Testosterone Replacement Therapy In Patients Research Articles

Testosterone replacement therapy in patients with cachexia: a contemporary review of the literature.

Patients with long-term chronic illnesses frequently present with hypogonadism, which is primarily managed through exogenous testosterone. These same patients also experience a high degree of cachexia, a loss of skeletal muscle and adipose tissue. To perform a contemporary review of the literature to assess the effectiveness of testosterone replacement therapy (TRT) for managing chronic disease-associated cachexia. We performed a PubMed literature search using MeSH terms to identify studies from 2000 to 2022 on TRT and the following cachexia-related chronic medical diseases: cancer, COPD, HIV/AIDS, and liver cirrhosis. From the literature, 11 primary studies and 1 meta-analysis were selected. Among these studies, 3 evaluated TRT on cancer-associated cachexia, 3 on chronic obstructive pulmonary disease, 4 on HIV and AIDS, and 2 on liver cirrhosis. TRT showed mixed results favoring clinical improvement on each disease. Cachexia is commonly observed in chronic disease states. Its occurrence with hypogonadism, alongside the shared symptoms of these 2 conditions, points toward the management of cachexia through the administration of exogenous testosterone. Robust data in the literature support the use of testosterone in increasing lean body mass, improving energy levels, and enhancing the quality of life for patients with chronic disease. However, the data are variable, and further studies are warranted on the long-term efficacy of TRT in patients with cachexia.

Testosterone Replacement Therapy in Klinefelter Syndrome-Follow-up Study Associating Hemostasis and RNA Expression.

Men with Klinefelter syndrome (KS) develop hypergonadotropic hypogonadism, are in need of testosterone replacement therapy (TRT), and present with a more than 4-fold increased risk of thrombosis. TRT in KS has the potential to modify thrombotic risk, but data are scarce. To assess effects of 18 months of TRT on hemostasis in KS and identify genes associated with the prothrombotic phenotype. Untreated and TRT-treated men with KS were included at baseline and matched to healthy controls. TRT was initiated in untreated KS and all groups were reassessed after 18 months of follow-up. Thrombin generation was evaluated with or without thrombomodulin, and fibrin clot lysis was evaluated by turbidity measurements. RNA expression was assessed in blood, fat, and muscle tissue of patients with TRT-treated KS and controls. Thrombin generation with thrombomodulin was slightly increased in untreated KS, but overall KS was not associated with a hypercoagulable state. KS presented with fibrinolytic impairment associated with higher body fat and higher levels of fibrinogen. Eighteen months of TRT in KS was associated with a reduction in body fat and fibrinogen, attenuating the prothrombotic profile. The expression of ENPP4 was higher in men with KS and served as a key player among a group of genes associated with impaired fibrinolysis. KS is associated with a specific expression profile contributing to fibrinolytic impairment and increased thrombotic risk in the patients. TRT in patients with KS has the potential for alleviating the prothrombotic phenotype, in particular by reducing body fat and fibrinogen.

(362) Testosterone Replacement Therapy for Management of Cachexia: A Review of Current Literature

Abstract Introduction Cachexia is a progressively debilitating loss of skeletal muscle often seen in late-stage chronic medical diseases, such as cancer, HIV/AIDS, chronic obstructive pulmonary disease (COPD), and liver cirrhosis. Cachexia contributes to mortality and morbidity with reduced quality-of-life (QoL) and disease treatment options, and can be associated with adult-onset hypogonadism (AOH), which is commonly treated with testosterone replacement therapy (TRT) in men. Objective This comprehensive review highlights the current literature on TRT for management of patients with chronic disease-associated cachexia, with an emphasis on clinical outcomes and side effects. Specifically, we identify and highlight relevant primary literature and reviews published since 2000 on TRT for management of patients with cancer, COPD, HIV/AIDS, and liver cirrhosis. Methods A comprehensive PubMed literature review was performed to identify articles published between 2000-2021 on TRT and cachexia-related chronic medical diseases (cancer, COPD, HIV/AIDS, and liver cirrhosis) to highlight the use of TRT for management of AOH in male patients with cachexia. The list of studies generated by the initial search was screened to identify eligible studies. Inclusion criteria included primary literature with clinical outcome measures related to changes in lean body mass, muscle mass, body composition, QoL, fatigue scores, and/or exercise scores, in addition to relevant meta-analyses. Results 12 studies were included in our review out of 653 initial search results (Table 1). In three studies of TRT in cancer patients, there were mixed results on the effects of TRT on QoL assessment. Across three studies of TRT in COPD patients, there was consistent improvement in exercise capacity and disease condition with TRT. Across four studies of TRT in HIV-infected men, TRT resulted in notable improvement in body weight, muscle mass, function, and QoL. Lastly, in two studies of TRT in patients with cirrhosis, testosterone therapy improved muscle strength and body composition across both cohorts. Conclusions Based on recent studies, there is robust data for the clinical benefits of TRT for the management of certain subgroups of cachexic patients, specifically those with COPD, HIV, and liver cirrhosis. Because of mixed results in cancer cachexia patients, further investigation of its long-term efficacy is warranted, in addition to hormonal therapy for female cachexic patients. Disclosure No

