Showing papers in "The World Journal of Men's Health in 2019"

Role of Androgen Receptor in Prostate Cancer: A Review.

Abstract: Androgen receptor (AR) is a steroid receptor transcriptional factor for testosterone and dihydrotestosterone consisting of four main domains, the N-terminal domain, DNA-binding domain, hinge region, and ligand-binding domain. AR plays pivotal roles in prostate cancer, especially castration-resistant prostate cancer (CRPC). Androgen deprivation therapy can suppress hormone-naive prostate cancer, but prostate cancer changes AR and adapts to survive under castration levels of androgen. These mechanisms include AR point mutations, AR overexpression, changes of androgen biosynthesis, constitutively active AR splice variants without ligand binding, and changes of androgen cofactors. Studies of AR in CRPC revealed that AR was still active in CRPC, and it remains as a potential target to treat CRPC. Enzalutamide is a second-generation antiandrogen effective in patients with CRPC before and after taxane-based chemotherapy. However, CRPC is still incurable and can develop drug resistance. Understanding the mechanisms of this resistance can enable new-generation therapies for CRPC. Several promising new AR-targeted therapies have been developed. Apalutamide is a new Food and Drug Administration-approved androgen agonist binding to the ligand-binding domain, and clinical trials of other new AR-targeted agents binding to the ligand-binding domain or N-terminal domain are underway. This review focuses on the functions of AR in prostate cancer and the development of CRPC and promising new agents against CRPC.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Abstract: Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

Growth Hormone and Aging: Updated Review.

Abstract: Role of growth hormone (GH) in mammalian aging is actively explored in clinical, epidemiological, and experimental studies. The age-related decline in GH levels is variously interpreted as a symptom of neuroendocrine aging, as one of causes of altered body composition and other unwelcome symptoms of aging, or as a mechanism of natural protection from cancer and other chronic diseases. Absence of GH signals due to mutations affecting anterior pituitary development, GH secretion, or GH receptors produces an impressive extension of longevity in laboratory mice. Extension of healthspan in these animals and analysis of survival curves suggest that in the absence of GH, aging is slowed down or delayed. The corresponding endocrine syndromes in the human have no consistent impact on longevity, but are associated with remarkable protection from age-related disease. Moreover, survival to extremely old age has been associated with reduced somatotropic (GH and insulin-like growth factor-1) signaling in women and men. In both humans and mice, elevation of GH levels into the supranormal (pathological) range is associated with increased disease risks and reduced life expectancy likely representing acceleration of aging. The widely advertised potential of GH as an anti-aging agent attracted much interest. However, results obtained thus far have been disappointing with few documented benefits and many troublesome side effects. Possible utility of GH in the treatment of sarcopenia and frailty remains to be explored.

Sleep, Sleep Disorders, and Sexual Dysfunction

Abstract: Good sleep is necessary for good health. Sleep health is increasingly recognized as important for physical and mental health by both the medical profession and the general public, and there is great interest in how to avoid and treat sleep disorders and problems. Recent research indicates that insufficient sleep, disrupted sleep, and sleep disorders affect many aspects of human health including sexual function. In fact, patients with urological disorders or erectile dysfunction (ED) may have a sleep disorder that contributes to their urological or sexual dysfunction. Obstructive sleep apnea, insomnia, shift work disorder, and restless legs syndrome are all common sleep disorders and are associated with ED and/or other urological disorders. Therefore, careful attention should be paid to the diagnosis and treatment of concomitant sleep disorders in patients with sexual dysfunction. In this review, we provide an overview of what sleep is and how it is assessed in the clinic or laboratory; our current understanding of the functions of sleep and sleep health; a description of common sleep disorders, as well as how they are diagnosed and treated; and how sleep and its disorders are associated with male sexual dysfunction. Sleep is considered to be a 'third pillar of health', along with diet and exercise. With an understanding of common sleep disorders and how they can impact male sexual function, the urologist can ensure that sleep disorders are considered as a contributor to sexual dysfunction in their patients in order to provide them with the optimal treatment for overall health.

Metabolic Syndrome and Male Fertility

Abstract: Metabolic syndrome (MetS) represents a cluster of conditions that have a negative impact on human health overall. Its prevalence has been rapidly increasing worldwide and has coincided with a global decrease in birth rates and fertility potential. This review aims to address this observation through studying the relationship between MetS and male reproductive health. The effects of obesity, dyslipidemia, hypertension, and insulin resistance on male fertility were examined and supporting evidence explaining the pathophysiology of sperm dysfunction with each MetS component were described. Adopting a healthy lifestyle appears to be the single most important intervention to prevent the unwanted effects of MetS on men's health and fertility. Further studies addressing the components of MetS and their impact on male reproduction are required to enhance our understanding of the underlying pathophysiology and to propose new methods for therapeutic intervention.

