Male fertility is complex and influenced by genetic, hormonal, environmental and lifestyle factors. However, limitations to human studies necessitate the use of reliable preclinical models to better understand the underlying mechanisms of male fertility. Rhesus macaques (Macaca mulatta), with their close genetic and physiological similarities to humans, offer an invaluable model for male reproductive health studies. The suitability of rhesus macaques for studying male infertility is based on similarities in spermatogenesis, hormonal cycles and the way in which assisted reproductive technologies can be applied, and key differences and similarities between human and rhesus macaque sperm structure, function and cryopreservation techniques highlight the translational potential of findings derived from macaque models. Furthermore, insights into the epigenetic and proteomic characteristics of sperm in both species improve understanding of how these findings can help to advance clinical diagnostics, male contraception and fertility preservation and illuminate the regulatory omics of normal reproduction. Thus, the rhesus macaque model offers critical insights into male fertility and studies in this species could contribute to advances in therapies for male infertility. Non-human primates, especially the rhesus macaque, provide a good preclinical model for research into male fertility, owing to their physiological and genetic similarities to humans. In this article, the authors examine the value and limitations of using non-human primates in studies to improve understanding of spermatogenesis, reproductive endocrinology and innovations in assisted reproductive technologies.

You have accessJournal of UrologyHistory of Urology Forum I (HF01)1 May 2024HF01-02 FORCED STERILIZATION IN CALIFORNIA: A HAUNTING PAST AND PERSISTENT INEQUITY Charles A. Loeb, Abigail Lavold, Thiago Pardini-Furtado, Jasper C. Bash, Juan Andino, and Jesse N. Mills Charles A. LoebCharles A. Loeb , Abigail LavoldAbigail Lavold , Thiago Pardini-FurtadoThiago Pardini-Furtado , Jasper C. BashJasper C. Bash , Juan AndinoJuan Andino , and Jesse N. MillsJesse N. Mills View All Author Informationhttps://doi.org/10.1097/01.JU.0001008828.35887.de.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In California (CA), a state consent and mandatory waiting period is required before any sterilization procedure, such as tubal ligation or vasectomy. This abstract explores the historical background of CA's state sterilization consent, aiming to understand its roots in eugenics and implications for health equity today. METHODS: A comprehensive review of historical literature was performed to shed light on the history of the CA eugenics movement and its role in shaping the state sterilization consent. RESULTS: California played an early and prominent role in the eugenics movement, becoming the third U.S. state to enact sterilization laws. By 1921, CA accounted for a staggering 80% of sterilizations in the nation. Between 1909 and 1979, an estimated 20,000 forced sterilizations occurred in state-run institutions.The Asexualization Act, CA's eugenics law enacted in 1909, allowed state institutions to control the reproductive capacity of those considered "unfit," primarily in state mental hospitals and the prison system. Medical superintendents were authorized to perform sterilizations without patient consent, and sterilization was even a prerequisite for release from certain institutions. The law remained in place until 1979, making it the legal framework for one of the most active sterilization programs in the U.S.A pivotal moment in the fight against forced sterilization was a class-action lawsuit in 1973. Ten Chicana women sued a medical center for being coerced into tubal ligation during labor. Despite a ruling in favor of the medical center, the case drew attention to the issue leading to significant reform. The practice ended in 1979 for state hospitals but persisted until 2010 in state prisons. In 2021, a compensation program was established, offering up to $25,000 per person. While hundreds of Californians may be eligible, public outreach to contact more victims has been challenging and it is unlikely that all will be compensated.CA currently mandates a 30-day waiting period prior to surgical sterilization. This can be reduced to 72 hours for many, but not by those with state-sponsored insurance, quietly perpetuating reproductive inequity. This disproportionately affects the underserved population which already struggles with access to care. CONCLUSIONS: California's history of forced sterilization, rooted in the eugenics movement, casts a shadow over current healthcare practices. The tiered waiting period for patients with different insurance plans, particularly Medi-Cal, highlights ongoing disparities. Recognizing this history is crucial for addressing health equity. