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Pure nanomaterials have limited applications, so to enhance the quality of the material, dopants play an important role in the application. It is important to find out whether the crystal structure of the dopant is rearranged or it preserves its crystal structure even after it is being doped in the pure material. Zinc Oxide has hexagonal structure and MgO has cubic structure. When Mg is doped in ZnO at various temperatures, MgO rearranges itself and it also has hexagonal structure in some cases and in other cases, it preserves or changes its crystal structure other than hexagonal structure represented as secondary peaks. Match 3 tool has been used for Mg doped ZnO at 500OC wherein MgO has rearranged itself into hexagonal structure and ZnO has rearranged itself into cubic structure. EDAX studies confirm that the synthesized material contains only Zn, O and Mg which confirm that the secondary peaks are due to structural interchange and not due to any other impurities.

Introduction Previous cross-sectional and longitudinal studies have described decreasing testosterone levels with age in men. However, the longitudinal impact of acquired comorbidities in aging males on the relationship between age and testosterone has not been thoroughly investigated. Objective In this longitudinal study, we aimed to evaluate the longitudinal association between age and testosterone levels and to investigate the impact of additive comorbidity burden on this relationship. We hypothesized that when controlling for the presence of comorbidities commonly acquired with age, there would be no association between age and serum total testosterone level. Methods Participants were selected from the Baltimore Longitudinal Study of Aging. Data was obtained on presence of several comorbidities and total testosterone level during each follow-up visit. All men with diagnosis of prostate cancer or documented use of testosterone replacement therapy during their follow-up period were excluded from analysis. A stepwise regression analysis was performed, including a final multivariate panel regression model in order to determine the impact of age on testosterone level while controlling for individual comorbidities. Results A total of 1,784 men were included in this study, with a mean age of 71 years and overall mean testosterone level of 463.2 ng/dL. Participants had an average of 3.23 comorbidities. On multivariable-adjusted panel regression analysis, age was not significantly associated with testosterone decline, while anemia, diabetes mellitus, heart failure, obesity, peripheral artery disease, and stroke were inversely associated with total testosterone level. We report no association between cancer and total testosterone. Conclusions In this large longitudinal study, we found that when adjusted for the presence of concomitant comorbidities, age does not predict a significant decline in testosterone level with age. With the overall increase in life expectancy, and the simultaneous rise in the incidence of comorbidities such as diabetes and dyslipidemia, our findings may help optimize screening and treatment for late-onset hypogonadism in patients with multiple comorbidities. Disclosure No

Introduction Surgery for male fertility is ergonomically demanding secondary to the tedious and lengthy nature of surgeries performed. The standard operating microscope places surgeons in uncomfortable positions including a “heads down” posture which has been demonstrated to predispose microsurgeons to cervical strain and chronic pain. The 4K-3D exoscope eliminates the need for eyepieces allowing for a “heads up” posture. Additionally, given the standing position of surgeons using the 4K-3D exoscope, it is thought that surgeons may be able to maintain a more “neutral” upper arm position therefore reducing upper body stress. Objective This study aims to stratify ergonomic risk amongst infertility surgeons using the 4K-3D exoscope versus the operating microscope with wearable technology. Secondary objectives included surveying for optical differences and teaching utility between surgical modalities during infertility microsurgery. Methods The participating right-handed surgeon was fitted and calibrated with three wearable sensor inertial measurement units (IMUs) on the head and upper arms in the neutral position. Each IMU is comprised of an accelerometer, magnetometer, and gyroscope. This allows for measurement of the surgeon’s joint angle change throughout 4K-3D and operating microscope use. Microscopic surgical procedures which were considered for inclusion were: vasovasostomy, vasoepididymostomy, varicocelectomy, testicular sperm extraction (mTESE), and microsurgical epididymal sperm aspiration (MESA). The previously validated rapid upper limb assessment (RULA) was used to determine the proportion of time spent in ranges of risk. Categories 1-4 were assigned for the head and upper extremities (4= highest ergonomic risk). Finally, a 5-point Likert scale questionnaire related to ergonomic, optical, and teaching metrics was administered to six microsurgeons. Chi-squared analysis was used to test for differences in proportions. Results A total of 500 and 479 microsurgical minutes from 4K-3D exoscope and operating microscope guided surgeries respectively were analyzed. Examination of the bilateral upper extremities showed that the 4K-3D exoscope significantly favored score 1 positioning compared to the operating microscope indicating a lower level of ergonomic stress with 4K-3D exoscope usage (75.3% vs. 51.5%; p < 0.0001). Finally, the operating microscope exposed the surgeon to a higher level 3 flexion (5.5% vs. 1.9%; p Conclusions The 4K-3D exoscope offers the surgeon favorable ergonomic positioning for the upper extremities which may reduce upper body work stress related injury. Similarly, a greater proportion of operative time was spent with the neck in mild extension with 4K-3D exoscope utilization which may place the patient in a “low risk” position (less than 20 degrees of extension) according to contemporary studies. Disclosure Yes, this is sponsored by industry/sponsor: Investigator Initiated Grant from Olympus. Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific.

Introduction To date, biomedical efforts against the SARS-CoV-2 virus have mainly focused on mitigating spread and primary infection mortality. While significant strides have been made in community response and vaccine production, post-acute COVID-19 syndromes (Long COVID) are growing in prevalence and becoming an increasing burden on public health. Current evidence suggests COVID-19 can affect the testis and cases of orchitis (testicular pain) appear to present in up to 20% of men with COVID-19. With an aim of uncovering causal mechanisms of COVID-19 sequela outside of pulmonary symptomology, a recent study from our group has identified a nonsynonymous non-frameshift mutation in the NACAD protein associated with COVID-19 orchitis and decreased ACE2 serum levels. NACAD is thought to prevent inappropriate targeting of non-secreted peptides to the endoplasmic reticulum. Objective We hypothesized that a defect in NACAD function/processing will decrease ACE2 serum levels by disrupting extracellular transport and endoplasmic reticulum interaction. We explored whether intracellular levels of ACE2 as well as TMPRSS2 were altered and if cell membrane protein deposition was increased, which may result in more severe effects to SARS-CoV-2 infection. Methods We obtained testis biopsies from men undergoing sperm retrieval for infertility. After siRNA NACAD knockdown, we analyzed total ACE2 expression using Western blot and qPCR as well as immunofluorescence/H&E staining for colocalization (with NACAD). Membrane-anchored ACE2 (mACE2) levels were quantified using immunostaining and flowcytometry while secreted ACE2 (sACE2) was analyzed by ELISA and Western blot. Results NACAD and ACE2 co-localize in both the Leydig and germ cells. When NACAD is knocked down, primary testes cells show 80% decreased mRNA and 50% total protein levels of ACE2. The secreted ACE2 was also reduced by nearly 50%. However, when we specifically measured the level of mACE2 on the cell surface, we found that the knockdown of NACAD did not lead to reduction. Conclusions NACAD likely specifically affects the level of sACE2, which is speculated to act as a protection factor by retaining the virus in serum and reducing cellular entry. While the exact reason for the differential effects of NACAD on mACE2 and sACE2 remain unclear, our data is consistent to other studies, which found a reduction of total ACE2 expression and sACE2 in patients is coupled with worse outcomes in COVID-19. We hope that establishing a relationship between NACAD and ACE2 expression will prove useful not only to elucidate why some men with COVID develop orchitis but, ultimately, why some men develop multiorgan failure with COVID infection whereas most do not. Disclosure No

