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Tanawin Poopuangpairoj, Kun Sirisopana, Chinnakhet Ketsuwan, Wisoot Kongchareonsombat, Yada Phengsalae, Wijittra Matang, Premsant Sangkum Division of Urology, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Premsant Sangkum, Division of Urology, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, Email premsanti@gmail.comObjective: The objective of this study was to evaluate major adverse cardiovascular events in erectile dysfunction (ED) patients who received testosterone replacement therapy (TRT) compared with those who did not.Materials and Methods: From January 2012 to October 2021, we collected the retrospective data of patients with ED at Ramathibodi Hospital. We divided the patients into two groups: those who received TRT (TRT group) and those with normal testosterone levels and therefore not requiring TRT (non-TRT group). The patients’ baseline clinicodemographic data were collected. Major adverse cardiovascular events, including cardiovascular death, ST- and non-ST-elevation myocardial infarction, hospitalization from congestive heart failure, transient ischemic attack, and ischemic stroke, were collected and analyzed within 2 years after treatment in all groups.Results: Of the 221 patients, 111 were in the TRT group and 110 were in the non-TRT group. In the non-TRT group, one event each of the following occurred: myocardial infarction, transient ischemic attack, and stroke. In the TRT group, no major cardiovascular event occurred during the 2-year follow-up period. However, no significant difference in major cardiovascular events was noted between the two groups (p = 0.314).Conclusion: TRT in ED patients with testosterone deficiency does not increase adverse cardiovascular events when compared with ED patients with normal testosterone level.Keywords: erectile dysfunction, testosterone deficiency, testosterone replacement therapy, major adverse cardiovascular events

Introduction. The influence of the length of the number of CAG repeats in the androgen receptor gene (nCAG AR) on endothelial dysfunction (EnD) is currently understudied.Objective. The study aimed to evaluate the relationship between the nCAG AR and the dynamics of biochemical and ultrasound markers of EnD in men with functional hypogonadism and type 2 diabetes mellitus (T2DM) receiving testosterone replacement therapy (TRT).Materials & methods. This study included 45 hypogonadal men with T2DM, receiving TRT for 1 year. Patients were assessed for carbohydrate and lipid metabolism parameters; total and free T; sex hormone-binding globulin; biochemical markers of EnD (NO, eNOS3, endothelin) and the nCAG AR; brachial artery (BA) vasoreactivity. Patients were divided into 3 groups: group I — 9 men with nCAG AR < 19; group II — 27 men with nCAG AR > 19 – 24; and group III — 9 men with nCAG AR >24.Results. Patients with nCAG AR < 19 exhibited a 2-fold greater and faster increase in BA vasoreactivity on TRT compared to patients with nCAG AR 19-24 and 3-fold greater than men with nCAG AR >24 (p < 0.05). Patients with nCAG AR < 19 also demonstrated the most pronounced rise in NO and eNOS3 on TRT compared to men with nCAG AR > 24. Patients with nCAG AR < 19 experienced the most pronounced decreases in weight, waist circumference, and HbA1c on TRT compared to other patients (p < 0.05).Conclusion. The nCAG AR length significantly affects the response to TRT in men with hypogonadism and T2DM. The most significant improvements are seen in patients with short nCAG AR.

