bluuebunny/crossref_metadata_2025 huggingface dataset:
(067) Oral Testosterone, Is It Ready for Prime Time? A Meta-analysis of Safety and Efficacy in Men with Testosterone Deficiency
Authors: Miller J , Nguyen T , Loeb C , Khera M , Yafi F
Published: May 2023

Introduction

The prescription rates of testosterone replacement therapy (TRT) have tripled within recent decades. Recently, two novel oral testosterone undecanoate (TU) options have obtained FDA approval and are now commercially available. We present the first meta-analysis analyzing the safety and efficacy of oral TRT in patients with testosterone deficiency (TD).

Objective

To evaluate the safety and efficacy of TU in the treatment of TD

Methods

Pair-wise meta-analyses were performed including randomized, placebo-controlled trials investigating the use of TU. Studies were included for analysis if participants received oral TRT or placebo for a period greater than one month and if adverse effects (AE) or changes in serum total testosterone (TT) were recorded.

Results

Nine studies including a total of 606 patients recorded changes in TT. When separated by population, studies including only men with TD saw improved TT (mean change 1.25 ng/mL, 95% CI: 0.22 to 2.29, I2: 0%). Eight studies including a total of 849 patients recorded rates of AE. There was no statistically significant change in the risk of AE in patients receiving oral TRT compared to placebo (log risk ratio -0.03, 95% CI: -0.08 to 0.03, I2: 0%) [Figure 1].

Conclusions

When separated by inclusion criteria, studies examining men with TD tended to report improved TT levels following treatment with TU compared to placebo. In studies examining the safety of oral TRT, its use was not associated with increased rates of AE when compared with placebo.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Antares Pharma; Clarus Therapeutics; Coloplast; Cynosure; Promescent; Sprout; Viome.
(070) Testosterone Therapy in Men with Klinefelter Syndrome: Analysis of a Global Federated Research Network
Authors: Carto C , Loloi J , Campbell K , Ramasamy R
Published: May 2023

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
(082) The Effect of Sex Steroids on RhoA/ROCK Pathway in Rat Distal Vagina
Authors: Cellai I , Comeglio P , Filippi S , Martinelli S , Amore F , Rapizzi E , Maseroli E , Raddi C , Guarnieri G , Cipriani S , Sarchielli E , Morelli A , Rastrelli G , Maggi M , Vignozzi L
Published: May 2023

Introduction

The RhoA/ROCK calcium-sensitizing pathway plays a role in clitoral contractility, and therefore we deemed interesting to investigate its involvement in the vagina.

Objective

The aim of this study was to investigate the sex steroid regulation of the vagina contractility through the RhoA/ROCK pathway, using a validated animal model.

Methods

Ovariectomized Sprague-Dawley rats (OVX) were treated with 17β-estradiol (E2), testosterone (T), with or without letrozole (T+L), and compared with intact animals. Contractility studies were performed on vaginal strips to test the effect of ROCK inhibitor Y-27632 and NO synthase inhibitor L-NAME. In vaginal tissues, ROCK1 immunolocalization was investigated, mRNA expression was analyzed by semi-quantitative RT-PCR, and RhoA membrane translocation was evaluated by Western blot (Wb) analysis. Finally, rat smooth muscle cells (rvSMCs) were isolated from distal vagina of intact animals and the quantification of RhoA inhibitory protein RhoGDI was performed by Wb after stimulation with NO-donor SNP, with or without the soluble guanylate cyclase inhibitor ODQ or the PKGR1 inhibitor KT5823 administration.

Results

The results show that ROCK1 was immunolocalized in the smooth muscle bundles and in the blood vessel wall of vagina, while a weak positivity was detected in the epithelium. Y-27632 induced a dose-dependent relaxation of noradrenaline pre-contracted vaginal strips, decreased by OVX and completely restored by E2, while T and T+L further decreased it even below OVX level increased it. Accordingly, in Wb analysis, compared to controls, OVX significantly induced RhoA activation, as reveled by its membrane translocation, with T reverting it at a level significantly lower than in controls. This effect was not exerted by E2. Abolishing the NO formation via L-NAME increased Y-27632 responsiveness in the OVX+T group; L-NAME had only a partial effect in controls whilst it did not modulate Y-27632 responsiveness in OVX. Finally, stimulation of rvSMCs with SNP significantly increased the RhoGDI protein expression, an effect counteracted by ODQ and, partially, by the protein kinase inhibitor KT5823 incubation.

Conclusions

In conclusion, in vagina androgen administration in OVX functionally decreases RhoA/ROCK activity by hampering RhoA membrane translocation and plays a critical role in the inhibitory mechanism of the smooth muscle distal vagina contractility. Accordingly, androgens, by inhibiting the RhoA/ROCK pathway, could positively contribute to vaginal smooth muscle relaxation, favoring the sexual intercourse.

