Sexual Medicine最新文献

Background: Hyperglycemia can cause endothelial cell (EC) and smooth muscle cell (SMC) death in the penile cavernous tissue of rats and lead to erectile dysfunction (ED).

Objectives: To investigate the proportions of apoptotic, pyroptotic, and ferroptotic cells among ECs and SMCs in the penile cavernous tissue of type 1 diabetic (T1DM) rats and the mechanism by which icariin (ICA) improves the erectile function of T1DM rats.

Methods: A total of 24 9-week-old Sprague-Dawley (SD) rats were randomly divided into 4 groups (n = 6): control group, control + ICA group, diabetic mellitus (DM) group, and DM + ICA group. T1DM rats were generated via the intraperitoneal injection of STZ (45 mg/kg). After 8 weeks, the rats in the control + ICA group and the DM + ICA group were administered ICA (10 mg/kg/d) by gavage for 4 weeks. ROS, MDA, SOD, GSH, SM/C, and NO levels, and GPX4, ACSL4, caspase-1, GSDMD, caspase-3, CD31, α-SMA, and p-eNOS/eNOS expression in penile cavernous tissue and the ICPmax/MAP of 21-week-old rats were detected.

Results: The percentage of pyroptotic SMCs in penile cavernosum was no statistically significant difference among these groups. Vs control group, the percentages of apoptotic (20.70% ± 1.60%), pyroptotic (21.02% ± 1.97%), and ferroptotic (9.01% ± 2.00%) ECs and the percentages of apoptotic (15.47% ± 1.36%) and ferroptotic (26.33% ± 3.11%) SMCs in the penile cavernous tissue of the DM group were significantly greater. Vs DM group, the percentages of apoptotic (9.13% ± 1.28%), pyroptotic (13.22 ± 1.26%), and ferroptotic (4.01% ± 0.86%) ECs and the percentages of apoptotic (11.60% ± 1.91%) and ferroptotic (12.71% ± 2.92%) SMCs of the DM + ICA group were significantly lower. Vs the DM group, the levels of caspase-1, GSDMD, ACSL4, and ROS were significantly lower in the penile cavernous tissue of the DM + ICA group. Meanwhile, the levels of GPX4 and maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) were significantly higher.

Clinical implications: The combined inhibition of apoptosis, pyroptosis, and ferroptosis in penile cavernous tissue by ICA provides a theoretical basis for the clinical development of multi-target drugs for the treatment of type 1 diabetes-induced ED.

Strengths and limitations: Further experiments are required to clarify whether other types of cell death are involved in the loss of ECs and SMCs in the penile cavernous tissue of T1DM rats.

Conclusion: Inhibiting oxidative stress and thereby inhibiting apoptosis, pyroptosis, and ferroptosis in ECs and SMCs of penile cavernous tissue constitute one of the mechanisms through which ICA improves erectile function in T1DM rats.

Background: The association between psychological stress and erectile dysfunction (ED) has been reported, but the causality of different types of stressors on ED is poorly understood.

Aim: This study aims to investigate the causal relationship between various forms of psychological stress and ED through Mendelian randomization (MR).

Methods: Several genome-wide association study (GWAS) datasets related to chronic psychological stress were used in this study for the identification of instrumental variables. Concurrently, a genome-wide association studies database provided the ED outcome data containing 6175 ED patients and 217 630 controls. The MR-Egger, inverse variance weighting (IVW), weighted median, and maximum likelihood methods were applied to conduct the MR study and IVW was taken as the primary criterion.

Outcomes: Mendelian randomization analyses revealed that financial difficulties were associated with a heightened risk of ED, whereas the absence of stressors was linked to a decreased risk.

Results: Among the various types of psychological stressors analyzed, financial difficulties were found to significantly increase the risk of ED (P = .022, OR = 4.343, 95%CI = 1.240-15.216). In contrast, other stressors did not significantly elevate the risk of ED. Furthermore, the absence of these stressors was associated with a reduced risk of ED (P = .009, OR = 0.211, 95% CI = 0.066-0.681).

Clinical implications: This study emphasizes the enormous impact of psychological stress, especially financial hardship, in increasing the risk of ED.

