Andrology最新文献

Erectile dysfunction (ED) diagnostics are in need of innovation, as traditional tools like the RigiScan face usability challenges and limited clinical adoption. Although several novel sensor systems have been proposed, none have undergone comprehensive clinical validation. This opinion article outlines a structured, three-phase validation framework comprising component validation, system feasibility testing, and clinical validation, aligned with European MDR requirements. Special attention is given to key aspects such as diagnostic accuracy, sleep-stage monitoring, and patient experience. By providing a clear validation pathway, this opinion article aims to support researchers in the development of reliable, patient-friendly, and regulatory-ready tools for non-invasive ED diagnosis.

Background: Androgen receptors are highly expressed in upper body muscles, but changes in maximal muscle strength and power in major upper body muscles have not been investigated during gender-affirming hormone therapy (GAHT).

Objective: To assess prospective changes in maximal muscle strength and muscle power from before and after 1 year of GAHT.

Design and methods: Clinical prospective study in 92 transgender persons: 26 transmasculine treatment-naïve (TransM_naïve), 27 transmasculine treatment-ongoing (TransM_ongoing), 29 transfeminine treatment-naïve (TransF_naïve), and 10 transfeminine treatment-ongoing (TransF_ongoing) were examined at baseline and after 1 year of GAHT. Primary outcomes were unilateral upper body maximal muscle strength (kg) and mean and maximal power (watt) measured by low-row dynamic testing. Dual-energy X-ray absorptiometry was conducted in all participants.

Results: In transmasculine persons, the median (quartiles) age was 22 (20; 30) years in TransM_naïve and 26 (22-29) years in TransM_ongoing (median GAHT duration 3 (2; 5) years) at study inclusion. Maximal muscle strength increased 6.3 kg (12%) in TransM_naïve (p ≤ 0.001) and 5.0 kg (7%) in TransM_ongoing (p ≤ 0.001), while maximal muscle power remained unchanged. ∆-muscle strength was positively associated with ∆-lean mass in arms and negatively associated with age at GAHT initiation. In transfeminine persons, the median age was 24 (22; 30) years in TransF_naïve and 40 (31-64) years in TransF_ongoing (median GAHT duration 4 (2; 6) years) at study inclusion. Maximal muscle strength decreased 17.5 kg (23%) in TransF_naïve and -5.0 kg (8%) in TransF_ongoing, which was accompanied by a decrease (23%) in maximal muscle power in TransF_naïve.

Conclusion: Upper body muscle strength but not power increased during masculinizing GAHT, whereas muscle strength and power decreased within the first year of feminizing GAHT.

Background: Although a nomogram for predicting the efficacy of dapoxetine (DapE-Nomo) has already been developed, its reliability is limited due to only 4 weeks of follow-up and a lack of external validation. Several patients with premature ejaculation (PE) achieve satisfactory therapeutic effects after longer periods of treatment clinically, we therefore aimed to develop and validate an 8-week DapE-Nomo.

Methods: The training cohort included 243 patients with lifelong PE from Xijing Hospital and Northwest Women's and Children's Hospital (Jan 2019-Jul 2020), while the validation cohort comprised 397 patients from Xijing Hospital and Xi'an Daxing Hospital (Aug 2020-Jan 2022). Efficacy was measured using the Clinical Global Impression of Change (CGIC) scale, with a CGIC score ≥ 1 indicating an improvement (iCGI). LASSO regression was utilized to identify the most valuable predictors (MVPs) of iCGI. The DapE-Nomo was developed utilizing logistic regression coefficients of MVPs and validated across both cohorts.

Results: After 8 weeks of medication, 47.7% of patients in the training cohort and 47.6% in the validation cohort achieved iCGI. MVPs of iCGI included intravaginal ejaculation latency time, difficulty delaying ejaculation, and education level. The DapE-Nomo showed discriminatory abilities of 0.722 and 0.709 in internal and external validations, respectively, with satisfactory calibration and clinical utility in both. The optimal cutoff value of the DapE-Nomo was identified as 153.4 in both cohorts. Individuals with scores ≥153.4 exhibited a 3.833-fold and 4.137-fold chance of achieving iCGI, respectively, compared with those with scores < 153.4.

Conclusion: We constructed and validated the inaugural 8-week DapE-Nomo. In outpatient settings, it will enable andrologists to more accurately evaluate the efficacy and promptly adjust treatment plans for patients with scores below 153.4. Moreover, It will help patients who've taken dapoxetine for 4 weeks with poor results decide whether to stop.

Background: Studies show that coenzyme Q10 (CoQ10) has multiple benefits for improving idiopathic male infertility. However, its protective effects against hypoxia-induced damage to the male reproductive system and varicocoele-associated spermatogenesis dysfunction need further investigation.

Objectives: This study aims to evaluate CoQ10's preventive efficacy against testicular damage caused by chronic hypoxia and varicocoele, and to explore the underlying mechanisms.

Materials and methods: Chronic hypoxia-induced and varicocoele male rat models were established. CoQ10 was administered intragastrically. Transcriptome analysis of testicular tissue, along with qRT-PCR and Western blot, was performed to elucidate mechanism and confirm gene and protein expression changes.

Results: The study revealed that both chronic hypoxia and varicocoele reduce sperm concentration, motility, vitality, and cause vacuolation of seminiferous tubules. Both conditions also lower reproductive hormone levels, increase oxidative stress, and promote germ cell apoptosis. CoQ10 treatment protected against these testicular changes and improved testosterone levels in rats. Seven differentially expressed genes (Slc38a5, Adgrg2, Gpc1, Arx, Egr2, Ebp, Il2rb) were identified in CoQ10-treated rats with either condition. Enrichment analysis highlighted inflammation as the main affected process in testes for both conditions. qRT-PCR and Western blot confirmed that CoQ10 significantly reduced IL1β, Egr2, Il2rb, and caspase-1 expression at both gene and protein levels.