Varicocele and Testicular Pain: A Review.

Abstract: Varicocele is the dilatation of the scrotal portion of pampiniform plexus and the internal spermatic venous system. About 15% of men suffer from scrotal varicocele and 2% to 10% of them complain of pain. The probable mechanisms for pain include compression of the surrounding neural fibers by the dilated venous complex, elevated testicular temperature, increased venous pressure, hypoxia, oxidative stress, hormonal imbalances, and the reflux of toxic metabolites of adrenal or renal origin. Testicular pain associated with varicoceles is typically described as a dull, aching, or throbbing pain in the testicle, scrotum, or groin; rarely, it can be acute, sharp, or stabbing. The management of testicular pain associated with varicocele starts with a conservative, non-surgical approach and a period of observation. Varicocelectomy in carefully selected candidates with clinically palpable varicocele resolves nearly 80% of all cases of testicular pain. Microsurgical techniques for varicocelectomy have gained popularity with minimal complication rates and favorable outcomes. The grade of varicocele, the nature and duration of pain, body mass index, prior conservative management, and the type of surgical method used, are predictors for the success of varicocelectomy.

The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review.

Abstract: Endoplasmic reticulum (ER) stress, defined as prolonged disturbances in protein folding and accumulation of unfolded proteins in the ER. Perturbation of the ER, such as distribution of oxidative stress, iron imbalance, Ca2+ leakage, protein overload, and hypoxia, can cause ER stress. The cell reacts to ER stress by activating protective pathways, called the unfolded protein response (UPR), which is comprised of cellular mechanisms aimed for maintaining cellular homeostasis or, in case of excessively severe stress, at the initiation of cellular apoptosis. The three UPR signaling pathways from the ER stress sensors are initiated by activating transcription factor 6, inositol requiring enzyme 1, and protein kinase RNA-activated-like ER kinase. A number of physiological and pathological conditions, environmental toxicants and variety of pharmacological agents showed disruption of proper ER functions and thereby cause ER stress in male reproductive organ in rat model. The present review summarizes the existing data concerning the molecular and biological mechanism of ER stress in male reproduction and male infertility. ER stress initiated cell death pathway has been related to several diseases, including hypoxia, heath disease, diabetes, and Parkinson's disease. Although there is not enough evidence to prove the relationship between ER stress and male infertility in human, most studies in this review found that ER stress was correlated with male reproduction and infertility in animal models. The ER stress could be novel signaling pathway of regulating male reproductive cellular apoptosis. Infertility might be a result of disturbing the ER stress response during the process of male reproduction.

Recovery of Spermatogenesis Following Cancer Treatment with Cytotoxic Chemotherapy and Radiotherapy

Abstract: The survival rates of boys and men with cancer have increased due to advances in cancer treatments; however, maintenance of quality of life, including fertility preservation, remains a major issue. Fertile male patients who receive radiation and/or chemotherapy face temporary, long-term, or permanent gonadal damage, particularly with exposure to alkylating agents and whole-body irradiation, which sometimes induce critical germ cell damage. These cytotoxic treatments have a significant impact on a patient's ability to have their own biological offspring, which is of particular concern to cancer patients of reproductive age. Therefore, various strategies are needed in order to preserve male fertility. Sperm cryopreservation is an effective method for preserving spermatozoa. Advances have also been achieved in pre-pubertal germ cell storage and research to generate differentiated male germ cells from various types of stem cells, including embryonic stem cells, induced pluripotent stem cells, and spermatogonial stem cells. These approaches offer hope to many patients in whom germ cell loss is associated with sterility, but are still experimental and preliminary. This review examines the current understanding of the effects of chemotherapy and radiation on male fertility.

Testosterone Is a Contraceptive and Should Not Be Used in Men Who Desire Fertility

Abstract: Testosterone has a variety of functions and is commonly used in older men to treat symptoms of hypogonadism, such as decreased libido, decreased mood and erectile dysfunction. Despite its positive effects on sexual function, it has a negative effect on fertility. Exogenous testosterone therapy can negatively affect the hypothalamic-pituitary gonadal axis and inhibit the production of follicle stimulating hormone and luteinizing hormone. The purpose of this review is to discuss the contraceptive properties of testosterone therapy and to discuss strategies to increase testosterone in men with the desire to preserve fertility.

Protective Effect of All-Trans Retinoic Acid in Cisplatin-Induced Testicular Damage in Rats.