Disclosure

No
(085) Montelukast, a LRRC8A Inhibitor Decreases the Contractile Response to Phenylephrine in the Corpus Cavernosum of Diabetic Mice
Authors: Wilczynski S , Garnto D , Garnto A , Dos Anjos Moraes R , Choi H , Arishe O , Lamb F , Priviero F , Webb R C
Published: May 2023

Introduction

Increased reactive oxygen species are often correlated with erectile dysfunction (ED) by enhancing contractility and favoring the flaccid state of the penis (which is mainly mediated by α-adrenergic innervation) and decreasing the relaxation of the corpus cavernosum (CC) associated with decreased nitric oxide (NO) bioavailability. Leucine Rich Repeat Containing 8 (LRRC8) Volume Regulated Anion Channels (VRACs) regulates Nox1 and modulates the extracellular production of superoxide anion (O2•-). Downregulation of LRRC8 is associated with decreased production of O2•- and we have demonstrated improved relaxation and reduced contraction of the pudendal artery in LRRC8A knockout mice.

Objective

In this study, we aim to test the hypothesis that inhibition of Nox or LRRC8A decreases phenylephrine (PE)-induced contraction in the CC of diabetic mice.

Methods

To test this hypothesis, the CC of diabetic (dbdb-/-, 16-week-old) mice were mounted in myographs, and the contraction elicited by PE was performed in the absence and repeated in the presence of the LRRC8 inhibitor, montelukast or Nox1/Nox4 inhibitor, GKT137831. The maximal contraction in the absence of the inhibitor was taken as 100%, and the contraction in the presence of the inhibitor was calculated as a percentage of the maximal contraction attained in the absence of the inhibitor.

Results

Contraction induced by phenylephrine in the CC of diabetic mice (1.27 + 0.2 mN) was similar to that observed in the control mice (1.26 + 0.4 mN). In the presence of the LRRC8 inhibitor, montelukast, PE-induced contraction of the CC was significantly reduced, reaching maximal contraction of 69 + 7% and 65 + 10% in the control and diabetic group, respectively. In the presence of the Nox1/Nox4 inhibitor, GKT137831, the contraction elicited by PE was reduced only in the diabetic group (68 + 9% of the maximal contraction), whereas in the control group this reduction was not significant (82 + 14% of the maximal contraction).

Conclusions

This is the first study demonstrating that, in the CC, LRRC8 modulates the contractile response induced by α-adrenergic stimulation and this may be associated with O2•- production, which plays a role in the development of ED. Since a great number of diabetic patients are not benefited by phosphodiesterase 5 inhibitors therapy, LRRC8 might be a potential therapeutic target for the development of new drugs to improve sexual function in diabetes.

Disclosure

No
(087) Association of ESRα T397C (rs2234693) with Male Infertility: A Meta-analysis
Authors: Javed N , Irfan M , Arshad A , Bibi A , Nik Hussain N H , Ismail S B
Published: May 2023

Introduction

Infertility is the incapability to achieve fertilization after a certain period following sexual intercourse without any contraceptive measures which affects 1 in 6 couples. Male factors contribute 50%. The male reproductive system is affected by both environmental and genetic factors. Genetics variations include chromosomal aberrations, genomic and/or mitochondrial single gene mutations or polymorphism, and multiple gene mutations or polymorphism that result in spermatogenic failure. Genetic variations of key genes might have a role in male infertility. In this regard, polymorphism in the estrogen receptor gene may be an important factor increasing the risk of male infertility. In men, estrogen is produced in the testis by Sertoli cell, Leydig cell and germ cells that play an important role in the maturation and capacitation of sperms. The action of estrogen is mediated by two specific Receptors: Estrogen receptors α (ESRα) and Estrogen receptor β (ESRβ). ESRα gene is present on chromosome 6q25. It consists of 8 exons which are parted by 7 intronic regions having a complete size of 140 kb. ESRα codes for 595 amino acid proteins. The most widely studied single nucleotide polymorphism (SNP) in ESRα is T397C (rs2234693). It is found in intron 1 and divided by 46 bp. Few previously published studies reported an association between this SNP in ESRα and male infertility, while others found no association.

Objective

The present study aims to estimate the association between ESRα T397C (rs2234693) and male infertility.

Methods

PUBMED, CENTRAL, Google Scholar and PMC articles were searched, whereas case-control, published studies regarding ESRα T397C (rs2234693) and male infertility were selected for this meta-analysis.

Results

Four studies finally fulfilled the criteria of the meta-analysis. No significant association (p > 0.05) was found overall, between ER alpha polymorphism and male infertility, based on all of the four genetic models. However, when stratified into two ethnic groups, ER polymorphism was found to be significantly associated with male infertility in the Caucasian group based on the dominant model (CC + CT vs TT: OR= 1.43, 95% CI [1.08-1.91], I2 = 89%) as well as recessive model (CC vs CT+TT: OR= 1.34, 95% CI [1.01-1.76], I2 = 0%), whereas, in the Asian group, only the dominant model (CC + CT vs TT: OR= 1.97, 95% CI [1.58-2.46], I2 = 98%) indicated significant association of ER alpha polymorphism with male infertility.

Conclusions

ESRα T397C (rs2234693) polymorphism is linked with male infertility in the two ethnic groups, i.e., homozygous conditions in Caucasian and dominant conditions in Asian populations.

