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Background: Varicoceles affect up to 30% of postpubertal adolescent males. Studying this population remains difficult due to this topic's sensitive nature. Using the popularity of social media in this cohort and natural language processing (NLP) techniques, our aim was to identify perceptions of adolescent males on an internet varicocele forum to inform how physicians may better evaluate and counsel this pediatric population., Objective: We aimed to characterize themes of discussion and specific concerns expressed by adolescents using a mixed methods approach involving quantitative NLP and qualitative annotation of an online varicocele community., Methods: We extracted posts from the Reddit community "r/varicocele" (5100 members) with criteria of discussant age ≤21 years and word count >20. We used qualitative thematic analysis and the validated constant comparative method, as well as an NLP technique called the meaning extraction method with principal component analysis (MEM/PCA), to identify discussion themes. Two investigators independently interrogated 150 randomly selected posts to further characterize content based on NLP-identified themes and calculated the Kaiser-Meyer-Olkin (KMO) statistic and the Bartlett test. Both quantitative and qualitative approaches were then compared to identify key themes of discussion., Results: A total of 1103 posts met eligibility criteria from July 2015 to June 2022. Among the 150 randomly selected posts, MEM/PCA and qualitative thematic analysis separately revealed key themes: an overview of varicocele (40/150, 27%), management (29/150, 19%), postprocedural experience (28/150, 19%), seeking community (26/150, 17%) and second opinions after visiting a physician (27/150, 18%). Quantitative analysis also identified "hypogonadism" and "semen analysis" as concerns when discussing their condition. The KMO statistic was >0.60 and the Bartlett test was <0.01, indicating the appropriateness of MEM/PCA. The mean age was 17.5 (SD 2.2; range 14-21) years, and there were trends toward higher-grade (40/45, 89% had a grade of ≥2) and left-sided varicoceles. Urologists were the topic of over 50% (53/82) of discussions among discussants, and varicocelectomy remained the intervention receiving the most interest. A total of 60% (90/150) of discussants described symptomatic varicoceles, with 62 of 90 reporting pain, 24 of 90 reporting hypogonadism symptoms, and 45 of 90 reporting aesthetics as the primary concern., Conclusions: We applied a mixed methods approach to identify uncensored concerns of adolescents with varicoceles. Both qualitative and quantitative approaches identified that adolescents often turned to social media as an adjunct to doctors' visits and to seek peer support. This population prioritized symptom control, with an emphasis on pain, aesthetics, sexual function, and hypogonadism. These data highlight how each adolescent may approach varicoceles uniquely, informing urologists how to better interface with this pediatric population. Additionally, these data may highlight the key drivers of decision-making when electing for procedural management of varicoceles., (©Grace E Sollender, Tommy Jiang, Ilana Finkelshtein, Vadim Osadchiy, Michael H Zheng, Jesse N Mills, Jennifer S Singer, Sriram V Eleswarapu. Originally published in JMIR Formative Research (https://formative.jmir.org), 10.10.2024.)

Purpose: To assess the quality and readability of online health information on vasectomy using validated readability and quality assessment tools., Materials and Methods: The top 50 search results for "vasectomy" on Google, Bing, and Yahoo were selected. Duplicate links, advertisements, blog posts, paid webpages, and information intended for healthcare providers were excluded. Flesch Reading Ease score, Flesch-Kincaid Grade level, Gunning Fog Index, and Simple Measure of Gobbledygook (SMOG) index were used to assess readability, with optimal readability level for online health information established as being at sixth grade reading level. DISCERN Instrument and JAMA Benchmark were used to assess the quality of selected webpages. Inter-assessment score correlation and results by webpage type were analyzed., Results: We analyzed 44 webpages, including 16 academic, 5 hospital-affiliated, 6 commercial, 13 non-profit health advocacy, and 4 uncategorized sources. The average readability of the evaluated webpages was at a 10th grade reading level as measured by the Flesch Kincaid Assessment tool, and an undergraduate reading level per the SMOG and Gunning Fog indices. Non-profit health advocacy webpages had the best reading level but still was not at the recommended level of grade 6 to 7. The overall DISCERN quality of the webpages was "fair", with non-profit health advocacy pages performing best., Conclusions: The assessed webpages offer education on vasectomy in a language that is too complex for the general population to understand. Furthermore, several sources for online health information, such as non-profits, outperformed webpages by academic institutions. Increased healthcare collaboration and dedication to producing quality online patient resources is necessary to address these shortcomings and build trust among patients to increase utilization of vasectomy and decrease decisional regret., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

In men with impaired semen parameters, empiric medical therapies such as clomiphene citrate, a selective estrogen receptor modulator (SERM), and anastrozole, a selective aromatase inhibitor, are often employed. The effects of jointly administering these agents on semen parameters are not well understood. Here, we describe the findings of our multi-center, retrospective cohort study of men with idiopathic primary or secondary infertility. Twenty-one men were treated with combination therapy (anastrozole and clomiphene) and 69 men were treated with monotherapy (anastrozole). Patients with pre-treatment normozoospermia and recent or current exogenous testosterone therapy were excluded. Baseline and post-treatment semen and sex hormone parameters were compared among groups. The median follow-up duration was 91 days [interquartile range (IQR), 64-117 days]. Following treatment, 43% of men in the combination therapy group demonstrated normozoospermia, compared to 25% in the monotherapy group. Furthermore, men in the combined group demonstrated marked improvements in total motile sperm count (TMSC) [11.3 vs. 2.1 million (M), P=0.03]. There were no significant differences in hormone levels among the two groups following treatment. Combination therapy with clomiphene citrate and anastrozole was associated with modest benefits in post-treatment semen parameters, when compared to anastrozole monotherapy. These benefits may contribute to improvements in pregnancy outcomes with less invasive assisted reproductive technologies, such as intrauterine insemination (IUI). Future investigations with larger sample sizes and prospective study designs are necessary., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-454/coif). V.O. received funding from the 2023 Urology Care Foundation Residency Research Award Program and the Russell Scott, Jr., MD, Urology Research. They were in no way involved in any part of the study design, analysis, manuscript writing, etc. J.N.M. is a consultant for Halozyme Pharma, Boston Scientific, and Endo Pharmaceuticals. N.P. is a consultant for Halozyme Pharma. The other authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility., (© 2024. The Author(s).)