Background and Objective Materials and Methods Results Discussion and Conclusions Clinical Trial Information Studies examining ambulatory blood pressure (BP) response to testosterone replacement therapy are needed owing to inconsistent prior findings across formulations. This study assessed testosterone gel 1.62% and 24‐h ambulatory BP.Single‐arm non‐inferiority trial (NCT04274894) conducted at 36 US sites enrolled 246 men with hypogonadism (mean age, 57.6 years; mean office systolic/diastolic BP [SBP/DBP], 129.8/79.5 mm Hg) who were treated for 16 weeks with once‐daily testosterone gel treatment (starting dose, 40.5 mg/day; min, max dose, 20.25, 81.0 mg/day) to achieve testosterone concentration of 350–750 ng/dL. Main outcome measures included mean change in 24‐h average SBP (primary endpoint) and DBP from baseline to week 16. The non‐inferiority threshold was a two‐sided 95% confidence interval (CI) upper limit <3.0 mm Hg for 24‐h average SBP.Increase in mean ± SD serum testosterone concentration to a physiologic level (baseline, 244.4 ± 93.9 ng/dL; week 16, 502.5 ± 394.4 ng/dL) was associated with a 1.9‐mm Hg mean change in 24‐h average SBP observed in the primary analysis (baseline, 123.5 mm Hg; week 16, 125.4 mm Hg; 95% CI, 0.63–3.13 mm Hg; n = 169). As the upper CI limit modestly exceeded the non‐inferiority margin (3 mm Hg), study drug effect on SBP could not be ruled out. Non‐inferiority was observed in subgroups without hypertension or diabetes (95% CI, upper limit <3.0 mm Hg) and was not observed in those with hypertension or diabetes. Daytime SBP and DBP changes were larger compared with nighttime. No clear cardiovascular adverse events or new safety signals were identified.While the effect of testosterone gel 1.62% on 24‐h average SBP could not be ruled out based on the study's non‐inferiority margin, the clinical relevance of the small‐magnitude mean increase of 1.9 mm Hg is anticipated to be minimal considering the results of the TRAVERSE study of testosterone gel 1.62% and major adverse cardiac events.ClinicalTrials.gov identifier: NCT04274894 (registered February 17, 2020) [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to perform a network meta‐analysis (NMA) to investigate the effects of different testosterone replacement therapy (TRT) administration routes on lower urinary tract symptoms (LUTS) in aging men with late‐onset hypogonadism (LOH). Methods: A systematic search of PubMed, Embase, The Cochrane Library, CNKI, WanFang Data, and VIP was conducted to identify randomized controlled trials (RCTs) reporting data on International Prostate Symptom Score (IPSS), prostate‐specific antigen (PSA) level, or prostate volume. NMA was performed, and subgroup analysis was conducted to assess the impact of TRT duration on outcomes. Results: A total of 21 RCTs involving 2453 participants were included. For pairwise meta‐analysis, p values for TRT delivered by transdermal, intramuscular, and oral routes were as follows: IPSS: 0.93, 0.20, and 0.76; PSA level: 0.20, 0.27, and 0.98; prostate volume: 0.18, 0.04, and 0.16. There were no significant differences in IPSS, PSA level, or prostate volume between TRT routes. In subgroup analysis, long‐term intramuscular TRT significantly decreased IPSS (p = 0.03), short‐term transdermal TRT increased PSA levels (p < 0.001), and short‐term intramuscular TRT increased the prostate volume (p = 0.04). Other forms of TRT showed no significant change in IPSS, PSA level, and prostate volume compared with the placebo. Indirect comparison of the three administration routes demonstrated no significant differences in IPSS, PSA level, and prostate volume. Nevertheless, surface under the cumulative ranking curve analysis indicated that intramuscular TRT had an 83% probability of being the best method for decreasing IPSS. Conclusions: The results demonstrate that TRT does not worsen LUTS regardless of the administration route. Intramuscular TRT may be the preferred treatment for aging men with LOH and LUTS. Intramuscular TRT may be the preferred treatment for men with LOH and LUTS. Further research is warranted to validate these findings and optimize TRT management strategies. [ABSTRACT FROM AUTHOR]

Testosterone replacement therapy (TRT) is a crucial intervention for men diagnosed with hypogonadism, a condition characterized by inadequate testosterone production. As primary care NPs play an essential role in managing patients with hypogonadism, they must comprehensively understand TRT. This article serves as a primer for primary care NPs, based on current guidelines, to provide evidencebased care for men with hypogonadism. It offers an overview of the etiology, clinical presentation, diagnostic criteria, and treatment options for hypogonadism, focusing on using TRT appropriately in primary care settings. [ABSTRACT FROM AUTHOR]

This paper provides a review of the historical and scientific evolution of testosterone and 5ARI research. It chronicles the evolution from early empirical practices like castration, through the formal discovery of testosterone in the 20th century, to the eventual synthesis of testosterone and identification of Leydig cells. Testosterone’s crucial role in male development and its influence on the development and maturation process of the prostate gland are also presented. The introduction of 5ARIs in the 1990s, such as finasteride, marked a significant advancement in managing BPH by reducing dihydrotestosterone (DHT) levels. The controversy regarding the therapeutic use of 5ARIs is discussed, given concerns about their association with high-grade prostate cancer and other systemic risks. Likewise, emerging evidence challenges the traditional view that testosterone exacerbates prostate conditions, suggesting that testosterone replacement therapy (TRT) may improve symptoms of low testosterone without increasing BPH symptoms, prostate cancer (PCa), or cardiovascular risk. Several new studies are discussed suggesting that low or declining testosterone level could be a risk factor for prostate tumorigenesis. This review emphasizes the need for continued research on Testosterone and 5ARI to further define their role in men’s health.

