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Phosphodiesterases, particularly the type 5 isoform (PDE5), have gained recognition as pivotal regulators of male reproductive physiology, exerting significant influence on testicular function, sperm maturation, and overall fertility potential. Over the past several decades, investigations have expanded beyond the original therapeutic intent of PDE5 inhibitors for erectile dysfunction, exploring their broader reproductive implications. This narrative review integrates current evidence from in vitro studies, animal models, and clinical research to clarify the roles of PDEs in effecting the male reproductive tract, with an emphasis on the mechanistic pathways underlying cyclic nucleotide signaling, the cellular specificity of PDE isoform expression, and the effects of PDE5 inhibitors on Leydig and Sertoli cell functions. Although certain findings suggest potential improvements in sperm motility, semen parameters, and a more favorable biochemical milieu for spermatogenesis, inconsistencies in study design, limited sample sizes, and inadequate long-term data temper definitive conclusions. Addressing these gaps through standardized protocols, larger and more diverse patient cohorts, and explorations of mechanistic biomarkers could pave the way for incorporating PDE5 inhibitors into evidence-based fertility treatment strategies. In the future, such targeted approaches may inform individualized regimens, optimize male reproductive outcomes, and refine the clinical application of PDE5 inhibitors as part of comprehensive male fertility management. [ABSTRACT FROM AUTHOR]

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms—encompassing DNA methylation, histone modifications, and non-coding RNA activity—are crucial both for spermatogenesis and sperm maturation. However, oxidative stress, driven by excessive reactive oxygen species, disrupts these processes, leading to impaired sperm function and male infertility. This disruption extends to epigenetic modifications, resulting in abnormal gene expression and chromatin remodeling that compromise genomic integrity and fertilization potential. Importantly, oxidative-stress-induced epigenetic alterations can be inherited, affecting the health and fertility of offspring and future generations. This review investigates how oxidative stress influences epigenetic regulation in male reproduction by modifying DNA methylation, histone modifications, and non-coding RNAs, ultimately compromising spermatogenesis. Additionally, it discusses the transgenerational implications of these epigenetic disruptions and their potential role in hereditary infertility and disease predisposition. Understanding these mechanisms is vital for developing therapeutic strategies that mitigate oxidative damage and restore epigenetic homeostasis in the male germline. By integrating insights from molecular, clinical, and transgenerational research, this work emphasizes the need for targeted interventions to enhance male reproductive health and prevent adverse outcomes in progeny. Furthermore, elucidating the dose–response relationships between oxidative stress and epigenetic changes remains a critical research priority, informing personalized diagnostics and therapeutic interventions. In this context, future studies should adopt standardized markers of oxidative damage, robust clinical trials, and multi-omic approaches to capture the complexity of epigenetic regulation in spermatogenesis. Such rigorous investigations will ultimately reduce the risk of transgenerational disorders and optimize reproductive health outcomes. [ABSTRACT FROM AUTHOR]

Background/Objectives: Beta-thalassemia (BTH), a genetic disorder resulting from beta-globin gene mutations, affects over 1.5 million people globally. The disorder's multifactorial impact on male fertility, particularly through oxidative stress (OS), warrants focused study. This review examines the mechanisms of OS in TM, its implications for male infertility, and the potential of antioxidant therapies to mitigate fertility challenges. Methods: A non-systematic review was conducted using the PubMed, Cochrane, and Medscape databases, focusing on studies on beta-thalassemia (BTH), erectile dysfunction (ED), hormonal alterations, and OS. Studies were screened based on relevance, language, and topic, with 71 articles meeting the inclusion criteria after removing duplicates. Results: The findings reveal that OS, exacerbated by iron overload from regular blood transfusions, is significantly associated with impaired sperm quality and fertility in patients with TM. Iron toxicity affects gonadotropin levels, reduces sperm quality, and contributes to hypogonadism. Additionally, antioxidant therapies show promise in reducing OS-induced sperm damage, though efficacy is limited by a lack of robust clinical trials. Conclusions: OS plays a considerable role in male infertility among patients with TM, primarily through iron-induced sperm damage and hormonal disruptions. While antioxidant therapies may offer a partial remedy, further research is necessary to understand OS's mechanisms in TM and develop effective fertility treatments. This review highlights the need for personalized antioxidant approaches to improve reproductive outcomes in this population. [ABSTRACT FROM AUTHOR]