The surgical management of prostate cancer through radical prostatectomy has the potential to impact patients' sexual function, including erectile dysfunction and Peyronie's disease (PD). Historical data suggests the incidence of PD in post-prostatectomy patients is higher than in the general population at 15.9%. Our study objective was to measure the rate of the development of PD among patients that receive penile rehabilitation (PR) regimen prior to and immediately after radical prostatectomy. In this study, we retrospectively reviewed the charts of 581 patients who were diagnosed with prostate cancer, treated with radical prostatectomy, and engaged in a PR program. Patients with the diagnosis of PD prior to prostatectomy were excluded from this study. The PR program consists of daily tadalafil, L-citrulline, and weekly vacuum erectile device with the option of intracavernosal injections if patients fail to respond to the regular regimen. We found the incidence of PD to be 2.9%, suggesting that PR regimens programs may be associated with a reduced incidence of PD in post-prostatectomy patients. Ten (out of 17) patients were diagnosed with PD after 2 years of follow up. The return of erections was not statistically different among patients who developed PD and the rest of the patients. Prospective, multi-institutional trials will be required to elucidate whether PR can prevent the development of PD in this patient population., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-281/coif). J.N.M. serves as a consultant to Boston Scientific Corporation, Endo Pharmaceuticals, and Halozyme Therapeutics and receives compensation. The other authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Background: Sperm banking refers to the collection and storage of sperm cells for future use. Despite the recommendations of major medical societies, sperm banking is not discussed sufficiently with patients at risk of future fertility. Majority of Americans utilize the internet regarding health information. The aim of this study is to assess the reading level and the quality of online health information on sperm banking., Methods: The top 50 search results from Google, Bing, and Yahoo were selected after searching for the term "sperm banking". Duplicate pages, advertisements, news and magazines, blog posts, videos, paid subscriptions, articles intended for health professionals, and non-related pages were excluded. Four validated readability and two quality assessment tools were used to score the text. Websites were divided into five categories: academic, hospital-affiliated, commercial, non-profit health advocacy, and non-categorized. Descriptive statistics, one sample t -test, and Pearson's correlation coefficient were used to analyze the data., Results: Forty-one webpages were included. The mean Flesch Reading Ease Score (FRES) for all pages was 46.9/100 and the mean reading level was 11th grade, compared to the recommended 6th grade level, across various assessment tools. Utilizing the DISCERN Instrument, quality of online health information was fair. Seven percent of pages received a "good" quality score and no pages received a score of "excellent". On average, 1.5 out of 4 criteria categorized by the JAMA Benchmark, a validated quality assessment tool, were met. The hospital-affiliated webpages received the best reading scores and commercial pages received the highest quality scores., Conclusions: Online health information on sperm banking available in English is of poor quality based on several quality assessment tools and at a reading level significantly higher than what is recommended. Further efforts are needed by providers and healthcare institutions to improve the quality of information available to patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-120/coif). The authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