Strengths and limitations: This study is the first to employ MR analysis to investigate the causal relationship between various stressors and ED. However, this study did not consider the influence of non-genetic factors such as living environment and lifestyles.

Conclusion: Psychological stress, particularly financial difficulties, can increase the risk of ED, while the absence of such stressors appears to be protective. Consequently, it is imperative to enhance medical education and awareness among economically disadvantaged populations and to address the detrimental effects of adverse lifestyles.

Background: The C-reactive protein-triglyceride glucose index (CTI) is a recently introduced index designed to simultaneously assess inflammation (via CRP) and insulin resistance (via the triglyceride-glucose index, TyG), both of which are recognized risk factors for declining testosterone levels in men.

Aim: This study investigates the association between CTI and low testosterone levels in American adult men, aiming to evaluate CTI as a predictor of low testosterone level.

Methods: Data from the 2015-2016 NHANES were used in this cross-sectional study, including men aged 20 and older. Multivariate linear and logistic regression models were employed to analyze the relationship between CTI, total testosterone levels, and the risk of low testosterone level. Receiver operating characteristic (ROC) curves were generated to assess the predictive performance of CTI for low testosterone level.

Outcomes: The primary outcome was testosterone levels, with low testosterone level defined as a serum testosterone level below 300 ng/dL in adult men.

Results: Among 878 participants, 189 had low testosterone level. The mean CTI was significantly higher in the low testosterone level group (9.39 ± 0.09) compared to the non- low testosterone level group (8.62 ± 0.05; P < .0001). After adjusting for covariates, higher CTI was significantly associated with lower total testosterone levels (β = -44.6, 95% CI: -66.34, -22.87, P < .001) and increased low testosterone level risk (OR = 1.84, 95% CI: 1.31, 2.57, P = .002). ROC analysis showed that CTI (AUC = 0.7357, 95% CI: 0.6975, 0.7739) outperformed TyG and VAI in predicting low testosterone level, highlighting its potential clinical value in assessing low testosterone status.

Clinical implications: Timely monitoring of testosterone levels in individuals with elevated CTI is clinically significant. Additionally, for those with TD, regular assessment of CTI may help in preventing future cardiovascular complications.

Strengths and limitations: This study is the first to explore the relationship between CTI and low testosterone using a large sample from the NHANES database. However, due to the cross-sectional design, causal inference regarding CTI and low testosterone level cannot be drawn.

Conclusions: CTI appears to be a more effective predictor of low testosterone level than TyG, CRP, or VAI, suggesting its usefulness as a simple, low-cost indicator for early TD risk assessment. Further research is needed to verify its clinical applicability across diverse populations.

Background: Transgender and gender diverse individuals (TGDIs) are people whose gender identity is not in line with their sex assigned at birth, but current surveys used for cisgender patients addressing sexual satisfaction and function (SFS) do not fit the needs of this unique population.

Aim: The authors of this project sought to create and validate a new comprehensive survey in North American English that differs from the current options for TGDI post-vaginoplasty.

Materials and methods: Using the current literature on SFS as a foundation, a 26-item survey was created and distributed to 16 TGDI at least 3 months post-vaginoplasty. Feedback and review for content validity took place in the forms of interviews with the 16 TGDI, an expert panel, and the creation of a community advisory board.

Outcomes: Feedback was incorporated to transform the original 26-item questionnaire into a 32-question survey with eight domains, named the SatisFunction Survey Post-Vaginoplasty, which represents the preliminary development and content validity of the survey, with its clinical use not recommended until further validation steps are completed.

Results: Feedback focused on improving the clarity of questions to address sexual vs non-sexual behaviors, providing definitions of terms in the question stems for improved user understanding, including more questions on specific anatomic locations, addressing gender dysphoria as it relates to genital self-image, specifying type of vaginoplasty and only including questions relevant to those with or without a vaginal canal.

Clinical implications: The authors foresee clinical use of the survey for recurrent assessment in the postoperative period as well as post-revision.

