Andrology最新文献

Background: Sperm-specific potassium channel (KSper) comprised of pore-forming subunit SLO3 and auxiliary subunit LRRC52 is of importance for sperm fertility. The deficiency of KSper in both mice and humans resulted in severe impairments of sperm functions including sperm hyperactivity and acrosome reaction. Previous reports suggested that mouse KSper modulated sperm function possibly by affecting sperm intracellular pH (pH_i). However, the precise signaling mechanism of human KSper (hKSper) on the regulation of sperm functions was largely unclear.

Objective: To explore the regulatory role of hKSper on sperm flagellar pH_i.

Materials and methods: More than 50 sperm donors were recruited during a period of 1 year. As reported in our previous work, we quantitatively measured flagellar pH_i by employing a single-cell pH fluorescent recording on human spermatozoa loaded with pH indicator pHrodo Red. Three different hKSper antagonists including clofilium, quinidine, and a polyclonal antibody of LRRC52 (LID1) were utilized to evaluate the effect of hKSper inhibition on sperm flagellar pH_i.

Results: Given the predominant role of hKSper on the regulation of membrane potential (Em), we first detected a considerable depolarization (about 25-30 mV) of Em evoked by clofilium and quinidine. Subsequently, it was shown that flagellar pH_i values of human spermatozoa were significantly decreased by the treatment of clofilium (50 µM, from 7.13 ± 0.11 to 6.43 ± 0.12), quinidine (500 µM, from 7.00 ± 0.11 to 6.64 ± 0.08) and LID1 (20 µg/mL, from 6.98 ± 0.16 to 6.67 ± 0.22). Moreover, we found that when human spermatozoa were pre-incubated with a high K⁺ solution (135 mM), both the depolarization of Em and the acidification of flagellar pH_i evoked by clofilium and quinidine were abolished. In addition, we found that extracellular substitution of N-methyl-D-glucamine for Na⁺ abolished pH_i acidification induced by hKSper inhibition.

Discussion and conclusion: Our results demonstrate that hKSper inhibition evokes flagellar pH_i acidification of human spermatozoa, suggesting that flagellar pH_i maintenance is an important signaling mechanism of hKSper on the regulation of sperm functions.

Background: Varicocele, a common vascular abnormality surrounding the testis, is known to be associated with impaired semen parameters and male infertility in adults. However, its impact on the adolescent and young adult (AYA) population is less well known.

Objectives: The study aimed to assess the improvement in sperm parameters following varicocelectomy in the AYA population, comparing them to matched adult counterparts, and investigating potential advantages of early intervention.

Methods: A retrospective analysis was conducted using a comprehensive database at the University of Miami spanning from 2012 to 2023. We included AYA (under 25 years of age) men who underwent varicocelectomy. To ensure comparability, they were matched with adult patients (over 30 years of age) based on preoperative follicle-stimulating hormone (FSH) values and varicocele grade in a 1:2 ratio. Semen parameters were evaluated before and after surgery, including sperm count, motility, morphology, and overall semen quality.

Results: We included 45 patients in the Adolescents and Young Adults (AYA) category, and matched them with 116 adults based on FSH and varicocele grade, all of whom underwent microsurgical varicocelectomy. The AYA group exhibited greater improvements post-varicocelectomy compared to the matched cohort. Furthermore, postoperative sperm concentration in the AYA men demonstrated a remarkable increase, with a 1.7-fold increase in mean concentration compared to the adult group (p < 0.001). Additionally, motility also displayed significant enhancement among the AYA men, with a final mean total motile sperm count (TMSC) improvement of 2.25-fold compared to the adult cohort (p = 0.002).

Discussion: This study highlights the potential benefits of varicocelectomy as a viable treatment option for adolescents and young adults with varicocele, particularly those with impaired semen parameters. By intervening at an earlier stage of development, patients in this age group can achieve significant improvements in semen quality, as compared to their adult counterparts.

Conclusion: These findings underscore the importance of considering varicocelectomy as a valuable therapeutic approach for the younger demographic, potentially alleviating future fertility concerns.

Background: Dietary factors and chronic gastrointestinal diseases are frequent determinants of sexual dysfunctions (SD). Whether inflammatory bowel diseases (IBD) are associated with SD is not well known as well as the role of diet and quality of life (QoL).