The tunica albuginea (TA) of the penis is an elastic layer that serves a structural role in penile erection. Disorders affecting the TA cause pain, deformity, and erectile dysfunction. There is a substantial clinical need for engineered replacements of TA, but data are scarce on the material properties and biochemical composition of healthy TA. The objective of this study was to assess tissue organization, protein content, and mechanical properties of porcine TA to establish structure-function relationships and design criteria for tissue engineering efforts. TA was isolated from six pigs and subjected to histomorphometry, quantification of collagen content and pyridinoline crosslinks, bottom-up proteomics, and tensile mechanical testing. Collagen was 20 ± 2%/wet weight (WW) and 53 ± 4%/dry weight (DW). Pyridinoline content was 426 ±131 ng/mg WW, 1011 ± 190 ng/mg DW, and 45 ± 8 mmol/mol hydroxyproline. Bottom-up proteomics identified 14 proteins with an abundance of >0.1% of total protein. The most abundant collagen subtype was type I, representing 95.5 ± 1.5% of the total protein in the samples. Collagen types III, XII, and VI were quantified at 1.7 ± 1.0%, 0.8 ± 0.2%, and 0.4 ± 0.2%, respectively. Tensile testing revealed anisotropy: Young's modulus was significantly higher longitudinally than circumferentially (60 ± 18 MPa vs. 8 ± 5 MPa, p < 0.01), as was ultimate tensile strength (16 ± 4 MPa vs. 3 ± 3 MPa, p < 0.01). Taken together, the tissue mechanical and compositional data obtained in this study provide important benchmarks for the development of TA biomaterials. STATEMENT OF SIGNIFICANCE: The tunica albuginea of the penis serves an important structural role in physiologic penile erection. This tissue can become damaged by disease or trauma, leading to pain and deformity. Treatment options are limited. Little is known about the precise biochemical composition and biomechanical properties of healthy tunica albuginea. In this study, we characterize the tissue using proteomic analysis and tensile testing to establish design parameters for future tissue engineering efforts. To our knowledge, this is the first study to quantify tissue anisotropy and to use bottom-up proteomics to characterize the composition of penile tunica albuginea., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To identify patient factors associated with a clinically significant improvement in semen parameters among infertile men treated with the aromatase inhibitor anastrozole., Design: Multi-institutional retrospective cohort study., Setting: Two Tertiary Academic Medical Centers., Patients: A total of 90 infertile men treated at 2 tertiary academic medical centers who met inclusion criteria and obtained pretreatment and posttreatment semen analyses., Intervention: Prescription of anastrozole (median 3 mg/wk)., Main Outcome Measures: Upgrade in the World Health Organization sperm concentration category (WHO-SCC). Univariate logistic regression, multivariable logistic regression, and partitioning analyses were performed to identify statistically significant patient factors capable of predicting treatment response., Results: With anastrozole treatment, 46% (n = 41/90) of men responded favorably with a WHO-SCC upgrade, and 12% (n = 11/90) experienced a downgrade. Responders exhibited lower pretreatment levels of luteinizing hormone (LH, 4.7 vs. 8.3 IU/L) and follicle-stimulating hormone (4.7 vs. 6.7 IU/mL), higher pretreatment levels of testosterone (T, 356 vs. 265 ng/dL), and similar baseline level of estradiol (E 2 , 73% vs. 70% with detectible level). Baseline semen parameters differed, with anastrozole responders demonstrating higher baseline semen concentration (3.6 vs. 0.3 M/mL) and higher total motile sperm counts (3.7 vs. 0.1 M). Anastrozole therapy converted 29% (n = 26/90) of the cohort to normozoospermia and enabled intrauterine insemination access in 31% (n = 20/64) of previously ineligible patients. Interestingly, neither body mass index nor the baseline E 2 level or E 2 -T ratio was associated with WHO-SCC upgrade. Multivariable logistic regression revealed the T-LH ratio (odds ratio: 1.02, 95% confidence interval: 1.00-1.03) and baseline nonazoospermia (odds ratio: 9.4, 95% confidence interval: 1.1-78.9) to be statistically significant predictors of WHO-SCC upgrade (area under receiver operating characteristic curve: 0.77). The final user-friendly partitioning model consisting of the T-LH ratio ≥100 and baseline non-azoospermia was 98% sensitive and 33% specific for WHO-SCC upgrades (area under the curve: 0.77)., Conclusion: Anastrozole therapy decreases serum E 2 levels, increases serum gonadotropins, and clinically improves semen parameters in half of men with idiopathic infertility. Nonazoospermic infertile men with T-LH ratios ≥100 are likely to benefit from anastrozole treatment irrespective of baseline E 2 level or E 2 -T ratio. Men with azoospermia rarely respond to anastrozole and should be counseled on alternative treatments., Competing Interests: Declaration of interests B.D.N. has nothing to disclose. T.J. has nothing to disclose. C.M.L. has nothing to disclose. T.S. has nothing to disclose. N.M. has nothing to disclose. R.C. has nothing to disclose. J.M. is a consultant and speaker for Halozyme Therapeutics, Boston Scientific, and Endo Pharmaceuticals. N. P. is a speaker for Halozyme Therapeutics. A.S.N. has nothing to disclose. S.C.V. has nothing to disclose. S.V.E. has nothing to disclose. S.D.L. has nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite a lack of evidence, a number of "regenerative" therapies have become popularized treatments for erectile dysfunction (ED). Platelet-rich plasma (PRP) injections and shockwave therapy have received significant attention through direct-to-consumer marketing and are advertised as viable alternatives to guideline-backed therapies. Additionally, focused low-intensity shock wave therapy (LiSWT) has become conflated with acoustic or radial wave therapy (rWT), although their mechanism of wave generation and tissue penetration is distinct. GAINSWave, a marketing platform for acoustic wave therapy, has also pervaded the marketplace. We aim to evaluate the relative impact of direct-to-consumer marketing of shockwave therapy and PRP by analyzing the quantity of Google internet search queries for selected regenerative and guideline-backed non-regenerative therapies for ED., Methods: National Google Search trends in the United States (www.google.com/trends) were analyzed to characterize interest in different forms of therapy for ED. Search trends for PRP, LiSWT (and various iterations), intracavernosal injections (ICI), intraurethral injections (IU), vacuum erectile device (VED), and GAINSWave were analyzed. Monthly search data were compiled over multiple years, ending at 2/28/2020, just before the COVID-19 pandemic and state of emergency in the United States. Macro-level changes in public interest were quantified using yearly averages., Results: Patterns in Google Search interest in PRP and LiSWT increased respectively by 3-fold and 275-fold over the decade, representing a larger share of Google Searches by 2020. Trends in Google Search interest in selected types of shockwave therapy for ED also show that queries for GAINSWave commanded public interest, increasing by 219-fold from 2016 to 2020., Conclusions: Regenerative therapies for ED have produced interest surpassing other adjunct guideline-backed therapies, despite receiving the designation of "experimental" or "investigational" therapies. The establishment of GAINSWave also constitutes an inflection point for the whole shockwave market: searches for shockwave therapy increased by 782% between 2016 and 2020. Direct-to-consumer marketing of PRP and shockwave therapy has upturned the customary role of physicians in counseling patients about evidence-based therapies for ED. This increase in public interest in GAINSWave emphasizes its success as a marketing platform. The urological community should consider strategies to address misinformation, such as search-engine optimization, social media, and educational outreach., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-309/coif). JNM receives consulting fees from Antares Pharma, Boston Scientific, and Endo Pharmaceuticals. The other authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Purpose: Clomiphene citrate (CC) is prescribed off-label in men to improve testosterone and sperm parameters, but the duration of treatment needed to reach maximal benefit remains unclear. Our objective was to examine temporal effects of CC on total testosterone (TT) and semen analysis (SA) using longitudinal follow-up data in treated men., Materials and Methods: We analyzed an IRB-approved database of men treated with CC (25 mg q.d. or 50 mg q.o.d.) from January 2016 through May 2021. We identified patients with 3, 6, 9, and 12 month follow-up data for TT and 3, 6, and 9 month follow-up SA. Mean absolute changes in TT and sperm concentration compared to baseline were calculated, along with 95% confidence intervals. Men with prior genitourinary procedures or hormone therapy were excluded. Paired t-tests were used to compare TT and sperm concentration at each time point to baseline (alpha=0.05)., Results: One hundered thirty-four men received CC, mean age 37.7 years (SD 6.7, range 24-52). TT at all follow-ups (3, 6, 9, and 12 months) were available for 25 men, and SA at 3, 6, and 9 months for 26 men. Baseline TT was 358±145 ng/dL and sperm concentration was 13±17.2 M/mL. Significant improvement in TT was identified at 3 months (62.7 ng/dL, 95% CI: 0.49-125.0, p=0.048), additional benefit at 6 months (181.8 ng/dL, 95% CI: 114.1-249.5, p<0.01), and plateau at 9 and 12 months. Improvement in sperm concentration was first observed at 9 months (20.7 M/mL, 95% CI: 10.2-31.2, p<0.01). Semen volume and sperm motility did not change., Conclusions: Duration of treatment with clomiphene may impact testosterone and sperm concentration, and the historical 3 month milestone may be insufficient for clinical and research evaluation. Men taking CC may experience plateau in TT at 6 months and first benefit in sperm concentration at 9 months., Competing Interests: Jesse N. Mills and Keith V. Regets are consultants for Antares Pharma, Boston Scientific, and Endo Pharmaceuticals. Sriram Eleswarapu, Tommy Jiang, Vadim Osadchiy, Alvaro Santamaria, Michael H. Zheng, Neilufar Modiri, and John T. Sigalos have no disclosures., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