Disclosure

No
(096) Chronic Oral Exposure to Short Chain - Chlorinated Paraffins Induced Testicular Toxicity by Promoting NRF2-mediated Oxidative Stress
Authors: Li C
Published: May 2023

Introduction

Chlorinated paraffins (CPs) are important additives in a variety of chemical processing. Based on the lengths of the carbon chains, CPs are classified into short-chain CPs (SCCPs, C10-13), medium-chain CPs (MCCPs, C14-17) and long-chain CPs (LCCPs, C18-30) with the chlorine content ranging from 30%-70%. SCCPs were listed in the persistent organic pollutants (POPs) by Stockholm Convention due to its toxicity, bioaccumulation potential, long range transport potential and environmental persistence. Numerous studies have analyzed the toxicities of SCCPs in various organisms, with the toxic effects including lethality and carcinogenicity, developmental toxicity, endocrine disrupting effect and immunomodulatory effect.

Objectives

As a widespread environmental contaminant, short chain chlorinated paraffins (SCCPs) has attracted great attention. However, the toxicity of SCCPs on male reproductive system remains ambiguous. In this study, we investigated the toxic effects of SCCPs on testis.

Methods

We treated mice with 1,10 or 100 mg/kg bm/d SCCPs by gavage once a day for 35 days. The tissues and blood samples were collected after treatment. The weight of mice and testes were measured. The organ index is the body weight divided by the weight of the testis. The left testes were used for protein extraction, RNA extraction and measurement of SOD, CAT, GST and MDA. The left epididymis was used for analysis of sperm parameters. The right testis and epididymis were fixed in Bouin’s solution for H&E and TUNEL staining. GC2 cell (mouse spermatocyte) treated with SCCPs was used to examined the cell viability by CCK8 kits. Cellular ROS generation was evaluated by 2',7'Dichlorodihydrofluorescein diacetate (DCFH-DA). We used Apoptosis Detection Kit to detect the cell apoptosis by dual staining cells with Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI).

Results

SCCPs resulted in disorderly arranged seminiferous epithelium and increased apoptotic cells in testes. Both in vivo and in vitro experiments indicated that the oxidative stress was induced after SCCPs exposure, and dysfunction of nuclear factor erythroid-related factor (NRF2) signaling pathway played a role in this process. Moreover, resveratrol, an NRF2 activator, could alleviate the damage of SCCPs on spermatogenetic cells in vitro. Our study indicated that oxidative stress is the key point for explaining the testicular toxicity caused by SCCPs, and NRF2 could be used as a potential target for clinical treatment to alleviate the reproductive toxicity induced by SCCPs.

Conclusions

Our study is the first to evaluate the toxic effects of SCCPs on male reproductive system, which is associated with overproduction of ROS. This study also indicates that NRF2/ARE pathway plays the vital role in the toxic effects of SCCPs in spermatogenesis, thus providing a target for the prophylaxis and treatment.

Disclosure

No
(100) Extended Reality-Assisted Surgery (XRAS): A Novel Surgical Training Tool During Cadaver Lab
Authors: Hakky T , Carrion RE , Crespo R , Henry G D , Jay Simhan J S , Shridharani A , Carrion R E
Published: May 2023

Introduction

XRAS (extended reality-assisted surgery) is a revolutionary modality that assists the surgeon in real-time by overlaying 3-dimensional computer-generated images into the users’ field of view.

Objective

To insert a Titan 3-piece inflatable penile implant (IPP) on cadaver A and a male virtue sling on cadaver B while utilizing XRAS as a training tool.

Methods

Two cadavers were used for this lab. While 2 surgeons were present and operating on the physical bodies, 2 additional physicians were remote and communicating via HoloLens 2 Developer Editions. By utilizing the Apoqlar©Hamburg, Germany application, the 2 remote surgeons could communicate, observe, and advise the live surgery. Cadaver A was in the supine position for a penoscrotal approach while B was in the lithotomy position for placement of the male virtue sling. A questionnaire was issued to attendees after the procedures to evaluate the role of the HoloLens in the operating room.

Results

While performing the respective surgeries on the two cadavers, XRAS was successfully implemented in real-time. Superimposed virtual surgical devices were placed and manipulated in 3D space during surgery to allow for augmented surgical technique during penile implant and male virtue sling insertion. The questionnaire yielded findings that, of the 4 attendees who participated in the surgery, all were in favor of integrating XRAS into the operating room. Attendees reported minimal overheating and discomfort, and sufficient battery life for a 90-minute interval.

Conclusions

XRAS represents the next paradigm shift in surgery and surgical training. It provides an augmented surgical view all while ergonomically positioned on the head of the surgeon. Implementation of XRAS in surgery can improve efficiency, education, accuracy, and surgical outcomes. Further studies and evolution of the software are needed to elucidate the value of such technology for real-time surgery.