(067) Oral Testosterone, Is It Ready for Prime Time? A Meta-analysis of Safety and Efficacy in Men with Testosterone Deficiency

Abstract Introduction The prescription rates of testosterone replacement therapy (TRT) have tripled within recent decades. Recently, two novel oral testosterone undecanoate (TU) options have obtained FDA approval and are now commercially available. We present the first meta-analysis analyzing the safety and efficacy of oral TRT in patients with testosterone deficiency (TD). Objective To evaluate the safety and efficacy of TU in the treatment of TD Methods Pair-wise meta-analyses were performed including randomized, placebo-controlled trials investigating the use of TU. Studies were included for analysis if participants received oral TRT or placebo for a period greater than one month and if adverse effects (AE) or changes in serum total testosterone (TT) were recorded. Results Nine studies including a total of 606 patients recorded changes in TT. When separated by population, studies including only men with TD saw improved TT (mean change 1.25 ng/mL, 95% CI: 0.22 to 2.29, I2: 0%). Eight studies including a total of 849 patients recorded rates of AE. There was no statistically significant change in the risk of AE in patients receiving oral TRT compared to placebo (log risk ratio -0.03, 95% CI: -0.08 to 0.03, I2: 0%) [Figure 1]. Conclusions When separated by inclusion criteria, studies examining men with TD tended to report improved TT levels following treatment with TU compared to placebo. In studies examining the safety of oral TRT, its use was not associated with increased rates of AE when compared with placebo. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Antares Pharma; Clarus Therapeutics; Coloplast; Cynosure; Promescent; Sprout; Viome.

Who are the fair candidates for testosterone replacement therapy in patients with late-onset hypogonadism symptoms?

Who are the fair candidates for testosterone replacement therapy in patients with late-onset hypogonadism symptoms?

How Low is Low Enough to be Given Testosterone Replacement Therapy in Patients with Late Onset Hypogonadism? What Should Be Evaluated? A Case Report

Abstract
 Background: Late Onset Hypogonadism (LOH) is a disease associated with advancing age, characterized by symptoms and a deficiency in serum testosterone. It is important to choose which patient suitable for testosterone replacement therapy (TRT), but there is no one consensus that fits for all. After treating patients with testosterone replacement therapy (TRT), several parameters need to be evaluated.
 Case: A 74-years old male came with chief complaint of difficulty to maintain erection since 2 years ago.. PADAM questionnaire was positive and IIEF-5 score was 6. Physical examination showed an underweight condition. Total testosterone level was 3,65ng/mL, and patient chose to be given TRT instead of evaluating his free testosterone. PDE-5 inhibitor and non-pharmacologic treatment was also given. Follow-up showed that his erection was improved.
 Discussions: At which level should testosterone be substituted is still debatable. Several consensuses issued by several organization still cannot be used universally. Study in Indonesia showed that symptoms of LOH had been occur when the testosterone level still in normal range. After giving TRT to our patients, routine follow up is needed. Non pharmacologic treatment also needs to be addressed to improve the outcome.
 Conclusions: Symptoms of LOH had been occurred even though testosterone level is still in normal range. The consideration made by clinician is the most important thing to be evaluated, whether to give TRT or not. Somatic and laboratory parameters mentioned in this study is important to be evaluated.

Effect of Testosterone Replacement Therapy on Quality of Life and Sexual Function in Testicular Cancer Survivors With Mild Leydig Cell Insufficiency: Results From a Randomized Double-blind Trial.