Abstract: Purpose To investigate the effects of all-trans retinoic acid (ATRA) in cisplatin (CP)-induced testicular damage in rats. Materials and methods Twenty-eight male Wistar rats were divided into four groups: Control, ATRA alone, ATRA+CP, and CP alone. Body weight, testicular weight, sperm count, sperm motility, percentage of abnormal sperm, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in testicular tissue, and testicular histopathology were compared among groups. Results The sperm count and motility significantly decreased and the percentage of abnormal sperm significantly increased in the CP group compared to the control and ATRA groups. CP+ATRA administration significantly increased the sperm count and motility, but reduced the abnormal sperm count. CP administration significantly increased TOS and OSI compared to the control group and the other groups. Administering CP+ATRA significantly decreased TOS and the OSI in testicular tissue and reduced spermatogenesis, but increased the Johnsen score. Conclusions The destructive effects of CP treatment on testicular tissue and spermatogenesis were reduced by administering ATRA.

Penile Prosthesis Infection: Myths and Realities

Abstract: Penile prosthesis infection is the most significant complication following prosthesis implant surgery leading to postoperative morbidity, increased health care costs, and psychological stress for the patient. We aimed to identify risk factors associated with increased postoperative penile prosthesis infection. A review of the literature was performed via PubMed using search terms including inflatable penile prosthesis, penile implant, and infection. Articles were given a level of evidence score using the 2011 Oxford Centre for Evidence-Based Medicine Guidelines. Multiple factors were associated with increased risk of post-prosthesis placement infection (Level of Evidence Rating) including smoking tobacco (Level 1), CD4 T-cell count 8.5 (Level 2). Factors with no effect on infection rate include: preoperative cleansing with antiseptic (Level 4), history of prior radiation (Level 3), history of urinary diversion (Level 4), obesity (Level 3), concomitant circumcision (Level 3), immunosuppression (Level 4), age >75 (Level 4), type of hand cleansing (Level 1), post-surgical drain placement (Level 3), and surgical approach (Level 4). Factors associated with decreased rates of infection included: surgeon experience (Level 2), "No Touch" technique (Level 3), preoperative parenteral antibiotics (Level 2), antibiotic coated devices (Level 2), and operative field hair removal with clippers (Level 1). Optimization of pre-surgical and intraoperative risk factors is imperative to reduce the rate of postoperative penile prosthesis infection. Additional research is needed to elucidate risk factors and maximize benefit.

Obstructive Sleep Apnea and Testosterone Deficiency.

Abstract: Obstructive sleep apnea (OSA) is a common disorder characterized by intermittent hypoxia and sleep fragmentation. OSA in middle-aged men is often associated with decreased testosterone secretion, together with obesity and aging. Although OSA treatment does not reliably increase testosterone levels in most studies, OSA treatment with testosterone replacement therapy (TRT) may not only improve hypogonadism, but can also alleviate erectile/sexual dysfunction. However, because TRT may exacerbate OSA in some patients, patients should be asked about OSA symptoms before and after starting TRT. Furthermore, TRT should probably be avoided in patients with severe untreated OSA.

Review of Guidelines for the Evaluation and Treatment of Leukocytospermia in Male Infertility.

Abstract: Leukocytospermia is an ill-defined and poorly understood condition affecting up to 30% of male factor infertility. Current guidelines on leukocytospermia vary significantly, although it has been linked to increased rates of infertility, uncertainty about its clinical significance, diagnosis, and treatment remains. The guidelines are conflicting with sparse data scattered across different specialties and continents. This study aims to compare and contrast available international guidelines and recommendations. In addition to these guidelines, we sought to consolidate the findings of trials over the last several decades. English language articles on human observational studies, retrospective, prospective, clinical trials and randomized control trials were searched for using the following terms: "leukocytospermia, pyospermia, and male infertility." Articles about treatment and management of leukocytospermia that were published between January 2010 and April 2018 were included, as well as four articles referenced in best practice and guideline statements from urological and andrological associations. Disagreements on this topic are highlighted as some guidelines describe no correlation between leukocytospermia and infertility while others show that treatment leads to improvement of sperm quality by many measures including improved pregnancy rate. Various treatments have been suggested including antibiotics, anti-inflammatory medications, and frequent ejaculation. There is a need for definitive characterization of Leukocytospermia as an infectious or inflammatory marker and a re-evaluation of the leukocyte concentration threshold. Additional studies investigating rates of conception as a measure of outcome are needed, to provide greater level of evidence and generalizability of leukocytopsermia management.

Traditional Chinese Medicine as a Remedy for Male Infertility: A Review.