In recent decades, reproductive science has revolutionized the options for biological parenthood for the 20-50% of infertility cases affected by male factors. However, current solutions exclude those who are infertile due to absent testicular tissue. This includes anorchic 46, XY individuals due to trauma or congenital factors and transgender men with a 46, XX genotype. There is a clinical need for methods to restore testicular function independent of pre-existing testicular tissue. This mini-review analyzes studies that have applied non-testicular cell lines to generate germline and non-germline testicular parenchymal components. While only 46, XY cell lines have been evaluated in this context to date, the potential for future application of cell lines from 46, XX individuals is also included. Additionally, the role of varied culture methods, media supplementation, and biologic and synthetic scaffolds to further support testicular parenchyma generation are critiqued. De novo testicular tissue generation in this manner will require a focus on both cellular and environmental aspects of tissue engineering. Put together, these studies highlight the future potential for expanded clinical, reproductive, and endocrine management options for individuals who are currently excluded from aspects of biologic reproduction most consistent with their gender identity and reproductive preferences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hosseini, DeBenedetto, Eleswarapu, Ng and Sturm.)

Background: Geosocial networking (GSN) apps play a pivotal role in catalyzing sexual partnering, especially among men who have sex with men., Objective: To quantify the prevalence and disparities in disclosure of pre-exposure prophylaxis (PrEP) use and COVID-19 vaccination among GSN app users, mostly men who have sex with men, in the United States., Methods: Web-based Grindr profiles from the top 50 metropolitan areas as well as the 50 most rural counties in the United States by population were randomly sampled. Grindr provides an option to disclose current PrEP use (HIV positive, HIV negative, or HIV negative with PrEP use). The free text in all profiles was analyzed, and any mention of COVID-19 vaccination was recorded. Multivariable logistic regression to assess independent associations with PrEP disclosure and COVID-19 vaccination was performed. Imputation analyses were used to test the robustness of the results., Results: We evaluated 1889 urban and 384 rural profiles. Mean age among urban profiles was 32.9 (SD 9.6) years; mean age among rural profiles was 33.5 (SD 12.1) years (P=.41). Among the urban profiles, 16% reported being vaccinated against COVID-19 and 23% reported PrEP use compared to 10% and 8% in rural profiles, respectively (P=.002 and P<.001, respectively). Reporting COVID-19 vaccination (adjusted odds ratio [aOR] 1.7, 95% CI 1.2-2.4), living in an urban center (aOR 3.2, 95% CI 1.8-5.7), and showing a face picture as part of the Grindr profile (aOR 4.0, 95% CI 2.3-7.0) were positively associated with PrEP disclosure. Self-identified Black and Latino users were less likely to report PrEP use (aOR 0.6, 95% CI 0.4-0.9 and aOR 0.5, 95% CI 0.4-0.9, respectively). Reporting PrEP use (aOR 1.7, 95% CI 1.2-2.4), living in an urban center (aOR 2.5, 95% CI 1.4-4.5), having a "discreet" status (aOR 1.6, 95% CI 1.0-2.5), and showing a face picture (aOR 2.7, 95% CI 1.5-4.8) were positively associated with reporting COVID-19 vaccination on their profile. Users in the southern United States were less likely to report COVID-19 vaccination status than those in the northeast United States (aOR 0.6, 95% CI 0.3-0.9)., Conclusions: Variations in PrEP disclosure are associated with race, whereas COVID-19 vaccination disclosure is associated with geographic area. However, rural GSN users were less likely to report both PrEP use and COVID-19 vaccination. The data demonstrate a need to expand health preventative services in the rural United States for sexual minorities. GSN platforms may be ideal for deployment of preventative interventions to improve access for this difficult-to-reach population., (©Thomas W Gaither, John T Sigalos, Raphael J Landovitz, Jesse N Mills, Mark S Litwin, Sriram V Eleswarapu. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.09.2022.)