Testicular cancer (TC) treatment leaves many patients with low levels of testosterone. While most TC patients with low testosterone (< - 2 SD) and hypogonadal symptoms will initiate testosterone replacement therapy (TRT), the role of TRT in patients with mild Leydig cell insufficiency, defined as elevated luteinizing hormone in combination with borderline low testosterone, is unknown. To clarify if TRT improves symptoms of depression and anxiety, sexual function, fatigue, and quality of life in TC survivors with mild Leydig cell insufficiency. In total, 69 men aged between 18 and 65 years with mild Leydig cell insufficiency after TC treatment were randomized 1:1 to 12 months daily transdermal testosterone (maximum dose 40 mg/daily) vs. placebo. Patient reported anxiety, depression, sexual function, fatigue, and overall quality of life were assessed at baseline, after 6- and 12 months treatment, and 3 months post-treatment using validated questionnaires. After 12 months of treatment, median luteinizing hormone and median free testosterone were normalized in the testosterone group. Compared to placebo, TRT was not associated with statistically significant improvement of symptoms of anxiety and depression, sexual function, fatigue, and overall quality of life. Testosterone replacement therapy did not improve anxiety, depression, sexual function, fatigue, or overall quality of life in patients with mild Leydig cell insufficiency compared to placebo. Routine TRT in TC survivors with mild Leydig cell insufficiency to improve sexual function and quality of life cannot be generally recommended. The findings should preferably be validated in a larger cohort.

Long-term outcomes of testosterone replacement therapy for patients with late-onset hypogonadism syndrome

ABSTRACT Introduction and Objective Testosterone replacement therapy (TRT) is effective for patients with late onset hypogonadism (LOH) syndrome. However, treatment compliance of long-term TRT for LOH syndrome patients remains unclear. We investigated the long-term outcomes of TRT for patients with LOH syndrome. Methods Forty-two patients (age: mean 55.9, SD 10.2) were diagnosed and then underwent TRT using testosterone enanthate between January 2010 and December 2014 at our hospital. We investigated long-term compliance of TRT, changes of subjective data, i.e. aging male symptom (AMS score) and, international index of erectile function (IIEF5), and objective data, i.e. free testosterone level and, serum PSA level, retrospectively. This study was approved by the Ethics Committee of our facility (Approval No.3043). Results At the time of TRT initiation, AMS score (mean, as mentioned below) was 55.1 (SD 10.1) points, IIEF5 was 7.9 (SD 3.8) points, free testosterone level was 5.8 (SD 1.9) pg/ml, and serum PSA level was 1.3 (SD 1.6) ng/ml. The duration of TRT was 27.7 (SD 29.4) months. Dose of testosterone enanthate was 183.1 (SD 69.2) mg/4weeks. AMS score and IIEF5 were significantly improved after TRT. Adverse events (AE) occurred in 9.6% of the patients, but these were no severe AE. TRT continuation rate was 50.0% at 12 months, 40.5% at 24 months, 35.7% at 36 months, and 33.3% at 48 months. In addition, there was a significantly higher rate in the group with severe AMS scores than in mild-moderate groups. In the discontinuation group of 25 patients (59.5%), the duration of treatment was significantly longer in the improvement group than in the ineffective group. Conclusions Testosterone replacement therapy for late onset hypogonadism syndrome is a safe and effective long-term treatment. The treatment continuation analysis showed that patients with severe AMS scores and better effect of TRT requested long-term treatment. Disclosure Work supported by industry: no.

Exploring the Role of Testosterone Replacement Therapy in Benign Prostatic Hyperplasia and Prostate Cancer: A Review of Safety

Increased risk of prostate diseases triggered by testosterone replacement therapy (TRT) remains a worldwide concern. That said, we reviewed the safety of TRT in the spheres of benign prostatic hyperplasia (BPH) and prostate cancer (PCa), exploring clinical findings in this regard. Compelling evidence based on meta-analyses of randomized and observational studies indicates safety for TRT in patients suffering from prostate disorders such as BPH and PCa, at the same time improving lower tract urinary symptoms. Thus, the harmful relationship geared toward androgens and BPH seems to be overestimated as TRT has sufficient safety and, if properly prescribed, may counteract several metabolic problems. Even after PCa treatment, the benefits of TRT could outweigh the risk of recurrence, but further long-term randomized clinical trials are needed to elucidate unresolved questions.