Abstract: Male infertility (MI) is a complex multifactorial disease, and idiopathic infertility accounts for 30% of cases of MI. At present, the evidence for the effectiveness of empirical drugs is limited, and in vitro fertilization is costly and may increase the risk of birth defects and childhood cancers. Therefore, affected individuals may feel obliged to pursue natural remedies. Traditional Chinese medicine (TCM) may represent a useful option for infertile men. It has been demonstrated that TCM can regulate the hypothalamic-pituitary-testicular axis and boost the function of Sertoli cells and Leydig cells. TCM can also alleviate inflammation, prevent oxidative stress, reduce the DNA fragmentation index, and modulate the proliferation and apoptosis of germ cells. Furthermore, TCM can supply trace elements and vitamins, ameliorate the microcirculation of the testis, decrease the levels of serum anti-sperm antibody, and modify epigenetic markers. However, the evidence in favor of TCM is not compelling, which has hindered the development of TCM. This review attempts to elucidate the underlying therapeutic mechanisms of TCM. We also explore the advantages of TCM, differences between TCM and Western medicine, and problems in existing studies. Subsequently, we propose solutions to these problems and present perspectives for the future development of TCM.

Epigenetics of Male Fertility: Effects on Assisted Reproductive Techniques.

Abstract: During the last decades the study of male infertility and the introduction of the assisted reproductive techniques (ARTs) has allowed to understand that normal sperm parameters do not always predict fertilization. Sperm genetic components could play an important role in the early stages of embryonic development. Based on these acquisitions, several epigenetic investigations have been developed on spermatozoa, with the aim of understanding the multifactorial etiology of male infertility and of showing whether embryonic development may be influenced by sperm epigenetic abnormalities. This article reviews the possible epigenetic modifications of spermatozoa and their effects on male fertility, embryonic development and ART outcome. It focuses mainly on sperm DNA methylation, chromatin remodeling, histone modifications and RNAs.

Extracorporeal Shock Wave Therapy in Peyronie's Disease: Clinical Efficacy and Safety from a Single-Arm Observational Study.

Abstract: PURPOSE In this study, we aimed to determine the role of extracorporeal shockwave therapy (ESWT) in the management of Peyronie's disease (PD). MATERIALS AND METHODS A total of 325 patients suffering from PD were enrolled in this single-arm clinical study. All patients were received ESWT using a schedule of 1 treatment/wk. Penile curvature was measured by a goniometer after intracavernosal drug-induced erection using Alprostadil. Plaque size was measured with a ruler and sexual function assessed by the international index of erectile function (IIEF)-15 score. Severity of erectile dysfunction was classified as severe (IIEF-15 ≤10), moderate (IIEF-15 between 11 and 16), or mild (IIEF-15 between 17 and 25). Results were evaluated at baseline and 3 months after the treatment. RESULTS All the patients completed the study protocol. Median age was 59.0 years (55.0-64.0 years). After treatment, the median (interquartile range, IQR) plaque size reduced from 1.78 cm² (1.43-2.17 cm²) to 1.53 cm² (1.31-1.96 cm²) (p<0.001); the median (IQR) penile length in erection increased from 13.0 cm (12.0-14.0 cm) to 14 cm (13.0-15.0 cm) (p<0.001) and the median (IQR) penile curvature from 30.4° (22.2°-35.4°) to 25.0° (20.2°-30.4°) (p<0.001). We also observed a decrease in pain assessed by visual analogue scale (7 vs. 3; p<0.001), an improvement in each of the IIEF sub-domains (p<0.001) and an improvement in all three PD questionnaire domains (p<0.001). CONCLUSIONS Based on our findings, ESWT could be considered a safe and efficient minimally invasive option for the management of the patients suffering from PD.

Type 2 Diabetes and Testosterone Therapy

Abstract: A third of men with type 2 diabetes (T2DM) have hypogonadotrophic hypogonadism (HH) and associated increased risk of cardiovascular and all-cause mortality. Men with HH are at increased risk of developing incident T2DM. We conducted MEDLINE, EMBASE, and COCHRANE reviews on T2DM, HH, testosterone deficiency, cardiovascular and all-cause mortality from May 2005 to October 2017, yielding 1,714 articles, 52 clinical trials and 32 randomized controlled trials (RCT). Studies with testosterone therapy suggest significant benefits in sexual function, quality of life, glycaemic control, anaemia, bone density, fat, and lean muscle mass. Meta-analyses of RCT, rather than providing clarification, have further confused the issue by including under-powered studies of inadequate duration, multiple regimes, some discontinued, and inbuilt bias in terms of studies included or excluded from analysis.

An Update on Minimally Invasive Surgery for Benign Prostatic Hyperplasia: Techniques, Risks, and Efficacy.