Objectives: To evaluate the prevalence of SD in a cohort of IBD patients and assess the role of clinical-demographic variables, adherence to Mediterranean diet (MD) and QoL.

Materials and methods: This is a cross-sectional observational study involving 301 patients (134 females and 167 males); 119 had Crohn's Disease and 182 had ulcerative colitis. SD were assessed through the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF). Adherence to MD was evaluated by the MD Score. QoL was investigated by the 12-item Short-Form Health Survey (SF-12) which yields summary scores of physical (PCS) and mental (MCS) health. Multiple logistic regression was used to identify predictors of SD.

Results: Prevalence of SD in females was 61.9%, while 52.1% of males had erectile dysfunction. No differences in the prevalence of SD were found between CD and UC in both males and females. IBD activity, as defined by patient-reported outcomes, was significantly associated with SD in both sexes. In females, MD adherence score (OR 0.8, 95% CI 0.653-0.974, p = 0.027), PCS (OR = 0.936, CI 95% = 0.891-0.983, p = 0.008), and MCS (OR 0.9, 95% CI 0.906-0.985, p = 0.008) were protective against SD, whereas in males a higher PCS was associated with a lower probability of SD (OR 0.9, 95% CI 0.891-0.978, p = 0.004) DISCUSSION: IBD patients had a significant prevalence of SD which occurred more frequently in females than in males. Disease activity is associated with a higher likelihood of SD in both sexes, whereas dietary factors are differentially associated with SD in males and females. A better QoL is associated with a lower risk of SD.

Conclusion: SD is prevalent among men and women with IBD. Adherence to MD, PCS and MCS in females as well as PCS in males were protective against SD. The assessment of sexual function in IBD patients could be relevant in order to reach an early diagnosis and a timely treatment.

Background: Premature ejaculation (PE) remains one of the most common male disorders. Many clinical trials have shown that cognitive behavioral therapy (CBT) has significant efficacy in the treatment of PE. The purpose of this article is to review the current evidence regarding the efficacy and safety of CBT combined with selective serotonin reuptake inhibitors (SSRIs) for treating PE.

Methods: We selected eligible randomized controlled trials (RCTs) from databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, VIP, China Biology Medicine (CBM), Pubmed, Embase, and Cochrane Library. All data in this paper were analyzed using STATA 17.1 software. Cochrane Evaluator's Manual 5.3 was used to assess the quality of the included literature. Data collection was conducted up until May 2024.

Results: Finally, 15 high-quality randomized controlled trials were included, with 1243 patients, 653 experimental groups and 590 control groups. The meta-analysis showed that, compared with SSRIs alone, behavioral therapy combined with SSRIs can significantly prolong the IELT of PE patients, and improve perceived control over ejaculation, Chinese Index of Premature ejaculation-5 (CIPE-5), sexual life satisfaction, and spouses' sexual life satisfaction. Furthermore, there were no significant differences in side effects between the two groups. In addition, the published bias test results showed no significant bias.

Conclusion: CBT combined with SSRIs could be a viable alternative for the treatment of PE. Both cognitive and behavioral training or behavioral training alone as a supplement to SSRIs are effective, with no significant increase in adverse reactions.

Background: Testicular torsion is a common urological emergency in children and teenagers that, in most cases, requires surgical exploration and detorsion. However, even after a successful intervention, a high number of patients still develop irreversible damage.

Objectives: To investigate whether the administration of phosphodiesterase inhibitors (PDE) in animal models of testicular torsion can reduce damages caused by the ischemia-reperfusion syndrome.

Materials and methods: A systematic search of the Medline, Web of Science, Embase, and Ovid databases for studies up to December 2023 was performed using PRISMA guidelines. A detailed search was conducted using the following key terms: "testicles," "ischemia," "reperfusion," and "phosphodiesterase inhibitors." There was no restriction regarding language or year of publication. We investigated spermatogenesis by the Johnsen's biopsy score (JTBS) and histological damage by the Cosentino's biopsy score (CBS). Malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) testicular levels were also analyzed.

