Sexual Medicine最新文献

Background: Erectile dysfunction (ED) is a multifactorial disorder, with mitochondrial dysfunction increasingly recognized as an important contributor to its pathogenesis.

Aim: This study aimed to characterize the single-cell landscape of ED and investigate the impact of mitochondrial function on cellular heterogeneity.

Methods: We performed single-cell RNA sequencing analysis on ED samples (GSE206528), screened for ED-related mitochondrial genes, evaluated mitochondrial activity using area under the curve cell scoring at the single-cell level, and conducted subclustering, cell-cell communication, pseudotime trajectory, and pathway enrichment analyses to systematically characterize key cell populations.

Outcomes: The principal finding is that fibroblasts (FB) and endothelial cells (EC) display significant mitochondrial heterogeneity associated with ED.

Results: A total of 64 993 high-quality cells were classified into seven major cell types. Among these, FB and EC exhibited significant mitochondrial heterogeneity. Seventy-three ED-related mitochondrial genes were identified, with 11 and six mitochondrial activity-associated genes in FB and EC, respectively. Subclustering analysis revealed six FB and four EC subpopulations, with distinct functional pathways. Cell-cell communication analysis indicated increased tumor necrosis factor, TNF-related apoptosis-inducing ligand, and wingless/integrated signaling in high-mitochondrial-activity groups. Pseudotime analysis suggested FB0 and EC1 as progenitor states, progressing toward FB4 and EC0, respectively. Pathway enrichment highlighted shared metabolic and stress-response pathways in FB and EC.

Clinical implications: These results suggest that targeting mitochondrial dysfunction in FB and EC may offer novel therapeutic approaches for ED.

Strengths & limitations: The study's strengths lie in its comprehensive single-cell characterization and functional annotation, while limitations include sample representativeness and the lack of direct experimental validation.

Conclusion: This study provides a comprehensive single-cell landscape of ED, identifying mitochondrial dysfunction as a key contributor to cellular heterogeneity. FB and EC emerged as critical regulators, with potential implications for targeted therapeutic strategies.

Introduction: According to the Obesity Medicine Association, obesity is a chronic, progressive, relapsing, multifactorial and treatable neurobehavioral disease. A small number of drugs have been approved by the Food & Drug Administration (FDA) for weight loss. Liraglutide, Tirzepatide, and Semaglutide are GLP-1 agonists and anti-diabetic drugs, and are some of the latest FDA-approved medications for weight loss. Up to 50% of patients experience gastrointestinal (GI) distress, a common side effect, while taking these medications. Other side effects include tachycardia, antibody-mediated angioedema, anaphylaxis, irritation at the injection site, and hypoglycemia. However, very little is known regarding sexual dysfunction as a side effect of GLP-1 agonists. The following case report discusses the potential negative impact on sexual function of these widely prescribed anti-diabetic, weight loss medications. The case report also discusses a proposed mechanism of action of GLP-1 agonists on sexual function.

Aims: To report the sexual side effects and plausible mechanism of female anorgasmia from GLP-1 agonists.

Methods: Chart review of the patient case was conducted. Consultation with a Doctor of Pharmacy was also requested for additional guidance on possible mechanisms of action of GLP-1 agonists on sexual function.

Results: Several proposed mechanisms causing anorgasmia were theorized, the most likely being GLP-1 agonist vasoconstriction of smooth muscle, which results in reduced oxygen delivery and blood flow to the genitals. This may hinder genital engorgement and arousal, in addition to causing impairment of smooth muscle contractions essential for orgasms. Other mechanisms of GLP-1 agonist-induced anorgasmia may involve their signaling in the brain due to their presence in the hypothalamus. GLP-1 receptor modulation in the hypothalamus may decrease dopamine and norepinephrine signaling, which are neurotransmitters crucial for motivation, pleasure, and orgasm as well as disrupt pathways involved in sexual desire and arousal.

Conclusion: Further investigation on the prevalence of sexual dysfunction with GLP-1 agonists and their mechanism of action is needed.

Background: Penile inversion vulvo-vaginoplasty with addition of a scrotal skin graft is a widely used technique in genital feminizing surgery for trans women.

Aim: To identify the types and frequencies of complications following genital feminizing surgery and assess associated risk factors.

Methods: A retrospective review was conducted on all trans women who underwent primary genital feminizing surgery at Lyon Sud University Hospital between 2008 and 2022. Inclusion criteria were age over 18 and a minimum follow-up of 1 year. Data were collected from electronic medical records and included demographic and clinical characteristics, surgical details, intraoperative events, postoperative complications, and revision procedures.

Outcomes: The study focused on the incidence of intraoperative, early, and late postoperative complications, as well as the frequency and types of surgical revisions.