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e279 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Charles A. Loeb More articles by this author Abigail Lavold More articles by this author Thiago Pardini-Furtado More articles by this author Jasper C. Bash More articles by this author Juan Andino More articles by this author Jesse N. Mills More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyHistory of Urology Forum II (HF02)1 May 2024HF02-12 A 25-YEAR CELEBRATION OF THE LITTLE BLUE PILL THAT REVOLUTIONIZED AN INDUSTRY Charles A. Loeb, Thiago Pardini-Furtado, Abigail Lavold, Jasper C. Bash, Jesse N. Mills, and Jacob Rajfer Charles A. LoebCharles A. Loeb , Thiago Pardini-FurtadoThiago Pardini-Furtado , Abigail LavoldAbigail Lavold , Jasper C. BashJasper C. Bash , Jesse N. MillsJesse N. Mills , and Jacob RajferJacob Rajfer View All Author Informationhttps://doi.org/10.1097/01.JU.0001008760.25751.09.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The 25th anniversary of sildenafil marks a significant milestone in the history of pharmaceutical innovation. We aim to provide a comprehensive overview of the impact and legacy of the little blue pill over the past quarter-century. METHODS: Extensive web-based research provided the primary source of information. RESULTS: Identified in the early 1990's by Pfizer as a possible therapeutic to enhance erectile function, the speed by which sildenafil went from bench to bedside took only an unheard of 6 years. The drug unequivocally changed the sexual landscape of America and the world. In 1998, sildenafil received FDA approval for the treatment of erectile dysfunction (ED), and men everywhere rushed to their doctors for a prescription for the blockbuster little blue pill. Sildenafil had some of the fastest prescription uptakes and sales growth of any medication ever. In the early days, up to 10,000 prescriptions daily were written. Urologists were using rubber stamps to churn out prescriptions. By 2008, the medication was bringing in $2 billion in annual sales. Since its debut in 1998 until the patent expiration 20 years later, the drug resulted in at least $40 billion in revenue. How Pfizer accomplished this unprecedented success and meteoric rise is remarkable. Pfizer deployed one of the most successful advertising campaigns in history, featuring Senator Bob Dole, who openly discussed his struggle with impotence. Dole transformed the conversation, destigmatizing impotence and establishing it as a medical problem that could be openly discussed by patients and providers. 'Erectile dysfunction' emerged as a medical diagnosis that could be treated and entered the common medical lexicon. Pfizer showed the medical community the power of a pharmaceutical company to change the mindset of the professional conversation and were even instrumental in the development of a standardized metric of erectile function, the IIEF, still used today. Now, 25 years later, the patent has expired, and sildenafil is generic. Established PDE5-i competitors offer various ED treatment options. Prescriptions declined over 20% since 2012. The name-brand is no longer the market force it once was, but its impact on modern sex and men's health remains unparalleled. CONCLUSIONS: The 25th anniversary of the little blue pill marks a remarkable journey from accidental discovery to a medical and cultural icon. Beyond financial success, sildenafil redefined discussions about modern sexuality, broke stigmas, and improved quality of life. This celebration underscores the profound, enduring impact of sildenafil on medicine and culture. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e277 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Charles A. Loeb More articles by this author Thiago Pardini-Furtado More articles by this author Abigail Lavold More articles by this author Jasper C. Bash More articles by this author Jesse N. Mills More articles by this author Jacob Rajfer More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 Apr 2023MP01-02 PROTEOMIC ANALYSIS OF SEMINAL FLUID IN RHESUS MACAQUES EXPOSED TO DELTA-9-TETRAHYDROCANNABINOL Jasper C. Bash, Lyndsey E. Shorey-Kendrick, Carol B. Hannah, Charles A. Easley, Eliot Spindel, Jamie O. Lo, and Jason C. Hedges Jasper C. BashJasper C. Bash More articles by this author , Lyndsey E. Shorey-KendrickLyndsey E. Shorey-Kendrick More articles by this author , Carol B. HannahCarol B. Hannah More articles by this author , Charles A. EasleyCharles A. Easley More articles by this author , Eliot SpindelEliot Spindel More articles by this author , Jamie O. LoJamie O. Lo More articles by this author , and Jason C. HedgesJason C. Hedges More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003212.