Abstract: Benign prostatic hyperplasia (BPH), a common cause of lower urinary tract symptoms in the elderly male population, has conventionally treated by transurethral resection of the prostate (TURP). During recent years, newer minimally invasive therapies (MITs) have entered the playing field and challenged TURP with their convenience, lack of sexual side effects, and overall safety. The present paper provides an update on the more heavily studied and most recent MITs, analyzing their mechanism of action, tolerability, and efficacy in clinical practice. Particularly, robust clinical data have propelled UroLift and Rezuum to the forefront in the armamentarium of minimally invasive BPH treatment. Newer mechanical therapies such as the temporary implantable nitinol device, ClearRing, ZenFlow Spring, and Butterfly are appealing options as they forego cutting, ablation, heating, or removing prostatic tissue. It is obvious that there is wide variation in the degree of clinical readiness of each modality and only time and long-term, multicenter studies will decide which of these therapies are accepted by the patient and urologist.

Finasteride and Erectile Dysfunction in Patients with Benign Prostatic Hyperplasia or Male Androgenetic Alopecia

Abstract: Finasteride is primarily used to treat benign prostatic hyperplasia (BPH) and male androgenetic alopecia (MAA). Five-alpha reductase inhibitors (5α-RIs) could induce male sexual dysfunction due to their effects on testosterone and dihydrotestosterone. There is evidence suggesting that 5α-RIs may independently increase the risk of erectile dysfunction (ED). However, many investigators believe that side effects of 5α-RIs will disappear with continuous treatment. Considerable controversy exists regarding the severity and persistence of side effects of finasteride on ED. The aim of this review was to summarize current research studies on finasteride associated with ED. The search strategy used each term of finasteride and ED against PubMed database to identify related studies. ED data reported from available trials for finasteride were summarized and reviewed. Although there is not enough evidence to prove the relationship between finasteride and ED, most studies in this review found that finasteride for BPH was correlated with ED. However, most studies included in this review revealed that finasteride for MAA was not correlated with ED. On the other hand, some studies reported side effects of finasteride associated with sexual dysfunction, including ED, male infertility, ejaculation problem, and loss of libido, even in MAA patients. Well-designed randomized controlled trials are needed to further determine the mechanism and effects of finasteride on ED. However, physicians should discuss with their patients possible long-term effects of finasteride on sexual function, although we do not have evidence showing that adverse events of sexual dysfunction are absolutely associated with 5α-RIs.

Changes in the Prevalence and Risk Factors of Erectile Dysfunction during a Decade: The Korean Internet Sexuality Survey (KISS), a 10-Year-Interval Web-Based Survey

Abstract: PURPOSE Although the prevalence of erectile dysfunction (ED) can be affected by social changes, this association has not been well evaluated. We aimed to evaluate the prevalence and risk factors of ED through a 10-year-interval web-based survey using the previous database of same group of panels, with same methodology. MATERIALS AND METHODS We sent e-mails and surveyed the panels registered in the Internet survey agency. RESULTS In total, 900 participants were recruited in 2016. The age-adjusted overall prevalences of self-reported ED (self-ED) and International Index of Erectile Function-5-assessed ED (IIEF-5-ED; score ≤21) in the 2016 study were 3.2% and 44.8%, respectively, which were lower than the prevalences of 8.1% (p=0.036) and 51.4% (p=0.323), respectively, in the 2006 study. The risk factors of IIEF-5-ED in their 20s and 30s in 2016 were psycho-social factors such as depression, low frequency of conversation about sex with sexual partner. The risk factors of IIEF-5-ED in their 40s to 60s in 2016 were organic factors, such as hypertension, diabetes mellitus, smoking, alcohol use, and self-reported premature ejaculation. CONCLUSIONS Although the age-adjusted overall prevalence of self-ED has decreased during a decade, there was no difference in the age-adjusted overall prevalence of IIEF-5-ED. Psycho-social support may be important for young men with ED and overall healthcare can be helpful for elderly men with ED.

Metabolic Syndrome Is an Independent Risk Factor for Acquired Premature Ejaculation.

Abstract: PURPOSE To determine the role of metabolic syndrome (MetS) as a risk factor for acquired premature ejaculation (PE) after considering the various risk factors, such as lower urinary tract symptoms, erectile dysfunction, hypogonadism, and prostatitis. MATERIALS AND METHODS From January 2012 to January 2017, records of 1,029 men were analyzed. We performed multivariate analysis to identify risk factors for PE, including the covariate of age, marital status, International Prostate Symptom Score, International Index of Erectile Function (IIEF) score, National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) score, serum testosterone levels, and all components of MetS. Acquired PE was defined as self-reported intravaginal ejaculation latency time ≤3 minutes, and MetS was diagnosed using the modified National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS Of 1,029 men, 74 subjects (7.2%) had acquired PE and 111 (10.8%) had MetS. Multivariate analysis showed that the IIEF overall satisfaction score (odds ratio [OR]=0.67, p<0.001), NIH-CPSI pain score (OR=1.07, p=0.035), NIH-CPSI voiding score (OR=1.17, p=0.032), and presence of MetS (OR=2.20, p=0.022) were significantly correlated with the prevalence of acquired PE. In addition, the Male Sexual Health Questionnaire for Ejaculatory Dysfunction scores and ejaculation anxiety scores progressively decreased as the number of components of MetS increased. CONCLUSIONS MetS may be an independent predisposing factor for the development of acquired PE. Effective prevention and treatment of MetS could also be important for the prevention and treatment of acquired PE.

