Testosterone Deficiency In Men Research Articles

Testosterone deficiency in men with end stage renal disease and kidney transplantation: a narrative review.

Testosterone deficiency is a prevalent condition that frequently affects individuals with end-stage renal disease (ESRD) and those who have undergone renal transplantation. While the etiology of this condition is complex, its implications in this population are far-reaching, impacting various domains such as endocrine profile, sexual and erectile function, bone mineral density (BMD), anemia, and graft survival following renal transplantation. Herein, we review the most recent literature exploring the pathophysiology of testosterone deficiency in ESRD and renal transplant patients, examining its diverse effects on this demographic, and assessing the advantages of testosterone replacement therapy (TRT). Existing evidence suggests that TRT is a safe intervention in ESRD and renal transplant patients, demonstrating improvements across multiple domains. Despite valuable insights from numerous studies, a critical need persists for larger, high-quality prospective studies to comprehensively grasp the nuances of TRT, especially in this vulnerable population. Proactive screening and treatment of testosterone deficiency may prove beneficial, emphasizing the urgency for further research in this area.

The influence of body composition on the response to dynamic stimulation of the endocrine pituitary-testis axis.

Testosterone treatment is generally not recommended in men with obesity induced low serum testosterone. However, distinguishing this condition from overt testosterone deficiency in men with obesity where treatment should be initiated is a diagnostic challenge and tools to differentiate these conditions are scarce but could be of important clinical relevance. To investigate the association between body composition and dynamic responses of the pituitary-testis axis in men. Single-center cross-sectional study including 112 healthy men. Participants went through a full biochemical assessment of the pituitary-testis axis, and dynamic stimulatory tests of luteinizing hormone (LH) secretion (gonadotropin-releasing hormone (GnRH)-test) and testosterone secretion (choriogonadotropin (hCG)-test). A subset (N = 78) further had a DXA-scan performed. A higher body mass index (BMI) was associated with lower basal serum LH (BU = -0.44, 95% CI: -0.88--0.01, p = 0.04). The GnRH-stimulated LH increase was not significantly associated with BMI (BU = -0.10, 95% CI: -0.72-0.51, p = 0.74). Furthermore, a high BMI was associated with low basal testosterone (BU -0.02, 95% CI: -0.03--0.02, p < 0.001), and free testosterone (BU -15.0, 95% CI: -19.9--10.0, p < 0.001) and men with overweight and obesity had significantly lower testosterone (9%, p = 0.003 and 24%, p < 0.001) and free testosterone (25%, p = 0.006 and 50%, p < 0.001) concentrations compared to men with normal weight. The HCG-stimulated testosterone increase was significantly less dependent on BMI compared to the influence of BMI on basal testosterone concentrations (p = 0.04 for the interaction). Dynamic sex hormone responses following pituitary-testis axis stimulation were less dependent on BMI, compared to the influence of BMI on basal hormone concentrations and could potentially assist clinical decision making in patients with obesity suspected of testosterone deficiency.