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cannabis use has been associated with male infertility, but the etiology is not well understood. Seminal fluid is comprised of multiple factors (e.g. proteins), that influence fertility. Our objective was to determine the impact of chronic delta-9-tetrahydrocannabinol (THC) use on the seminal fluid proteome in a rhesus macaque (RM) model. METHODS: 6 adult RMs were given a daily THC edible over 280 days (∼4 spermatogenesis cycles) with serial non-sedated semen collection. Differential expression of proteins in the seminal fluid at baseline (pre-THC), high-THC dose (2.5 mg/7 kg/day), and post-THC discontinuation for 140 days (∼2 spermatogenesis cycles) was evaluated. Proteomic analysis was performed by liquid chromatography tandem mass spectrometry followed by statistical analysis to identify differentially expressed proteins. RESULTS: Proteomic analysis resulted in 1,395 quantifiable proteins (Figure 1A). The average percent identity was 88.6% (SD=14.9%). All RM proteins were matched to human proteins with 99.4% of the RM proteins (1,386) exceeding an identity cutoff of 44.3% (average minus 3 SDs). 7 proteins reached FDR significance in any contrast, thus we focused downstream analyses on nominally significant candidate proteins. Ingenuity Pathway Analysis (Figure 1B) revealed that high-THC exposure was associated with dysregulation of pathways related to “Remodeling of Epithelial Adherens Junctions”, “Axonal Guidance Signaling”, and “Glucocorticoid Receptor Signaling”. THC discontinuation for 140 days was associated with decreased “LXR/RXR Activation”, “Acute Phase Response Signaling”, and “Production of Nitric Oxide and ROS in Macrophages”. 5 proteins dysregulated with THC and significantly restored to baseline included products of CHIT1, FGG, MMP9, TGFBI, and CFB genes (Figure 1D). CHIT1 has been associated with oligozoospermia and MMP9 protein with sperm motility. CONCLUSIONS: This study demonstrated the translational strength of the RM model to study male reproductive health; there was significant seminal fluid proteome homology between humans and RMs. THC-exposed RMs are likely to exhibit proteins in their seminal ejaculate that are involved in regulatory processes that could potentially contribute to male infertility. Source of Funding: OHSU Faculty SEED Award and ASRM Pilot and Exploratory Grant © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jasper C. Bash More articles by this author Lyndsey E. Shorey-Kendrick More articles by this author Carol B. Hannah More articles by this author Charles A. Easley More articles by this author Eliot Spindel More articles by this author Jamie O. Lo More articles by this author Jason C. Hedges More articles by this author Expand All Advertisement PDF downloadLoading ...

Cannabis is the most commonly used illicit drug by reproductive age males and emerging evidence suggests it may impact fertility. Our objective was to determine the effect of chronic delta-9-tetrahydrocannabinol (THC) use on the sperm epigenome and whether these changes are permanent with THC cessation in a rhesus macaque (RM) model. Prior studies have linked sperm DNA methylation alterations with impaired spermatogenesis and infertility. We performed whole genome bisulfite sequencing (WGBS) of DNA extracted from sperm collected from 6 adult RM at baseline (pre-THC), at a high-THC dose (2.5mg/7kg/day), and post-THC discontinuation for 140 days (∼2 spermatogenesis cycles). Overlap of genes annotated to differentially methylatedregions (DMRs) in our RM following THC with published gene lists of human cannabis users and non-users was more than expected by chance (p= 1.7e-13). Pre-THC vs post-THC DMRs were similarly enriched for genes annotated to methylation differences between pre-cannabis exposure vs. post-cannabis discontinuation in humans. We identified 1,613 DMRs between pre-THC and heavy-THC that intersected DMRs in heavy-THC versus post-THC sperm samples and demonstrated a reversal in methylation post-THC toward the level of methylation pre-THC. Genes annotated to a smaller number of DMRs (1,601) between pre-THC and heavy-THC did not return to baseline levels after the THC washout period. Both the restored and non-restored DMRs were highly enriched for genes in the "synaptogenesis signaling pathway" (e.g., BDNF, several integrin, glutamate receptor, and synapsin genes), as well as for genes in the "sperm motility" canonical pathway (e.g., ADCY10, CNG, and PLA2). From the literature we identified 217 genes reported to play a key role in male infertility, of which 55 were differentially methylated with THC. We highlight a subset of these THC-DMRs in Table 1. Chronic THC use in RM alters genes related to several key regulatory pathways including fertility. Discontinuation of THC restored methylation in only a subset of DMRs.