Introduction A progressive decline in the quality of semen over the past few decades has been reported. The reason for this decline remains controversial. Semen analysis guidelines have become increasingly strict which may account for the decline. Additionally, this decline may be attributable to growing rates of obesity, environmental, and other health issues. However, it remains unknown as to whether this decline is of clinical relevance with an impact on fertility rates. Objective To determine if there is a temporal trend in both fertility rates and semen parameters, we assessed semen parameters in a population of healthy male sperm donors and fertility rates for King County, WA over the course of a decade. We hypothesized that there would be both a decrease in semen parameters as well as a decrease in fertility rate due to health, environmental, and social factors. Methods Semen parameters from sperm donors at a sperm bank were obtained from 2008 and 2020. To delineate differences over time, semen parameters were assessed from two 3-year periods 2009-2011 and then from 2018-2020. Sperm donations occurred in King County, WA. Donors were from within 50 miles of the donation site. Fertility rates for the same two time periods were calculated for King County, WA using census data from SEER to find number of women aged 15-49 and the number of births were found using CDC Wonder data. Results There was a total of 28,576 sperm donor records included in our study. The mean sperm concentration and total motile sperm count for sperm donors declined from 2009-2011 to 2018-2020 respectively by 20.8% and 47.6% (Figure 1). Progressive motility also decreased from an average of 80% in 2009-2011 down to an average of 60% from 2018-2020. The fertility rate for King County, WA was 58 births per 1000 women from 2009-2011 and declined to 49 births per 1000 women in 2018-2020 (Figure 1). Strengths of the study include both report of both sperm count and fertility rate, large sample size and contemporary cohort of semen analyses performed using the latest WHO standards. Limitations of the study include possible inter-observer variability among laboratory technicians performing semen analyses and inability to account for co-morbidities as they are not available in the dataset, and female factors that are associated with birth rates were not accounted for in this study. Conclusions There was an overall decrease in the quality of semen parameters over time for donors. Concurrently, we observed a decline in fertility rates for the same county in which the sperm donors were from. While there are certainly confounding variables we cannot account for in determining the association, our results show that both semen parameters and fertility rate have declined within the same geographic area over the same period. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals Consultant, Grant Recipient Boston Scientific Consultant, Grant Recipient Coloplast Consultant, Grant Recipient Endo Pharmaceuticals Consultant, Grant Recipient Empower Pharmacy Grant Recipient Nestle Health Consultant Olympus Grant Recipient Hims, Inc Advisory Board

Introduction Peyronie’s disease (PD) affects between 0.4% and 13% of the male population. It leads to inelastic scar tissue in the tunica albuginea which in turn leads to penile curvature, deformity, and shortening. Collagenase clostridium histolyticum (CCH) is the only FDA approved intralesional medication for PD, but its efficacy in calcified PD remains controversial. The two large, double-blind, placebo controlled randomized clinical trials, known as the IMPRESS trials, excluded men with calcified plaques, which occurs in 25-30% of all patients with PD. Objective We aimed to evaluate change in penile curvature in men with calcified PD plaques after 8 injections of CCH in a large cohort of men Methods We prospectively evaluated men with PD presenting to our clinic from October 2018 to November 2020 electing CCH treatment. All men received a pre-treatment penile duplex ultrasound with artificial erection to assess degree of calcification and curvature. We used a grading system to assess calcification: Type 1: The plaque appears as a thickening of the tunica albuginea without acoustic shadowing; Type 2: A moderately calcified plaque with a typical ultrasound shadow, and Type 3: A severely calcified plaque with complete ultrasound shadowing. All men received CCH (0.58 mg) injected directly into the primary plaque at the point of maximal penile curvature using a standardized injection technique following the manufacturer's instructions. Cycles were terminated early if the patient was satisfied with the curvature or subjects reached less than 15 degrees. We remeasured the curvature in patients 4-6 weeks after the final CCH with artificial erection. All results are presented as mean ± standard deviation (SD) Results In total, 60 patents presented with calcified PD plaques with 32 (53.3%) receiving all 8 injections and another 5 patients were satisfied with results and elected to stop treatment. The remaining 23 (38.3%) discontinued before finishing; on average they received 5.6 injections. There were no differences in baseline characteristics between men who completed treatment and those that discontinued. In patients who were satisfied there was significant (p Conclusions Overall, CCH appears effective in the treatment of patients with calcified PD plaques. In patients who successfully completed 8 injections or was satisfied there was a significant difference in curvature after treatment and can help inform patients about treatment benefits despite calcification. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study

Introduction Congenital Bilateral Absence of the Vas Deferens (CBAVD) is a condition leading to obstructive azoospermia and male infertility. CBAVD is associated with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Congenital Unilateral Absence of the Vas Deferens (CUAVD), where only one vas deferens is missing, is also associated with mutations in the CFTR gene. However, the genetic causes of both conditions are not fully understood and warrant further investigation. We present two brothers, one with CBAVD and one with CUAVD, who were subjected to whole exome sequencing. Objective To assess genetic similarities using whole exome sequencing between two brothers with differing reproductive capacities. Methods Whole exome sequencing was performed in two brothers. Subject A was 39-year-old-male who had previously fathered a child and was diagnosed with CUAVD during his vasectomy. Subject B was a 37-year-old male diagnosed with CBAVD, and genetic testing significant for one copy of a mutated cystic fibrosis gene (unaffected CF carrier). Whole blood was collected. DNA was extracted and quality assessed. Finally, whole exome sequencing was completed. Results Whole exome sequencing results were subjected to annotation and filtering. Both subjects were noted to share a rare mutation in the CFTR gene (p.R347H). CFTR mutations are the most common cause of CBAVD and have also been linked to CUAVD. However, this is a unique case of two brothers with the same genetic mutation but different phenotypic expressions of the mutation. Conclusions We have identified a rare CFTR variant (p.R347H) in two brothers with different reproductive capacities. We present evidence that absence of the vas deferens (unilateral or bilateral) may be associated with CFTR mutations, even in the absence of diagnosed cystic fibrosis. Understanding the phenotypic spectrum of CFTR gene mutations is pivotal to treating associated male infertility. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Nestle Health, Olympus, Hims Inc.

Introduction Fertility Preservation (FP) for children and adolescents with cancer is underutilized. In prepubertal individuals, ovarian and testicular tissue can be frozen; however, this is still considered largely experimental. Objective Identify trends of FP in prepubertal individuals in the United States. Methods We performed a retrospective study of prepubertal children with cancer identified through the Pediatric Health Information System from 2011 to 2020. Children who underwent a testicular or ovarian biopsy were included. Any patients with testicular or ovarian malignancy, or other diagnoses which may have required a gonadal biopsy were excluded. Results A total of 418 boys under 13 and 333 girls under 12 who underwent a gonadal biopsy were identified. There was a total of 66929 new cancer diagnoses in girls and 86001 new cancer diagnoses in boys during this time. The most common cancer diagnosis was hematologic in both boys (50.96%) and girls (36.64%). A concurrent procedure at time of gonadal biopsy was performed in 84% of boys and 62% of girls, with line insertion being the most common. The only predictive variable of receiving a gonadal biopsy was increasing year. Overall, only 0.04% of children had a gonadal biopsy for FP during this time period. Conclusions Gonadal biopsy rates have increased in prepubertal children with cancer, presumably for FP. While recent international guidelines support FP in this group, our findings highlight the need to establish protocols and tracking for FP procedures in the US. Disclosure No

Introduction Variation in testosterone levels by season and month have been reported, however results have been inconsistent across studies. Large series are conflicting with reported peaks in June, October, December, and January. Testosterone levels in most of these studies nadir in the spring. The etiology for the variability remains unknown but is likely multifactorial including sunlight exposure, sleep duration, and outdoor temperature. Objective To determine if there is seasonal variability in testosterone levels in a large cohort of men and if this variability may be clinically relevant. Methods Using a single institutional database, testosterone levels were obtained for men ages 18-99 from 2010-2021 who had at least 2 testosterone levels drawn within a 2-year period. Patients who were currently or previously on exogenous testosterone, testosterone stimulating medications, testosterone suppressing medications, and aromatase inhibitors were excluded from the study. Climate data including mean monthly temperature for Miami-Dade County, FL was obtained from the PRISM Climate Group. Minutes of daylight on the fifteenth day of each month was applied as the representative daylight duration for each month. Results There were 3,377 total patients included in the study, there were 9495 total testosterone levels measured with all patients having 2 or more levels. The mean age was 58.8 years old. In the winter the mean testosterone level in the was 422 ng/dl (Figure 1.), the average time of daylight was 682 minutes, and the average temperature was 68 F. In the spring the mean testosterone level was 412 ng/dl, the average time of daylight was 801 minutes, and the average temperature was 78.4 F. In the summer the mean testosterone level was 416 ng/dl, the average time of daylight was 780 minutes, and the average temperature was 83.6 F. In the fall the mean testosterone level in the fall was 417ng/dl, the average time of daylight was 661 minutes, and the average temperature was 75.3 F. Conclusions Our findings suggest seasonal variability in testosterone levels with the highest testosterone levels in the winter, the lowest levels in the spring and a steady increase in testosterone levels in the summer and fall. However, this variation is minor and not likely to be clinically relevant. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals Consultant, Grant Recipient Boston Scientific Consultant, Grant Recipient Coloplas tConsultant, Grant Recipient Endo Pharmaceuticals Consultant, Grant Recipient Empower Pharmacy Grant Recipient Nestle Health Consultant Olympus Grant Recipient Hims, Inc Advisory Board.