Background: Peyronie's disease (PD) can be subdivided into acute and chronic phases. Intralesional collagenase Clostridium histolyticum has been shown to improve curvature in the chronic phase. Initial clinical trials excluded patients in the acute phase from treatment. Recent studies show comparable results among men in the acute phase. The definition of acute phase varies among existing studies, but it is generally understood to last 12-18 months and is accompanied by penile pain and progression of deformity. We sought to evaluate the safety and efficacy of intralesional collagenase injection therapy during the acute phase of PD using multiple definitions of the acute phase., Methods: All men receiving intralesional collagenase for PD from October 2015 through December 2020 at a single academic institution were retrospectively assessed for patient demographics and comorbidities, pre- and post-treatment curvature, and adverse events. Two definitions of acute phase were used: (I) acute phase duration ≤6 months, chronic phase duration >6 months; and (II) acute phase duration ≤12 months with penile pain, chronic phase duration >12 or no penile pain., Results: Of 330 patients identified, 229 underwent intralesional collagenase treatment with pre- and post-treatment erect penile goniometry. 65 (28%) met criteria for definition 1 of acute phase, 37 (16%) met criteria for definition 2, and 76 (33%) met criteria for either. Percent change in penile curvature was not significantly different between acute and chronic phases using definition 1 (16.0% vs. 16.6%, P=0.89), definition 2 (19.9% vs. 15.7%, P=0.43), or either (16.5% vs. 16.3%, P=0.96). The rates of development of bruising, swelling, hematoma, or corporal rupture were not significantly different between the acute and chronic phases under either definition (all P>0.05)., Conclusions: This single-center, retrospective cohort analysis suggests that intralesional collagenase is both safe and effective for the treatment of men with acute phase PD. Limitations exist inherent to retrospective review, since many men did not return for post-treatment goniometry, possibly skewing our cohort toward incomplete responders. Prospective, randomized studies will be required to confirm these findings., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-188/coif). JNM is a consultant for Endo Pharmaceuticals, Incorporation, Boston Scientific Corporation, and Antares Pharma, Incorporation. AJS has received an investigator-initiated Publication Logistical Support Grant from Endo Pharmaceuticals, Incorporation. The other authors have no conflicts of interest to declare., (2022 Translational Andrology and Urology. All rights reserved.)

Background: Efficacy of clomiphene citrate (CC) in the treatment of male subfertility remains unclear, with inconsistent results in the literature and limited guidance from professional organizations. We sought to stratify the response to clomiphene in men based on their initial gonadotropins and semen parameters., Methods: We conducted a retrospective analysis of 234 patients from an academic center who took CC for subfertility. Patients with pre-treatment and 3 months follow-up total testosterone (TT) and semen analyses were included. Patients with previous hormone therapy, genitourinary surgery, prior success in conceiving pregnancy, or only one semen analysis were excluded. Primary outcomes were magnitudes of improvement in TT and semen parameters at 3 months. Student's t -test (alpha =0.05) was used for univariate analyses; multivariable linear regression was used for multivariate analysis., Results: One hundred and thirty-seven patients met inclusion criteria. Thirty-four percent of patients experienced improvement in sperm concentration after 3 months of CC treatment, 13% decreased, and 53% showed no change. Using a pre-treatment TT cutoff of 300 ng/dL and gonadotropin thresholds of 7 miU/mL, initial TT did not affect magnitude of improvement in semen parameters, while lower initial gonadotropins showed statistical improvement across all outcomes. Multivariate analysis showed pre-treatment follicle stimulating hormone (FSH) was inversely correlated with improvement in TT [odds ratio (OR): 2.64e-05, 95% confidence interval (CI): 1.32e-09 to 5.28e-01, P=0.04] and sperm concentration (OR: 0.22, 95% CI: 5.70e-02 to 8.48e-01, P=0.03). We also provide initial gonadotropin cutoffs that suggest statistical benefit from CC use., Conclusions: Men with lower gonadotropin levels may expect greater degree of improvement in both hormone and semen parameters with use of CC. Men with azoospermia do not benefit based on semen analyses alone. Degree of non-azoospermia does not affect magnitude of improvement. CC had decreasing efficacy at higher initial gonadotropin levels. These data may provide guidance in stratifying and counseling men for CC treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-21-987/coif). KVR and JNM are consultants for Antares Pharma, Boston Scientific, and Endo Pharmaceuticals. The other authors have no conflicts of interest to declare., (2022 Translational Andrology and Urology. All rights reserved.)

