A primer on the restorative therapies for erectile dysfunction: a narrative review.

INTRODUCTION: Erectile dysfunction (ED) is a common condition that affects millions worldwide. Patients and urologists alike are seeking alternative therapies that can provide long-lasting results in the treatment of ED. This review provides a comprehensive overview of restorative treatments available for ED, such as platelet-rich plasma, stem cell therapy, and shockwave therapy. OBJECTIVE: The aim of this narrative review is to provide a primer for urologists and general practitioners on the basics of implementing ED restorative therapies in their practice. METHODS: The PubMed, MEDLINE, and Google Scholar databases were searched for articles in the English language through August 31, 2023, that included key terms such as "erectile dysfunction," "restorative therapy," "shockwave therapy," "platelet-rich plasma," "stem cell therapy," and "stromal vascular fraction." Reference lists of selected studies were manually reviewed to find articles not identified by the initial database search. RESULTS: Shockwave therapy has demonstrated effectiveness in treating ED, with devices like the Medispec ED1000 and Storz Duolith showing statistically significant improvements in patient scores for International Index of Erectile Function (IIEF)-Erectile Function scores in clinical trials. In reported studies of platelet-rich plasma injections, a substantial percentage of patients reached a minimal clinically important difference in the IIEF-Erectile Function scale after treatment. Studies of ED treatment with stem cell therapy, while limited and with small sample sizes, have demonstrated encouraging improvements in patient scores for the abridged 5-item version of the IIEF after treatment. CONCLUSION: Shockwave, platelet-rich plasma, and stem cell therapies are important, novel, noninvasive restorative treatments for ED that can provide relief for patients wishing to avoid a more invasive approach. While these therapies have shown promising results in clinical trials, more research is required to establish them as standardized and efficacious options in the management of ED.

Return to Play After Hook of Hamate Fracture: A Systematic Review and Meta-Analysis.

In athletes, a hook of hamate fracture is concerning in terms of time to return to sport and effect on performance upon return. This study aims to analyze the treatment of hook of hamate fractures in athletes to determine their rates of return to play, timelines of recovery, and performance level upon return to play. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to perform this analysis. The PubMed database was queried to perform the literature search. Data were pooled and analyzed. P values <.05 were considered significant. Data were analyzed using the Comprehensive Meta-Analysis software to determine heterogeneity. Twenty studies with 823 patients sustaining hook of hamate fractures that reported any competitive level of play were included in the analysis. Of the 823 patients, 778 (94.5%) were able to return to play with 91.2% (506/555) of patients demonstrating similar or improved performance. The mean time to return to play was 45 days (range: 21-168 days). Treatment included surgical excision for 787 patients (95.6%), open reduction and internal fixation for 18 patients (2.2%), stress reduction/casting for 13 patients (1.6%), and loss to follow-up or surgery refusal for 5 patients (0.6%). A very high number of athletes return to play following a hook of hamate fracture at the same or improved level of performance. In our study, the majority of injuries were treated with surgical excision of the fractured hook of hamate fragment. Most athletes returned to their sport at an average of 45 days.

Fertility outcomes in men with prior history of anabolic steroid use.

OBJECTIVE: To study sperm parameters recovery and fertility outcomes in men with azoospermia or severe oligospermia caused by anabolic steroid use who underwent a standardized treatment regimen for spermatogenesis recovery. DESIGN AND SUBJECTS: A retrospective analysis of a cohort of men with a prior history of anabolic steroid use and infertility complaints (between 2018 and 2022) was conducted. EXPOSURE: The standardized treatment approach involved discontinuing testosterone replacement therapy and administering a combination regimen of clomiphene citrate and human chorionic gonadotropin for a minimum of 3 to 6 months. MAIN OUTCOME MEASURES: The main outcome measures included changes in sperm parameters, predominantly sperm concentration, and subsequent pregnancy outcomes. RESULTS: A total of 45 men (median age 37 years, IQR 32-45) met the inclusion criteria for this analysis. Median duration of prior T use was 4 years (IQR 1.3-10), with the 2 most common modalities consisting of injection therapy (43.5%) and oral therapy (34.8%). The median initial sperm concentration was 0 million/cc (IQR 0-1.15), and 23 (51.1%) men initially presented with azoospermia. The median duration of combination human chorionic gonadotropin/clomid therapy was 5 months (IQR 3-12). In initially azoospermic men (N: 23), 5 were lost to follow-up, 6 (33.3%) progressed to severe oligospermia (<5 million/cc), 6 (33.3%) to oligospermia (<15 million/cc), 1 (5.6%) to normozoospermia (>15 million/cc), and 5 (27.8%) remained azoospermic after medical treatment for 6 months. Among the 24 couples who responded to the follow-up call, a total of 9 (37.5%) achieved a successful subsequent pregnancy. Of these, 33.3% (3 couples) used assisted reproductive technology, whereas 66.7% (6 couples) conceived naturally. On logistic regression analysis, no significant predictors for improved sperm parameters or successful pregnancy were identified. CONCLUSION: Despite appropriate treatment regimens, a significant proportion of men with a prior history of anabolic steroid use continue to exhibit severe oligospermia, with more than half showing limited improvement in semen parameters after 6 months of treatment. Only a fraction of men achieves normozoospermia after treatment. Further research is needed to explore predictors for improved sperm parameters and successful pregnancy outcomes in men with a history of anabolic steroid use.

Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study.

Introduction Infertility and hypogonadism in males can greatly affect their reproductive health and overall well-being. Since exogenous testosterone administration for hypogonadism management may disrupt the normal hormonal cascade necessary for spermatogenesis, clomiphene citrate (CC) and enclomiphene citrate (EC) are medications often used to manage hypogonadism and male infertility. This study aims to directly compare the effects of CC and EC on serum testosterone levels and semen parameters in men to determine which medication may have an advantage in managing these conditions. Materials and methods We retrospectively analyzed ≥18-year-old men presenting with primary infertility, abnormal semen parameters, or hypogonadism who received CC or EC monotherapy for at least three months between January 2021 and December 2022. We compared baseline and follow-up hormone levels, semen parameters, and demographics. Variables were compared using paired and unpaired t-tests. Significance was assessed at p<0.05. Results A total of 46 men received EC and 32 men received CC. The median age was 42 (IQR: 34-47.75) years in men who received EC and 41 (IQR: 36-44) years in men who received CC (p=0.450). The two treatment groups exhibited a significant increase in serum total testosterone, while only EC had a statistically significant increase in FSH and LH. Semen volume and concentration did not significantly change with either treatment. Sperm motility increased in both groups, but total motile sperm count (TMSC) only significantly increased in men who received EC.  Conclusions Our study found that EC and CC are effective treatments in increasing total testosterone without negatively affecting spermatogenesis. EC demonstrated to be more effective in raising gonadotropin levels and TMSC.

The influence of SARS-CoV-2 vaccination on post-operative outcomes in microsurgery patients.

BACKGROUND: The healthcare industry's efforts to immunize the global community against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been unprecedented. Given the fast-tracking of the novel vaccine, its short- and long-term medical implications remain largely to-be-determined in most patient populations. This study aims to analyze 90-day post-operative outcomes in microsurgical patients, who have received or not received SARS-CoV-2-vaccination, using a continuously updated federated electronic medical record network (TriNetX Inc, Cambridge, MA). METHODS: After screening 70 million de-identified records, 16,799 microsurgery patients aged 18-99 meeting medical coding criteria were allocated into two cohorts. Cohort One received SARS-CoV-2-vaccination prior to undergoing microsurgery whereas Cohort Two did not. Two equally sized cohorts, totaling 818 patients were created after propensity score matching for characteristics including: age, race, ethnicity, smoking, hypertension, heart disease, diabetes, obesity, chronic obstructive pulmonary disease, and history of SARS-CoV-2 exposure. Postoperative outcomes within 30-, 60-, and 90-days of microsurgery were analyzed. RESULTS: Patients who were SARS-CoV-2-immunized experienced significantly lower (p < .01) surgical site infections (Absolute Risk Reduction (ARR)[95%CI]) = (3.79%-5.36% [0.84-8.54]) ICU admission (9.47%-9.82%[5.45-13.88]), generalized infections (7.68%-9.92%[3.15-14.64]), and hospitalizations (28.48%-32.57%[20.99-40.13]) within 30-, 60-, and 90-days of microsurgery. Additionally, SARS-CoV-2-vaccinated patients also experienced significantly less flap failure (2.49%[0.97-4.02]) and death (2.46%[0.96-3.97]) within 30- and 60-days post-operatively. CONCLUSION: Our analysis examines the potential protective effect of SARS-CoV-2-vaccination in microsurgical patients. Limitations include the retrospective nature of this analysis and the inherent reliance on medical coding. Future prospective studies are warranted to better understand if in fact pre-operative SARS-CoV-2-vaccination has the potential to protect against post-operative microsurgery outcomes.

Positive effects of thyroid replacement therapy on assisted reproductive technology outcomes in women with subclinical hypothyroidism with positive thyroid peroxidase autoantibodies.