(298) AUA vs AI: An Inquiry into Testosterone Guidelines

Abstract Introduction ChatGPT is an artificial intelligence with an accessible user interface that allows for conversational input. It uses deep learning, a subset of machine learning based on artificial neural networks, to “speak” to the user. Patients and clinicians alike have been querying ChatGPT with medical questions, and recent publications have shown that the validity of responses vary. Limited information is available pertaining to ChatGPT’s capacity to accurately discuss testosterone management and deficiency. It is imperative for the medical community to be aware of potentially accurate or inaccurate information sources. This project is designed to assess ChatGPT’s clinical competency compared to the American Urologic Association (“AUA”) guidelines regarding the evaluation and management of testosterone deficiency. Objective To assess the competency of ChatGPT to answer general and clinical questions related to testosterone deficiency and replacement compared to the AUA guidelines. Methods The AUA guidelines for evaluation and management of testosterone deficiency include 31 main points. Each point was prompted to ChatGPT in the form of a question, accompanied by requests for validation of information, providing further information, or clinical next-step recommendations. The answers were then sorted into 3 categories all relative to the AUA guidelines, being accurate and complete, (AC), accurate but incomplete (AI), and incorrect or misleading (IM). Results Of the 31 guideline-based questions queried, 22/31 (71%) were AC, 4/31 (13%) were AI, and 5/31 (16%) were IM. The highest number of AI answers pertained to treatment related queries. The highest number of IM answers pertained to counseling, particularly on commonly contested topics, such as the relationship between testosterone and prostate cancer or cardiovascular health. Conclusions When queried about the evaluation and management of testosterone deficiency, ChatGPT offered complete and accurate answers in 71% of cases. It had increased accuracy of even up to 100% when answering regarding firmly established or more binary topics, such as diagnosis requirements or recommended adjunct testing. As such, patients and providers may consider using ChatGPT as an ancillary resource for uncomplicated or firmly established testosterone related queries. However, it did much more poorly when discussing more contested topics such as testosterone’s relationship to prostate cancer, or when approaching elements of medicine that require a more personalized human touch, such as counseling. While ChatGPT may be helpful in the base or binary matters, interpersonal and patient specific matters are best handled by experts in the field. Disclosure No.

(300) Impact of Intranasal Testosterone versus Intramuscular Testosterone cypionate on Hematocrit of Hypogonadal Men: Data from an ongoing Phase IV, Open-label, Randomized Clinical Trial.

Abstract 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&amp;lt;0.001) at follow-up, where NT saw no changes. Neither regimen significantly impacted PSA at follow-up. 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

(306) U-shaped Curvilinear Relationship Between the Prevalence of Testosterone Deficiency and Low-density Lipoprotein Cholesterol (LDL) Levels in Nonstatin Users

Abstract Introduction Contradictory data have been reported about the association between testosterone levels and the levels of low-density lipoprotein cholesterol (LDL). Objective The aim of this study was to elucidate the association between testosterone and LDL levels. Methods A cross-sectional study was conducted that included 7,268 men who had participated in a health examination. Men who took agents that influence serum lipid profiles within the previous 6 months were excluded. A full metabolic work-up and serum testosterone level checks were performed. The main outcome measures included the testosterone level and testosterone deficiency (TD) prevalence of each decile of LDL and their polynomial trendlines and the odds ratio (OR) of TD according to the LDL level. Results The polynomial trendline suggests an inverted U-shaped curvilinear relationship between LDL and testosterone levels (figure 1) and a U-shaped curvilinear relationship between LDL levels and the prevalence of TD (figure 2). The adjusted ORs of TD in men in the lowest and highest deciles were significantly higher than those of men in the 10th – 90th deciles of LDL (90th LDL, OR for TD: 1.277, 95% CI: 1.006–1.621), which reinforces the U-shaped curvilinear relationship between LDL levels and the prevalence of TD. Conclusions There was a U-shaped curvilinear relationship between LDL levels and the prevalence of TD. Both low LDL and high LDL levels were significantly and independently associated with TD. Care should be taken to screen for TD in men with low LDL levels or high LDL levels. Further study to elucidate the effect of extremely lowering LDL levels on TD is needed. Disclosure No

(070) Testosterone Therapy in Men with Klinefelter Syndrome: Analysis of a Global Federated Research Network

Abstract 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 &amp;lt; 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

(069) Increased Risk of Major Adverse Cardiovascular Events in Testosterone Deficient Men and in Men Receiving Testosterone Replacement Therapy