Objective: To determine whether discontinuation of delta-9-tetrahydrocannabinol (THC) use mitigates THC-associated changes in male reproductive health using a rhesus macaque model of daily THC edible consumption. Design: Research animal study. Setting: Research institute environment. Patient(s): Adult male rhesus macaques (age, 8-10 years; n 1/4 6).Intervention(s): Chronic daily THC edible administration at medically and recreationally relevant contemporary doses followed by cessation of THC use. Main Outcome Measure(s): Testicular volume, serum male hormones, semen parameters, sperm deoxyribonucleic acid (DNA) frag-mentation, seminal fluid proteomics, and whole genome bisulfite sequencing of sperm DNA. Result(s): Chronic THC use resulted in significant testicular atrophy, increased gonadotropin levels, decreased serum sex steroid levels, changes in seminal fluid proteome, and increased DNA fragmentation with partial recovery after discontinuation of THC use. For every increase of 1 mg/7 kg/day in THC dosing, there was a significant decrease in the total testicular volume bilaterally by 12.6 cm(3) (95% confidence interval [CI], 10.6-14.5), resulting in a 59% decrease in volume. With THC abstinence, the total testicular volume increased to 73% of its original volume. Similarly, with THC exposure, there were significant decreases in the mean total testosterone and estradiol levels and a significant increase in the follicle-stimulating hormone level. With increasing THC dose, there was a significant decrease in the liquid semen ejaculate volume and weight of coagulum; however, no other significant changes in the other semen parameters were noted. After discontinuing THC use, there was a significant increase in the total serum testosterone level by 1.3 ng/mL (95% CI, 0.1-2.4) and estradiol level by 2.9 pg/mL (95% CI, 0.4-5.4), and the follicle-stimulating hormone level significantly decreased by 0.06 ng/mL (95% CI, 0.01-0.11). Seminal fluid proteome analysis revealed differential expression of proteins enriched for processes related to cellular secretion, immune response, and fibrinolysis. Whole genome bisulfite sequencing identified 23,558 CpGs differentially methylated in heavy-THC vs. pre-THC sperm, with partial restoration of methylation after discontinuation of THC use. Genes associated with altered differentially methylated regions were enriched for those involved in the development and function of the nervous system. Conclusion(s): This is the first study demonstrating that discontinuation of chronic THC use in rhesus macaques partially restores adverse impacts to male reproductive health, THC-associated sperm differentially methylated regions in genes important for development, and expression of proteins important for male fertility. (Fertil Sterile 2023;120:163-74. (c) 2023 by American Society for Reproductive Medicine.)