Background and Objectives: Varicocele repair in men with non-obstructive azoospermia (NOA) remains a subject of debate due to inconsistent outcomes. This study aimed to evaluate the impact of microsurgical varicocelectomy on sperm recovery rates in men with NOA and to assess the role of varicocele grade and testicular histopathology in predicting postoperative outcomes. Materials and Methods: A retrospective cohort study was conducted of 78 men diagnosed with NOA and clinical varicocele who underwent microsurgical subinguinal varicocelectomy with simultaneous diagnostic and therapeutic testicular biopsy at the Department of Urology of the University of Ioannina between September 2013 and December 2021. Varicoceles were graded I to III based on physical examination and Doppler ultrasound. Histopathological patterns were classified as hypospermatogenesis (HYPO), early maturation arrest (EMA), late maturation arrest (LMA), or Sertoli cell-only syndrome (SCOS). Patients were followed postoperatively at 3, 6, 9, and 12 months, with semen analyses performed according to World Health Organization guidelines to assess sperm presence. Results: At the 12-month follow-up, spermatozoa were detected in the ejaculate of 26 out of 78 patients, resulting in an overall sperm return to ejaculate rate of 33.3%. Varicocele grade significantly influenced outcomes: patients with Grade II varicoceles had the highest sperm return to ejaculate rate (45.2%, 14/31), followed by Grade III (39.1%, 9/23) and Grade I (12.5%, 3/24) (p-value < 0.05). The sperm retrieval rate (SRR) from testicular biopsies also varied with varicocele grade: Grade II had the highest SRR (54.8%, 17/31), followed by Grade III (47.8%, 11/23) and Grade I (33.3%, 8/24). Histopathological findings were significant predictors of sperm retrieval: patients with HYPO had an SRR of 84.8% (28/33) and a sperm return to ejaculate rate of 66.7% (22/33); those with LMA had an SRR of 47.1% (8/17) and a sperm return rate of 23.5% (4/17). No sperm retrieval was observed in patients with EMA (0%, 0/4) or SCOS (0%, 0/24) (p-value < 0.01). Multivariate logistic regression identified varicocele grade and histopathology as independent predictors of sperm retrieval, with higher grades and favorable histopathology associated with increased likelihood of success. Conclusions: Microsurgical varicocelectomy can induce spermatogenesis in a significant proportion of men with NOA, particularly those with higher-grade varicoceles and favorable histopathological patterns such as HYPO or LMA. Varicocele grade and histopathological findings are important predictors of postoperative outcomes and should inform patient selection and counseling. These findings provide valuable insights for optimizing fertility treatments in men with NOA undergoing varicocele repair. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recurrent pregnancy loss (RPL) affects numerous couples worldwide and has traditionally been attributed mainly to maternal factors. However, recent evidence highlights significant paternal influences on pregnancy viability and outcomes. This review aims to comprehensively examine male contributions to pregnancy loss, focusing on underlying mechanisms, novel biomarkers, and integrated strategies for improved reproductive success. Materials and Methods: A comprehensive narrative review was conducted by searching databases including PubMed and Embase for the literature published from January 2004 to October 2024. Studies focusing on paternal influences in RPL—encompassing oxidative stress, genetic and epigenetic mechanisms, health conditions, lifestyle factors, environmental exposures, and advancements in sperm proteomics—were included. Inclusion criteria were peer-reviewed articles in English that directly addressed paternal factors in RPL; studies not meeting these criteria were excluded. Results: The review identified that paternal factors such as advanced age, metabolic and cardiovascular health issues, chronic diseases, lifestyle habits (e.g., smoking, alcohol consumption, poor diet), and environmental exposures significantly affect sperm integrity through mechanisms like oxidative stress, DNA fragmentation, and epigenetic alterations. Advanced paternal age and poor health conditions are associated with increased risks of miscarriage and adverse pregnancy outcomes. Novel sperm proteomic biomarkers have been identified, offering potential for enhanced diagnostics and personalized interventions. Integrated approaches involving multidisciplinary assessments, preventive strategies, and genetic counseling are essential for