Introduction Peyronie’s Disease (PD) is prevalent in approximately 7.1% of the general population. Current treatment approaches include medical therapy and surgical intervention, and intervention only occurs once the disease process has entered the chronic, stable phase. The only FDA-approved medical therapy involves use of intralesional collagenase clostridium histolyticum injection and surgical interventions include tunica albuginea plication, plaque excision without grafting, or placement of penile prothesis. Autologous platelet rich plasma (PRP) may prove to be a viable treatment for this patient population due to its ability to facilitate tissue repair and wound healing via various growth factors. Objective We hypothesized that PRP can be safely utilized in patients with PD, with minimal adverse events. Methods We reviewed data for an initial series of men recruited into an ongoing randomized double-blind placebo-controlled cross-over study at the University of Miami from April 2021 to June 2022. Patients received a total of two injections of PRP or placebo directly into the dominant plaque, separated by two weeks. Patients were observed immediately post-injection and assessed with Visual Analogue Pain Scale, and at follow-up for complications and tolerability. Patients are followed three- and six-months post-injection, of which then the patient crosses over into the other treatment / placebo arm. The patient undergoes goniometer measurement with an artificial erection, IIEF-15 and PDQ questionnaire assessment prior to crossover and at the end of the study. ClinicalTrials.gov Identifier: NCT04512287. Results We report data from 24 men who completed two injections for Arm 1 (PRP or placebo) and 15 men who completed two injections (PRP or placebo) after cross-over. No post-procedural minor adverse events were seen in any of the men. None of the participants reported adverse effects such as penile bruising, swelling, edema, allergy, penile fracture, or mild pain at injection site. Six men completed 6-month follow-up and no complications were reported. No worsening curvature was observed in men completing pre/post evaluations. Conclusions PRP appears to be a safe and feasible treatment modality in patients with PD from our limited data accumulated thus far in our ongoing randomized placebo-controlled trial with PRP for PD. We expect to report efficacy data as soon as it becomes available. Our study is the first study in the USA accruing men with PRP for PD in a clinical trial and believe that safety and efficacy data accumulated from our study will be important for patient counseling. Disclosure No

Introduction Testosterone therapy is available in multiple delivery systems such as gels and injections; however, oral formulations have been unavailable in the United States due to hepatotoxicity and variable bioavailability. Oral formulations of testosterone are convenient, easy to use, and avoid the problems of other forms of testosterone therapy. Jatenzo (testosterone undecanoate) is a novel US FDA-approved oral testosterone capsule that provides a uniform response in patients with testosterone deficiency. Objective This study evaluates patient satisfaction with Jatenzo in men with a recent history of alternative testosterone therapy. Methods Patients between 18 and 65 years of age with a diagnosis of testosterone deficiency were recruited. Testosterone deficiency was defined as two measurements of serum total testosterone below 300 ng/dL combined with clinical symptoms in accordance with American Urological Association guidelines. Patients were required to have received previous testosterone therapy and completed an adequate washout period prior to starting Jatenzo. The primary outcomes were patient satisfaction, measured by the Treatment Satisfaction Questionnaire for Medication (TSQM-9); and changes in testosterone deficiency symptoms, measured by the quantitative Androgen Deficiency in Aging Males (qADAM) questionnaire at the 3- and 6-month intervals relative to baseline. Serum testosterone, PSA, hematocrit, and estradiol were also evaluated at each time point. Results Of the 41 patients recruited into the study, 46% had previously received subdermal pellets, 41% intramuscular injections, 6% transdermal gels, and 7% intranasal gels. Total testosterone levels increased from a baseline after appropriate washout from a mean of 187 ng/dL to 773 ng/dL at 1 month, 434 ng/dL at 3 months, and 397 at 6 months of treatment with Jatenzo. Patient satisfaction with Jatenzo as measured by TSQM-9 improved to 52 and 59.3 at the 3-month and 6-month time points, respectively, relative to 38.5 with previous testosterone therapy. Testosterone deficiency symptoms as measured by qADAM were 34 with Jatenzo and 33.5 with previous testosterone therapy. No significant difference was noted in side effects such as polycythemia or changes in estradiol or PSA. Conclusions Jatenzo appears to provide similar patient satisfaction and similar improvement in testosterone deficiency symptoms relative to other forms of testosterone therapy. In addition, Jatenzo increases serum total serum testosterone to reference range (300 – 1000 ng/dL) in >90% of men without a difference in side effect profile. Disclosure Yes, this is sponsored by industry/sponsor: Clarus Therapeutics Clarification Industry funding only - investigator initiated and executed study

Introduction Testosterone (T) plays an important role in properly developing and maintaining male reproductive tissues. The normal serum testosterone levels can vary between 300 to 1000 ng/dL or 10.4 to 34.7 nmol/L. However, it is unclear whether androgen receptor signaling can vary based on serum T levels or the half-life of testosterone therapy. What remains unknown is whether there is a uniform serum T level above which androgen receptor signaling within the tissue remains similar (saturation hypothesis). Objective We first evaluated whether varying serum levels of T alter androgen receptor (AR) signaling in human penile tissue. Then, we evaluated and compared AR signaling in corpus cavernosum tissue of men treated with short-acting vs. long-acting testosterone. We hypothesized that we would find similar AR signaling in the penile tissue of both eugonadal and hypogonadal men as well as those men receiving short and long-acting testosterone. Methods We obtained human corpus cavernosum (hCC) tissue biopsies during penile surgery (for erectile dysfunction) from 14 men. We recorded their serum T levels on week prior to surgery before 10AM. We used western blot to evaluate adrenergic receptor (AR) and VEGF protein levels. Men without erectile dysfunction undergoing penile surgery for Peyronie's disease were used as controls. Results The median age of participants was 61 (IQR 12) and the median T level was 325ng/dL (IQR 201.45). The results of western blot showed expression of similar levels of VEGF in hCC samples from men with T >200ng/dL. However, men with serum T levels lower than 200 ng/dL had decreased expression of VEGF and AR. Conclusions This finding is significant because it demonstrates that serum testosterone beyond a certain threshold may have a minimal impact on erectile function. If a serum testosterone threshold is identified, this threshold could be a valuable target for future studies on the effects of testosterone on ED. It may alter the treatment threshold for men who have ED as their primary symptom of hypogonadism. This data also suggests the saturation value for penile androgen receptors. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Nestle Health, Olympus, Hims, Inc

Introduction Inclusion of ethnic/racial minorities in clinical trials is essential to fully assess therapeutic efficacy. It is well-known that populations respond dissimilarly to interventions. This concept has been research ed thoroughly in the context of urologic oncology research, however research into the impact of demographic characteristics in andrology trials is lacking. Objective To analyze the inclusion of historically under-represented minority men in clinical trials for Erectile Dysfunction (ED) in comparison to Prostate Cancer (PC) trials. Methods We searched ClinicalTrials.gov for the disease keyword: “Erectile Dysfunction” and used “Prostate Cancer” trials for comparison. Completed trials that had available demographic data were included for analysis. Literature was reviewed to determine the prevalence of ED and PC diagnosed among Hispanic, Black, White, and Asian men. The proportion of individuals of each group that participated in trials is divided by the proportion of each group in the disease population to calculate the “Participation to Prevalence Ratio” (PPR). PPRs between 0.8-1.2 indicates adequate representation, 1.2 is over-representation. Results A total of 312 trials were assessed: 289 for prostate cancer and 23 for ED. Hispanic men comprised 11.8% of ED trial participants and 4.61% of prostate cancer trial participants, yet represented 18% of ED patients and 7.3% of PC patients. Black/African-American (AA) men accounted for 10.2% of ED trial participants and 9.4% of PC trial participants, but comprised 16% of ED patients, and 16.3% of PC patients. Hispanic and AA men are under-represented in trials for ED and Prostate Cancer (Hispanic ED PPR=0.66; Hispanic PC PPR=0.63; AA ED PPR=0.42; AA PC PPR=0.58). Conclusions Our findings show that both Hispanic and AA men are underrepresented in both ED and PC clinical trials. A greater emphasis must be placed on achieving representative enrollment in clinical trials for ED and PC in order to address this disparity and improve generalizability of the findings. Disclosure No