Results: Among 407 patients (mean (SD) age of 38.6 (12.7) years, mean (SD) BMI of 24.7), intra-operative rectal injury occurred in 5 patients (1.2%). Early graft failure requiring revision was seen in 1%, and 23.1% underwent secondary revisions. Late complications included recto-neovaginal fistula (0.5%) and vaginal stenosis requiring revision (3.4%). Labiaplasty was the most frequent revision procedure (n = 68). Younger age was associated with increased early revisions, while BMI and smoking were not.

Clinical implications: Clear, individualized preoperative counseling is essential to prepare patients for the potential need for revision surgery.

Strengths & limitations: This study benefits from a large sample size and long follow-up but is limited by its retrospective design and reliance on electronic records.

Conclusion: Penile inversion vulvo-vaginoplasty with scrotal skin graft is a generally safe procedure; detailed knowledge of complications supports better patient counseling and informed decision-making.

Background: Male Sexual Dysfunction (MSD), comprising erectile dysfunction (ED) and premature ejaculation (PE), exhibits an age-related prevalence affecting 50% of males beyond their fourth decade. Beyond physiological manifestations, MSD with comorbid anxiety and depression exerts profound psychosocial impacts. Emerging evidence suggests Chinese Herbal Medicine (CHM) may offer therapeutic potential for addressing this clinical intersection.

Aim: To systematically assess the efficacy of CHM on alleviating anxiety and depression in patients with MSD via a comprehensive systematic review and meta-analysis.

Methods: This study systematically searched four Chinese databases (China National Knowledge Infrastructure, Wanfang Database, China Biomedical Database, and VIP Database) and four international databases (PubMed, Web of Science, EMBASE, and Cochrane Library). Randomized controlled trials (RCTs) investigating CHM interventions for MSD with comorbid anxiety and depression were identified.

Outcomes: The primary outcome focused on changes in symptoms of anxiety and depression, while secondary outcomes encompassed overall male sexual function improvement.

Results: By synthesizing data from 12 RCTs involving 1050 participants, our findings provide the first robust evidence that CHM significantly alleviates anxiety and depression in MSD, while concurrently improving core symptoms of MSD, such as PE and ED. Notably, CHM formulations demonstrated superior efficacy over SSRIs in improving both psychological scales, including Self-Rating Anxiety Scale [MD = -9.11, 95% CI (-11.53, -6.70), P < .05], Self-Rating Depression Scale [MD = -9.85, 95% CI (-14.07, -5.63), P < .05], the Hamilton Depression Rating Scale (HAMD) [MD = -5.30, 95% CI (-11.61, 1.01), P > .05], and the Hamilton Anxiety Rating Scale [MD = -3.89, 95% CI (-4.52,-3.27), P < .05], as well as MSD-specific metrics, such as International Index of Erectile Function-5 [MD = 3.26, 95% CI (1.98, 4.53), P < .05] and intravaginal ejaculation latency time [MD = 1.60, 95% CI (0.82, 2.37), P < .05]. Importantly, the lack of statistical significance in HAMD scores in our analysis may be attributed to the differences in treatment responses between the PE and ED populations.

Clinical implications: It provides evidence-based support to address the limitations of separating physical and mental symptoms in traditional treatment, further substantiates its application value within the integrated medical model, and explores new research avenues for designing personalized treatment plans for patients.

Strengths and limitations: A first-of-its-kind systematic evaluation was conducted to assess the comprehensive efficacy of traditional CHM in alleviating anxiety and depression symptoms while improving sexual function indic

Background: Sexual health is an often-overlooked component of clinical care that has significant implications for patients' quality of life.

Aim: To evaluate the practices, attitudes, and barriers faced by Israeli obstetrician-gynecologists (OB-GYNs) in addressing female sexual health, and to identify factors that influence engagement.

Methods: During April-December 2024, a cross-sectional survey was conducted that assessed Israeli OB-GYNs' socio-demographics, frequency of initiating discussions, perceived training adequacy, and barriers to addressing sexual health.

Outcomes: The primary outcomes were the frequency of initiating discussions on sexual health and the perceived adequacy of training in addressing sexual dysfunction.

Results: Among 504 participants, 19.1% routinely initiated discussions on sexual health, while 45.8% rarely did. Female compared to male OB-GYNs (P = 0.002), and infertility compared to other specialists (P = 0.003) were more likely to engage in these discussions. Barriers included limited clinic time (57.5%), insufficient knowledge of treatment options (48.2%), a lack of strategies for initiating discussions (27.0%), and discomfort discussing these issues (15.9%). OB-GYNs aged 60 years and older, compared to 20-29 years, and those who graduated in Israel, rather than abroad (P < 0.001 for both), were more likely to report feeling comfortable addressing sexual health topics. OB-GYNs in central Israel and Jewish participants were more likely to feel comfortable, compared to their southern and Muslim counterparts (P < 0.001 for both). Training was rated as poor or very poor by 43.2% for discussing sexual health and 60.2% for treating sexual dysfunction. Compared to their counterparts, poor training was reported by OB-GYNs under age 60 years, with degrees from abroad, and with less experience. The respective odds ratios were 2.70 (95% CI 1.47-4.96, P = 0.001), 1.799 (95% CI 1.24-2.60, P = 0.002), and 1.72 (95% CI 1.04-2.82, P = 0.033). Most respondents supported integrating sexual health education into medical curricula (69.5%) and OB-GYN residency programs (89.1%).