effectively addressing RPL. Conclusions: Integrating paternal factors into clinical evaluations is crucial for effectively addressing recurrent pregnancy loss. Recognizing and modifying paternal risk factors through lifestyle changes, medical interventions, and environmental management can improve pregnancy outcomes. The findings underscore the need for incorporating paternal assessments into standard care and highlight the importance of future research focusing on standardizing diagnostic protocols, expanding studies on paternal contributions, and integrating proteomic biomarkers into clinical practice to facilitate personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Non-obstructive azoospermia (NOA) is a severe form of male infertility characterized by the absence of sperm in the ejaculate due to impaired spermatogenesis. Testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection is the primary treatment, but success rates are unpredictable, causing significant emotional and financial burdens. Traditional clinical and hormonal predictors have shown inconsistent reliability. This review aims to evaluate current and emerging non-invasive preoperative predictors of successful sperm retrieval in men with NOA, highlighting promising biomarkers and their potential clinical applications. Methods: A comprehensive literature review was conducted, examining studies on clinical and hormonal factors, imaging techniques, molecular biology biomarkers, and genetic testing related to TESE outcomes in NOA patients. The potential role of artificial intelligence and machine learning in enhancing predictive models was also explored. Results: Traditional predictors such as patient age, body mass index, infertility duration, testicular volume, and serum hormone levels (follicle-stimulating hormone, luteinizing hormone, inhibin B) have limited predictive value for TESE success. Emerging non-invasive biomarkers—including anti-Müllerian hormone levels, inhibin B to anti-Müllerian hormone ratio, specific microRNAs, long non-coding RNAs, circular RNAs, and germ-cell-specific proteins like TEX101—show promise in predicting successful sperm retrieval. Advanced imaging techniques like high-frequency ultrasound and functional magnetic resonance imaging offer potential but require further validation. Integrating molecular biomarkers with artificial intelligence and machine learning algorithms may enhance predictive accuracy. Conclusions: Predicting TESE outcomes in men with NOA remains challenging using conventional clinical and hormonal parameters. Emerging non-invasive biomarkers offer significant potential to improve predictive models but require validation through large-scale studies. Incorporating artificial intelligence and machine learning could further refine predictive accuracy, aiding clinical decision-making and improving patient counseling and treatment strategies in NOA. [ABSTRACT FROM AUTHOR]

Background/Objectives: Varicoceles are a common contributor to male infertility, significantly impacting male-factor infertility cases. Traditional diagnostic methods often lack the sensitivity to detect the molecular and cellular disruptions caused by varicoceles, limiting the development of effective, personalized treatments. This narrative review aims to explore the advancements in proteomics and metabolomics as innovative, non-invasive diagnostic tools for varicocele-associated male infertility and their potential in guiding personalized therapeutic strategies. Methods: A comprehensive literature search was conducted using databases such as PubMed, Scopus, and Web of Science up to October 2024. Studies focusing on the application of proteomic and metabolomic analyses in varicocele-associated male infertility were selected. The findings were critically analyzed to synthesize current knowledge and identify future research directions. Results: Proteomic analyses revealed differentially expressed proteins in the sperm and seminal plasma of varicocele patients, revealing disruptions in pathways related to oxidative stress, mitochondrial dysfunction, apoptosis, and energy metabolism. Key proteins such as heat shock proteins, mitochondrial enzymes, and apoptotic regulators were notably altered. Metabolomic profiling uncovered specific metabolites in seminal plasma—such as decreased levels of lysine, valine, and fructose—that correlate with impaired sperm function and fertility potential. The integration of proteomic and metabolomic data provides a comprehensive molecular fingerprint of varicocele-induced infertility, facilitating the identification of novel biomarkers for early diagnosis and the development of personalized therapeutic interventions. Conclusions: Advances in proteomics and metabolomics have significantly enhanced our understanding of the molecular mechanisms underlying varicocele-associated male infertility. These "omics" technologies hold great promise for improving diagnostic accuracy and personalizing