Introduction The potential increase in hematocrit and subsequent risk of polycythemia has been regarded as one of the most worrisome adverse effects of testosterone therapy (TT). Recent evidence has shown that the modality of delivery and half-life of each formulation may affect the incidence of these side effects. Therefore, we hypothesized that longer-acting intramuscular testosterone would increase hematocrit to a higher degree than the shorter-acting nasal formulations that can more closely mimic normal physiology. Objective To compare the effects of Intranasal Testosterone (NT) and Intramuscular Testosterone (TC) on hematocrit and serum testosterone levels in testosterone deficient men over 4 months. Methods This Phase IV, randomized, open-label clinical trial was performed on 39 symptomatic, testosterone deficient (TD) men with at least two serum testosterone levels below 300 ng/dL drawn before 10AM. Men were randomized (1:1) to receive either nasal gel three times per day (5.5mg per nostril) and intramuscular TC (200mg) once every two weeks. The primary outcomes were changes in Hematocrit and serum T before and after four months. Secondary outcomes were changes in estradiol (E), PSA and 17-OHP. Data analysis was performed using two-sample and single-sample T tests (Microsoft Excel v.16.60). Results A total of 39 men with testosterone deficiency were randomized to receive either NT (n=15) or TC (n=24). The median participant age was 46 years old with a mean serum T of 237.1 ng/dL and hematocrit of 43.3%. Prevalence of participants who screened positive for OSA on STOP-BANG questionnaire for NT and TC group were 67% and 71%, respectively. Compared to their respective baselines, men in both groups saw significantly increased serum testosterone levels (p 52%) after 4 months was 0% in NT group and 4.2% in TC. Those taking TC saw increases in E (p=0.003) and decreases in 17-OHP (p Conclusions Both Intranasal and Intramuscular testosterone regimens are effective in treating hypogonadal men. However, short-acting nasal T does not appear to impact hematocrit levels especially when compared to testosterone cypionate. Those who are at increased risk of developing polycythemia or want to avoid changes in their E or 17-OHP levels may benefit from short-acting T formulations. Disclosure Yes, this is sponsored by industry/sponsor: Acerus Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals

Introduction The goal of treatment for infertile men with testosterone deficiency is to improve intratesticular androgen levels with the aim of increasing the last step of maturation in spermatogenesis. Medical therapy for male factor infertility remains largely empiric and relies on off-label use of medications known to increase intratesticular testosterone levels, such as selective estrogen receptor modulators (clomiphene citrate and enclomiphene citrate) and gonadotropins (human chorionic gonadotropin). There is scarce data of whether the above-mentioned treatment options offer different success rates in improving testosterone levels and sperm parameters. Objective To compare the improvement in total testosterone, intratesticular testosterone, and sperm parameters between patients receiving medical treatment with clomiphene citrate (CC), enclomiphene citrate (ECC), or clomiphene citrate + human chorionic gonadotropin (HCG). Methods We conducted a retrospective study from 2018 to 2022 of men with primary infertility, testicular deficiency, and secondary hypogonadism receiving ECC, CC or CC+HCG for at least 3 months. Among the different treatment groups, we assessed baseline and follow-up total testosterone, 17-hydroxyprogesterone (17-OH), semen parameter(s), and demographics. Semen quality improvement was based on assisted reproduction eligibility according to the total motile sperm count (TMSC) value: in-vitro fertilization ( 9 million). Intratesticular testosterone upgrading was based on 17-OH level, with expected values being ≥55 ng/dL. Variables were compared using paired t-test and ANOVA. Results A total of 18 men received ECC, 19 received CC and 9 received CC+HCG. Mean age was 41.1±2.28 years in the ECC group, 40.62±1.17 in the CC group, and 45±2.75 in the CC+HCG group (p=0.458). Overall, the mean follow-up was 3.64 ±2.14 months (p=0.242). The 3 treatment groups exhibited a statistically significant increase in total testosterone (table 1), but only the CC and CC+HCG groups had a statistically significant improvement in the level of 17-OH (p 9 million. Conclusions Our study showed that ECC, CC and CC+HCG are effective treatment regimens for improving total testosterone without negatively affecting spermatogenesis. Nonetheless, their effects on intratesticular testosterone and sperm parameters varied, suggesting that choosing the best treatment option for improving sperm parameters should be an individualized patient decision. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus, Boston Scientific, Endo Pharmaceuticals and Coloplast.

Introduction Peyronie’s disease (PD), estimated to affect around 10% of the male population, is an acquired disorder of penile fibrotic tissue. The only FDA approved medical treatment for PD is Intralesional Collagenase Clostridium Histolyticum (CCh). CCh is a mixture of AUX1 and AUXII, two different forms of collagenase that cleave collage type I and type III, leading to plaque degradation. PD plaques, however, also contain fibrin and calcium which CCh is unable to digest. It is unknown if plaque calcification prevents collagenolysis with CCh. Objective To determine if calcification prevents collageolysis of PD plaques with CCh. Methods Calcified PD plaques were collected from five males undergoing excision and grafting for PD. Control tissue was collected from five males undergoing penile implant surgery for erectile dysfunction, with no known history of PD. Tissue samples were then divided into equal weights and incubated with CCh or PBS for 24 hours. The CCh or PBS was injected into the tissue (control or plaque) to mimic administration of CCH for treatment of PD. Following incubation, the fluid (CCh or PBS) was measured for soluble collagen amount and tissue was subjected to Picrosirius Red and H&E staining. Results There was a higher concentration of soluble collagen in the tissue (control and plaque) incubated in CCh (301ug, SD 21.1) compared to the issue incubated in PBS (32.5ug, SD 3.7) (p=0.02). Additionally, there was less type 1 and 3 collagen present in the CCh condition (mean 0.12, SD=0.08), when compared to the PBS condition (0.44, SD=0.17) (p=0.002). However, when comparing within the CCh condition to look at differences between tissue types (calcified vs. control) no differences were found. There was a similar amount of soluble collagen in the CCh control condition (316ug, SD 35) and the CCh calcified condition (286ug, SD 11) (p=0.06). Similarly, the PBS control condition (30ug, SD17) and the PBS calcified condition (35ug, SD 48) were found to have no significant differences in collagen concentration (p=0.4). Finally, there were no significant differences found in type I/III collagen staining between tissues in the CCh condition, with control (0.08, SD=0.02) and calcified (0.17, SD=0.09) demonstrating no significant difference (p=0.08). Tissues in the PBS condition, control (0.5, SD=0.23) and calcified (0.39, SD=0.39), similarly were not significant (p=0.2) (table 1). Conclusions CCh is capable of breaking down collagen in calcified plaques. Further research into CCh as a treatment option for PD calcified plaques is necessary. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Nestle Health, Olympus, Hims, Inc.

Introduction Elevated C-Reactive Protein (CRP) and testosterone deficiency are associated with advanced age and chronic inflammatory diseases, such as cancer, obesity, diabetes, and cardiovascular disease. Further, serum CRP has proven to be a robust predictor of major adverse cardiovascular events. Testosterone decreases inflammation through several mechanisms, and testosterone replacement therapy (TRT) has been shown to consistently lower CRP levels in aging, hypogonadal men. While cross-sectional studies have shown an inverse relationship between CRP and total testosterone (TT) levels, mixed findings have been reported when individual components of metabolic syndrome and additional comorbidities are considered. Given that androgens have been implicated in anti-inflammatory pathways, we hypothesize that men with testosterone deficiency will have low CRP levels, independent of added comorbidities. Objective We evaluated the relationship between CRP and TT levels in men from 2004-2018 using the Baltimore Longitudinal Study of Aging. Methods Male participants with a documented serum TT level measured via mass spectroscopy during two separate visits >3 years apart were included in our cohort. CRP, High-Density Lipoprotein (HDL), and Triglyceride levels were collected via blood specimens. Comorbidity data were documented for all participants at each follow-up visit. Patients with serum TT or CRP levels >3 standard deviations from the mean of each respective variable were removed. Men with documented use of any form of TRT or a history of prostate cancer were excluded. Panel regression, a statistical technique implemented to analyze the relationship of a series of independent variables collected in pooled cross-sectional observations over time with a dependent variable, was used for univariable and multivariable modeling of CRP. P-value < 0.05 was considered statistically significant. Results A total of 347 patients (694 visits) met the inclusion criteria of this study. The median age of our sample was 71 years with a follow-up time of 8 years (range: 3-13 years). Participants had a median CRP level of 1.03 mg/dL [0.52, 2.11] and a median TT level of 446 ng/dL [339, 560]. In terms of comorbidities, diabetes was documented most frequently, followed by congestive heart failure (CHF) and cancer (Table 1). On univariable analysis TT, cancer, and HDL were associated with a decline in CRP, while BMI, CHF, Diabetes, and Triglycerides were associated with increased CRP. Age was not associated with CRP (Table 2). On multivariable analysis, we found that increasing TT was associated with a decline in CRP levels, independent of comorbidities (p = 0.022; Table 2). The strengths of our study include having well-documented laboratory values and comorbidity information for patients at multiple visits. However, causal associations cannot be inferred due to the retrospective nature of the data. Conclusions We report that an increase in TT is associated with a decline in CRP levels, after controlling for components of metabolic syndrome and other related comorbidities. This finding is consistent with the anti-inflammatory effects of androgens, which decrease pro-inflammatory mediators and leukotriene biosynthesis. Our study further highlights the benefits of restoring eugonadal testosterone levels in older, hypogonadal men via hormone replacement, potentially lowering CRP levels and reducing cardiovascular risk. Disclosure No