Predictive factors for elevated prostate specific antigen and hematocrit levels during testosterone replacement therapy in patients with testosterone deficiency

Objective: We examined risk factors associated with prostate specific antigen (PSA) and hematocrit (hct) elevation during testosterone replacement therapy (TRT) in patients with testosterone deficiency (TD). Methods: We retrospectively analyzed the medical records of patients receiving TRT for ≥3 months. We investigated the following parameters: age, body mass index, comorbidities, TRT type, TRT duration, pre-TRT prostate volume, pre- and post-TRT serological tests, prostate biopsies, prostate cancer diagnoses, pre- and post-TRT aging male symptom scale scores, hct elevation, and PSA elevation. The patients were divided into two groups based on the PSA elevation status for comparison, following which we analyzed the predictive factors for PSA elevation. They were also divided into two groups based on hct elevation status. Results: The PSA elevation group showed a statistically significantly higher mean age, pre-TRT prostate volume, and PSA level compared to the non-elevation group. The PSA non-elevation group showed a significantly higher percentage of smokers, while the PSA elevation group showed a statistically significantly higher prevalence of benign prostatic hyperplasia (BPH_LUTS). The results demonstrated that a large pre-TRT prostate volume, high pre-TRT PSA levels, BPH_LUTS, and being a non-smoker were the contributing factors for PSA elevation. The hct elevation group showed statistically significantly higher pre-TRT Hb, hct, and post-TRT testosterone levels, and dyslipidemia rates, as well as a non-statistically significant prevalence of testosterone enanthate (TE) and testosterone undecanoate (TU) intramuscular injection. The pre-TRT Hb and hct levels were contributing factors for hct elevation during TRT. TE injection showed marginal statistical significance. Conclusions: We identified large prostate volumes, high PSA levels, BPH_LUTS, and being non-smokers prior to TRT as risk factors for PSA elevation during TRT. Interestingly, we found that TRT-induced hct elevation was likely to occur in patients with high pre-TRT Hb and hct levels. Additionally, the hct levels should be monitored when using TE for TRT.

Testosterone replacement therapy and its relationship with hyperestrogenism and obesity. Problems of laboratory diagnostics of hyperestrogenism

Testosterone replacement therapy (TRT) is one of the most effective and common treatments for testosterone deficiency today. It is often prescribed, focusing only on the level of testosterone and the presence of patient complaints about a decrease in sexual function. Quite rarely, doctors additionally assess the level of estradiol and, as a consequence, the initial presence of a symptom of hyperestrogenism. One of the likely consequences of the appointment of TRT may be an excess of estradiol, the excess formation of which is associated with the enzyme aromatase, which converts testosterone into estradiol. Despite the availability of laboratory determination of the level of estradiol, the result may not always coincide with the clinical picture, one of the reasons is the difference in the methods for determining the level of estradiol in each laboratory, there is no single standard or «reference» today. This article describes the evolution of TRT, and also focuses on the variability of estradiol levels from laboratory to laboratory, and explains in detail why the assessment of estradiol over time should be carried out in only one laboratory. A systematic literature search was carried out in the databases Medline, Scopus, Web of Science and Elibrary, CyberLeninka.The purpose of our review was the need to engage the attention of specialists to the problem of hyperestrogenism, the not always justified prescription of TRT in patients with obesity, hypogonadism and hyperestrogenism, as well as to the problem of laboratory diagnosis of hyperestrogenism, which is acute not only in our country, but all over the world.

Testosterone replacement therapy in hypogonadal male patients with hypogonadism and heart failure: a meta-analysis of randomized controlled studies.

The recently published guidelines of the European Academy of Andrology (EAA) recommended not to prescribe testosterone replacement therapy (TRT) in male patients with hypotestosteronemia and severe heart failure (HF) [New York Hearth Association (NYHA) class III and IV] since the risk in these patients has not been formally documented. Therefore, the aim of this study was to systematically evaluate the risk of TRT on the cardiac function and angina, in male patients with hypotestosteronemia and HF or coronary heart disease. Randomized controlled trials (RCTs) on male patients with hypotestosteronemia and chronic HF (ejection fraction <40%) or stable angina documenting the effect of TRT on NYHA class, left ventricular ejection fraction (LVEF), adverse events, ST depression and other indexes of cardiovascular function. Seven articles were included, for a total of 140 participants with HF (71 on TRT and 69 on placebo or no treatment). Included patients were of NYHA class II and III. TRT had no effect on death and rehospitalization rates of patients with HF and significantly delayed the time to ischemia in patients with chronic angina. TRT had no effect on the NYHA class, the LVEF, and on the Minnesota Living with Heart Failure questionnaire. Although a significant increase of oxygen consumption was found in the TRT group, no improvement to the physical exercise tolerance tests was observed. TRT showed no effect on systolic nor diastolic blood pressure, but it significantly ameliorated the heart rate. It significantly decreased the insulin serum levels and the HOMA index. These results suggest the safety of TRT, in patients with hypotestosteronemia and severe HF (class NYHA II and III). Although deriving from a limited number of studies, these data could prompt to perform other RCTs on the effects of TRT in patients with hypotestosteronemia and severe HFrEF (NYHA class III).