treatment, ultimately leading to better outcomes for affected men. Future large-scale clinical trials and validations are essential to confirm these biomarkers and facilitate their integration into routine clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic catheterization remains the only attractive option in specific circumstances, especially in neurologically impaired patients. Complications produced by the indwelling catheters, like patulous urethra and bladder neck destruction, usually lead to severe incontinence and significant nursing difficulties. Here, we describe a rare case, a urinary bladder opening representing massive and extensive destruction of the urethra and bladder sphincter due to an indwelling catheter. Case presentation We present a 46-year-old paraplegic woman complaining of recurrent febrile urinary tract infections and severe urinary incontinence. She suffered from persistent malodorous urine and skin breakdowns from constant urine leakage. The vaginal examination revealed extensive destruction of the urethra and a 10 cm opening permitting the urinary bladder wall to prolapse into the vagina. The patient underwent a combined surgical approach; a transvaginal bladder closure with anterior colporrhaphy and a Mitrofanoff procedure to ensure a continent stoma for future clean intermittent self-catheterization (CISC). The patient is compliant with CISC and, remains continent twelve years after surgery. Conclusion This case demonstrates that in the era of CISC, there are still neurologically impaired females suffering from rare but critical adverse effects of indwelling catheters. The urethra and bladder neck erosion represent a demanding treatment assignment. The Mitrofanoff procedure for continent stoma and the transvaginal closure of urinary bladder opening produced a lifesaving potential treatment.

Background/Objectives: Multiple sclerosis (MS) frequently results in both urinary and sexual dysfunction, which significantly impairs quality of life. Conventional treatments for bladder dysfunction often prove insufficient, leading to the exploration of alternative therapies such as percutaneous tibial nerve stimulation (PTNS). This study aimed to assess the impact of PTNS on sexual function and bladder symptoms in female MS patients with neurogenic detrusor overactivity (NDO) and female sexual dysfunction (FSD). Methods: A total of 65 female MS patients with NDO were evaluated and underwent 12 weeks of standardized PTNS treatment. Sexual function was assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R), while bladder symptoms were evaluated using the OAB-v8 questionnaire. Participants were grouped based on the presence of sexual dysfunction and distress and compared to a control group of 20 patients who declined PTNS. Results: Significant improvements were observed in FSFI scores across multiple domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) in the treatment groups (p < 0.05). Additionally, 58.46% of patients showed positive responses to PTNS regarding overactive bladder symptoms (OAB-v8 score), while the control group showed no significant changes. Conclusions: PTNS appears to be an effective therapeutic option for improving sexual function and urinary symptoms in female MS patients with NDO and FSD, offering a promising non-invasive alternative for managing these conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is one of the most common cancers in men worldwide, and its causes are influenced by both genetic and lifestyle factors. One lifestyle factor that has shown mixed evidence is alcohol consumption. While some studies suggest that heavy drinking increases prostate cancer risk, others show little to no connection. This research aims to clarify the relationship between alcohol consumption and prostate cancer by reviewing and analyzing global studies. By exploring how different types of alcohol and drinking patterns may influence cancer risk, the goal is to provide more precise guidance for healthcare providers and patients. These findings can help inform public health recommendations and future research on cancer prevention strategies, especially for higher-risk populations. Background/Objectives: Prostate cancer (PCa) is a significant global health issue. The relationship between alcohol consumption and PCa risk has been the subject of extensive research, yet findings remain inconsistent. This review aims to clarify the association between alcohol intake and PCa risk, its aggressiveness, and the potential metabolic pathways involved in PCa onset. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed and MEDLINE, focusing on epidemiological studies, meta-analyses, cohort studies, and case–control studies. Studies evaluating alcohol consumption, prostate-specific antigen (PSA) levels, and PCa risk were included. The review also explored the roles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in alcohol metabolism. Results: The analysis reveals a complex relationship between alcohol consumption and PCa. Heavy alcohol intake is associated with an increased risk of PCa, particularly more aggressive forms, and higher mortality rates. However, studies also show weak or no association between moderate alcohol consumption and PCa. The variability in findings may be attributed to differences in alcohol types, regional factors, and study methodologies. Conclusions: The link between alcohol consumption and PCa risk is multifaceted. While heavy drinking appears to increase the risk of aggressive PCa, the overall relationship remains unclear. Further research is needed to better understand these associations and inform public health recommendations and cancer prevention strategies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Male infertility is a prevalent issue impacting numerous couples worldwide. This review aims to evaluate the effectiveness of empirical therapies for male infertility, focusing on both lifestyle modifications and medical treatments. This study provides a comprehensive overview of interventions aimed at improving male fertility outcomes. Methods: A thorough review of the existing literature was conducted, encompassing studies on lifestyle changes such as dietary changes, smoking cessation, alcohol moderation, and exercise. Additionally, medical treatments including selective estrogen receptor modulators, gonadotropins, aromatase inhibitors, phosphodiesterase-5 inhibitors, antioxidants, dopamine agonists, kallikrein, indomethacin, low-dose corticosteroids, alpha-blockers, and nitric oxide donors were evaluated. The study population included males diagnosed with infertility, focusing on various underlying causes. Results: Lifestyle modifications were found to have a positive impact on sperm quality. Evidence shows that a healthy diet, smoking cessation, moderate alcohol consumption, and regular exercise improve fertility outcomes. Medical treatments demonstrated significant improvements in sperm production and quality. Selective estrogen receptor modulators and gonadotropins enhanced sperm parameters. Aromatase inhibitors and phosphodiesterase-5 inhibitors specifically improved sperm motility and increased pregnancy rates. Antioxidants, such as vitamins E and C and coenzyme Q10, reduced oxidative stress and enhanced sperm counts, motility, and morphology. Dopamine agonists, particularly cabergoline, normalized prolactin levels and improved fertility outcomes. Kallikrein therapy improved sperm parameters and increased pregnancy rates. Indomethacin treatment was associated with increased sperm concentrations and motility. Low-dose corticosteroids and alpha-blockers showed variable results, and nitric oxide donors like L-arginine enhanced sperm counts and motility. Conclusions: Empirical therapies, including lifestyle modifications and medical treatments, significantly enhance sperm quality and reproductive potential. These integrated approaches are essential in improving fertility outcomes in males. However, further extensive randomized trials are necessary to definitively establish the most effective treatments. [ABSTRACT FROM AUTHOR]

Endometriosis is a debilitating gynecological condition commonly seen in individuals designated female at birth; however, there has been limited research focused on its prevalence and impact among transgender men. This narrative review aims to fill a critical knowledge gap by exploring the epidemiology, clinical manifestations, management strategies, and quality-of-life implications of endometriosis among transgender individuals who identify as male. Specifically, this study seeks to estimate the prevalence rates and describe the symptoms experienced by transgender men undergoing testosterone therapy. Additionally, it addresses the diagnostic challenges posed by hormonal treatments and the lack of culturally competent healthcare services for this population. Recent molecular studies indicate that hormonal imbalances, such as increased estrogen synthesis and progesterone resistance, are significant factors in the persistence of endometriosis symptoms despite testosterone therapy. Moreover, evidence suggests that testosterone therapy may not always suppress endometrial activity completely, contributing to the persistence of symptoms in some individuals. Endometriosis in transgender men requires personalized approaches that consider both testosterone therapy and its interactions with endometriosis, as well as fertility preservation and the psychosocial aspects of treatment. This review emphasizes the necessity of taking an inclusive approach in both research and clinical practice to improve healthcare outcomes for this underserved population. The results demonstrate how continued research, education, and healthcare services tailored specifically to transgender men are necessary to better understand and treat endometriosis, thus improving both their overall health and quality of life. [ABSTRACT FROM AUTHOR]