Disclosure

Yes, this is sponsored by industry/sponsor: Coloplast

Clarification

Industry funding only - investigator initiated and executed study

Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast
(115) Mechanical and Anatomic Indications for Inflatable Penile Prosthesis Revision
Authors: Smelser A , Nealon S , Badkhshan S , Sanders S , Monaghan T , Langford B , Vandyke M , Morey A
Published: May 2023

Introduction

Implantation of an inflatable penile prosthesis (IPP) is considered the gold standard for definitive treatment of men with refractory erectile dysfunction. As mechanical devices, IPPs have a finite lifespan, thus often requiring surgical revision or replacement of components over time.

Objective

To characterize the location of IPP mechanical component failure in patients presenting for revision or explant and stratify them by device manufacturer [Boston Scientific (BSc) and Coloplast (CP)].

Methods

A retrospective chart review of our large, single-surgeon, tertiary referral center penile prosthesis database between 2007-2022 was completed to identify all men who underwent IPP revision (partial or full device) or explant. Only cases having intraoperative documentation of cause for IPP failure and device manufacturer were included. Reasons for revision or replacement surgery were categorized into mechanical (tubing, cylinder, or reservoir leak and pump malfunction) and non-mechanical (component herniation, erosion, or crossover). All revisions performed due to non-mechanical reasons were excluded from analysis. Chi-square analysis was used to assess failure rates and causes. A Student’s T-test was used to assess time to revision and demographics.

Results

Among 933 IPP cases, we identified 133 patients who underwent 272 revision procedures; 154 met inclusion criteria (96 BSc and 58 CP). Forty-four (29%) of those surgeries were revisions of devices placed by outside surgeons, and 110 (71%) were revisions of IPPs inserted at our institution. Average patient age was 67 years for BSc and 63 years for CP (p = 0.086), and the average BMI was 28.7 for BSc and 30.8 for CP (p = 0.122). Time to revision was similar between brands at an average of 39 months for BSc and 56 months for CP (p = 0.11). Eighty-one (53%) of the surgeries were revisions of one affected implant component, 56 (36%) were full device removal/replacement, and 17 (11%) were full explants. Coloplast devices required revision more frequently due to tubing fracture (p < 0.01), and BSc devices required revision more frequently due to pump malfunction (p = 0.02). Both devices rarely failed due to cylinder or reservoir defects (Figure).

Conclusions

Although time to revision was similar between the two brands, CP devices malfunctioned more often due to tubing fracture whereas BSc devices failed more often due to pump malfunction.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast
(116) Comorbidity Profile Network Analysis of Men with Erectile Dysfunction
Authors: Greear G , Dadhich P , Stanaway I , Walsh T , Nicholson T , Wessells H , Holt S , Hehemann M
Published: May 2023

Introduction

The modern understanding of the comorbidities associated with erectile dysfunction (ED) has been shaped by the findings of decades-old survey-based epidemiologic studies. The demographic structure and comorbidities of the United States population have since changed. A contemporary assessment of the comorbidity profile of men with ED is timely and indispensable for the efficient care of these men.

Objective

The objectives are to describe the comorbidity profile of a contemporary cross-section of men with erectile dysfunction, to identify clinically meaningful health trends, and to evaluate whether clusters of men with distinct comorbidity profiles can be discerned.

Methods

A cross-sectional analysis of the MarketScan® administrative claims database from 2008 to 2019 was performed. Inclusion criteria were men 18 to 64 years of age with a diagnosis of ED or phosphodiesterase type 5 inhibitor (PDE5i) prescription with at least 1 year of enrollment before the index date, as well as age-matched controls without an ED diagnosis or related prescription. Comorbidities were extracted by ICD-9/10 diagnosis codes and categorized by the Elixhauser Comorbidity Index. The trends in prevalence of comorbidities and odds of comorbidity diagnosis, overall and by age group, were analyzed. To elucidate the relationships between common comorbidities, a novel comorbidity network was performed with comorbidity strength estimated by observed-to-expected ratio (OER) of disease (prevalence > 0.01) in pairs with a comorbid prevalence > 0.001.

Results

The prevalence of all comorbidities in men with and without ED increased over the study period. The five most prevalent comorbidities (and percentage increase) among men with ED were hypertension (108%), diabetes without complication (78%), obesity (357%), chronic pulmonary disease (124%), and depression (164%) (Figure 1). The association of ED with comorbidities such as complicated diabetes and paralysis tended to be more pronounced among men in the younger cohort (18-45 years of age, vs 46-64 years of age) (Figure 2). Between 2008 and 2014, a generalized increase in the strength of association of ED with prevalent comorbidities is observed (Figure 3).

Conclusions

The comorbidity profile of men with ED has evolved since its initial characterization nearly 30 years ago. Increases in comorbidities associated with obesity and metabolic syndrome, as well as mental health disorders, are particularly notable. The findings illustrate the complex interplay of chronic health conditions in men with ED, and serve to justify the comprehensive evaluation of men of all ages who present with ED.

Disclosure

No
(127) Relationship Between Severity of Erectile Dysfunction and Systemic Immune Inflammation Index and Neutrophil Lymphocyte Ratio
Authors: Culha M G , Ward S , Baran C , Ermec B
Published: May 2023

Introduction

Endothelial dysfunction has an important place in the pathogenesis of erectile dysfunction (ED).