Strength and limitations: Community-based research is essential in developing an assessment tool tailored to the unique needs of a specific population. This study presents the findings of preliminary content validation but requires further validation before clinical use, and is limited by a small sample size from a single-site institution.

Conclusion: Future directions involve completing the validation process for the survey with distribution to a larger TGDI population with other validated surveys with a subsequent cohort interview to address construct and divergent validity as well as reliability.

Background: Aesthetic procedures for penile enhancement, such as the Penuma silicone sleeve implant, have gained increasing attention for addressing concerns like perceived size, buried or retractile penis, and mild curvature.

Aim: To assess the online search interest over time for penile enhancement modalities, analyze the trends, and explore any regional disparities in search patterns.

Methods: Google Trends data from June 18, 2018, to June 11, 2023, were utilized to analyze search interest for Penuma, penile implant, penile girth, Hyaluronic acid (HLA) injection, and penis injection. The results were compared to the trend data for Penuma from 2004 to 2023. Trendlines were generated to assess the changes in search interest over time and determine if they followed a random or polynomial trend. The highest search interest locations were identified for each term, and the corresponding regional gross domestic product values were collected.

Outcomes: Search interest was assessed in terms of volume, temporal trends, and regional disparities.

Clinical implications: Understanding regional and temporal search patterns for penile enhancement can guide healthcare professionals and policymakers in developing targeted educational initiatives and allocating resources to meet patient needs.

Strengths and limitations: The use of Google Trends provides a comprehensive and real-time assessment of public interest over a broad timeframe and geographic range. However, search interest data may not fully capture actual patient behaviors or clinical demand, and the analysis relies on assumptions about search terms accurately reflecting consumer intent.

Results: Penuma initially garnered interest upon its introduction in 2004 but experienced a decline until around March 2021. Comparing Penuma with other terms, general searches for penile implant and penile girth exhibited significantly higher interest than Penuma. The trendlines indicated increasing search interest for penile implant and HLA injection, while Penuma demonstrated a declining trend. In terms of regional disparities, the highest search interest for Penuma was observed in San Antonio, TX, while penile girth searches were highest in Oklahoma City, OK. Penile implant searches were prominent in Mobile, AL, and Birmingham, AL. Notably, HLA injection searches peaked in New York, NY, and penis injection searches were most prevalent in Los Angeles, CA.

Conclusion: This study reveals that online interest in Penuma lags other penile enhancement terms, with notable regional disparities in search patterns. These findings underscore the need for further research to understand the factors influencing these trends and to help healthcare professionals tailor educational efforts and resources to diverse consumer needs.

Background: The poor clinical situation of type 2 diabetes-induced erectile dysfunction (T2DMED) creates an urgent need for new therapeutic targets.

Aim: To reveal the conserved molecular mechanism of T2DMED across species.

Methods: T2DMED rat and mouse models were constructed to extract mRNA from corpus cavernosum for high-throughput sequencing. The differentially expressed genes (DEGs) were analyzed and the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Protein-Protein Interaction Networks were performed by bioinformatics methods. Immunohistochemistry, immunofluorescence, hematoxylin- eosin and Masson staining were used for subsequent verification.

Outcomes: Cross-species transcriptomics of T2DMED rats and mice were analyzed and validated.

Results: Gene expression patterns in normal corpus cavernosum of mice and rats showed a strong correlation (r = 0.75, P < 2.2 × 10^-16), with a total of 15 691 homologous genes identified. In both species, 553 homologous down-regulated DEGs were identified, mainly enriched in pathways related to smooth muscle and mitochondrial functions, as revealed by KEGG and GO analyses. Immunohistochemistry and immunofluorescence confirmed the decreased expression of α-smooth muscle actin and Uqcr10 in cavernosum tissues of T2DMED mice and rats. Additionally, 239 homologous up-regulated DEGs were identified, which were enriched in the Wnt signaling pathway and extracellular matrix composition. Subsequent experiments confirmed increased β-catenin expression and significant collagen accumulation, indicating fibrosis in T2DMED.

Clinical implications: To provide a new direction for improving the erectile ability of patients with T2DMED.