Objective: To study the beneficial effects of thyroid replacement therapy (TRT) on pregnancy outcomes in patients with subclinical hypothyroidism (SCl hypoT) with respect to thyroid peroxidase (TPO) autoantibodies. Design: Retrospective study of 706 patients. Setting: Not applicable. Patients: The study evaluated 706 patients, who were divided into 3 cohorts: euthyroid patients, with pre-in vitro fertilization thyroid-stimulating hormone levels of <2.5 µIU/mL; patients with SCl hypoT, defined as thyroid-stimulating hormone levels of >2.5 µIU/mL and <4 µIU/mL, who were not treated; and patients with SCl hypoT who received TRT. The 3 cohorts were further subclassified into 2 groups, each based on TPO antibody levels. Interventions: The cohorts were compared for the effects of TRT on pregnancy outcomes. Main Outcome Measures: Identification of effects of TRT on assisted reproductive technology outcomes. Results: Patients with SCl hypoT had significantly fewer positive pregnancy outcomes than euthyroid patients. Importantly, low-dose TRT was found to be beneficial in improving IVF success and pregnancy outcomes in patients with SCl hypoT. The original cohort of patients, further classified into 2 subgroups on the basis of antithyroid (TPO) antibodies, showed that low-dose TRT was associated with improved pregnancy outcomes in women with SCl hypoT and TPO-positive antibodies. Conclusions: Our findings demonstrate that low-dose TRT may be beneficial in improving in vitro fertilization success and pregnancy outcomes in women with SCl hypoT and TPO-positive antibodies.

Evaluation of Bacteria in a Novel In Vitro Biofilm Model of Penile Prosthesis.

BACKGROUND: Delayed infection, thought to be due to gradual biofilm formation, remains a feared complication after inflatable penile prosthesis (IPP) insertion. Understanding and preventing biofilm formation is necessary to prevent infections. AIM: To develop an in vitro model and compare growth of biofilm by different bacteria on IPPs and evaluate the anti-infective efficacy of the Coloplast Titan and AMS 700 InhibiZone. METHODS: Sterile IPPs (Coloplast) were cut into rings and incubated with S. epidermidis, S. aureus, P. aeruginosa, A. baumannii, or K. pneumoniae cultures in tryptic soy broth (TSB) (4 hour) to ensure adequate bacteria attachment, and then in only TSB (120 hours) to allow for biofilm formation. Rings were fixed with ethanol and biofilm measured by spectrophotometer (OD570) after crystal violet staining. This methodology was repeated for S. epidermidis and P. aeruginosa with Coloplast rings dipped in 10 ml of a 10 mg/ml Rifampin, 1 mg/ml Gentamicin, and deionized water solution and undipped AMS InhibiZone rings. Crystal violet assay (OD570) was repeated after incubation within bacteria (2 hour), and then only TSB (120 hours). OUTCOMES: The primary outcome of the study was OD570 readings, indirectly measuring biofilm mass on implant rings. RESULTS: S. epidermidis, S. aureus, A. baumannii, P. aeruginosa, and K. pneumoniae all formed significant biofilm. P. aeruginosa showed the strongest predilection to grow biofilm on IPPs. P. aeruginosa also formed significant biofilm on antibiotic-treated Coloplast and AMS rings, while S. epidermidis was inhibited. No significant difference was found in biofilm inhibition between the implants. CLINICAL TRANSLATION: Our findings suggest gram-negative bacteria may form biofilm more proficiently and quickly on IPPs than gram-positive organisms. Commonly used antibiotic treatments on IPPs may be effective against S. epidermidis but not against P. aeruginosa biofilm formation. STRENGTHS & LIMITATIONS: This is the first study comparing biofilm formation by different bacteria organisms on IPPs and the inhibitive ability of Coloplast and AMS implants against biofilm formation. Clinical data on organisms responsible for infected IPPs is needed to determine the clinical relevance of our findings. CONCLUSION: Our novel in vitro model of biofilm formation of IPPs evaluated the effect of a gentamicin/rifampin antibiotic dip on Coloplast Titan implants and the anti-infective capacity of the minocycline/rifampin precoated AMS 700 InhibiZone against S. epidermidis and P. aeruginosa. P. aeruginosa was able to grow on both antibiotic-treated implants, with no significant difference, and should continue to be a specific target of investigation to reduce delayed post-operative IPP infections. Narasimman M, Ory J, Bartra SS, et al. Evaluation of Bacteria in a Novel In Vitro Biofilm Model of Penile Prosthesis. J Sex Med 2022;19:1024-1031.