Objective

The aim of this study was to evaluate the relationship between ED severity and systemic immune inflammation index (SII) and neutrophil lymphocyte ratio (NLR).

Methods

The data of male patients over the age of 18 who applied to the urology clinic with the complaint of ED between January 2018 and September 2021 were analyzed. Patients with known diabetes mellitus, hypertension, coronary artery disease, and previous pelvic surgery were excluded from the study. The erectile functions of the patients were evaluated with the international erectile function index-erectile function (IIEF-EF). The patients were divided into two groups according to the severity of ED as mild (IIEF-EF>17) and moderate-severe (IIEF-EF≤17). Demographic data of the patients were recorded. SII value was calculated by neutrophil*platelet/lymphocyte formula and NLR was recorded.

Results

A total of 185 patients were included in the study (mild ED: 74, moderate-severe: 111). The mean age of the patients was 48.18±11.58(20-79), and the mean IIEF-EF was 13.34±6.55 (0-25). The mean SII was 594.89±348.90, and the mean NLR was 2.27±1.19. The mean total testosterone level of the patients was 3.25±1.48ng/dl. When the patients were divided into two groups according to the severity of ED, a significant difference was observed between IIEF-EF scores and SII values of the patients (p<0.001 for IIEF-EF, p=0.008 for SII). No significant difference was found with NLR values (p=0.950). There was a moderate negative correlation between IIEF-EF score and SII value (p=0.042, r=-0.569). No significant correlation was observed between NLR and IIEF-EF (p=0.625, r=-0.124). SII cut-off value was determined as 436.73 and AUC was 0.674 (CI 95%: 0.448-0.717). At this value, the sensitivity was 70.1% and the specificity was 64.8%.

Conclusions

SII index was negatively correlated according to the severity of ED, and erectile functions decreased with the increase in systemic inflammation. During the evaluation of patients, the severity of ED can be revealed more clearly with the use of SII. Further studies are needed to better understand the relationship between SII and ED.

Disclosure

No
(136) Long-term Durability of Response to Complete Vestibulectomy Surgery for Neuroproliferative Vestibulodynia
Authors: Yee A , Goldstein S , Drian A , Goldstein I
Published: May 2023

Introduction

In 2006, Goldstein et al published on the surgical outcomes of the largest-to-date patient series undergoing complete vestibulectomy with vaginal advancement flap reconstruction for neuroproliferative vestibulodynia (NPV). One hundred and thirty-four patients underwent surgery over a 5 year period, and 93% of the 104 patients who agreed to participate were satisfied/very satisfied with their surgical outcome. The mean time to follow up was 26 months, range 12 – 72 months. NPV is hypothesized to be, in part, a result of accumulation of excess mast cells in the epithelial basement membrane and sub-epithelial stroma that may release nerve growth factor promoting sub-epithelial nerve ending proliferation (Figure 1). The excess nerve endings are hypothesized to result in bothersome, persistent, and unrelenting provoked vestibular allodynia and hyperalgesia that are characteristic of NPV. Durability of post-operative outcomes past 72 months has yet to be addressed. It is still unknown if the pathologic findings of excess mast cells and nerve endings ever regenerate in the vestibule and cause recurrent allodynia, hyperalgesia and entrance dyspareunia.

Objective

We wished to assess, for the first time, the long-term surgical outcome durability data (>5 years) of those NPV patients who claimed successful resolution of their entrance dyspareunia following complete vestibulectomy surgery in the first 5 years post-operatively.

Methods

We routinely perform post-operative follow-up of surgical patients who undergo complete vestibulectomy surgery with vaginal advancement flap reconstruction for NPV. We identified those who claimed successful resolution of their entrance dyspareunia following complete vestibulectomy surgery in the first year post-operatively and thereafter for the next 4 years, and asked them if they continued to have resolution of their entrance dyspareunia.

Results

Fifty-seven patients had complete vestibulectomy with vaginal advancement flap reconstruction between 2007 and 2017 (> 5 years ago). Forty-one patients responded to the routine contact for long term follow-up. Thirty-four patients (78%) had resolution of pain in the first year post-operatively. Upon repeat interview, all 34 (100%) continued to note excellent durability of their surgical result, a mean of 9.3 years after their vestibulectomy (range 5-14 years).

Conclusions

Based on this small series, it appears that if a patient is a treatment responder following complete vestibulectomy, there is strong durability of the surgical result with no evidence of recurrent allodynia or hypoalgesia. These data suggest that in treatment responders, there is no evidence of re-accumulation of excess mast cells and nerve endings in the introitus. These data support that the pathology of NPV lies in the endodermal vestibule and that complete excision may be an important long-term treatment strategy in many NPV patients.