Abstract Introduction Testosterone deficiency (TD) has been shown to be associated with cardiovascular risk factors and an increased risk of cardiovascular events. Conversely, literature surrounding testosterone replacement therapy (TRT) and major adverse cardiovascular events (MACE) is conflicting. Currently, the Food and Drug Administration requires warnings regarding a possible increased cardiovascular risk for TRTs. Objective This study sought to investigate the association between TD and MACE. It also sought to investigate the association between TRT and MACE using a large population based database. The hypotheses were that TD men will have a higher risk of MACE, while men receiving TRT will also have a higher risk of MACE compared to controls. Methods A propensity-weighted, retrospective cohort study was conducted by accessing provincial health administrative databases. Eligibility criteria included men 18 years and older, with no prior TRT or MACE, who had at least 1 year of provincial health coverage from their index date between April 1st, 1995 to December 31st, 2018. TD was defined as men who had a serum testosterone level between 57-300 ng/dL. TRT was defined as having at least two testosterone prescriptions filled within one year (including capsules, gels, patches, and/or injections). MACE was defined as myocardial infarction, coronary revascularization procedures, ischemic stroke, or hospitalizations for heart failure. Controls were assigned a pseudo-index date at random based on the frequency distribution of index dates in the study group. Logistic regression model that included age, socioeconomic status, index year, diabetes, hypertension, dyslipidemia and renal disease was used to determine the propensity score. Stabilized inverse propensity treatment weighting was then applied to the propensity score. A cox proportional hazard model was used to examine our primary outcome of time to a MACE. Results Among 7918 men with TD and 442286 controls, men with TD were associated with a 87 % higher risk of a MACE (Hazard Ratio 1.76, 1.63 – 1.89) in unweighted and 21% higher risk (Hazard Ratio 1.27, 1.16 – 1.39) in weighted analyses. Among 6893 men receiving TRT and 415377 controls, men receiving TRT were associated with a 76% higher risk of a MACE (Hazard Ratio 1.76, 1.63 – 1.89) in unweighted and 26% higher risk (Hazard Ratio 1.27, 1.16 – 1.39) in weighted analyses. Conclusions This study demonstrates that both TD men and men receiving TRT had a higher risk of MACE as compared to controls. Whether TRT itself increases the odds of MACE requires further elucidation. Our study is limited by its retrospective nature and inability to capture for all confounders. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific.

A practical guide to the assessment and management of testosterone deficiency in adult men

Testosterone deficiency is increasingly common and has significant health implications, but it can be challenging to diagnose and treat. Here the authors present a summary of a recent update to the British Society for Sexual Medicine (BSSM) guidelines on male adult testosterone deficiency.

Testosterone deficiency in men with obstructive sleep apnea syndrome: is hepcidin a player in the game?

Testosterone deficiency in men with obstructive sleep apnea syndrome: is hepcidin a player in the game?

MP79-03 COMPARISON OF HEMATOCRIT CHANGE IN TESTOSTERONE-DEFICIENT MEN TREATED WITH INTRANASAL TESTOSTERONE GEL VERSUS INTRAMUSCULAR TESTOSTERONE CYPIONATE: A SINGLE-CENTER RANDOMIZED CLINICAL TRIAL