Clinical implications: Significant gaps in the training and practices of Israeli OB-GYNs underscore the need for enhanced education tailored to address cultural and demographic factors.

Strengths and limitations: The large, diverse sample provides valuable insights. However, the self-reported data may have introduced bias, and the cultural diversity may limit generalizability.

Conclusion: Substantial gaps were reported in the training and practices of Israeli OB-GYNs regarding female sexual health. These findings underscore the need for enhanced education and structured training programs, tailored also to address cultural and demographic

[This corrects the article DOI: 10.1093/sexmed/qfaf036.].

Background: Phosphodiesterase type 5 (PDE5) inhibitors are used to treat erectile dysfunction, but their cost can limit access.

Aim: This study examines PDE5 inhibitors pricing and demographic data across rural and urban New York State (NYS) counties, as well as small, large, and online pharmacies.

Methods: Prices from 133 chain pharmacies were collected from 15 randomly selected urban and 15 rural NYS counties. Counties without at least two large chain pharmacies were excluded. Data included small chains (n = 49), large chains (n = 84), rural (n = 57), urban (n = 76), and online pharmacies (n = 12). Prices for 20 tablets of sildenafil (100 mg) and tadalafil (20 mg) were gathered using GoodRx standard coupons. Price per unit for online pharmacies was calculated for quantities closest to 20 pills. Demographic data was sourced from the U.S. Census Bureau. This study was considered exempt from IRB review. Statistical analyses including t-tests, Wilcoxon rank-sum, and Kruskal-Wallis tests were performed using R Version 4.4.1 (2024-06-14).

Outcomes: The cash price of the PDE5 inhibitors across various pharmacy chain types and county types.

Results: Prices were lower in small chain pharmacies compared to larger chains (P < .001), but did not significantly differ between rural and urban counties (P > .6). Small chain rural pharmacies were cheaper than urban counterparts for sildenafil (P = .032). Online pharmacies offered the lowest and highest prices, with significant differences by chain type (P < .001) but not by county type (P > .100) for both drugs. Rural counties had a smaller Native Hawaiian (P = .001), Asian, Black/African American population and a larger White (P < .001) and American Indian population (P = .031). Median income was higher in urban counties (P = .010), but the percentage of the population without health insurance coverage did not differ (P = .177).

Clinical translation: This study aims to highlight the pricing variability of PDE5 inhibitors to help patients identify cost-effective options to circumvent potential financial barriers.

Strengths and limitations: This study was the first to examine PDE5 inhibitors pricing specifically within rural populations while also providing a comparative analysis of pricing differences between small and large pharmacy chains serving these communities. The study's limitations include a relatively small sample size of rural and small chain pharmacies resulting in power levels of 75% and 69%, respectively, which may impact the generalizability of the findings.

Conclusion: Enhancing drug price transparency for PDE5 inhibitors is vital for increasing access and pricing flexibility.

Background: The linkage between type 2 diabetes (T2DM) and erectile dysfunction (ED) is not yet fully understood.

Aim: This study aims to evaluate the causal influence of T2DM on ED and to determine whether plasma proteins mediate this relationship using Mendelian randomization (MR).

Methods: We extracted data on T2DM and plasma proteins from multiple genome-wide association study databases, encompassing European and East Asian populations. The ED dataset comprised 223 805 individuals of European descent. A 2-sample MR analysis was conducted using inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode methodologies. Additionally, mediation and sensitivity analyses were performed to assess the robustness of the findings and the mediating role of plasma proteins.

Outcomes: The MR analysis revealed a significant increase in ED incidence associated with T2DM (IVW-fixed odds ratio [OR] = 1.091, 95% confidence intervals [CI]: 1.084-1.098), with sensitivity checks confirming no pleiotropic outliers.

Results: We identified 127 plasma proteins linked to ED, of which 15 were influenced by T2DM. The mediation MR analysis indicated 9 plasma proteins with consistent mediation effects: SERPINA10, MATN4, NAB1, NUCB1, SLAMF6, and ANG were associated with negative effects, while NCAM1, CTSB, and WFIKKN2 demonstrated protective effects.

Clinical translation: These findings suggest that T2DM has a direct causal effect on ED, with several plasma proteins serving as potential mediators, highlighting the importance of targeting these proteins for future therapeutic interventions in ED among T2DM patients.

Strengths and limitations: This study leverages a comprehensive MR approach and a large sample size, though it is limited by the observational nature of genetic associations and the necessity for further clinical validation.

Conclusion: The study enhances our understanding of the biological mechanisms linking T2DM and ED, highlighting plasma proteins as potential mediators and targets for therapeutic development.