Disclosure

No
(159) The Discontinue Rate with Collagenase Clostridium Histolyticum for Peyronie’s Disease in a High-Volume Practice is Unexpectedly High: Identifying Opportunities for Patient Care Improvement
Authors: Lehner K , Byrne E , Rochandel M R , Alom M , Helo S , Kohler T , Ziegelmann M
Published: May 2023

Introduction

Collagenase Clostridium Histolyticum (CCH) is an FDA-approved treatment for Peyronie’s Disease (PD). Based on phase-3 trials, the recommended treatment course consists of 8-injections over the course of roughly 18-20 weeks. While its efficacy has been established, less is known about patient-specific reasons for electing to discontinue CCH injection therapy.

Objective

To evaluate patient-reported factors associated with premature CCH discontinuation.

Methods

We queried a database of all patients (n=406) who underwent CCH at a single institution from 2014-2021. Patients who did not complete the recommended 8 injections were identified, and a detailed review was undertaken to determine causes of discontinuation. Patients were excluded from our analysis for the following reasons: deceased at the time of chart review, declined to participate, or could not be reached in 3 phone calls.

Results

Out of 406 patients who underwent Xiaflex treatment at our single institution, 133 did not complete 8 injections (32.8%). The mean number of CCH injections was 4.42 (SD 1.65). The most common reasons for discontinuing Xiaflex were satisfactory curve reduction (27%), unsatisfactory curve reduction (21%), bothersome side effect (15%), and decision to pursue surgery (12%) [Figure 1]. Other less common reasons included other health concerns, pausing treatments due to the Covid-19 pandemic, high treatment cost, transferring care elsewhere, and lack of awareness that more injections were indicated.

Conclusions

In our single institution study, we find that nearly 1/3 of patients who begin Xiaflex injections will not complete the full recommended treatment course. Understanding the reasons for discontinuation can help providers better stratify patients for Xiaflex treatment versus other modalities. In addition, given previous studies that indicate that 2/3 of men who fail to achieve a 20% curve reduction after their first 4 injections will go on to achieve this curve reduction after their final 4 injections, our data points to the potential impact of improved patient education for the 21% of individuals who discontinue due to unsatisfactory curve reduction (Alom et al 2021).

Disclosure

No
(165) Role of Penile Veno-occlusive Dysfunction in Peyronie’s Disease Patients with Erectile Dysfunction
Authors: Sikka S , Panner Selvam M K , Almajed W , Shalaby H , Hampel G , Greenberg J , Hellstrom W
Published: May 2023

Introduction

The incidence of Peyronie's disease (PD) is 4% in the U.S. male population. Many PD patients also suffer from erectile dysfunction (ED). The etiology of ED incidence in PD men is not known, although veno-occlusive dysfunction (VOD) is often suggested. It is important to appreciate the influence of VOD in PD patients with ED, especially in regard to successful PD treatment.

Objective

The main objective of this study is to assess the penile hemodynamic response to intracavernous injection (ICI) of a vasoactive agent in order to evaluate the incidence of VOD in PD patients with or without ED.

Methods

A total of 333 men, diagnosed either with PD (n=202) or ED (n=68) or both PD and ED (n=63), visiting our Andrology clinic were included in this study. Initial ED was determined by using the International Index of Erectile Function (IIEF) score, whereas patients with penile curvature ≥30° were categorized as having PD. Penile color duplex Doppler ultrasound (CDDU) data was retrospectively collected from these patients, and parameters such as peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were used for analysis. RI (=PSV-EDV/PSV) was calculated, and VOD was confirmed when PSV ≥30 cm/sec, EDV ≥6 cm/sec, and RI <0.8 based on previously published guidelines for standardization of penile CDDU parameters. Statistical analysis was performed using MedCalc statistical software version 20.019 (MedCalc Software bv, Ostend, Belgium).

Results

Table 1 summarizes the CDDU results of all 333 patients. Age of the study subjects was 55.6 ± 11.3 years, with no difference between groups. Incidence of penile VOD was higher in patients with ED without PD (58.8%) or with PD (52.4%) compared to PD alone (44.6%). RI values of PD patients without ED were higher (>0.8) compared to PD patients with ED having VOD (<0.7) (P<0.001).

Conclusions

The current study results indicate that lower RI values suggest a higher incidence of VOD in PD patients. VOD plays an important role in the onset of ED in men with PD. Furthermore, this demonstrates the importance of performing CDDU and diagnosing the presence of VOD in further understanding the pathophysiology of PD.

Disclosure

No
(166) Characteristics of Veterans Suffering Corporeal Rupture after Collagenase Clostridium Histolyticum
Authors: Zucker I , Ghomeshi A , Weber A , Masterson T
Published: May 2023

Introduction

Collagenase clostridium histolyticum is the only guideline and US FDA approved intralesional treatment for Peyronie's disease (PD). The most feared complication is corporeal rupture which occurs in less than 0.5% of treated patients. In the largest clinical trial, only 3 occurred, however this was enough to include a black box warning and recommend patients to abstain from sexual intercourse for 6 weeks. To date, there have been few studies evaluating the timing and causes of fracture after injection.

Objective

To determine the incidence and factors leading to penile fracture in men with PD treated with CCH.