You have accessJournal of UrologyCME1 Apr 2023MP01-06 DELTA-9-TETRAHYDROCANNABINOL USE ALTERS SPERM DNA METHYLATION IN RHESUS MACAQUES Jason Hedges, Lyndsey Shorey-Kendrick, Carol Hanna, Jasper Bash, Eliot Spindel, Charles Easley, Susan Murphy, and Jamie Lo Jason HedgesJason Hedges More articles by this author , Lyndsey Shorey-KendrickLyndsey Shorey-Kendrick More articles by this author , Carol HannaCarol Hanna More articles by this author , Jasper BashJasper Bash More articles by this author , Eliot SpindelEliot Spindel More articles by this author , Charles EasleyCharles Easley More articles by this author , Susan MurphySusan Murphy More articles by this author , and Jamie LoJamie Lo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003212.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cannabis is the most commonly used drug by reproductive age males. Our objective was to determine the effect of chronic delta-9-tetrahydrocannabinol (THC) use on the sperm epigenome and whether these changes are permanent or temporary with discontinuation of THC in a rhesus macaque (RM) model. METHODS: We performed whole genome bisulfite sequencing (WGBS) of DNA extracted from sperm collected from 6 adult RM at baseline (pre-THC), at a high-THC dose (2.5 mg/7kg/day), and post-THC discontinuation for 140 days (∼2 spermatogenesis cycles). Bioinformatic analysis included QA/QC assessments, alignment to the rhesus reference genome, and identification of differentially methylated regions (DMRs). RESULTS: Overlap of genes annotated to DMRs in our RM following THC with published gene lists of human cannabis users and non-users was more than expected by chance (p=2.00e-82; Figure 1A). Pre-THC vs post-THC DMRs were similarly enriched for genes annotated to methylation differences between pre-cannabis exposure vs. post-cannabis discontinuation in humans (Figure 1B). Pre-THC vs high-THC DMRs annotated to 3,902 unique genes annotated and were significantly enriched for genes previously associated with autism spectrum disorder (ASD) (Figure 1C). We identified 2,759 DMRs between pre-THC and high-THC that intersected DMRs in high-THC vs post-THC sperm samples and demonstrated a reversal in methylation post-THC toward the level of methylation pre-THC (Figure 1D). A smaller number of DMRs between pre-THC and high-THC (n=1,898) did not return to baseline levels after THC abstinence (Figure 1E). Using Ingenuity Pathway Analysis, the top canonical pathway associated with THC and restored to baseline levels was the “synaptogenesis signaling pathway” and top biofunctions included “nervous system development and function” and “tissue development”. Similarly, the 1,898 non-restored DMRs were also enriched for genes in the “synaptogenesis signaling pathway” and “nervous system development and function”, as well as for genes in the “sperm motility” canonical pathway. CONCLUSIONS: Chronic THC use in RM alters genes related to nervous system development and function, and autism spectrum disorder that may impact longterm offspring outcomes. Discontinuation of THC resulted in restored methylation in only a subset of DMRs. Source of Funding: NICHD, NIDA, Silver Family © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e3 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jason Hedges More articles by this author Lyndsey Shorey-Kendrick More articles by this author Carol Hanna More articles by this author Jasper Bash More articles by this author Eliot Spindel More articles by this author Charles Easley More articles by this author Susan Murphy More articles by this author Jamie Lo More articles by this author Expand All Advertisement PDF downloadLoading ...

Introduction: Ureteropelvic junction obstruction is a common cause of upper tract obstruction that often necessitates surgical intervention because of its severe implications. A high proportion of these surgeries include pathologic analysis of this tissue with unclear clinical value. We examined our institution's practices concerning sending the ureteropelvic junction (UPJ) specimens for pathology analysis, its clinical value, and the associated costs for both pediatric and adult cases. Methods: We performed retrospective chart review using Current Procedural Terminology codes for pyeloplasty over 8 years. Clinical variables were extracted from operative reports, path reports, and postoperative clinic notes. Pathology results were classified dichotomously as “benign” or “malignant” and subsequently assigned to 1 of 4 categories—inflammation, fibrosis, muscular hyperplasia, or no atypical findings. Results: Two hundred sixty-nine pyeloplasty surgeries were included, 68% of which were in children. Pathologic analysis was requested in most of the cases (91%), and this was slightly more common in adults (94%) than in pediatric patients (90%). All available pathology reports found benign findings in the UPJ specimen, mostly commonly categorized as “normal.” No cases of malignancy were noted. At the list price for pathologic analysis, $103,027 was spent over 8 years without the discovery of clinically significant pathology findings. Conclusions: There was a lack of clinically meaningful results from pathologic analysis of UPJ specimens excised during pyeloplasty. A UPJ specimen should not be routinely sent for pathologic analysis rather selectively if there is clinical concern for nonbenign etiology of UPJ obstruction.