You have accessJournal of UrologyCME1 Apr 2023MP79-03 COMPARISON OF HEMATOCRIT CHANGE IN TESTOSTERONE-DEFICIENT MEN TREATED WITH INTRANASAL TESTOSTERONE GEL VERSUS INTRAMUSCULAR TESTOSTERONE CYPIONATE: A SINGLE-CENTER RANDOMIZED CLINICAL TRIAL Marco-Jose Rivero, Jesse Ory, Halifax Canada, Parris Diaz, Raul Clavijo, Nannan Thirumavalavan, Ruben Blachman-Braun, Justin Loloi, Ari Bernstein, and Ranjith Ramasamy Marco-Jose RiveroMarco-Jose Rivero More articles by this author , Jesse OryJesse Ory More articles by this author , Halifax CanadaHalifax Canada More articles by this author , Parris DiazParris Diaz More articles by this author , Raul ClavijoRaul Clavijo More articles by this author , Nannan ThirumavalavanNannan Thirumavalavan More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Justin LoloiJustin Loloi More articles by this author , Ari BernsteinAri Bernstein More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone therapy is associated with rise in hematocrit (HCT) and subsequent risk of polycythemia and thrombotic events. Incidence of these side effects may vary depending on the route of administration of testosterone therapy formulation. In this study, we compared the effects of intranasal testosterone gel (NT) and intramuscular testosterone cypionate (TC) on HCT and serum total testosterone (T) levels in testosterone-deficient men over 4 months. METHODS: Patients between 18 and 75 years of age with a diagnosis of testosterone deficiency were recruited. Testosterone deficiency (TD) was defined as two measurements of serum total testosterone below 300 ng/dL combined with one or more characteristic clinical symptoms. Men were randomized (1:1) to receive either NT (5.5 mg per nostril) three times a day or TC (200 mg intramuscularly) once every two weeks. The primary outcomes were changes in HCT and serum T before and after 4 months of treatment. Secondary outcomes were changes in estradiol, prostate-specific antigen, and 17-hydroxyprogesterone. RESULTS: 49 men were randomized to receive either NT (n=20) or TC (n=29). The median participant age was 47 years with a mean serum T of 236.6 ng/dL and mean HCT of 43.3%. The prevalence of participants who screened positive for obstructive sleep apnea on STOP-BANG questionnaire was 70% for the NT group and 72% for the TC group. Men in both groups experienced significantly increased serum T levels throughout the study period (p<0.001), although a larger increase was seen in the TC group. There was an increase in the mean HCT of the TC group from 42.6% to 46.0% at 4-month follow-up (p=0.006), while the NT group experienced no significant changes in mean HCT (p=0.903). The TC group experienced significant increases in estradiol (p<0.001) and decreases in 17-hydroxyprogesterone (p<0.001) at 4-month follow-up, while the NT group experienced no such changes. CONCLUSIONS: Although both NT and TC regimens are effective in treating men with TD, NT does not appear to significantly affect HCT levels. Patients who are at increased risk of developing polycythemia or those who wish to avoid changes in estradiol or 17-hydroxyprogesterone levels may benefit from short-acting testosterone therapy formulations such as NT. Source of Funding: This project was funded by an investigator-initiated grant provided by Acerus Pharmaceuticals © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1142 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marco-Jose Rivero More articles by this author Jesse Ory More articles by this author Halifax Canada More articles by this author Parris Diaz More articles by this author Raul Clavijo More articles by this author Nannan Thirumavalavan More articles by this author Ruben Blachman-Braun More articles by this author Justin Loloi More articles by this author Ari Bernstein More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

MP79-01 PATIENT SATISFACTION WITH ORAL TESTOSTERONE UNDECANOATE IN TESTOSTERONE-DEFICIENT MEN WITH PREVIOUS TESTOSTERONE THERAPY: AN OPEN-LABEL, SINGLE-CENTER, PHASE IV CLINICAL TRIAL