Long-Term Results after Surgical Treatment of Congenital Penile Curvature Using a Modified Nesbit Technique.

Abstract: Purpose Congenital penile curvature (CPC) is a rare condition with surgical correction being the standard therapy. In the current study, we report long-term results analyzing the surgical and functional outcomes using a modified Nesbit technique. Materials and methods Patients with CPC were included. After penile degloving and mobilization of the neurovascular bundle an artificial erection was performed. An ellipsoid part of the tunica albuginea was excised at the point of maximum curvature on the convex side of deviation. The tunical defect was then closed by interrupted absorbable sutures with inverted knots. Results of correction were documented intra- and postoperatively by artificial erection. Pre- and postoperative evaluation included measurement of penile length and curvature after pharmacological erection. Erectile function, alteration in glans sensation, palpable suture as well as short- and long-term complication were also recorded using validated questionnaires and objective examinations. Results Fifty-five patients with mean age 26.93 years (14-66 years) and mean curvature 69.81° (25°-90°) were included in the study. Ventral or ventrolateral curvature was observed in 83.6%. Mean operative time was 106.8 minutes (55-169 minutes). Totally straightness of the penis was achieved in 51/55 patients (92.8%). After a mean long-term follow-up of 36.68 months (4-87 months), erectile function worsened in 3.6% of patients. Median penile length loss associated with this technique was 1.7 cm (0-3.0 cm). Conclusions Surgical therapy of CPC using our modified Nesbit technique is feasible, safe and provides reliable long-term outcomes, representing an alternative for surgical correction of CPC.

Sperm and Seminal Plasma Proteomics: Molecular Changes Associated with Varicocele-Mediated Male Infertility.

Abstract: Male infertility is a rising problem and the etiology at the molecular level is unclear. Use of omics has provided an insight into the underlying cellular changes in the spermatozoa of infertile men. Proteomics is one the promising omics techniques for biomarker screening that can provide complete information on molecular processes associated with male infertility. Varicocele is a pressing issue in the field of male infertility and the search for an appropriate diagnostic and therapeutic biomarker is still ongoing. In this review, we discuss the reports on proteomic profiles of sperm and seminal plasma in male infertility and provide an in-depth insight into varicocele studies associated with male infertility.

The Impact of Clostridium Histolyticum Collagenase on the Prevalence and Management of Peyronie's Disease in the United States

Abstract: PURPOSE We evaluated the impact of collagenase clostridium histolyticum (CCH) on rates of diagnosis, treatment, and corporal rupture in Peyronie's disease (PD). We examined the impact of CCH on cost of PD treatment. MATERIALS AND METHODS We extracted data on PD diagnosis (ICD-9 607.95 and ICD-10 N48.6), corporal rupture (ICD-9 959.13 and ICD-10 S39.840A), CCH use (J0775), penile injections (CPT 54200), and corporal rupture repair from 2008 to 2016 in men over 40 years old using the Clinformatics® Data Mart Database (3.7 to 4.9 million males). We analyzed for prevalence of PD, rates of PD treatments, cost associated with treatment, and rates of corporal rupture and repair by year. RESULTS The prevalence of PD was 0.29% in 2013 and did not increase after CCH entered the market in 2014. An average of 2.52% of men with PD received treatment before CCH, compared with 3.75% after (p<0.0001). Penile injection rates increased (1.34% vs. 2.61%, p<0.0001), while rates of surgical treatments decreased between these periods. There was no change in rate of corporal rupture in men with PD before (0.024%) and after (0.024%) CCH. Overall, only 20.0% of corporal ruptures were repaired. After CCH entered practice, a significant increase in cost occurred (p=0.013). CONCLUSIONS The prevalence of men with PD did not change after CCH. However, more men with PD received treatment due to an increase in penile injections. The cost of treating PD increased after CCH became available. The overall prevalence of corporal rupture did not change after CCH entered the market.