The prevalence of males on testosterone therapy (TT) seeking vasectomy reversal (VR) is rising. As medical therapy (MT) to recover spermatogenesis after TT has been previously described, our study's objective is to present our institution's management and outcomes of VR in men previously on TT. We performed a retrospective case series of vasectomy patients on TT with subsequent VR by a single microsurgeon between March, 2010 and March, 2022. 14 men undergoing VR during the study period met inclusion criteria. The median age at VR was 43 years with a median obstructive interval of 11 years. Median time from MT to VR was 5 months. Post-operative semen analysis was performed in 10 men and all demonstrated patency. 2 patients had very low sperm counts secondary to continuing TT following VR contrary to medical advice and 5 men with patency achieved pregnancy. Our study noted a high rate of vasovasostomy (VV) (96%) and sustained patency despite a 12-year median obstructive interval. Our findings support favorable outcomes with less stringent VV indications after MT in patients previously on TT that desire VR. The use of MT reduces the recommended wait times for VR after TT discontinuation by more than half.

To determine the dose-response effect of chronic delta-9-tetrahydrocannabinol (THC) use on testicular size and if discontinuation of use resolves THC-associated changes in reproductive health using a non-human primate model.

Objective: To determine the dose-dependent effect of delta-9-tetrahydrocannabinol (THC) exposure on male testes and reproductive health in a nonhuman primate model. Design: Research animal study. Setting: Research institute. Animal(s): Adult male rhesus macaques 8-10 years of age (n = 6). Intervention(s): Daily edible THC at medically and recreationally relevant doses. Main Outcome Measure(s): Testicular volume and epididymal head width, serum levels of inhibin B, albumin, total testosterone, prolactin, follicle-stimulating hormone, estradiol, and luteinizing hormone; semen volume; and sperm motility, morphology, and concentration. Result(s): For each 1 mg/7 kg/day increase in THC dosing, there was a marked loss in total bilateral testicular volume of 11.8 cm(3) (95% confidence interval [CI]: 8.3-15.4). In total, average bilateral testicular volume decreased by 58%. Significant dose-response decreases in mean total testosterone level by 1.49 ng/mL (95% CI: 0.83-2.15) and in estradiol level by 3.8 pg/mL (95% CI: 2.2-5.4) were observed, but significant increases in the levels of follicle-stimulating hormone by 0.06 ng/mL (95% CI: 0.02-0.10), luteinizing hormone by 0.16 ng/mL (95% CI: 0.08-0.25), and prolactin by 7.4 ng/mL (95% CI: 3.4-11.3) were observed. There were no statistically significant changes in semen parameters. Conclusion(s): In rhesus macaques, chronic exposure to THC resulted in significant dose-response testicular atrophy, increased serum gonadotropin levels, and decreased serum sex steroids, suggestive of primary testicular failure. Further studies are needed to determine if reversal of these observed adverse effects would occur if THC was discontinued and for validation of thefindings in a human cohort. ((C) 2021 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.

You have accessJournal of UrologyCME1 May 2022PD36-03 CHRONIC MARIJUANA USE IMPACTS TESTICULAR VOLUME AND MALE REPRODUCTIVE HEALTH IN RHESUS MACAQUES Jasper C. Bash, Jason C. Hedges, Emily R. Boniface, Victoria H. J. Roberts, Carol B. Hannah, and Jamie O. Lo Jasper C. BashJasper C. Bash More articles by this author , Jason C. HedgesJason C. Hedges More articles by this author , Emily R. BonifaceEmily R. Boniface More articles by this author , Victoria H. J. RobertsVictoria H. J. Roberts More articles by this author , Carol B. HannahCarol B. Hannah More articles by this author , and Jamie O. LoJamie O. Lo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002594.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Marijuana is the most commonly used federally illegal drug in the US, but our understanding of its effects on male fertility is limited. The objective of our study was to determine the dose-response effect of chronic contemporary marijuana (delta-9-tetrahydrocannabinol, THC) use on male testes and reproductive health in a non-human primate (NHP) model. METHODS: Adult reproductive age male rhesus macaques (n=6) of similar weight and prior proven fertility were on a standard chow diet with a daily THC edible. All animals were titrated to 2.5 mg/7 kg/day of THC (equivalent to a heavy human medical marijuana dose) over 280 days. Testicular volume, serum hormones, and semen samples were assessed at pre-THC, moderate-THC and heavy-THC dosing timepoints. A subcohort of animals (n=3) also underwent a 140 day period of THC discontinuation