You have accessJournal of UrologyCME1 Apr 2023MP79-01 PATIENT SATISFACTION WITH ORAL TESTOSTERONE UNDECANOATE IN TESTOSTERONE-DEFICIENT MEN WITH PREVIOUS TESTOSTERONE THERAPY: AN OPEN-LABEL, SINGLE-CENTER, PHASE IV CLINICAL TRIAL Marco-Jose Rivero, Rohit Reddy, Akhil Muthigi, and Ranjith Ramasamy Marco-Jose RiveroMarco-Jose Rivero More articles by this author , Rohit ReddyRohit Reddy More articles by this author , Akhil MuthigiAkhil Muthigi More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone therapy (TTh) is available in multiple modalities. Oral formulations, previously unavailable in the United States due to variable bioavailability, are convenient, easy to use, and free of painful injections. Testosterone undecanoate (TU) is a recently approved oral testosterone capsule that provides a uniform response in patients with testosterone deficiency. In this study, we evaluated patient satisfaction with TU in men with a recent history of alternative TTh. METHODS: Patients between 18 and 65 years of age with a diagnosis of testosterone deficiency were recruited. Testosterone deficiency (TD) was defined as two measurements of serum total testosterone below 300 ng/dL combined with one or more characteristic clinical symptoms. Patients were required to have received previous TTh and completed an adequate washout period prior to starting TU. The primary outcomes were patient satisfaction, measured by the Treatment Satisfaction Questionnaire for Medication (TSQM-9); and TD symptom control, measured by the quantitative Androgen Deficiency in Aging Males (qADAM) questionnaire at 3- and 6-month intervals. Routine blood tests were also performed at each time point. RESULTS: Of the 43 patients recruited into the study, 47% had previously received subdermal pellets, 40% intramuscular injections, and 12% intranasal gels. After the appropriate washout period, serum total testosterone levels increased from a baseline mean of 193.4 ng/dL to 747.9 ng/dL at 1 month, 500.6 ng/dL at 3 months, and 692.2 ng/dL at 6 months of treatment with TU. Mean global satisfaction measured by TSQM-9 progressed from 64.1 with previous TTh to 80.2 at 3 months (p=0.011) and 88.8 at 6 months (p<0.001) of treatment with TU. Similar 6-month changes were observed for TSQM-9 measures of effectiveness (p<0.001) and convenience (p<0.001). Mean TD symptom control measured by qADAM at 6 months (35.0) was statistically unchanged from baseline (36.8, p=0.154). No significant changes were noted in hematocrit, prostate-specific antigen, or estradiol throughout the study period. CONCLUSIONS: TU provides patient satisfaction and TD symptom control that is noninferior compared to other forms of TTh. In addition, TU increases serum total testosterone to reference range (300–1000 ng/dL) in >90% of men without a difference in side effect profile over 6 months of treatment. Source of Funding: This project was funded by an investigator-initiated grant provided by Clarus Therapeutics © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1141 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marco-Jose Rivero More articles by this author Rohit Reddy More articles by this author Akhil Muthigi More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

A novel quadruple templates molecularly imprinted polymer electrochemical sensor assisted by second-order calibration methods for detection of Sustanon abuse

Sustanon (SUS) consists of testosterone propionate (TP), testosterone phenylpropionate (TPP), testosterone isocaproate (TIC) and testosterone decanoate (TD) which is generally used as a medication to treat the testosterone deficiency in men. Misuse of SUS to enhance the ability of the athletes can be a very serious risk for their health which is discouraged. Therefore, the main aim of this work was based on developing a novel biosensing system for determination of different types of testosterones in SUS to monitor it. A rotating glassy carbon electrode (GCE) was modified with fullerene C60-multiwalled carbon nanotubes-ionic liquid (C60-MWCNTs-IL) and used as the working electrode for recording second-order hydrodynamic square wave voltammetric (hydrodynamic SWV) data at different step potentials including 0.02, 0.025, 0.03, 0.035, 0.04 and 0.045 V as a sensitive method. Different types of testosterones were extracted and preconcentrated by quadruple templates molecularly imprinted polymers (QTMIPs) and they were determined by C60-MWCNTs-IL/GCE. The testosterones showed severely overlapped peaks at the surface of C60-MWCNTs-IL/GCE which were resolved by three-way calibration based on second-order hydrodynamic SWV data. Therefore, a novel sensor assisted by QTMIPs and second-order calibration methods was developed which had a very good performance for the analysis of synthetic and real matrices in simultaneous determination of TP, TPP, TIC and TD with aim of monitoring the SUS.

Role of miR-300-3p in Leydig cell function and differentiation: A therapeutic target for obesity-related testosterone deficiency