Elevated Body Mass Index Is Associated with Secondary Hypogonadism among Men Presenting to a Tertiary Academic Medical Center

Abstract: PURPOSE To characterize the population of hypogonadal men who presented to a tertiary academic urology clinic and evaluate risk factors for primary vs. secondary hypogonadism. MATERIALS AND METHODS We evaluated all men with International Classification of Diseases-9 diagnosis codes R68.82 and 799.81 for low libido, 257.2 for testicular hypofunction, and E29.1 for other testicular hypofunction at a tertiary academic medical center from 2013 to 2017. We included men who had testosterone (T) and luteinizing hormone (LH) drawn on the same day. We classified men based on T and LH levels into eugonadal, primary, secondary, and compensated hypogonadism. Risk factors including age, body mass index (BMI) over 30 kg/m², current smoking status, alcohol use greater than 5 days per week, and Charlson comorbidity index greater than or equal to 1 were investigated and measured in each group using the eugonadal group for reference. RESULTS Among the 231 men who had both T and LH levels, 7.4%, 42.4%, and 7.4% were classified as primary, secondary, and compensated hypogonadism, respectively. Only elevated BMI was associated with secondary hypogonadism compared to eugonadal men (median BMI, 30.93 kg/m² vs. 27.69 kg/m², p=0.003). BMI, age, comorbidities, smoking, or alcohol use did not appear to predict diagnosis of secondary hypogonadism. CONCLUSIONS Secondary hypogonadism appears to be the most common cause of hypogonadism among men complaining of low T and decreased libido at a tertiary academic medical center. Secondary hypogonadism is associated with elevated BMI and therefore obesity should be used as a marker to evaluate men for both T and LH levels.

Microsurgical Denervation of Spermatic Cord for Chronic Idiopathic Orchialgia: Long-Term Results from an Institutional Experience

Abstract: PURPOSE Chronic testicular pain remains an important challenge for urologists At present there are many treatment modalities available for chronic orchialgia Some patients remain in pain despite a conservative treatment Microsurgical denervation of spermatic cord appears to be successful in relieving pain in patients who fail conservative management We assessed the long-term efficacy, complications and patient perceptions of microsurgical denervation of the spermatic cord in the treatment of chronic orchialgia MATERIALS AND METHODS A prospective study was conducted from January 2007 to January 2016 which included men with testicular pain of >3 months duration, failure of conservative management, persistent of pain for >3 months after treating the underlying cause Total 48 patients with 62 testicular units (14 bilateral) showed the response to spermatic cord block and underwent Microsurgical Denervation of Spermatic Cord RESULTS Out of 62 testicular units (14 bilateral) which were operated, complete 2 years follow-up data were available for 38 testicular units Out of these 38 units, 31 units (8157%) had complete pain relief, 4 units (1052%) had partial pain, and 3 units (789%) were non-responders Complications were superficial wound infection in 3 units (483%), hydrocele in 2 units (322%), subcutaneous seroma in 2 units (322%), and an incisional hematoma in 1unit (161%) out of 62 operated testicular units CONCLUSIONS Idiopathic chronic orchialgia remains a difficult condition to manage If surgery is considered, microsurgical denervation of spermatic cord should be considered as a first surgical approach to get rid of pain and sparing the testicle

Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment.

Abstract: Purpose The current study is aimed to assess whether a longer duration of 5α-reductase inhibitor (5α-RI) exposure was associated with higher rate of permanent erectile dysfunction (ED) in a rat model. Materials and methods Male Sprague-Dawley rats (n=76) were assigned to five groups: (i) normal control group; (ii) dutasteride (0.5 mg/rat/d) for 4-weeks group; (iii) dutasteride for 4-weeks plus 2-weeks of resting group; (iv) dutasteride for 8-weeks group; and (v) dutasteride for 8-weeks plus 2-weeks of resting group. In vivo erectile responses to electrical stimulation, and changes of fibrotic factors and smooth muscle/collagen contents in the corpus cavernosum were evaluated in each group. Results Dutasteride administration for 4 and 8 weeks significantly decreased erectile parameters compared with the control group. Reduced erectile responses were recovered during 2 weeks of drug-free time in the 4-week treatment group, but were not in the 8-week group. Protein levels of fibrosis-related factors transforming growth factor (TGF)-β1, TGF-β2, and p-Smad/Smad (Smad 2/3) in the corpus cavernosum showed no significant change after 4 weeks of dutasteride oral administration, but were enhanced after 8 weeks. Dutasteride markedly decreased smooth muscle content and increased collagen after 4 and 8 weeks of use, but no nuclear size changes; however, neither group showed significant improvement in the smooth muscle to collagen ratio after the rest period. Conclusions Our study showed that recovery from ED depended on the duration of medication, and administration of dutasteride for more than 8-weeks in rats could result in irreversible ED even after discontinuation of medication.