with testicular, serum and semen evaluations at 70 and 140 days. Random intercept mixed effects models with a linear spline at start of THC abstinence were used to determine the average change in testes, serum, and semen measurements with increasing THC dose and after discontinuation. RESULTS: For every 1 mg/7 kg/day increase in THC dosing, there was a significant decrease in total testicular volume bilaterally by 13 cm3 (95% CI -15.40- -10.9, p <0.001 (Fig. 1A). A similar dose-response significant decrease in liquid semen ejaculate volume (p=0.043), mean total testosterone (p <0.001) and estradiol (p <0.001), but significant increase in FSH (p=0.017), LH (p=0.013), and prolactin (p=0.01) was observed (Fig 1B). No other significant changes in semen parameters were present (Fig 1C).Every 70 days of THC abstinence (n=3), total testicular volume increased significantly by 5 cm3 (95% CI 3.2-6.9, p<0.001) to 82% of its original volume by 140 days after THC discontinuation (Fig. 1D). Serum T (p=0.001) and LH (p=0.019) both rose significantly, and FSH (p=0.008) decreased significantly (Fig. 1E). There were no significant changes to semen parameters after THC discontinuation (Fig. 1F). CONCLUSIONS: Chronic THC use in rhesus macaques resulted in significant dose-response testicular atrophy, increased gonadotropins, decreased serum sex steroids, and semen volume. Abstinence from THC resulted in incomplete recovery of testicular volume. Source of Funding: ASRM, NIH/NICHD K12 HD00849, Medical Research Foundation - OHSU © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e633 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jasper C. Bash More articles by this author Jason C. Hedges More articles by this author Emily R. Boniface More articles by this author Victoria H. J. Roberts More articles by this author Carol B. Hannah More articles by this author Jamie O. Lo More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 May 2022MP34-07 VASECTOMY REVERSAL OUTCOMES AND MANAGEMENT OF PATIENTS ON TESTOSTERONE REPLACEMENT THERAPY Jasper C. Bash, Akash Kapadia, Malachi Mason, and Jason C. Hedges Jasper C. BashJasper C. Bash More articles by this author , Akash KapadiaAkash Kapadia More articles by this author , Malachi MasonMalachi Mason More articles by this author , and Jason C. HedgesJason C. Hedges More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002588.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Over the last decade, a 4-fold rise in treatment of late onset hypogonadism with testosterone therapy (TT) has been observed in the United States. More men with a prior vasectomy on TT are seeking vasectomy reversal (VR). Medical management (MT) strategies for these patients prior to VR include using clomiphene citrate (CC) or human chorionic gonadotropin (hCG) to recover spermatogenesis, however, there is very limited data on these strategies. We present our management and outcomes of VR in men previously on TT. METHODS: We reviewed all patients who underwent VR from 2008 to 2021 from our institution. Patients who started on TT following their vasectomy prior to VR procedure were included in the study. Along with discontinuation of TT, patients were offered CC with or without hCG. Testosterone and FSH levels were obtained 4 weeks following initiation of MT for dose adjustment. VR procedures were performed after 3 months of MT. Intraoperative findings, patency rates and hormone levels were assessed. RESULTS: Of the men who underwent VR during the study period, 15 men met our inclusion criteria. Median age at VR was 45 with a median obstructive interval of 12 years. In our cohort, 1 patient elected to forego MT and wait 12 months off TT prior to VR. For the remaining 14 patients, the median time from MT to VR was 5 months. We performed vasovasostomy (VV) on 29/30 testicles based on the characteristics of the vasal fluid and/or microscopic findings. All 15 men had sperm on post-operative semen analysis. Six men achieved pregnancy. CONCLUSIONS: Our findings confirm the expediency of MT for spermatogenesis in patients previously on TT who desire VR. Median time from MT to VR of 5 months reduces the recommended wait time with TRT discontinuation alone by more than half. An interesting finding of our study is a high rate of VV (96%) despite a 12-year median obstructive interval suggesting a decrease of epididymal obstruction due to decrease in spermatogenesis due to TT. These data will help guide management strategies. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e580 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jasper C. Bash More articles by this author Akash Kapadia More articles by this author Malachi Mason More articles by this author Jason C. Hedges More articles by this author Expand All Advertisement PDF DownloadLoading ...