Current Treatment Modalities Targeting Tumor Microenvironment in Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) is responsible for significant cancer-related morbidity and mortality following local treatment failure in men. The initial stages of PCa are typically managed with a combination of surgical resection and/or androgen deprivation therapy (ADT). Unfortunately, a significant proportion of PCa continues to progress despite being at castrate levels of testosterone (<50 ng/dl), at which point it is coined castration-resistant prostate cancer (CRPC). In recent years, many novel therapeutics and drug combinations have been created for CRPC patients. These include immune checkpoint inhibitors, chemokine receptor antagonists, steroidogenic enzyme inhibition, and novel tyrosine kinase inhibitors as well as combinations of drugs. The selection of the most appropriate therapy depends on several factors like stage of the disease, age of the patient, metastasis, functional status, and response towards previous therapies. Here, we review the current state of the literature regarding treatment modalities, focusing on the treatment recommendations per the American Urological Association (AUA), recent clinical trials, and their limitations. An accurate and reliable overview of the strengths and limitations of PCa therapeutics could also allow personalized therapeutic interventions against PCa.

Clinical Update on Home Testing for Male Fertility.

Male factor infertility accounts for about 50% of the incidence of infertility in couples. In current practice, the men must attend a clinic or hospital facility to provide a semen analysis, which is key to the diagnosis of the male reproductive potential. However, many men are often embarrassed with the process and conventional semen analysis requires complex, labor intensive inspection with a microscope. To mitigate these problems, one of the solutions can be at-home semen analysis. In this review we examine the literature of currently available at home semen analysis test kits, describe their limitations, and compare them to the conventional lab-based methods.

How defective spermatogenesis affects sperm DNA integrity.

Spermatogenesis is the essential process to maintain and promote male fertility. It is extraordinarily complex with many regulatory elements and numerous steps. The process involves several cell types, regulatory molecules, repair mechanisms and epigenetic regulators. Evidence has shown that fertility can be negatively impacted by reduced sperm DNA integrity. Sources of sperm DNA damage include replication errors and causes of DNA fragmentation which include abortive apoptosis, defective maturation and oxidative stress. This review outlines the process of spermatogenesis, spermatogonial regulation and sperm differentiation; additionally, DNA damage and currently studied DNA repair mechanisms in spermatozoon are also covered.

A systematic review and evidence-based analysis of ingredients in popular male testosterone and erectile dysfunction supplements.

The objective was to study available evidence for ingredients of popular over-the-counter testosterone and erectile dysfunction (ED) supplements. The top 16 male testosterone and 16 ED supplements in the USA were identified from the most popular online retailers: A1 Supplements, Amazon, Vitamin Shoppe, and Walmart. In total, 37 ingredients were identified and PUBMED online database was reviewed for randomized-controlled trials (RCT) studying their efficacy. Ingredients were categorized based on evidence quantity using an adapted version of the American Heart Association scoring system. In total, 16 ingredients from testosterone supplements and 21 from ED supplements were identified. Tribulus, Eurycoma longifolia, Zinc, L-arginine, Aspartate, Horny goat weed, and Yohimbine were most common. In all, 105 RCTs studying the identified ingredients were found. No whole supplement products have published RCT evidence. 19% of ingredients received an A grade for strong positive evidence with net positive evidence in two or more RCTs. In total, 68% received C or D grades for contradicting, negative, or lacking evidence. Overall, 69% of ingredients in testosterone supplements and 52% of ingredients in ED supplements have published RCT evidence. Many male supplements claim to improve testosterone or ED parameters; however, there is limited evidence, which should be considered when counseling patients.

Laboratory and clinical management of leukocytospermia and hematospermia: a review.

Leukocytospermia and hematospermia are defined as the presence of abnormally high white blood cell and red blood cell concentration in the semen, respectively. Numerous etiologies and various implications on fertility have been identified. In a small proportion of men, the presence of white blood cells or red blood cells can adversely affect sperm quality by the production of reactive oxygen species. Several methods have been used to assess the presence of white blood cells and red blood cells in samples, such as identification of round cells, immunohistochemical staining using monoclonal antibodies, the Endtz test, the peroxidase test, and flow cytometry or microscopy. In addition, techniques have been identified to separate sperm samples from white blood cells and red blood cells for cryopreservation to improve outcomes in assisted reproductive technology. In this review, laboratory and clinical management of leukocytospermia and hematospermia are discussed. Currently available diagnostic methods and treatment options are outlined, and available optimal cryopreservation techniques for samples with white blood cells or red blood cells are summarized.