Introduction In modern times, the widespread use of mobile phones is a notable source of radiofrequency–electromagnetic radiation (RF-EMR) with a potential impact on human health. The advancements in technologies such as Bluetooth earphones have increased the time the cell phone resides inside the pant pockets of men, in close contact with their testicles. As a result, it makes the testicles more prone to RF-EMR exposure for longer. Recent literature has shown that such long exposure is likely to cause damage to the sperm quality and functioning in several ways, including the increase in local body temperature, high oxidative stress, reactive oxygen species, and free radical formation (1,2). However, the causing effect of modern cell phones and wireless communication networks (4G and 5G) on sperm quality has not been explored. Objective The aim of our study was to investigate the effect of cell phone radiations emitted through communication technologies - 4G, 5G and WIFI on sperm motility and viability using an in-vitro approach and further try to shed light if physical barriers or distance ease these effects. Methods Normozoospermic men (n=18) aged 25-35 were recruited whose samples after semen analysis were divided into three parts i) in close contact with sample without cover ii) mobile phone covered with physical barrier, and iii) phone kept at distance from the samples. Standard semen analysis was carried according to WHO laboratory manual for the examination and processing of human semen, 5th ed. Voice calls over the internet were made using 4G, 5G, or WIFI and using these, RF-EMF exposure was given for six hours which was measured by RF-EMR detection meter. In addition, to check for the heating effect, samples were kept inside the incubator at 37°C for samples exposed to WIFI effects. Continuous variables were presented as medians and interquartile ranges [25th - 75th], and comparison between groups was performed using the U Mann Whitney test. SPSS v.28 was used for statistical analysis. Results A decrease in both parameters under study was evident with WIFI (Motility (50% vs. 38%, p = 0.024; viability 60% vs 47%, p = 0.003), while no decrease was noted with 4G or 5G RF-EMR. Samples connected with WIFI were warmer but samples inside the incubator, when observed had decreased progressive motility (40% vs 24%, p= 0.04). On the other hand, the effect of RF-EMR by WIFI on smartphone was mitigated both for sperm motility and viability (p = 0.01, p = 0.01), n = 18) with the use of a case and on increasing the distance of the contact respectively. Conclusions The result from the study suggests that the radiation emitted by WIFI do have an adverse impact on the motility and viability of sperm. It seems plausible that the effect maybe a result of excess heat generation which was most evident with mobile phones connected to WIFI. However, further studies utilizing different phones and different time periods of exposure are warranted to effectively conclude the findings Disclosure No

Introduction Despite the demonstrated safety of COVID-19 mRNA vaccines, potential impact on fertility remains a major concern for vaccine hesitancy. Objective We conducted a single-center prospective study to investigate the long-term impact of COVID-19 vaccination on sperm parameters of healthy men. We hypothesized that COVID-19 vaccination (and booster doses) would not negatively impact sperm parameters in the long-term. Methods Twelve healthy male volunteers between the ages of 18-50 years old with pre-vaccination semen analyses completed follow-up analyses between September 2021 - March 2022. Participants were required to provide documentation demonstrating at least two mRNA vaccine doses after a minimum of 9 months prior to the first vaccine. Semen analyses evaluated volume, sperm concentration, total motility, and TMSC. The number of days abstinent prior to sample collection was documented during the visit. The primary outcome was median change in the total motile sperm count at least 9 months following fully vaccinated COVID-19 status. Individuals who admitted a history of infertility or previous azoospermia were excluded from study participation. After calculating data distribution on normality test, medians, and interquartile ranges (IQRs) were reported for all variables. The Wilcoxon rank sum test was used to compare pre- and post-vaccination semen parameters. A 2-tailed P Results A total of 12 men volunteered in our study (median age 26 [25 - 30] years. Subjects provided follow-up semen samples at a median of 10.5 months following the second vaccine dose. There were no significant changes in any semen parameters between baseline, 3 months, and 10 months following vaccination. Baseline samples demonstrated median sperm concentrations and TMSC of 29.5 million/cc [9.3 – 49] and 31 million [4-51.3], respectively (Table 1). At follow-up, sperm concentration and TMSC were 43 [20.5 – 63.5] (p=0.050) and 43.5 [8.5 – 102.8] (p=0.407), respectively. Of note, there were no significant changes in semen volume nor total motility (%) for participants at follow-up. Two of the men had semen analyses demonstrating oligospermia at baseline. Of these two men, one was found to be normospermic at follow up from 8 to 25 million/mL, and the other remained oligospermic. Conclusions COVID-19 mRNA vaccines and booster doses do not appear to negatively impact the semen parameters of healthy males even 10 months following vaccination. Our study and future studies should add to the growing body of the evidence on the long-term safety of vaccines and potentially decrease vaccine hesitancy. Disclosure No

Introduction Among US adults, the prevalence of melatonin supplement consumption significantly increased in the last two decades across all demographic groups. Despite scant evidence, melatonin is widely used as an over-the-counter sleep aid. Because sleep disorders are associated with testosterone deficiency, we examined the associati.n between melatonin supplementation and serum testosterone levels. Objective Evaluate the association between melatonin supplementation and serum testosterone levels in adult males living in the United States. Methods The National Health and Nutrition Examination Survey (NHANES) was used to analyze interviews, physical examinations, and laboratory tests. Data from three cycles (2011-2012, 2013-2014, and 2015-2016) was combined (appended) to study the association between melatonin usage and early morning serum total testosterone (TT) levels. Selection criteria included men aged 18 and older; exclusion criteria included the reported use of testosterone, clomiphene, or anastrozole medications or supplements in the past 30 days. Additionally, participants with missing values for age, body mass index (BMI), sleep habits, or EMSTT were excluded from the analysis. Statistical analysis was performed using SPSS v.28. Continuous variables were presented as medians and interquartile ranges [25 - 75]. To determine the association between of low EMSTT (T < 300 ng/dL = low) and clinical variables, demographics characteristics, a multivariable-adjusted logistic regression analysis was performed. Results After selection, 7,656 participants were analyzed, of those, the median age was 47 [31 - 63] years old, the median TT level was 389.9 [289 - 513.9] ng/dL, and 27.4% of participants were found to have low TT, and 51 (0.7%) reported melatonin supplementation. Among individuals who reported melatonin intake in the past 30 days, the average intake was approximately 1 mg/day. On multivariable adjusted analysis increase age (OR = 1.019, p < 0.001), and BMI (OR = 1.133, p < 0.001) were associated with increased risk of low TT. However, we did not find an association with low testosterone among men who reported melatonin supplementation (p=0.898) even after analyzing for confounding variables. Conclusions These findings suggest that melatonin supplementation within the past 30 days was not associated with low TT levels in a nationally representative sample of men aged 18 and older. Further analyses are needed to highlight the dose-response relationship and examine the potential effects of exposure to supratherapeutic doses and chronic intake. Disclosure No

Introduction The primary source of testosterone (T) in men are Leydig cells (LCs) and their dysfunction can lead to T deficiency. Testicular microenvironment (TME) which is comparised of cells such as Sertoli and Peritubular myoid cells releases the paracrine factors to influence the growth and differentiation of LCs. Leptin is a 16-kDa protein produced primarily by adipose tissue and exerts a significant influence on hormonal regulation. In our recent study, we demonstrated that Leptin, a paracrine factor secreted by TME, is critical for Leydig stem cell (LSCs) differentiation and subsequent T production under the regulation of the desert hedgehog signalling pathway. We also showed that this regulation is inverse concentration dependent such as Leptin increases LSC differentiation at low doses and decrease it at higher doses. However, an in-depth understanding of mechanisms that derive the Leptin secretion and decide the fate of LCs are still unclear and is the focus of the present study. Objective To study the mechanisms that derive the Leptin secretion and decide the fate of LCs. Methods A total of 18 men with testicular failure underwent testis biopsies. The testicular cells were characterized using Flow cytometry, Immunostaining and RNA sequencing then the cells were also treated with Leptin in a dose dependent (0, 1, 10 ng/mL respectively) and time dependent (24, 48, 72, and 96 hours) manner. For the functional studies, UCSC genome browser was used to study the transcription factor genes (TFs) binding the leptin receptor (LEPR) promoter. The list of TFs was subjected to enrichment analysis. To evaluate the effects of shortlisted TFs on leptin-LEPR-DHH to induce EMT in LSCs, qPCR and western blotting were performed. For statistical analysis GraphPad Prism was used. For statistical analysis GraphPad Prism was used. All data were presented as the means ± SEM. All data were presented as the means ± SEM Results Over 60 TF’s were identified by UCSC Genome browser, which were subjected to enrichment analysis using ENRICHR and Ingenuity pathway analysis. Output revealed TFs; SOX2, SOX8 and SOX9 that were enriched for mechanisms influencing hormonal regulation via hypothalamic pituitary gonadal axis. The role of these TFs has been well established in epithelial to mesenchymal transition in different cancer types, however their impact on LSC differentiation remained underexplored. RNA sequencing data from cells exposed to different concentrations of Leptin showed an inducing effect of Leptin on SOX2, SOX8 Sox9 respectively. This was confirmed at RNA as well as at protein levels. Consequently, upon inhibition of LEPR, the expression of SOX2, SOX8 and SOX9 was reduced as well. Furthermore we used SOX8, SOX9 and SOX2 antagonists in the presence or absence of Leptin to validate the effects on EMT of LCs. Conclusions Our results demonstrate that Leptin-LEPR-DHH induced Leydig stem cells differentiation in testis is modulated by EMT inducing transcription factors which binds to LEPR. Further studies are ongoing to explore the potential therapeutic effects of leptin treatment in improving fertility. Disclosure No