Results: Initially, 296 articles were identified. However, only 20 studies met the inclusion criteria. PDE inhibitors improved JTBS (MD = 2.53, CI = 1.94 to 3.13), CBS (MD = -1.11, CI = -1.25 to -0.97) and SOD (SMD = 3.27, CI = 1.59 to 4.95) outcomes. PDE did not improve MDA (SMD = -0.93, CI = -2.19 to 0.34), NO (SMD = -0.54, CI = -1.56 to 0.48), and GPx (SMD = 0.77, CI = -0.38 to 1.92) outcomes. A higher dose of PDE inhibitors only improved CBS outcome.

Discussion and conclusion: This review indicates that the administration of PDE inhibitors in rats ameliorated the outcomes, representing a promising complementary strategy for spermatogenesis recovery following testicular torsion. Our review suggests that JTBS and CBS could be translated into future human studies, validating and extending these findings within the context of human physiopathology, while providing applicability of interventions in real clinical practice.

Background: Intracavernosal injection therapy is often used as second-line therapy for erectile dysfunction associated with radical prostatectomy when therapy with phosphodiesterase-5 inhibitors has failed, but prostaglandin E1-containing vasoactive agents are associated with penile pain in some men.

Objectives: To define the incidence of pain with prostaglandin E1-containing intracavernosal injection mixtures for erectile dysfunction associated with radical prostatectomy when therapy with phosphodiesterase-5 inhibitors has failed, and whether pain was a predictor of erectile function recovery.

Materials and methods: Men who underwent radical prostatectomy and were commenced on intracavernosal injection within 12 months of radical prostatectomy were included. A pain visual analog scale (0-10) was used to assess the degree of pain. Erectile function recovery was defined as the International Index of Erectile Function domain score ≥24 using phosphodiesterase-5 inhibitors at 24 months.

Results: The study included 566 patients, mean age was 58 ± 14 (42-74) years. Duration post-radical prostatectomy at intracavernosal injection training was 3.5 ± 3.5 m. Nerve sparing status: bilateral 76%, unilateral 13%, and non-nerve sparing 11%. Incidence of pain with intracavernosal injection per nerve sparing status: bilateral 10% of patients, unilateral 32%, non-nerve sparing 92% (p < 0.001). Median visual analog scale in those experiencing pain: bilateral 4 (interquartile range 3, 5), unilateral 5.5 (interquartile range 3, 6), non-nerve sparing 7 (interquartile range 3, 9) (p < 0.001). Phosphodiesterase-5 inhibitors success at 24 months (no pain vs. pain): bilateral 70% vs. 40% (p < 0.001), unilateral 50% vs. 28% (p < 0.001), non-nerve sparing 10% vs. 0% (p < 0.001). On multivariate analysis, predictors of failure to respond to phosphodiesterase-5 inhibitors at 24 months post-radical prostatectomy included baseline erectile function, increasing age, incomplete nerve-sparing surgery, and presence of pain.

Discussion: The presence of penile pain with intracavernosal injection is associated with poorer erectile function recovery post-radical prostatectomy.

Conclusions: Incidence of pain is high in men with non-nerve sparing radical prostatectomy; older patient age, poorer nerve sparing, poor baseline erectile function, and the presence of penile pain with prostaglandin E1-containing intracavernosal injection medication, were predictive of poor erectile function recovery using phosphodiesterase-5 inhibitors at 24 months.

Background: Growing evidence indicates that paternal condition significantly influences pregnancy outcomes and offspring health. However, assessing the safety of paternal drug exposure via randomized controlled trials poses ethical challenges, and relevant clinical studies consume a lot of resources to evaluate only a few drugs. Currently, safety data on paternal drug exposure are scarce.

Objectives: To investigate the impact of paternal drug exposure on fertility, pregnancy outcomes, and offspring health.

Materials and methods: Data from the FDA adverse event reporting system (FAERS) were analyzed (2010-2022). Disproportionality analyses were used to identify signals of each drug-adverse event pair associated with paternal drug exposure in a different hierarchical manner.