Compliance with Testosterone Replacement Therapy in Patients with Testosterone Deficiency Syndrome: A 10-Year Observational Study in Korea.

PurposeTo determine the compliance rate with testosterone replacement therapy (TRT) in patients with testosterone deficiency syndrome (TDS), we evaluated the treatment continuation rate and the reasons for discontinuation of initial treatment according to each formulations and patient characteristics.Materials and MethodsAmong men over 40 years of age who were diagnosed with TDS and then underwent TRT, their medical records were retrospectively analyzed for those who were followed up for more than 10 years.ResultsA total of 640 patients were included in the analysis. It was found that 75.9% of patients continued treatment for 1 year after starting. Patients treated with 1,000 mg of testosterone undecanoate injection had the highest treatment rate. Inconvenience of medication was the most common reason for discontinuing treatment, followed by cost, concern about side effects, lack of efficacy, and symptom recovery. The reasons for discontinuing treatment differed according to the xlink:type of formulations, and the longest continuous treatment period in all patients was 15.4±7.6 months on average. The treatment continuation rate tended to be high in patients with low serum total testosterone before starting treatment, in patients with severe erectile dysfunction, and in patients using phosphodiesterase-5 (PDE5) inhibitors.ConclusionsAmong the various formulations of TDS, testosterone undecanoate injection (1,000 mg) had the highest compliance rate. In addition, it was found that the reasons for discontinuation of treatment varied according to the characteristics of each formulation.

Hypogonadism and cancer survivorship

Hypogonadism is highly prevalent among not only patients with a history of prior treatment for cancer, but also among those patients with a new oncologic diagnosis who have not yet received any cancer therapy. Hypogonadism can cause a wide array of signs and symptoms including: deceased muscle mass; increased fat mass; decreased energy, mood, and overall sense of well being; diminished bone mineral density; infertility; and impaired libido and sexual function. This purpose of this manuscript is to review the mechanisms by which cancer and oncologic treatment regimens can adversely affect the hypothalamic pituitary gonadal axis, resulting in hypogonadism. Risks and benefits associated with the treatment of testosterone deficiency are also discussed, which are important considerations for clinicians caring for affected patients. Hypogonadism has a high prevalence in the setting of cancer and is an important survivorship issue. Recent randomized controlled trials confirm testosterone's therapeutic benefits in terms of sexual function, mood body composition, and bone health, but the specific benefits in terms of quality of life are less clear. More prospective studies are needed to further delineate the risks, benefits, and overall outcomes of testosterone replacement therapy in patients with cancer and cancer survivors.

Obstructive Sleep Apnea and Testosterone Replacement Therapy

The evidence on the role of obstructive sleep apnea (OSA) in the pathogenesis of hypogonadism and the impact of testosterone replacement therapy (TRT) in OSA patients are still contradictory. OSA is generally considered to be a relative contraindication as TRT is feared to worsen sleep apnea so that ventilatory capacity should be strictly investigated in advance and monitored thereafter. Few controlled studies have been released on the long-term effects of TRT in patients with OSA due to methodological limitations at study entry. Data from recent randomized placebo-controlled studies show a time-dependent influence on nocturnal hypoxia, and a positive impact after a longer time of exposure in selected patients. Since these results await further confirmation from larger studies, we suggest to use TRT cautiously in obese hypogonadal patients with hypoventilatory syndrome, especially if they are not on continuous positive airway pressure treatment.

21 - Discontinuation of testosterone replacement therapy in patients with late-onset hypogonadism: A 10-year observational study

21 - Discontinuation of testosterone replacement therapy in patients with late-onset hypogonadism: A 10-year observational study

USE OF TESTOSTERONE REPLACEMENT THERAPY AFTER RADICAL PROSTATECTOMY MIGHT KILL TWO BIRDS WITH ONE STONE FROM THE PERSPECTIVE OF MEN’S HEALTH AND DISEASE CONTROL

Testosterone plays an important role in promoting the differentiation and stimulation of prostate epi-thelial cells. Adding to the basic physiology of testosterone, several studies led to the dissemination of the historical androgen hypothesis that higher circulating androgen levels promote prostate cancer cell growth and make the tumor more aggressive. Whereas, the prostate saturation model accounted for the androgen sensitivity of testosterone stimulation in the prostate up to a saturation point, which occurred near the level of castration. Testosterone is related to prostate cancer metabolism in a com-plex manner; however, within the reference range, high or normal testosterone levels are expected to maintain benign and malignant prostate cells in a differentiated state. Accumulating evidence has suggested that testosterone replacement therapy (TRT) might prevent the development of prostate cancer and even reduce prostate cancer risk. There is no change in the clinical guidelines to be followed when considering TRT in patients with a history of prostate cancer, but it is necessary for the physician to inform patients of the positive effects of TRT on male health and prostate cancer.