Introduction Klinefelter syndrome (KS) is a genetic condition in which a male is born with an extra X-chromosome and is one of the on-label indications for testosterone replacement therapy (TRT). The prevalence of testosterone deficiency in men with KS is difficult to predict and not well described in the literature. Furthermore, there is no previous literature detailing the rates of TRT prescription in men diagnosed with KS. Objective We aimed to determine the rates of hypogonadism and prescription of TRT in men with KS using a large, federated research database. We hypothesized that men with KS are undertreated for testosterone deficiency with TRT due to a combination of factors including a poor understanding of hypogonadism in this population and neurocognitive issues leading to delay in seeking treatment for hypogonadism. Methods We queried TriNetX, a large, multicenter electronic health record database, to identify all men with a diagnosis of Klinefelter syndrome (ICD-10-CM Q98.4) excluding men with prescription of TRT prior to diagnosis of KS or a diagnosis of KS more than 20 years ago. Descriptive analysis on associated comorbidities and demographic characteristics was performed. We then filtered the initial cohort to find men who received a laboratory measurement of testosterone level on the day of diagnosis with KS or later. Prevalence of testosterone deficiency was determined as defined by testosterone level < 300 ng/dl. The primary outcome of the study was prescription of any of the following forms of TRT on the day of diagnosis or later using associated medication codes: testosterone, testosterone 17-phenylpropionate, testosterone enanthate, testosterone cypionate, testosterone undecanoate. Rates of TRT prescription were determined for both the initial cohort and the hypogonadal subgroup. Results There were 5,437 total men with diagnosis of KS. A total of 1,581 men with KS received laboratory measurement of testosterone level, 1,113 (70.4%) of whom were hypogonadal. Mean testosterone level in this group was 354 ng/dL [50 – 658]. Of the 1,113 men found to be hypogonadal, only 657 (59.0%) men were given prescription for TRT. Conclusions This is the first study to evaluate TRT prescribing habits in men with KS. In this large, retrospective study, TRT was under-prescribed in men with KS. Further studies are needed to corroborate these findings and to evaluate the barriers to receiving care in this population. Disclosure No

Introduction Testosterone deficiency (TD) is a prevalent condition, especially in men ≥ 45 years old, and testosterone therapy (TTh) can improve quality of life in these patients. Objective In this abstract, we aim to evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the pharmacokinetics between compounded and FDA approved testosterone pellets (Testopel®) for TTh. Methods This was a prospective, Phase 3, randomized, non-inferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 ratio to Testopel® and a 100mg compounded pellet group. The patients were implanted with their respective treatment: Testopel® (10 pellets of 75mg) or compounded testosterone pellets (8 pellets of 100mg). Results After randomization, there were 35 participants enrolled in the Testopel® 75mg arm and 40 participants in E100 arm. Serum T levels were similar between the groups at 2, 4 and 6 months, with most men (82%) dropping below 300 ng/dL by the end of the trial. Adverse events such as elevations in prostate specific antigen, estrogen and hematocrit in each group were similar. Most dropouts were related to persistent TD symptoms and serum T < 300ng/dL, with similar rates between the two groups in the study. Conclusions Men treated with Testopel® and compounded pellets had comparable serum testosterone levels and similar adverse events rates. Compounded testosterone pellets can provide an effective choice of long term TTh among men with TD comparable to Testopel®. Disclosure Yes, this is sponsored by industry/sponsor: Empower Pharmaceuticals. Clarification Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Empower Pharmacy.

Introduction Over the past several years there has been a rise in the number of clinics offering novel treatments for erectile dysfunction and Peyronie’s disease such as stem cell therapy, platelet rich plasma, and shockwave therapy Objective In this study, we attempt to identify to identify experimental treatment approaches for ED and PyD used by various clinics across the country. Methods Using a systematic search of online website directories, we identified 26 clinics were surveyed for PRP treatment, 27 for shockwave therapy, and 26 for stem cell therapy A standard questionnaire was used to retrieve information from all clinics regarding cost of treatment, duration of therapy, medical staff involved, and patient outcome data. Results We found that the cost of treatment varied widely between groups. PRP cost between $500 to $2400, Shockwave total cost was between $1500 - $7500, and stem cell therapy cost ranged between $3,800 to $16,000 USD. Across all clinics surveyed, a physician was involved in 67% of treatments and over 75% of clinics reported patient satisfaction following treatment. Conclusions Although the number of human clinical trials evaluating novel treatments for ED and PyD are limited, several clinics are offering these therapies with promises of success without evidence to support the claims. Our data demonstrates the wide use of experimental therapies for ED and PyD across the US. Clinical outcome data available for patients is largely up to the clinics discretion, and was only given to us in subjective measurements and testimonials. Disclosure No

Introduction Elevated hematocrit (Hct > 52%) in men receiving testosterone therapy (TTh) has been associated with major adverse cardiac events (MACE), but it remains unclear if the degree of change from baseline Hct after starting TTh confers additional MACE risk. Objective The objective of this study is to assess if greater changes in Hct after initiation of TTh for men is associated with greater risk of MACE. Methods We compared the occurrence of MACE within 3 and 24 months of initiating TTh in men who did and did not experience an increase in Hct after TTh initiation. We queried the TriNetX Research network database, a health research network of 88 million patients, encompassing healthcare encounters and prescriptions between 2009-2021. Men without unstable angina or heart failure over age 18 were included if their Hct was tested within 1 year prior to initiating TTh and had follow up Hct within 3 and 24 months after beginning TTh. Men with and without increase in Hct after TTh were propensity matched on age, race/ethnicity, hypertension, diabetes, hyperlipidemia, prior myocardial infarction or stroke, and number of hospital/outpatient visits. MACE were defined as myocardial infarction (ICD-10: I21-22), stroke (I60-63), or death. Results A total of 11,561 men with an increase in Hct and an equal number of controls were included (average age 49.4 years). When compared to men who received TTh who did not have an increase in Hct, the majority of men with an increase in subsequent Hct a statistically significant increase risk of MACE (Table 1). For example, men with baseline Hct of 44-47% and saw a subsequent increase of Hct to 48-51% were twice as likely to experience MACE (Risk Ratio: 2.07, 95% Confidence Interval 1.13-2.43) when compared to men whose baseline and subsequent Hct was 44-47% after TTh. As the change in Hct from baseline becomes larger, the magnitude of the risk ratio increased. Conclusions While absolute Hct is associated with increased risk of MACE after initiating TTh, we demonstrate that increases in Hct from baseline are associated with dose-dependent increased risk of MACE, compared to men with minimal changes to Hct who receive TTh. Disclosure No