Results: Out of the 16,180,533 reports, 3210 were related to paternal exposure, encompassing 7808 concomitant adverse events. Drugs used to treat rheumatoid arthritis, cancer, and infections were primary sources of paternal exposure. Analysis identified 115 signals concerning reproductive health. Notably, the signals of diazepam-small for dates baby and finasteride-cryptorchidism were particularly significant (reporting odds ratio, ROR > 800, N > 10). Moreover, spontaneous abortion signals occur frequently in biologics for the treatment of immune inflammation; the use of immunosuppressive drugs was associated with the highest number of congenital anomalies, with the strongest signals for belatacept-skeletal dysplasia, and tacrolimus-talipes. Only mycophenolic acid, estrogen and imatinib have signals on male fertility. Anti-tumor agents had high numbers of each reproductive toxicity, with the highest values of trisomy 13 signals associated with etoposide and cisplatin.

Conclusions: This is the first research to fully assess the safety of paternal exposure to the majority of medications in terms of reproduction. Clinical and scientific researchers should pay close attention to the list of risk medications included in this study, particularly the following association combinations: biologics used to treat inflammatory diseases-abortion, diazepam-small for date baby, finasteride-cryptorchidism, etoposide and cisplatin-13 trisomy.

Background: Dietary patterns may affect sperm quality, but the scientific evidence is limited.

Objective: To evaluate the association between adherence to different a-priori dietary patterns and sperm quality parameters in healthy reproductive-age men.

Materials and methods: A cross-sectional analysis was conducted using data from 200 young men enrolled in the Led-Fertyl study. Tertiles of six a-priori dietary patterns were estimated: four healthy dietary patterns [Mediterranean Diet Adherence Screener (MEDAS), Dietary Approaches to Stop Hypertension (DASH), Healthful Plant-Based Diet Index (hPDI) and EAT-Lancet Score], and two unhealthy dietary patterns [Western Diet and Unhealthful Plant-Based Diet Index (uPDI)]. Sperm quality parameters (count, concentration, vitality, total and progressive motility, and normal morphology) were considered the main outcomes.

Results: Compared with the lowest tertile, participants in the highest MEDAS tertile had higher total sperm count (β = 3.2;95%CI: 1.0, 5.5) and concentration (β = 1.8;95%CI: 0.6, 3.0), and total (β = 8.2;95%CI: 1.3, 15.1) and progressive motility (β = 7.1;95%CI: 0.2, 14.0). Similarly, participants in the highest hPDI tertile had higher total sperm count (β = 3.4;95%CI: 1.4, 5.5) and concentration (β = 1.2;95%CI: 0.0, 2.3) compared with those in the lowest tertile. When these dietary patterns were modelled as continuous variables (for each 1-point increment in the specific score), an inverse association was found between the uPDI and Western and total sperm count [(β = -2.7;95%CI: -4.8, -0.7) and (β = -3.8;95%CI: -5.8, -1.7), respectively] and sperm concentration [(β = -1.2;95%CI: -2.4, -0.1) and (β = -1.7;95%CI: -2.8, -0.5), respectively]. Compared with participants in the lowest tertile, those in the highest uPDI tertile presented higher odds of abnormal sperm concentration (OR: 4.6;95%CI: 1.0, 19.9) and one or more seminogram abnormalities (OR: 2.3;95%CI: 1.1, 5.0).

Conclusions: Our findings suggest that higher adherence to healthy dietary patterns (Mediterranean and healthful plant-based diet) was positively associated with better sperm quality parameters, in contrast, greater adherence to unhealthy dietary patterns was inversely associated.

Introduction: To date, there are only case reports of penile amputation, a rare urological emergency with a low-treatment successful rate, and there are still no advanced, detailed surgical or perioperative treatment plans. Effective treatments for these rare diseases are urgently needed.

Method: The researchers summarized the perioperative experience of 20 patients who underwent replantation after complete penile amputation at several hospitals over the past 5 years and shared experience in detail.

Results: Only 1 of the 20 surgeries failed, and both urinary and erectile functions were successfully restored in other cases, indicating that the surgical methods and perioperative treatments summarized by researchers are feasible and highly successful for replantation following complete penile amputation.

Conclusion: Researchers have summarized the method and perioperative plan for replantation following penile amputation based on a summary of 20 cases, thereby providing guidance for urologists and andrologists.