MicroRNAs (miRNAs) regulate various cellular functions, but their specific roles in the regulation of Leydig cells (LCs) have yet to be fully understood. Here, we found that the expression of miR-300-3p varied significantly during the differentiation from progenitor LCs (PLCs) to adult LCs (ALCs). High expression of miR-300-3p in PLCs inhibited testosterone production and promoted PLC proliferation by targeting the steroidogenic factor-1 (Sf-1) and transcription factor forkhead box O1 (FoxO1) genes, respectively. As PLCs differentiated into ALCs, the miR-300-3p expression level significantly decreased, which promoted testosterone biosynthesis and suppressed proliferation of ALCs by upregulating SF-1 and FoxO1 expression. The LH/METTL3/SMURF2/SMAD2 cascade pathway controlled miR-300-3p expression, in which luteinizing hormone (LH) upregulated SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) expression through methyltransferase like 3 (METTL3)-mediated Smurf2 N6-methyladenosine modification. The Smurf2 then suppressed miR-300 transcription by inhibiting SMAD family member 2 (SMAD2) binding to the promoter of miR-300. Notably, miR-300-3p was associated with an obesity-related testosterone deficiency in men and the inhibition of miR-300-3p effectively rescued testosterone deficiency in obese mice. These findings suggested that miR-300-3p plays a pivotal role in LC differentiation and function, and could be a promising diagnostic or therapeutic target for obesity-related testosterone deficiency.

Risk of testosterone deficiency in men with type 2 diabetes depending on the level of glycated hemoglobin

Risk of testosterone deficiency in men with type 2 diabetes depending on the level of glycated hemoglobin

New antidiabetic drugs' role in the management of testosterone deficiency and of the cardiovascular disease in hypogonadal diabetic men

The known hallmarks of type 2 diabetes mellitus (T2DM), such as hyperglycemia, insulin resistance, visceral adiposity, inflammation, endothelial dysfunction, and oxidative stress, are known to influence the hypothalamus-pituitary-gonadal axis, leading to functional hypogonadism. Both the consequent testosterone (T) deficiency and diabetes are recognized factors influencing cardiovascular (CV) risk. In this context, T replacement therapy showed an improvement in glycemic control and metabolic, anthropometric, and body composition parameters in hypogonadal diabetic individuals. Observational and randomized studies on T replacement therapy suggested the beneficial effect of this treatment on CV risk, although inconclusive results should still be evaluated, particularly when subgroups of patients have to be considered. In this setting, the novel antidiabetic drugs have demonstrated beneficial effects on T levels, due to their positive effects on the hypothalamic–pituitary–gonadal axis, in addition to a proven CV protective action. Thus, the combined metabolic and CV effects of T replacement therapy and novel antidiabetic drugs are of great interest. In this review, we aimed to summarize the present state of the art concerning the association between T deficit and CV risk in diabetic people by analyzing the relationship between endogenous T and CV system in diabetic men. In particular, the impact of novel antidiabetic drugs on male hypogonadism, and the combined cardio-metabolic effects of T supplementation and novel antidiabetic drugs were discussed.

An Approach to Testosterone Therapy in Men After Treatment for Localized Prostate Cancer

Testosterone therapy (TTh) is a well-established and safe treatment for men with testosterone deficiency. Historically, great caution has been used in the use of testosterone in men with prostate cancer (PCa) given the pioneering work by Huggins and Hodges showing castration decreased serum acid phosphatase in men with metastatic PCa. For the past several decades new theories including the saturation model have gained traction and as a result the treatment of testosterone deficiency in men with PCa has been transformed. In men treated for localized PCa with prostatectomy a growing body of evidence exists supporting its safety and efficacy in these men. In addition, it has been suggested that TTh may decrease biochemical recurrence. The data are more limited in men treated with radiation and there are no studies currently with a control group. Overall, the body of literature continues to grow suggesting the safety of TTh in well-selected men treated for localized PCa.

Reply by Authors.

