexual Knowledge Index scores were independently associated with lower FSDS-R total scores (F = 4.32, P = .039), whereas the PRL status × Sexual Knowledge interaction was not significant. Discussion:Elevated PRL was independently associated with greater female sexual distress, and exploratory quartile analyses supported higher distress in the upper PRL quartile without evidence that the lowest PRL quartile was associated with worse distress. Higher sexual knowledge was independently associated with lower distress. These findings support a biopsychosocial framework in which hormonal and cognitive-educational factors contribute to women's subjective sexual well-being. Key limitations include the cross-sectional design, single PRL measurement, absence of routine macroprolactin screening, lack of menstrual-cycle-phase standardization, and use of an exploratory Sexual Knowledge Index.
Background:Despite increasing use of peptides in sexual medicine, interstate differences in access are not fully explained by federal approval status and may instead reflect variation in state-level healthcare delivery structures. Aim:To systematically compare state-level environments affecting access to peptide-based sexual medicine therapies using objective proxy measures and to generate a clinician-friendly framework for identifying geographic disparities. Methods:We conducted a cross-sectional, state-level analysis of all 50 U.S. states and the District of Columbia. Access environments were characterized using three reproducible proxy variables reflecting clinical feasibility of care: (1) telehealth prescribing permissiveness, (2) nurse practitioner (NP) practice authority, and (3) availability of FDA-registered 503B outsourcing facilities normalized by population. Each variable was coded on a standardized scale and averaged to generate a compositive Peptide Access Environment Score (PAES). States were stratified into high-, moderate-, and low-access tiers. Regional differences were evaluated using nonparametric statistical testing and geographic visualization. Outcomes:Primary outcomes included state-level PAES values and access tier classification. Secondary outcomes included regional variation and concordance between telehealth regulation and compounding infrastructure. Results:PAES values ranged from 0.33 to 1.56, demonstrating substantial interstate variability. High-access environments clustered predominantly in the Northeast and West, while low-access states were most frequently observed in the South and parts of the Midwest. Regional differences in PAES were statistically significant (p < .001). Discordance between telehealth prescribing permissiveness and compounding infrastructure was identified, with multiple states permitting telehealth initiation of care despite lacking in-state 503B facilities, and others possessing compounding capacity but maintaining restrictive telehealth regulations. Clinical implications:State-level healthcare delivery policies and infrastructure may meaningfully influence patient access to peptide-based sexual medicine therapies independent of peptide-specific regulatory status. Strengths and limitations:Strengths include a transparent, reproducible methodology using publicly available data and a clinically grounded, multidimensional access framework. Limitations include reliance on proxy measures, exclusion of physician assistant autonomy, and inability to assess within-state socioeconomic or urban-rural heterogeneity. Conclusion:Interstate differences in telemedicine permissiveness, NP practice authority, and compounding infrastructure are associated with significant geographic disparities in access to peptide-based sexual medicine therapies in the United States.
Background:The impact of statins on erectile dysfunction (ED) remains a subject of intense clinical debate. Previous observational studies have yielded inconsistent results and are often limited by confounding factors and reverse causation. Methods:To investigate the causal relationship between statin use and ED risk through a 2-sample Mendelian randomization (MR) analysis of genome-wide association study summary data from the UK Biobank and FinnGen. Genetic variants for general statins and specific types (atorvastatin, simvastatin, and rosuvastatin) were utilized as instrumental variables. The primary effect was estimated using the inverse variance weighted (IVW) method. Sensitivity analyses, including MR-Egger, weighted median, and MR-PRESSO, and leave-one-out analyses, were conducted to ensure the robustness of the findings, alongside the MR Steiger directionality test to validate causal orientation. Results:IVW analysis demonstrated that general statin use is associated with a higher risk of ED (OR = 1.064; 95% CI, 1.011-1.119; P = .018). Subgroup analysis revealed that lipophilic statins significantly increased ED risk: atorvastatin (OR = 27.892; 95% CI, 1.912-40.977; P = .015) and simvastatin (OR = 4.948; 95% CI, 1.598-15.319; P = .006). In contrast, no causal relationship was found for hydrophilic rosuvastatin (P = .428). Sensitivity analyses confirmed the absence of horizontal pleiotropy and heterogeneity. The MR Steiger directionality test confirmed that the causal direction from statin use to ED was robust. Additionally, the leave-one-out analysis demonstrated that the overall results were not driven by any single SNP. Conclusion:Statin use, particularly atorvastatin and simvastatin, causally increases the risk of ED, whereas rosuvastatin appears to have a neutral effect.