Penile fracture (PF) is a surgical emergency. Given its rarity, we queried a national cohort over an 11-year period to study the temporal and demographic variations in presentation, evaluation, and management of patients with PF compared with a cohort of control patients. The National Inpatient Sample was queried between the years 2005 and 2016 for patients with a diagnosis of PF. Appendectomy patients were selected as a control cohort, given the non-discriminatory nature of this disease. Clinical and demographic data of the patients were compared with that of controls. Presenting symptoms, rates of surgical repair, and rates of associated surgical procedures were evaluated in the PF cohort. During the study period, 5802 patients were hospitalized for PF. The annual incidence of PF remained unchanged at 1.0-1.8 cases per 100 000 hospitalizations over the study period. Compared with the control cohort, PF patients were more likely to be younger (38.7 years vs 41.2 years, P ≤ 0.001), have lower rates of comorbidities except erectile dysfunction (1.4% vs 0.1%, P ≤ 0.001), and were more likely of Black race (25.4% vs 6.2%, P ≤ 0.001). Notably, PF patients had significantly higher rates of substance abuse (26.4% vs 18.1%, P ≤ 0.001), despite no difference in the diagnosed psychiatric disorders. PF rarely presented with hematuria (3.5%); however, urethral evaluation was performed in 23.1%, most commonly with cystoscopy (19.2%). PF occurs more commonly in a younger, healthier male population, and among minorities. Importantly, rates of substance abuse appear to be higher in the PF cohort compared with those of controls., Competing Interests: None

Background: Despite the results of the Testosterone Trials, physicians remain uncomfortable treating men with hypogonadism. Discouraged, men increasingly turn to social media to discuss medical concerns., Objective: The goal of the research was to apply natural language processing (NLP) techniques to social media posts for identification of themes of discussion regarding low testosterone and testosterone replacement therapy (TRT) in order to inform how physicians may better evaluate and counsel patients., Methods: We retrospectively extracted posts from the Reddit community r/Testosterone from December 2015 through May 2019. We applied an NLP technique called the meaning extraction method with principal component analysis (MEM/PCA) to computationally derive discussion themes. We then performed a prospective analysis of Twitter data (tweets) that contained the terms low testosterone, low T, and testosterone replacement from June through September 2019., Results: A total of 199,335 Reddit posts and 6659 tweets were analyzed. MEM/PCA revealed dominant themes of discussion: symptoms of hypogonadism, seeing a doctor, results of laboratory tests, derogatory comments and insults, TRT medications, and cardiovascular risk. More than 25% of Reddit posts contained the term doctor, and more than 5% urologist., Conclusions: This study represents the first NLP evaluation of the social media landscape surrounding hypogonadism and TRT. Although physicians traditionally limit their practices to within their clinic walls, the ubiquity of social media demands that physicians understand what patients discuss online. Physicians may do well to bring up online discussions during clinic consultations for low testosterone to pull back the curtain and dispel myths., (©Vadim Osadchiy, Tommy Jiang, Jesse Nelson Mills, Sriram Venkata Eleswarapu. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 07.10.2020.)

Purpose: Infertile couples increasingly turn to the internet for medical guidance. The aims of this study were: (1) to identify popular male infertility content on social media, and (2) to assess the accuracy and quality of this content. We hypothesized that inaccurate/misleading information proliferates online., Materials and Methods: We used the analytics module BuzzSumo to identify article links that were most shared on Facebook, Pinterest, Reddit, and Twitter related to male infertility during September 2018 to August 2019. We excluded articles with <100 engagements, defined as "likes," "comments," and "shares." Two researchers graded content as accurate, misleading, or inaccurate by comparing content to references cited and contemporary research. Inter-rater reliability was determined with Cohen's κ. Binary logistic regression was performed to compare user engagement with accurate versus inaccurate/misleading articles., Results: Fifty-two unique article links were identified, with 421,004 total engagements. Thirty-four articles referenced 15 scientific studies; no reference was available for 18 links. Fifty-six percent of articles were accurate and 44% misleading/inaccurate (κ=0.743). No significant difference was found in total engagement between accurate vs. misleading/inaccurate links (p=0.805). Twenty-four percent of engagements referenced studies using non-human models, and 26% of studies had sample sizes <100., Conclusions: Social media platforms foster engagement with male infertility information. However, sensationalism predominates, as patients are highly likely to encounter misleading/inaccurate information, articles that overstate implications of animal research, and conclusions made based on limited sample sizes. Urologists should consider adding social media to their armamentarium to stave off misinformation and engage proactively with patients., Competing Interests: Sriram V. Eleswarapu is a consultant for Metuchen Pharmaceuticals. Jesse N. Mills is a consultant for Antares Pharma, Boston Scientific, and Endo Pharmaceuticals. The other authors have nothing to disclose., (Copyright © 2020 Korean Society for Sexual Medicine and Andrology.)

Streaming video has emerged as a dominant content-delivery medium for healthcare information, with over 30 million visitors daily to the YouTube platform alone. Videos related to men's health have proliferated, but content produced by trained health care providers remains scarce. We evaluated educational YouTube streaming videos created in collaboration with a large, university-based health system focused on male factor infertility, men's health, and Peyronie's disease, uploaded during 2016-2018. All videos featured a board-certified urologist with fellowship training in andrology. Using YouTube's native analytics tools, we extracted data on views, engagement, and geographic reach through 8/2019. We obtained data for streaming videos on male infertility (n=3), general men's health (n=2), and Peyronie's disease (n=1). Video length ranged from 29 to 51 min, with a mean video duration of 39 min 41 sec. Actual mean watch time by viewers ranged from 3:45 to 8:30. The total view count was 646,684, with a watch time of nearly 3 million mins, reaching viewers in 47 countries. Fifty-three percent of watch time was on a mobile device and 33% on a personal computer. As patients increasingly turn to the internet for health information, health systems and physicians may wish to leverage high impact social media platforms such as YouTube to share evidence-based content. This study highlights the impressive reach a health system-sponsored video intervention using YouTube can have in sharing accurate video content related to a diverse range of men's health topics. This is the first health systems-based streaming-video intervention to leverage the video streaming and social media platform YouTube, to facilitate sharing reputable, high quality, and evidence-based men's health content., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-580). SVE reports Research Scholar Award from the Urology Care Foundation and the American Urological Association, outside the submitted work; and Consultant for Metuchen Pharmaceuticals. JNM reports being a consultant for Antares Pharma, Boston Scientific, and Endo Pharmaceuticals. The other authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