Introduction There is increasing evidence that gender dysphoria (GD) is more prevalent in the Klinefelter Syndrome (KS) population than in males in the general population; however, the exact incidence is uncertain. The aim of this study was to further explore the prevalence of gender-related issues, the role that physical characteristics play in gender identity, and the issues surrounding Hormone Replacement Therapy (HRT) in KS.Methods As part of a registered Quality Improvement Project (QIP), one online 23-point questionnaire on KS patient attitudes toward gender identity was shared with members of the Klinefelter Syndrome Association (KSA). In total, 139 anonymous responses were collected between December 2021 and January 2023. The questionnaire was developed with the guidance of multiple clinicians (including gender psychiatrists, urologists, psychosexual medicine specialists, and endocrinologists) and patient Delphi rounds. Data was reviewed and analyzed by 4 independent researchers within the QIP team.Results Only 53% of KS patients responding to this survey fully identified as male and 19% stated that they did not enjoy living as the sex on their birth certificate, with 43% considering changing aspects of their physical appearance to better match their gender. Regarding HRT, 67% of respondents were receiving Testosterone Replacement Therapy (TRT). 63% wanted TRT and 17% wanted estrogen, including 6% of TRT users who would prefer estrogen instead. 36% that were currently receiving TRT did not identify as male, and 3 participants stated that they have GD.Conclusion These results indicate that a significant proportion of KS patients do not fully identify with the male gender and are unhappy living as the sex on their birth certificate. Although TRT worked for most, its use should be discussed carefully with those with gender identity concerns.

IntroductionWith thirty percent of the world’s population not getting enough exercise, Worldwide, physical inactivity ranks as one of the most common causes of premature mortality. Rapid drops in physical activity, decreased mobility, and early morbidity are aging characteristics. As the population over 80 continues to rise, aging raises the danger of age-related illnesses and changes in hormone release.AimUnderstanding the aging process is useful in developing pharmacological therapies and identifying therapeutic targets for age-related testosterone deficiency. Therefore, this study’s purpose is to present a thorough evaluation of the effects of anti-aging strategies on testosterone levels in older, inactive men.MethodsA literature search was completed for clinical and preclinical studies published in English between 2014 and 2024 related to age, sedentary life, testosterone, and anti-aging strategies.ResultsA sedentary lifestyle and low testosterone are linked to a vicious cycle. A sedentary lifestyle lowers testosterone levels, which leads to depression, exhaustion, low energy, and weakened bone and muscle strength. These effects exacerbate the detrimental consequences of aging and physical inactivity. Anti-aging techniques can prevent and treat age-related diseases, including calorie restriction, a balanced diet, regular exercise, weight control, diabetes management, and quitting smoking. Regular exercise raises total testosterone, free testosterone, and muscle steroidogenesis. In older men, testosterone replacement treatment increases bone density, cholesterol, protein synthesis, strength, erectile function, sexual desire, and general cognitive performance. However, some studies suggest dehydroepiandrosterone supplementation may provide health improvements without negative effects, potentially reversing arterial aging and reducing cardiovascular disease risk.ConclusionThis article evaluates the prospects for anti-aging procedures to assist in reducing the adverse effects of aging and physical inactivity in men.

Childhood cancer survivors are at risk of various endocrine late effects affecting their quality of life. The aim of this study was to assess the prevalence and predictors of endocrine and reproductive outcomes in young adult survivors. A secondary aim was to assess possible associations between testosterone replacement therapy (TRT) and other endocrine, cardiovascular and psychosocial late effects. This nationwide study comprised 1212 male childhood cancer survivors aged 19–40 years, identified through the National Quality Registry for Childhood Cancer in Sweden. Median age at diagnosis during 1981–2017 was 7 (range 0–17) and at study 29 (19–40) years. The study combined self‐report survey data with cancer treatment data from the national registry. Hormone‐induced puberty was self‐reported by 3.8% of the survivors and ongoing TRT by 6.0%. In separate logistic regression analyses, these treatments were associated with hematopoietic stem cell transplantation and cranial radiotherapy. Hormone‐induced puberty was additionally associated with younger age at diagnosis. Men with TRT had a higher prevalence of other endocrine deficiencies, cholesterol medication, depressive symptoms and fatigue as well as a lower probability of living with a partner, having a biological child or current occupation. In the total male cohort, 28.2% reported having a biological child. Reassuring reproductive outcomes after less intensive therapies and low frequency of TRT were observed in young adult male childhood cancer survivors treated in the most recent treatment era. However, men with TRT suffered from several other endocrine, cardiovascular and psychosocial late effects, indicating a need for long‐term monitoring of this high‐risk group. [ABSTRACT FROM AUTHOR]