Methods

We queried the VA Informatics and Computing Infrastructure, to identify veterans with a diagnosis of PD by ICD-9 (607.85) or ICD-10 (N48.6) code between 2015-2020. We searched medication codes for CCH and ICD-9 (959.13) and ICD-10 (S39.840) codes for penile fracture to determine which patients had fractures. All patients with penile fracture codes were manually reviewed. Only patients with penile fractures after administration of CCH were included in the study.

Results

In total, 17,647 veterans were diagnosed with PD with 1,541 (8.7%) treated with CCH. In total, 11 patients (0.7%) had penile fracture after treatment with CCH. Table 1 shows patient demographic and clinical information for 11 patients with penile fracture post CCH treatment. Within these 11 patients, the median number of CCH injections was 6 with a median initial curvature of 35°. Fracture occurred at a median of 8 days after CCH injection with all occurring secondary to spontaneous ejections or sexual intercourse. Finally, 6 patients had their fracture repaired with surgery while the remaining were managed conservatively.

Conclusions

The highest risk of penile fracture appears to be within two weeks of the second injection of a CCH cycle. Only one fracture occurred after three weeks, and one occurred after the first injection of a cycle. Our data supports the warning to avoid sexual activity for 4 weeks after CCH injection.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Endo pharmaceuticals.
(172) TrueNorth Sexual Health and Rehabilitation eTraining (SHAReTraining) in Prostate Cancer: Evaluation of an Online Course for Practitioners
Authors: Matthew A , Robinson J , Mcleod D , Petrella A , Walker L , Wassersug R , Guirguis S , Incze T , Macdonald L , Elterman D
Published: May 2023

Introduction

Sexual dysfunction (SD) is a prevalent and distressing side effect for survivors of prostate cancer (PCa). Unfortunately, many health care practitioners (HCPs) report a lack of training and confidence in addressing the sexual health needs of PCa patients. Consequently, many PCa patients do not receive the comprehensive sexual healthcare needed to manage their SD.

Objective

To address the gap in HCP training, the Movember Foundation funded the development and evaluation of a 12-week, faculty-facilitated, online course designed to train HCPs in the delivery of PCa specific sexual health counselling: the TrueNorth Sexual Health And Rehabilitation eTraining (SHAReTraining). Course content includes, SD assessment and intervention, professional ethics, unique needs of sexual and gender minority populations, and approaches to implementing sexual health programming in a healthcare setting.

Methods

Participants completed a pre-course survey (n=23), a retrospective pre-post survey (n=19), and a 3-month follow-up survey (n=19) to assess retention of relevant outcomes. Outcomes included HCP perceived knowledge and self-efficacy to conduct assessments and provide interventions across a number of relevant physical, functional, psychological, and relational domains of SD in PCa survivors and their partners. Additionally, completed a course satisfaction survey at the conclusion of the course.

Results

Descriptive analysis of the pre-post survey revealed that graduates perceived knowledge of sexual health counselling improved from a mean of 51.12% pre-course to 75.18% post-course across all measured domains. Similarly, graduate ratings of self-efficacy in providing comprehensive care increased from a mean of 56.63% pre-course to 79.73% post-course. The follow-up survey demonstrated participants’ self-efficacy remained high 3-months post-course at 79.75%. Graduate experience taking the course was uniformly positive with a vast majority (94.7%) agreeing that they were satisfied with the course.

Conclusions

For HCPs seeking specialized sexual health care training for PCa patients, the TrueNorth SHAReTraining course is an accessible and effective resource. Graduates of the course have the potential to improve the quality of SD care they provide to their patients.

Disclosure

No
(175) Readability Assessment of Online Men's Health Education Materials from the Sexual Medicine Society of North America, Urology Care Foundation, and European Association of Urology
Authors: Callegari M , Pominville R , Zhou C , Piyevsky B , Jesse E , Prunty M , Loeb A , Thirumavalavan N , Abou Ghayda R
Published: May 2023

Introduction

The use of online health information by patients has gained considerable attention during the last decade. With this attention has come exponential adoption towards online resources. Existing literature has shown that a significant majority of patient education materials (PEM) available online exceed the literacy and comprehension of the audience reading them. The National Institute of Health (NIH) and American Medical Association (AMA) advocate the dissemination of accessible and readable resources targeted towards a fifth to seventh grade reading level. As the rise of mens health and sexual health continues to grow, understanding what resources may currently exist and how they meet or fail to meet patients needs is of growing concern.

Objective

We aimed to evaluate the readability of online patient resources from the Sexual Medicine Society of North America (SMSNA), American Urological Association and European Urological Association websites.

Methods

Content published under the web-section “SMSNA: For Patients - conditions and topics” portal (n=16) were reviewed. Identical topics published online via Urology Care Foundation (ie AUA; n=8) and the European Association of Urology (ie EAU; n=8) were also reviewed. Readability and estimated educational level required for understanding was assessed using validated readability and English language assessment tools including the Flesh Reading Ease score, Flesch Kincade, Gunning Fog, Simple Measure of Gobbledygook (SMOG), Coleman-Liau and Automated Readability index.