To evaluate the efficacy of a novel, multi-modal, preoperative approach to postprostatectomy penile rehabilitation (PR), we performed a retrospective review of patients who underwent nerve-sparing robotic-assisted laparoscopic prostatectomy (NS-RALP). All patients were evaluated at a comprehensive, academic sexual medicine clinic between 2016 and 2017. The "prehabilitation" PR group (n = 106) consisted of men who were seen in the pre-op period and began tadalafil and L-citrulline 2 weeks prior to surgery. Vacuum erectile device (VED) therapy was started at 1-month post-op. These interventions were continued throughout the 12-month follow-up period. Individuals refractory to these therapies could start treatment with intracavernosal injections. The postprostatectomy PR group (n = 25) consisted of men who were not seen in the pre-op period and started the above therapies immediately following their first visit. A higher percentage of men in the prehabilitation group reported return of erectile function within 12 months (56% vs. 24%, P = 0.007). The prehabilitation group also showed better compliance with PR (PDE5i [96% vs. 64%, P < 0.001], L-citrulline [93% vs. 49%, P < 0.001], and VED [55% vs. 20%, P < 0.001]). Seventy-eight percent of men who attended 4-5 follow-up visits reported return of erectile function. Our results suggest that men undergoing a preoperative protocol show superior recovery of erectile function following NS-RALP. Further studies with prospective designs are warranted.

Background: Couples struggling with infertility are increasingly turning to the internet for infertility-related content and to connect with others. Most of the published data on infertility and the internet only address the experiences of women, with limited studies focusing exclusively on internet discussions on male factor infertility., Objective: The aim of this study was to understand the concerns and experiences of discussants on an online male infertility community and to provide insight into their perceptions of interactions with health care professionals., Methods: Using the large-scale data analytics tool BigQuery, we extracted all posts in the r/MaleInfertility community (877 members) of the social media website and discussion board Reddit from November 2017 to October 2018. We performed a qualitative thematic analysis and quantitative semantic analysis using Language Inquiry and Word Count 2015 of the extracted posts to identify dominant themes and subthemes of discussions. Descriptive statistics and semantic analytic Z-scores were computed., Results: From the analysis of 97 posts, notable themes and subthemes emerged: 70 (72%) posts shared personal experiences, including feeling emasculated or isolated or describing a negative (28/97, 29%), positive (13/97, 13%), or neutral (56/97, 58%) experience with a health care professional; 19% (18/97) of the posts posed questions about personal semen analysis results. On the basis of semantic analysis, posts by men had higher authenticity scores (Z=3.44; P<.001), suggesting more honest or personal texts, but lower clout scores (Z=4.57; P<.001), suggesting a more tentative or anxious style of writing, compared with posts by women., Conclusions: To our knowledge, this study represents the first evaluation of a social media community focused exclusively on male infertility using mixed methodology. These results suggest a role for physicians on social media to engage with patients and connect them to accurate resources, in addition to opportunities to improve in-office patient education., (©Vadim Osadchiy, Jesse Nelson Mills, Sriram Venkata Eleswarapu. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 10.03.2020.)

Men's health is a unique field that requires a multi-disciplinary approach to appropriately treat the full spectrum of men's health needs. Given that interest in men's health is relatively new, the definition of a men's health clinic continues to evolve. Originally conceived as testosterone replacement centers, men's health clinics are increasingly understood to encompass male endocrine, surgical, urologic, physical performance, and psychological issues. As interest in men's health continues to grow, it is important to focus on the field's future, including pharmacies, telemedicine, and the diffusion of healthcare., Competing Interests: Conflicts of Interest: The focused issue “Contemporary Issues and Controversies in Men’s Health” was commissioned by the editorial office without any funding or sponsorship. The authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

Inflatable penile prosthesis (IPP) is an effective treatment for erectile dysfunction refractory to nonsurgical management. The infrapubic approach for IPP placement is less frequently employed than the penoscrotal approach, with only about 25% of IPPs placed via this method. Underutilization of the infrapubic method may be due to fear of injuring the penile dorsal neurovascular bundle, perceived difficulties of scrotal pump placement through a distant location, or insufficient distal corporal exposure. However, this approach appears to result in favorable operative times, faster time to device activation, equivalent postoperative satisfaction and quality of life, and similar complication rates. We provide a contemporary review of literature published before May 2019 regarding the infrapubic approach for IPP placement, technical considerations, and postoperative expectations.