Testosterone deficiency encompasses clinically low serum testosterone levels accompanied by signs and symptoms. This testosterone decline is expected in older men and begins in middle age (40 to 64 years) and is commonly treated through Testosterone Replacement Therapy (TRT). This review aims to look at the mechanisms of TRT, physiological and societal motivations to seek TRT, ethical and medical considerations behind its use, and future research directions. From the review of numerous papers looking at testosterone therapy in middle-aged men, various mechanisms for the delivery of testosterone were isolated, each with sufficient risks and benefits. Of all the mechanisms looked at, buccal testosterone and implants had more benefits than others in patient adherence and normal circadian variations in serum testosterone, unlike Intramuscular testosterone. Both physiological and societal changes in middle-aged men cause them to seek therapy. Some of these physiological changes include sarcopenia, reduction in bone mineral density, depressive mood symptoms, reduced libido, and erectile dysfunction. Societal changes, which also influence treatmentseeking, include feelings of "lost masculinity" associated with loss of strength and virility with old age. This societal pressure can lead to a desire to maintain youthful vigor, a significant motivator for seeking TRT. Due to substantial societal and media changes, TRT use in the United States has tripled between 2001 and 2011, raising concerns that many individuals may be receiving treatment without being appropriately informed on the risks and benefits and without clear clinical indications. Although extensive research is available in this field, there remain unanswered questions regarding the effects on non-communicable diseases like cardiovascular disease and cancers. While prostate cancer, in particular, is not related to TRT use, further research is needed to prove the relationship. Additionally, there is untapped potential for TRT beyond the scope of hypogonadism, but researchers have yet to explore these areas of benefit. [ABSTRACT FROM AUTHOR]

Introduction: Previous work has demonstrated a deficiency in urology resident education when it comes to andrology and male infertility. We analyzed the top 100 most frequently cited and influential articles published on testosterone deficiency and its associated therapy, allowing trainees and clinicians to review and understand the characteristics of impactful literature for self-directed learning purposes. Methods: The ISI Web of Knowledge database was used to find articles on testosterone deficiency, hypogonadism, and replacement therapies. Relevant, peer-reviewed, English articles were included. Article details, including title, citation count, publication year, and more, were gathered. Articles were classified based on content (e.g. clinical outcomes, anatomy, and trends) using defined criteria. Results: The top 300 most cited were reviewed with 100 included. The most cited article had 774 citations, averaging 234 in the top 100. Publication years had peaks in 2003–2004 and 2006–2007. The US led in publications (56), followed by England (16), Germany (14), and Italy (13). Common affiliations included US Department of Veteran Affairs, Veterans Health Administration, RIC Research Education Clinical Center, and University of California System. Articles were categorized as LOE 2 (47), LOE 1 (22), and LOE 5 (21). Articles focused on clinical outcomes (71.7%), anatomy/biomechanics/physiology (14.1%), clinical guidelines (8.1%), and screening (4%). The " Journal of Clinical Endocrinology & Metabolism " published 26 of the top 100 cited articles. Conclusions: This analysis highlights influential articles regarding testosterone deficiency and management. The discussed articles have significant clinical and therapeutic implications for the practicing urologist which may bolster deficits in current resident education. [ABSTRACT FROM AUTHOR]

Objective: This study aims to comprehensively assess TRT's cardiovascular safety in males with hypogonadism, providing valuable insights for treatment decisions. Material & Methods: Adhering to PRISMA guidelines, we registered our PROSPERO protocol and analyzed relevant English-language randomized clinical trials published from 2008 to 2023. Results: Among 1187 initial papers, 7 studies met inclusion criteria, with 6 in quantitative analysis and all 7 in qualitative assessment. Our findings indicate that TRT does not significantly increase the risk of cardiovascular events compared to placebo. Specifically, the analysis of major adverse cardiac events (MACE) yielded an OR of 0.90 (95% CI: 0.74, 1.10; I² = 26%; p = 0.25), while the evaluation of all cardiovascular adverse events revealed an OR of 1.37 (95% CI: 0.73, 2.55; I² = 75%; p = 0.001). Conclusion: This study offers reassurance for clinical decision-making by suggesting that TRT is not significantly associated with an elevated cardiovascular risk in hypogonadal men, addressing the ongoing debates on this issue. Keywords: Cardiovascular safety, hypogonadism, testosterone replacement therapy.