Results

SMSNA online patient education materials (PEM), on average, are written at a college sophomore reading level (14th grade). This is 6.5 and 8 grade levels higher than the average U.S. adult and recommended reading levels for PEM, respectively. Comparable AUA and EAU resources were an average of 10th (p<0.05) and 12th (p=0.854) grade reading levels, respectively.

Conclusions

Men’s sexual health PEM’s published online are written at an advanced reading level, most notably the SMSNA compared to equivalent professional sources. This could pose a barrier to patient understanding and impact patients’ engagement and health decision-making. One proposed mitigatory strategy is for PEM to provide improved readability, and appropriate user-friendly language to facilitate easier and inclusive understanding, outreach and educational support.

Disclosure

No
(194) Dyspareunia as a Sign of UTI
Authors: Dominguez-Bali A , Coburn A , Shah P , Hassan Z , Dominguez-Bali C
Published: May 2023

Introduction

Dyspareunia has been defined by the American College of Obstetricians and Gynecologists as pain with sexual intercourse. While dyspareunia has been described as only a part of the symptomatology spectrum of interstitial cystitis, it has never been used as a primary symptom to diagnose uncomplicated or complicated UTIs. Dyspareunia and lower abdominal pain are the most common symptoms followed by dysuria, urodynia, pollakiuria, urgency, nocturia, tenesmus, headache and fever. Increased awareness of the association of dyspareunia with UTI’s will improve the diagnosis of UTIs.

Objective

UTI’s are under-diagnosed in emergency rooms, as clinicians increasingly rely on urinalysis rather than symptomatology. The presence of dyspareunia is rarely inquired during an evaluation of the patient. The objective of this research is to inform clinicians that dyspareunia is a common symptom of urinary tract infections. By increasing awareness of the association between UTI’s and dyspareunia, clinicians will include it in the assessment of a patient, rather than relying solely on a urinalysis. Additionally, our objective is to educate the patient population that dyspareunia is not normal, and it is a medical condition that can be resolved and investigated.

Methods

In 2009-2010, a review of 3,000 charts was conducted to determine the sexual attitudes and behaviors of the female Latin American community in South Florida. Analysis of the data shows a correlation between dyspareunia and urinary tract infections, a finding that has not been described before.

Results

The association between a UTI and dyspareunia was found to be approximately 80% in premenopausal women of reproductive age. In post menopausal women, UTIs are the second most common cause of dyspareunia following vaginal dryness.

Conclusions

This analysis has determined that dyspareunia is a significant aspect of the semiology of a UTI, thus clinicians should be aware of this association in order to accurately diagnose UTIs in patients.

Disclosure

No
(199) Anterolateral Thigh Flap Phalloplasty for Micropenis
Authors: Schirmann A , Ralph D , Christopher N , Lee W G
Published: May 2023

Introduction

Congenital micropenis is defined as a normally formed penis with a stretched penile length less than 2.5 standard deviations below the mean for that man’s age and ethnicity. Micropenis may present as an isolated condition or with other genital or multi-system abnormalities. Penile reconstruction or phalloplasty may be required where topical and systemic hormonal treatment have failed. The most common flap used for phalloplasty is the radial artery forearm free flap phalloplasty. Other alternatives include the anterolateral thigh (ALT), musculocutaneous latissimus dorsi and abdominal flaps.

Objective

The aim of this video is to illustrate the technique for penile reconstruction using a pedicled ALT flap without integrated urethra.

Methods

A 21-year-old man with micropenis and hypospadias from a disorder of sexual differentiation (46XY) presents for penile reconstruction following multiple failed attempts at hypospadias repair. He requested an ALT flap without integrated urethra because he is dependent on a long-term suprapubic catheter due to a hypocontractile bladder. Intraoperative vascular doppler identified 3 perforators from the descending branch of the lateral circumflex iliac artery of the left leg. The flap was designed centred on the perforators with dimensions of 14cm (length), 13cm (width at base) and 12cm (width at tip). The flap was raised carefully and transferred to the recipient groin. The neophallus was constructed and microsurgical anastomosis of the lateral cutaneous of the thigh to one of the dorsal penile nerves with 8/0 nylon was completed. The partially divided left vastus lateralis muscle was re-approximated and the skin edges drawn in and flattened. The left thigh was then resurfaced with a 14/1000 of an inch split-thickness skin graft from the contralateral thigh. All wounds were dressed.

Results

The man had an uneventful post-operative course with careful vascular monitoring, and he was discharged on day 10. He is currently awaiting glans-sculpting and will eventually proceed with insertion of an inflatable erectile device.

Conclusions

Penile reconstruction using an ALT flap can be offered to a well-informed and motivated man with a micropenis following appropriate assessment. As shown, the technique requires careful dissection of the perforator vessels and can usually be transferred as a pedicled flap. Pedicled flaps do not require microvascular anastomosis and therefore have a lower risk of vascular compromise. Further esthetic and functional refinements like the insertion of an erectile device are possible in later stages, if desired.

Disclosure

No