A persistent hurdle in the field of tissue regeneration is to produce tissues with biochemical and biomechanical properties robust enough to meet the aggressive physiological demands of the native milieu. In an effort to improve these properties tissues grown in vitro are often subjected to mechanical stimuli that aim to recapitulate the in vivo physiology. These mechanical stimuli are thought to produce downstream alterations in intracellular ion concentrations, which ultimately give rise to increased biosynthesis. There is mounting evidence that these perturbations in the cellular microenvironment are regulated by the Ca(2+)-permeable transient receptor potential vanilloid 4 (TRPV4) channel. In this study we examined the effects of targeted TRPV4 activation on self-assembled articular cartilage constructs. The objectives of this study were: (i) to determine whether TRPV4 activation would enhance self-assembled constructs; (ii) to identify an optimal treatment time window for TRPV4 activation; and (iii) to compare TRPV4 activation which Na(+)/K(+) pump inhibition, which has previously been shown to improve the construct tensile properties. This study employed a two phase approach. In Phase I self-assembled constructs were grown for 4weeks and subjected to treatment with the TRPV4 agonist 4α-phorbol-12,13-didecanoate (4α-PDD) during three treatment time windows: t=6-10, t=10-14, and t=14-18days. Treatment for t=10-14days produced an 88% increase in collagen and a 153% increase in tensile stiffness. This treatment window was carried forward to Phase II. In Phase II we performed a head to head comparison between TRPV4 activation using 4α-PDD and Na(+)/K(+) pump inhibition using ouabain. Treatment with 4α-PDD produced improvements on a par with ouabain (91-107% increases in tensile stiffness). The results of this study demonstrate the effectiveness of ion channel modulation as a strategy for improving engineered tissues. To our knowledge this is the first study to examine TRPV4 channel activation in tissue engineering., (Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The major connective tissues of the knee joint act in concert during locomotion to provide joint stability, smooth articulation, shock absorption, and distribution of mechanical stresses. These functions are largely conferred by the intrinsic material properties of the tissues, which are in turn determined by biochemical composition. A thorough understanding of the structure-function relationships of the connective tissues of the knee joint is needed to provide design parameters for efforts in tissue engineering., Methodology/principal Findings: The objective of this study was to perform a comprehensive characterization of the tensile properties, collagen content, and pyridinoline crosslink abundance of condylar cartilage, patellar cartilage, medial and lateral menisci, cranial and caudal cruciate ligaments (analogous to anterior and posterior cruciate ligaments in humans, respectively), medial and lateral collateral ligaments, and patellar ligament from immature bovine calves. Tensile stiffness and strength were greatest in the menisci and patellar ligament, and lowest in the hyaline cartilages and cruciate ligaments; these tensile results reflected trends in collagen content. Pyridinoline crosslinks were found in every tissue despite the relative immaturity of the joints, and significant differences were observed among tissues. Notably, for the cruciate ligaments and patellar ligament, crosslink density appeared more important in determining tensile stiffness than collagen content., Conclusions/significance: To our knowledge, this study is the first to examine tensile properties, collagen content, and pyridinoline crosslink abundance in a direct head-to-head comparison among all of the major connective tissues of the knee. This is also the first study to report results for pyridinoline crosslink density that suggest its preferential role over collagen in determining tensile stiffness for certain tissues.

Several prior studies have been performed to determine the feasibility of tissue decellularization to create a non-immunogenic xenogenic tissue replacement for bladder, vasculature, heart valves, knee meniscus, temporomandibular joint disc, ligament, and tendon. However, limited work has been performed with articular cartilage, and no studies have examined the decellularization of tissue engineered constructs. The objective of this study was to assess the effects of different decellularization treatments on articular cartilage constructs, engineered using a scaffoldless approach, after 4wks of culture, using a two-phased approach. In the first phase, five different treatments were examined: 1) 1% SDS, 2) 2% SDS, 3) 2% Tributyl Phosphate, 4) 2% Triton X-100, and 5) Hypotonic followed by hypertonic solution. These treatments were applied for either 1h or 8h, followed by a 2h wash in PBS. Following this wash, the constructs were assessed histologically, biochemically for cellularity, GAG, and collagen content, and biomechanically for compressive and tensile properties. In phase II, the best treatment from phase I was applied for 1, 2, 4, 6, or 8h in order to optimize the application time. Treatment with 2% SDS for 1h or 2h significantly reduced the DNA content of the tissue, while maintaining the biochemical and biomechanical properties. On the other hand, 2% SDS for 6h or 8h resulted in complete histological decellularization, with complete elimination of cell nuclei on histological staining, although GAG content and compressive properties were significantly decreased. Overall, 2% SDS, for 1 or 2h, appeared to be the most effective agent for cartilage decellularization, as it resulted in decellularization while maintaining the functional properties. The results of this study are exciting as they indicate the feasibility of creating engineered cartilage that may be non-immunogenic as a replacement tissue.

Objective: Ascertaining how mechanical forces and growth factors mediate normal and pathologic processes in single chondrocytes can aid in developing strategies for the repair and replacement of articular cartilage destroyed by injury or disease. This study examined effects of transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-I (IGF-I) on the biomechanics and cytoskeleton of single zonal chondrocytes., Method: Superficial and middle/deep bovine articular chondrocytes were seeded on tissue culture treated plastic for 3 and 18 h and treated with TGF-beta1 (5 ng/mL), IGF-I (100 ng/mL), or a combination of TGF-beta1 (5 ng/mL)+IGF-I (100ng/mL). Single chondrocytes from all treatments were individually studied using viscoelastic creep testing and stained with rhodamine phalloidin for the F-actin cytoskeleton. Lastly, real-time RT-PCR was performed for beta-actin., Results: Creep testing demonstrated that all growth factor treatments stiffened cells. Image analysis of rhodamine phalloidin stained chondrocytes showed that cells from all growth factor groups had significantly higher fluorescence than controls, mirroring creep testing results. Growth factors altered cell morphology, since chondrocytes exposed to growth factors remained more rounded, exhibited greater cell heights, and were less spread. Finally, real-time RT-PCR revealed no significant effect of growth factor exposure on beta-actin mRNA abundance. However, beta-actin expression varied zonally, suggesting that this gene would be unsuitable as a PCR housekeeping gene., Conclusions: These results indicate that TGF-beta1 and IGF-I increase F-actin levels in single chondrocytes leading to stiffening of cells; however, there does not appear to be direct transcriptional regulation of unpolymerized beta-actin. This suggests that the observed response is most likely due to signaling cross-talk between growth factor receptors and integrin/focal adhesion complexes.