Conclusion: These findings suggest that CoQ10 improves chronic hypoxia-induced and varicocoele-related spermatogenesis dysfunction by reducing inflammation via the caspase1-IL1β-egr2 pathway. The study highlights CoQ10's protective role in male reproduction and its potential for treating male infertility linked to hypoxia and varicocoele.

Background: The oxytocin receptor (OR) is a G-protein-coupled receptor recently identified in human spermatozoa, whose origin and role in sperm physiology remain unknown.

Objectives: In this study, using the pig as a model, we examine the presence of the OR in ejaculated spermatozoa through immunofluorescence and immunoblotting, and investigate the receptor's origin in the male gamete via immunohistochemistry in testicular and epididymal tissues. Additionally, we assess the involvement of the OR in in vitro capacitation and the acrosome reaction by utilizing physiological concentrations of agonists (oxytocin and carbetocin) and an antagonist (L-371,257).

Results: The results indicate that, in addition to the expected presence in ejaculated spermatozoa, the OR is expressed during spermatogenesis. Besides, this receptor is found in Leydig and Sertoli cells, as well as in the principal, basal, and apical cells of the epididymis. Furthermore, our data suggest that, during epididymal maturation, the OR could be incorporated in spermatozoa via extracellular vesicles within the apical blebs. The OR is involved in sperm capacitation, as the combination of the antagonist (L-371,257) and the agonist (carbetocin) increases intracellular calcium levels and membrane lipid disorders, which are known as capacitation markers.

Conclusions: The presence of the OR in mammalian spermatozoa could originate from both spermatogenesis and epididymal maturation. Moreover, in the male gamete, this receptor regulates sperm capacitation by interacting with its ligand in the female reproductive tract.

Background: Grading premature ejaculation (PE) may hold significant value. However, although previous studies have attempted to achieve a uniform severity scale for PE, this has not been widely accepted since design and methodological limitations.

Objectives: In patients with lifelong PE (LPE), we re-evaluated the items suitable for severity grading and established the appropriate severity classification reference through reasonable statistical methods and logic.

Materials and methods: Patient perceived intravaginal ejaculatory latency time (PIELT) and premature ejaculation diagnostic tool (PEDT) scores from 264 men (149 with LPE and 115 without PE) were used to analyze surrogate item suitable for classification. Classification and Regression Trees were used to determine the optimal score interval for different severity levels in patients with LPE.

Results: For the LPE population with PIELT < 3.5 min, PIELT had no value in the classification of severity of LPE patients. PEDT items 1 and 4, showing high correlation (0.84 and 0.89, respectively) with PEDT total score, reflect the physical and mental effects of LPE patients in terms of ejaculatory control and interpersonal relationship. These items may serve as proxy for the severity scale of LPE patients. Hence, patients diagnosed with LPE can be classified into the following grades based on PEDT scores: mild (11-14), moderate (15-17), severe (18-20). Substantial agreement was shown between these predicted and "true" classes (weighted kappa 0.71).

Discussion: Assessing LPE according to three dimensions is a widely accepted definition. While PIELT showed no statistically significant differences in the classification (p > 0.05), the two subjective dimensions of ejaculation control and negative psychological influence did predict the severity grading of LPE. Not only can grading the subjective feelings of patients with LPE help them to self-assess the extent of the disease, but also provide a valuable reference for further treatment.

Conclusion: Within the PIELT of 3.5 min, the severity of LPE can be classified into severe, moderate, and mild categories based on the PEDT score.

Background: Penile sexual sensation relies on intricate neural structures that remain incompletely characterized. Immunohistological insights into their development and organization can enhance understanding of penile neuroanatomy and function, while optimizing surgical outcomes.

Objectives: To elucidate the ontogeny, organization, and immunohistological features of human penile innervation in fetal and adult specimens, primarily focusing on the frenular delta, sensory corpuscles, and related structures to address gaps in anatomical knowledge and inform surgical practices.

Materials and methods: Formalin-fixed, paraffin-embedded tissues from 30 fetal (8-24 weeks) and 14 adult cadaveric penile specimens were analyzed. Routine histological stains and immunohistochemical markers targeting neural structures were applied. Serial sections were examined for histology, neuroanatomical mapping, sensory corpuscle characterization, and neural density assessments.

Results: Fetal penile neurodevelopment exhibited two phases: the pre-corpuscular stage (8-16 weeks), marked by axonal hyperinnervation and exuberant ventral intraepithelial nerve fibers, and the corpuscular stage (17-24 weeks), characterized by Pacinian corpuscle emergence and targeted neural pruning. Adult specimens showed region-specific neural distributions, with heightened densities in the frenular delta. Intracorporeally, sensory corpuscles exhibited a bimodal intraspongiosal distribution, with Pacinians in the bulb and glans. Molecular profiles of sensory corpuscles, including novel immunoreactivities, were comprehensively documented. The preputial dartos and vasculature displayed dense autonomic innervation. A superficial glans tunica albuginea was identified, with implications for neural organization.

Discussion: These findings reveal previously unrecognized transitions during fetal penile neural development and into adulthood, providing a foundation for the neurodevelopmental biology of the human penis and documenting the frenular delta's unique innervation. The characterization of penile neural components and the glans tunica albuginea addresses longstanding anatomical and sexological questions. Our results inform current debates on penile circumcision and neurotomy.

Conclusion: This study provides a comprehensive ontogenetic framework of penile innervation, emphasizing the frenular delta as a specialized center of sexual sensation.