Introduction Worldwide 10–15% of male adolescents have a varicocele, which is the most common surgically correctable cause of male subfertility. In young adult men, varicocele can be associated with smaller testis volume and abnormal semen parameters. However, there is still controversy in whether surgical repair has better long-term outcomes than just active surveillance. Objective To evaluate satisfaction, symptoms improvement, hypogonadism, and paternity in patients who underwent varicocelectomy when they were adolescents. Methods We performed a retrospective chart review of adolescents undergoing varicocelectomy from 2011-2021. Inclusion criteria were having primary varicocele, having 12-21 years at time of surgery, having had the varicocelectomy >1-year ago, ≥1 postoperative visits, and having answered the questionnaire. Exclusion criteria were having a diagnosis of secondary varicocele (renal malignancy or venous abnormality) and incomplete records. Data about clinical, surgical, and postoperative outcomes were gathered. Patients were contacted by phone and were asked about orchialgia, paternity, varicocele recurrence, diagnosis and treatment for hypogonadism, and satisfaction after surgery. Descriptive analysis and paired t-test were used, statistical significance was assessed at p Results From a total of 50 patients meeting the inclusion criteria, we were able to contact 23 patients. The mean age at varicocele diagnosis was 17.43±2.52 years. Varicocele was grade 3 in 16 (69.6%) patients and left-sided in 17 (73.9%) patients. Eight (34.8%) patients had a preoperative testicular ultrasound, that in 2(25%) patients showed testicular volume discrepancy >20%. At the physical exam, 6(26.1%) patients were found to have asymmetric testicles. Overall, 2(8.7%) patients had a previous varicocele repair and 7(30.4%) had a preoperative abnormal semen analysis. Mean age at surgery was 18.78±2.02 years. Microscopic varicocelectomy was performed in 22 (95.7%) patients, mainly in the left-side (78.3%). Pre- and postoperative FSH and T levels were done in 10 patients, without any significant difference after surgery (p=0.074 and p=0.069, respectively). Pre- and postoperative semen analysis were performed in 12 patients and showed a significant improvement in motility after varicocelectomy (p=0.022). Mean follow-up after surgery was 1.42±1.40 months. The questionnaire was performed in a mean of 3.43±2.55 months after varicocelectomy and the mean age of the responders was 22.3±3.11 years. Orchialgia persisted in 7 patients (30.4%), predominately in the left side (71.4%). None of the patients had been diagnosed with varicocele recurrence nor had required a surgical reintervention. Twenty-one (86.9%) patients were not actively trying to achieve a natural conception nor had been involved in a pregnancy after varicocelectomy. Two patients (8.7%), with a preoperative abnormal semen analysis, were able to conceive. None of the patients referred to have hypogonadism nor being under testosterone therapy. The majority of patients (86.9%) referred to be satisfied with the postoperative results. Conclusions Our results suggested that long-term outcomes of varicocelectomy in adolescents would show high patient satisfaction, low rate of recurrence, no association with hypogonadism, and a significant persistence of testicular pain. Although male fertility after varicocelectomy demonstrated promising results, a longer follow-up assessment should be done when patients are actively trying to conceive, to have a more representative sample size. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus, Boston Scientific, Endo Pharmaceuticals and Coloplast

Introduction Platelet Rich Plasma (PRP) is a novel restorative therapy rich in growth factors and cytokines used to target the underlying causes of erectile dysfunction (ED). It is not known, however, if the composition of growth factors in PRP varies between men. Objective This study aimed to evaluate PRP growth factor variability among men with ED. Methods Whole blood was collected from sixteen men, eight participants with at least a six-month history of ED. The others were the control group, including seven men with Peyronie’s Disease (PD) and one healthy man without sexual dysfunction. PRP was extracted from whole blood using the Arthrex Angel system. A Human Growth Factor Antibody Array for 41 proteins was performed. Using all 16 samples, quantitative detection of GM-CSF, VEGF, and TGF-β were validated by western blot. Results From the growth factor array, two growth factors - Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Transforming Growth Factor-beta (TGF-β) - were identified as having a 1.5-fold decrease between the participants and the control. In addition to the shortlisted growth factors, VEGF was selected because androgens can upregulate VEGF production. Other than a weak negative correlation between VEGF expression and age, we found no correlation between growth factor expression for GM-CSF or TGF-β and age, BMI, or comorbidities. Conclusions PRP growth factor concentration appears to vary among men with ED. Depending on individual growth factor concentration, PRP treatment for ED may need to be personalized for patients. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Nestle Health, Olympus, Hims, Inc.

Introduction Ischemic priapism is a urologic emergency which results in permanent erectile dysfunction if not managed immediately. There is a dearth of studies evaluating long term erectile function after episodes or treatment for priapism. Objective We evaluated the functional outcomes of a larger, multi-institutional population of men with priapism due to recreational use of ICIs. Methods Men who presented with ischemic priapism due to recreational use of ICIs to Cedars-Sinai Medical Center (Los Angeles, CA), University of California at San Francisco (San Francisco, CA), and Jackson Memorial Hospital (Miami, FL) from January 2010 to December 2018 were contacted via telephone. All participants completed the five-item international index of erectile function (IIEF-5). Results A total of 19 men aged 24 – 59 (mean 47.9) were recruited from the 3 sites. Mean follow up was 77.2 months (+/− 27.6). 17 men (89%) were white; the one man was Asian (5.5%) and one man was Hispanic (5.5%). Seven men (37%) had been diagnosed with ED prior to their priapism episode however none of the men had a prescription for ICIs. Four men (21%) required no intervention at all, eleven men (58%) required phenylephrine irrigation alone, four men (21%) required distal shunting. No men required proximal shunting. None of the men had no ED, 31.6% had mild ED, 36.8% had mild-moderate ED, 26.3% had moderate ED, and 5.3% had severe ED. Mean IIEF-5 for the population was 13.4 (+/− 3.9). Strengths of our study included the large population size give the relative rarity of this condition as well as the geographic diversity of our population. Limitations include our low overall recruitment rate and lack of objective measures of erectile function prior to priapism. Conclusions Men who suffer ischemic priapism secondary to recreational use of ICIs appear to retain some erectile function following their priapism episode. Nevertheless, 100% report some level of ED. This is likely due a combination of adequate erectile function at baseline and expeditious treatment of priapism in a minimally invasive manner. Disclosure No

Introduction In our current technology-driven society, patients and healthcare professionals alike are becoming increasingly reliant on online platforms for disseminating and obtaining health information. Previous research has shown that the quality of information available on the internet about novel medical therapies is generally poor and frequently misleading. Therefore, we hypothesized that online sources regarding novel erectile dysfunction treatment options, such as shockwave therapy, would be fraught with misleading claims and unreliable health information. Objective To evaluate the quality and readability of online health information on shockwave therapy as a treatment for erectile dysfunction. Methods Websites were generated using a Google search of “shockwave therapy for erectile dysfunction” with location filters disabled. Advertisements, scientific research articles, clinical trials, and websites that required subscriptions to access information were excluded from analysis. The websites included were from universities, private clinics, and news media outlets. Readability was analyzed using the Readable software (Readable.com, Horsham, UK). The content quality was graded using the DISCERN tool, a questionnaire that assesses the quality of written information on treatment choices for a health problem. Screening was done independently by 3 reviewers. Statistical analysis was conducted using the Student’s t-test. Results Nine articles that resulted from the Google search had mean readability scores as follows: Flesch-Kincaid grade level (10.8), Gunning-Fog Index (13.67), Coleman-Liau Index (12.74), Simple Measure of Gobbledygook (SMOG) Index (13.33), FORCAST Grade Level (11.33), and Automated Readability Index (11.08). The mean Flesch-Kincaid reading ease index was 46.4, which is difficult. No single article was at the 6th or 8th grade reading level, as recommended by the American Medical Association (AMA) and National Institutes of Health (NIH), respectively. There was no significant difference between the overall website ratings based on the DISCERN instrument (p= 0.565). The articles had a mean DISCERN score of 3.1, which refers to moderate quality (potentially important but not serious shortcomings). Four articles were from websites of private medical practices that each offered shockwave therapy for ED with a mean DISCERN score of 2.1. Five of the nine articles were from universities (n=2) or news sources (n=3) with a significantly higher mean DISCERN score of 4.0 (p Conclusions Overall, the quality of online information on shockwave therapy for ED is adequate. However, while articles from private clinics are just as readable as those from universities or news media, they are significantly more biased and misleading. The current online material may not support patients in making medical decisions and garnering knowledge, necessitating closer collaboration between the sources disseminating information and urologists. Disclosure Yes, this is sponsored by industry/sponsor: National Institutes of Health Grant R01 DK130991, American Cancer Society Clinician Scientist Development Grant. Clarification Industry funding only - investigator initiated and executed study.