The Relationships between Thyroid Hormone Levels and Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia.

Abstract: Purpose We examined the association between thyroid hormone and lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). Materials and methods A total of 5,708 middle aged men were included. LUTS/BPH were assessed using the international prostate symptom score (IPSS), total prostate volume (TPV), maximal flow rate (Qmax), and a full metabolic workup. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were measured using chemiluminescence immunoassay. We divided participants into quartiles based on their TSH and FT4 levels: first to fourth quartile (Q1-Q4). Results There was a significant increase in the percentage of men with IPSS>7, Qmax 7 were significantly different between FT4 quartile groups (ORs; [5-95 percentile interval], p; TPV≥30 mL, Q1: 0.000 [references]; Q2: 1.140 [0.911-1.361], p=0.291; Q3: 1.260 [1.030-1.541], p=0.025; Q4: 1.367 [1.122-1.665], p=0.002; IPSS>7: Q1: 0.000 [references]; Q2: 0.969 [0.836-1.123], p=0.677; Q3: 1.123 [0.965-1.308], p=0.133; Q4: 1.221 [1.049-1.420], p=0.010). In men with above median levels of testosterone, the FT4 correlated positively with TPV, even after adjusting for confounders. However, the FT4 was not correlated with TPV in men with below median levels of testosterone. TSH was not related to LUTS/BPH measurements. Conclusions TPV, IPSS, and Qmax were significantly related to FT4. TPV and IPSS were significantly and independently related to FT4. Additionally, the relationship between FT4 and TPV was distinct when testosterone levels are high.

Vactosertib, a Novel, Orally Bioavailable Activin Receptor-Like Kinase 5 Inhibitor, Promotes Regression of Fibrotic Plaques in a Rat Model of Peyronie’s Disease

Abstract: Purpose To examine the therapeutic effect of Vactosertib, a small molecule inhibitor of transforming growth factor-β (TGF-β) type I receptor (activin receptor-like kinase-5, ALK5), in an experimental model of Peyronie's disease (PD) and determining anti-fibrotic mechanisms of Vactosertib in primary fibroblasts derived from human PD plaques. Materials and methods Male rats were randomly divided into three groups (n=6 per group); control rats without treatment; PD rats receiving vehicle; and PD rats receiving Vactosertib (10 mg/kg). PD-like plaques were induced by administering 100 μL of each of human fibrin and thrombin solutions into the tunica albuginea on days 0 and 5. Vactosertib was given orally five times a week for 2 weeks. On day 30, we performed electrical stimulation of the cavernous nerve to measure erectile function, and the penis was obtained for histological examination. Fibroblasts isolated from human PD plaques were used to determine the anti-fibrotic effects of Vactosertib in vitro. Results Vactosertib induced significant regression of fibrotic plaques in PD rats in vivo through reduced infiltration of inflammatory cells and reduced expression of phospho-Smad2, which recovered erectile function. Vactosertib also abrogated TGF-β1-induced enhancement of extracellular matrix protein production and hydroxyproline content in PD fibroblasts in vitro by hindering the TGF-β1-induced Smad2/3 phosphorylation and nuclear translocation, and fibroblast-to-myofibroblast transdifferentiation. Conclusions In view of the critical role of TGF-β and the Smad pathway in the pathogenesis of PD, inhibition of this pathway with an ALK5 inhibitor may represent a novel, targeted therapy for PD.

C-Type Natriuretic Peptide/Natriuretic Peptide Receptor 2 Is Involved in Cell Proliferation and Testosterone Production in Mouse Leydig Cells

Abstract: Purpose This study investigated the role of natriuretic peptide receptor 2 (NPR2) on cell proliferation and testosterone secretion in mouse Leydig cells. Materials and methods Mouse testis of different postnatal stages was isolated to detect the expression C-type natriuretic peptide (CNP) and its receptor NPR2 by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Leydig cells isolated from mouse testis were cultured and treated with shNPR2 lentiviruses or CNP. And then the cyclic guanosine monophosphate production, testosterone secretion, cell proliferation, cell cycle and cell apoptosis in mouse Leydig cells were analyzed by ELISA, RT-qPCR, Cell Counting Kit-8, and flow cytometry. Moreover, the expression of NPR2, cell cycle, apoptosis proliferation and cell cycle related gene were detected by RT-qPCR and Western blot. Results Knockdown of NPR2 by RNAi resulted in S phase cell cycle arrest, cell apoptosis, and decreased testosterone secretion in mouse Leydig cells. Conclusions Our study provides more evidences to better understand the function of CNP/NPR2 pathway in male reproduction, which may help us to treat male infertility.