Strengths and limitations: The main strength is that cross-species transcriptomic sequencing has revealed the conserved molecular mechanisms of T2DMED. The main limitation is the lack of further validation in the T2DMED patients.

Conclusions: Cross-species transcriptomic comparisons may offer a novel strategy for uncovering the underlying mechanisms and identifying therapeutic targets for T2DMED.

Introduction: Persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD) is a debilitating, but poorly understood disorder. To address the lack of knowledge regarding mechanism and treatments, the International Society for the Study of Women's Sexual Health (ISSWSH) consensus statement proposed a region-based approach for management of PGAD/GPD, including possible etiologies. Annular tears of the lumbar intervertebral disc are a recently acknowledged etiology of PGAD/GPD, and current evidence suggests that management of symptomatic tears resistant to non-invasive treatment may require lumbar endoscopic spinal surgery.

Aim: This case series offers 10 cases of PGAD/GPD symptoms, in order to describe resource efficient management, including use of epidural spinal injections to reduce barriers to care for this debilitating condition.

Methods: Individuals were identified by investigators in clinical practice. Electronic medical record notes and relevant imaging from the past 3 years were reviewed.

Results: Half of the patients tried three or more treatments before finding any symptomatic relief. Two patients, with annular tears evident on magnetic resonance imaging (MRI), found complete relief with epidural spinal injections. A patient with hypertonic pelvic floor found total relief with pelvic floor physical therapy. Two patients found alleviation of symptoms with discontinuation of triggering medications, and four patients had palliation of symptoms with gabapentin and/or pregabalin.

Conclusion: These cases demonstrate the utility of the ISSWSH consensus algorithm in guiding initial diagnosis and treatment of PGAD/GPD. However, flexibility is important in management to choose the appropriate treatment pathway to provide the most effective symptom management. Current evidence suggests the use of epidural spinal injections for temporary symptom relief, however, this case series suggests its use for long term management.

Background: Fluctuation in sex hormones and the occurrence of sleep disturbance are 2 major health challenges among midlife women. However, the temporal relationship between them remains unclear.

Methods: This study included 2488 females (mean ± SD age, 49.0 ± 2.70 years) with an average follow-up of 6.95 years. We constructed a composite score by summing items related to sleep problems to reflect the comprehensive sleep status of the participants in the Study of Women's Health Across the Nation. Cross-lagged path analysis was used to examine the temporal relationship between sex hormones and sleep status. Sensitivity analyses were conducted in nonoverweight and overweight groups and adjusted for vasomotor symptoms in the main model.

Aim: In this study, we aimed to examine the temporal relationship between sex hormones and sleep status in midlife women using cross-lagged path analysis.

Outcomes: The primary outcomes included results of the cross-lagged path analysis between sex hormones and sleep status.

Results: After adjusting for age, race, income, menopausal status, body mass index, hormone therapy use, smoking, and drinking, the cross-lagged path coefficients from baseline follicle-stimulating hormone (FSH) and estradiol (E2) to follow-up sleep status were 0.054 (P = .017) and -0.054 (P = .016), respectively. The path coefficient from baseline sleep to follow-up dehydroepiandrosterone sulfate (DHAS) was 0.042 (P = .017). The path coefficients between testosterone and sleep were not statistically significant. In the nonoverweight group, the patterns of the temporal relationship between sex hormones and sleep were the same as the total sample, and the point estimates were larger. However, the temporal relationships in the overweight group were nonsignificant. After adjustment for vasomotor symptoms in the main model, results were basically consistent.

Clinical implications: Given the temporal relationship between sex hormones and sleep, our findings will provide scientific perspectives to benefit health management in the transition of menopause.

Strengths and limitations: This study used a longitudinal theoretical model to distinguish the temporal relationship between sex hormones and sleep status in midlife women. Limitations include limited causal evidence in observational studies, unknown confounders, and careful extrapolation.

Conclusion: There were distinct patterns in the unidirectional temporal relationship between (1) FSH, E2, and DHAS and (2) sleep. Changes in FSH and E2 occurred earlier than the change of sleep, while the change of DHAS was later. In contrast, there was no temporal relationship between testosterone and sleep.