No AccessJournal of UrologyAdult Urology1 Dec 2022Reply by Authorsis a reply to letterEditorial CommentEditorial Comment Alex Zhu, Juan Andino, Stephanie Daignault-Newton, Zoey Chopra, Aruna Sarma, and James M. Dupree Alex ZhuAlex Zhu *Correspondence: 1500 E. Medical CenterDr., Ann Arbor, Michigan 48109 telephone: 949-633-6048; email: E-mail Address: [email protected] Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author , Juan AndinoJuan Andino Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author , Stephanie Daignault-NewtonStephanie Daignault-Newton Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author , Zoey ChopraZoey Chopra University of Michigan Medical School,Ann Arbor, Michigan More articles by this author , Aruna SarmaAruna Sarma Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author , and James M. DupreeJames M. Dupree Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002928.03AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Reply by Authors." The Journal of Urology, 208(6), p. 1302 Reference 1. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018; 200(2):423-432. Link, Google Scholar © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology25 Oct 2022Editorial CommentJournal of Urology25 Oct 2022Editorial Comment Volume 208Issue 6December 2022Page: 1302-1302 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alex Zhu Department of Urology, University of Michigan, Ann Arbor, Michigan *Correspondence: 1500 E. Medical CenterDr., Ann Arbor, Michigan 48109 telephone: 949-633-6048; email: E-mail Address: [email protected] More articles by this author Juan Andino Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author Stephanie Daignault-Newton Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author Zoey Chopra University of Michigan Medical School,Ann Arbor, Michigan More articles by this author Aruna Sarma Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author James M. Dupree Department of Urology, University of Michigan, Ann Arbor, Michigan More articles by this author Expand All Advertisement PDF downloadLoading ...

HYPOGONADISM AND TESTOSTERONE THERAPY AMONG MEN WITH KLINEFELTER SYNDROME: ANALYSIS OF A GLOBAL FEDERATED RESEARCH NETWORK

Klinefelter syndrome (KS) is one of the on-label indications for testosterone therapy. The prevalence of testosterone deficiency in men with KS is estimated to be 65-85%. Klinefelter syndrome is underdiagnosed in affected men, as men don’t often seek care and clinical presentation is highly variable. However, KS is associated with several comorbidities. Therefore, we hypothesized that men with KS are undertreated for testosterone deficiency. We used a national database to report the rates of prescription of testosterone replacement therapy (TRT) in men with KS.

Long-term efficacy of varicocele repair in middle-aged men with erectile dysfunction (ED) and low testosterone: Five cases with follow-up from 16 to 60 months

We report five cases of middle-aged men with low testosterone levels and erectile dysfunction (ED) who were successfully treated with varicocelectomy with long-term follow-up. All five patients presented to our clinic with ED. Upon initial physical examination, each patient had varicoceles on his scrotum, and two consecutive morning samplings showed testosterone levels below 400 ng/mL. Age at varicocelectomy was from 40 to 53 years. Four patients underwent microscopic subinguinal varicocelectomy, whereas one patient underwent inguinal varicocelectomy. After surgery, testosterone increased in all cases, and the normal testosterone level was maintained during follow-up (16–60 months). In addition, all cases reported improvement of ED after surgery. In our clinical cases, microscopic varicocelectomy increased serum testosterone levels and improved erectile function, and this increase and improvement continued up to a follow-up of 60 months. Varicocelectomy would be a good option to treat testosterone deficiency in men with varicocele.

Deficiency of mature B cells does not alter the atherogenic response to castration in male mice

Testosterone deficiency in men is associated with increased atherosclerosis burden and increased cardiovascular risk. In male mice, testosterone deficiency induced by castration increases atherosclerosis as well as mature B cell numbers in spleen. As B cells are potentially pro-atherogenic, we hypothesized that there may be a link between these effects. To address whether mature B cell deficiency alter the atherogenic response to castration, we studied B cell-deficient μMT and genotype control male mice on an atherosclerosis-prone Apoe−/− background that were castrated or sham-operated pre-pubertally and fed a high-fat diet between 8 and 16 weeks of age to accelerate atherosclerosis development. Genotype did not affect the effects of castration on body weight or weights of fat depots and there were no differences in serum cholesterol levels across the four groups. Atherosclerosis assessed by quantification of lesion area in serial sections of the aortic root was significantly increased by castration and by the μMT mutation, with no significant interaction between genotype and surgery. In conclusion, castration evokes a similar atherogenic response in B cell-deficient μMT and control mice. These data suggest that atherogenesis following castration is unrelated to the effects of androgens on mature B cell numbers.