Introduction Restorative therapies are advertised as a cure for erectile dysfunction (ED) despite lack of data. One such therapy is platelet-rich plasma (PRP). PRP is created through centrifugation of autologous blood and separation of the platelet rich layer containing cytokines and growth factors involved in wound healing. We are conducting an ongoing, single center, prospective, one-to-one randomized, double blind, placebo controlled clinical trial assessing the safety and efficacy of PRP for ED (NCT04396795. Registered April 3, 2020). To reduce the variability in PRP concentration inherent to most PRP systems, we are using the Arthrex angel, the only system with an optical sensor to tailor PRP dose. Objective To assess the safety of injecting intracavernosal PRP in men with ED. Methods We retrospectively reviewed our clinical safety and adverse events data from September 2020 to May 2022. Patients receive either two injections of PRP or saline (placebo) four weeks apart. Patients were observed immediately post injection for adverse events. Additionally, patients were evaluated at 1-, 3- and 6-month periods. Finally, a Doppler ultrasound was completed at 6 months after last injection to assess for any structural or vascular changes to penis. For this analysis, we did not unblind patient groups. We report data from men who have received any injection with PRP or placebo and compared group A and B. We assessed statistical significance through t-test, where alpha=0.05. Results In total, 60 trial patients were included, 28 in group A and 32 in group B. There was no difference in pain with injection 1 (p=0.69) or injection two (p=0.99) (table 1). In each group, no major adverse events were recorded. In group A, only 1 minor adverse event, new penile plaque, was found (4.3%). This is similar to group B, where only 1 minor adverse event was reported (4.3%). No other minor adverse events were reported. Conclusions PRP appears safe to inject intracorporeally in patients with ED in our ongoing randomized placebo-controlled trial. Efficacy could not be assessed at this time. However, our study can help counsel patients on the side effects and complications associated with PRP. Disclosure No

Despite apoptosis processes being conserved, cancer cells have developed mechanisms to inhibit apoptosis by altering anti-apoptotic molecules or inactivating pro-apoptotic. The aim of this study was to determine the palmitic acid of Musa paradisiaca var. sapientum (L) Kunz (MP) stem extracts against human oral squamous cell carcinoma (hOSCC) through caspase-3.Ethanol and ethyl acetate extracts of MP stem were analyzed by gas chromatography-mass spectrometry (GC-MS). Computerized models of chemically active compounds were used to predict anticancer activity. Cytotoxicity was evaluated in Artemia salina Leach and hOSCC (OM-1) culture at concentrations 100, 90, 80, 70, 60, 50, 40, 30, 20, and 10 µg/mL respectively. The expression level of caspase-3 on hOSCC was measured by enzyme-linked immunoassay (ELISA).We found seven chemically active compounds in the ethanol extract and 15 compounds in the ethyl acetate extract of MP stem. The major component was hexadecanoic acid of palmitic acid derivates, and this was predicted to have anticancer activities as apoptosis through caspase-3 stimulants. However, cytotoxicity effects against hOSCC culture were assessed by values of the 50% inhibitory concentration (IC50) of 15.00 µg/mL for the ethanol extract, and an IC50 of 10.61 µg/mL for the ethyl acetate. There was a significant increase of caspase-3 level on treatment groups compared to control.Hexadecanoic acid of MP stem extracts has anticancer activity by inhibiting cell growth of hOSCC culture through caspase-3 stimulants.

Aim: The present study aims to explore the psychological correlates that are related to career oriented positive psychological strengths, namely, Career Adaptability, Career Optimism and Perceived Knowledge among the panchayat school students. Materials and Methods: It is basically a report of the pilot study for a major ICSSR fellowship study which is exploratory and descriptive in nature. A popular village panchayat school in Salem district with a 300 students was chosen as the target school. 134 students were randomly selected. Of them 80 were girls and 54 were boys. They were all administered career futures inventory developed by Patrick Joseph Rottinghaus (2004). It measures career optimism, career adaptability capacities and perceived knowledge. In this study these variables are considered positive psychological variables for positive psychology has emerged as a separate branch of study and the field has started attracting controlled randomized experimental investigations. Synopsis of the Result: The percentage analysis revealed that 70.1% of students have chosen a career and have not investigated about their chosen career. 21.6% of students investigated a number of careers and have selected only one. 47.8% of the students quite often think about their career goals. 40.3% of students said they put high level of effort for their school work. 66.4% of students said they put high level of effort for learning about their career options. During a typical week, only 2.2% of students spent over 60 hours of activities related to their school work. 4.5% of students are found to be very dissatisfied about their current major. 41% of students are spending 16-30 hours and 6% are over 60 hours to explore their career options during the last 6 months. The analysis of correlation revealed no significant relationship among these three variables. However, results of independent t’ test revealed that Female village panchayat school students were found to have more career adap

Introduction Peyronie's Disease (PD) is prevalent in approximately 7.1% of the general population. Current treatment approaches include medical therapy and surgical intervention, and intervention only occurs once the disease process has entered the chronic, stable phase. The only FDA-approved medical therapy involves use of intralesional collagenase clostridium histolyticum injection and surgical interventions include tunica albuginea plication, plaque excision without grafting, or placement of penile prothesis. Additional PD therapies are needed as current treatment modalities have limited efficacy and considerable side effects. Platelet-derived therapies have seen increased use across various specialties in medicine, especially in orthopedics, due to their potential ability in wound healing and tissue regeneration. As calcified scar plaques are frequently identified in PD patients, autologous platelet rich plasma (PRP) may prove to be a viable treatment for this patient population. Objective We reviewed an initial series of patients receiving PRP vs placebo for PD to assess safety and feasibility among men recruited in a double-blind placebo controlled single-center clinical trial. Methods We reviewed data for men recruited into the clinical trial treated with PRP vs placebo at our center from April 2021 to July 2021. Patients were observed immediately post-injection and at follow-up for complications and tolerability. Where applicable, International Index of Erectile Function (IIEF-5) scores were reviewed before and after injections for PD. Results We report data from the men who have completed 2 completed injections (PRP or placebo). No post-procedural minor adverse events were seen in any of the men. None of them reported adverse effects such as penile bruising, swelling, edema, allergy, penile fracture, or mild pain at injection site. No patients experienced complications at follow-up. No worsening curvature was observed in men completing pre/post evaluations. Conclusions PRP appears to be a safe and feasible treatment modality in patients with PD from our limited data accumulated thus far in our ongoing randomized placebo-controlled trial with PRP for PD. Our study is the first study in the USA accruing men with PRP for PD and believe that safety and efficacy data accumulated from our study will be important for patient counseling. Disclosure No

Introduction Men taking testosterone therapy (TT) have potential side effects such as polycythemia, testicular atrophy, and decreased spermatogenesis. Recent evidence has shown that the modality of delivery may affect the prevalence of these side effects. We hypothesized that intranasal short-acting testosterone will have a lower rate of polycythemia than injectable long-acting testosterone because shorter-acting formulations can more closely mimic normal physiology. Objective To compare the effects of Natesto and Testosterone Cypionate (TC) on hematocrit and serum testosterone levels in testosterone deficient men over 4 months. Methods This Phase IV, randomized, open-label clinical trial was performed on 30 symptomatic, testosterone deficient men with at least two serum testosterone levels below 300 ng/dL drawn before 10AM. Men were randomized (1:1) to receive either Natesto three times per day (5.5mg per nostril) and intramuscular TC (200mg) once every two weeks. Hematocrit and serum testosterone were evaluated before and after four months. The primary outcome was changes in hematocrit. Secondary outcomes were changes in E, DHT, PSA and 17-OHP. Data analysis was performed using two-sample and single-sample T tests, and determination of equal or unequal variances was computed using F tests. Results The median participant age was 45 years old. At baseline, serum T of all participants was 239.6 ng/dL and hematocrit of 43.1. Prevalence of participants who screened positive for OSA on STOP-BANG questionnaire for Natesto and TC group were 75% and 78%, respectively. The 4-month change in hematocrit in the Natesto group (-1.1 from baseline) was significantly less than the change in hematocrit seen in the TC group (+5.1 from baseline), (p < 0.001, t = -7.6). Prevalence of polycythemia (HCT > 52%) after 4 months was 0% in Natesto group and 5.5% in TC. Both groups increased testosterone levels above baseline at 1 and 4 months, with a larger increase seen in the TC group compared to Natesto (p = 0.029, t = 1.71), (Figure 1B). In the Natesto group, secondary outcomes E, DHT, PSA, and 17-OHP changed -2.9 (p = 0.54), +4.3 (p = 0.64), +0.34 (p = 0.52), and +1.6 (p = 0.88) from baseline, respectively (Figure 1C). In the TC group, secondary outcomes E, DHT, PSA, and 17-OHP changed +21.2 (p= 0.019), +4.3 (p = 0.64), -0.34 (p = 0.52), and -42.9 (p > 0.001) from baseline, respectively (Figure 1C). Conclusions Short-acting nasal testosterone does not appear to increase serum hematocrit when compared to intramuscular testosterone cypionate, while both modalities returned men to a eugonadal serum testosterone level (>300 ng/dL) in 83% of men. In men who are at risk of developing polycythemia (obstructive sleep apnea, high baseline hematocrit), nasal testosterone gel or other short acting formulations should be strongly considered. Disclosure Yes, this is sponsored by industry/sponsor: Acerus Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study