Trends in reported incidence of erectile dysfunction, hypogonadism, PDE5i prescriptions and TRT in patients with type 2 diabetes in primary care

BackgroundErectile dysfunction (ED) and testosterone deficiency (TD) are complications of type 2 diabetes mellitus (T2DM), and predictors of cardiovascular disease. Guidelines recommend that men with T2DM are assessed and treated for ED/TD, which was included into the Quality and Outcomes Framework (QOF) from 2013–2014 only.AimExplore the effects of QOF on ED/TD diagnoses and management in T2DM patients.MethodThe study population included males (≥18 years) with T2DM and contributing to UK GP electronic health records from 1999–2016. Adjusted incidence rate ratios (IRRs) were estimated using multivariable Poisson regression.ResultsIn total 135 342 adult males (mean age 60 years) with T2DM were included. During follow-up, 60 819 (45%) had a recorded ED assessment, 23 834 (18%) an ED diagnosis and of these 73% received a phosophodiesterase-5 inhibitor (PDE5i). ED assessments increased from 7.6 per 1000 PYAR in 2012 (95% confidence interval [CI] = 7.0 to 8.3) to 620 in 2013 (95% CI = 614 to 626) when included into QOF but dropped to 59.4 (95% CI = 56 to 63) in 2016. Compared with 2012, the adjusted incidence of recorded ED diagnoses and PDE5i prescriptions doubled in 2013 (incidence rate ratio [IRR] 2.0; 95% CI = 1.8 to 2.1) before falling to below pre-QOF levels in 2016 (IRR 0.89; 95% CI = 0.82 to 0.97). Of 1187 diabetic men diagnosed with ED or receiving a PDE5i in 2015, 213 (18%) had minimum one testosterone measurement, of which 45 (21%) met criteria for hypogonadism (testosterone ≤8nmol/l). Nine (20%) subsequently received testosterone replacement therapy (TRT).ConclusionTo improve diagnosis and management of ED/TD in T2DM patients and thereby (cardiovascular) health and quality of life, incorporation of guidelines into a GP framework and/or financial incentives may be required alongside GP education.

122 Diagnosis and Management of Testosterone Deficiency – Comparison of Current Guidelines

Testosterone deficiency (TD) is characterized by low levels of testosterone (T) with associated signs and symptoms. Several controversies related to the diagnosis and management of TD have been identified. In an attempt to provide clarity for patients and healthcare providers, several professional organizations have developed clinical practice guidelines focused specifically on TD. We compare current guidelines for the diagnosis and management of TD, as well as special considerations for specific patient populations. Guidelines from the following organizations were included for analysis: American Urological Association (AUA – 2018), Canadian Medical Association (CMAJ – 2015), European Association of Urology (EAU – 2018), and Endocrine Society (ES – 2018). The comparison focused on the biochemical definition (cut-off) for low T, principles of management of TD, and recommendations for patients with low-to-normal total testosterone, prostate cancer, or cardiovascular disease. General diagnostic and management principles are in agreement, however specific biochemical cut-offs range between 8 to 10.4 nmol/L (Table 1). The CMAJ guideline has no specific cut-off for low T and requires only one lab measurement of total T as opposed to the two measurements required in other guidelines. In patients with low-to-normal total T, there is consensus among the guidelines in recommending further hormonal evaluation. However, only the CMAJ guideline provides additional recommendations for testosterone replacement therapy (TRT) by suggesting a 3-month therapeutic trial if patients are symptomatic. The ES guideline has the strictest recommendations for patients with TD and prostate cancer. Other guidelines generally recommend against TRT in patients with metastatic prostate cancer. Although there is limited evidence linking TRT and risk of cardiovascular events (MI, stroke, sudden CV death), the AUA and EAU guidelines impose more restrictions in offering TRT to patients with cardiovascular disease. Notably, the AUA guideline recommends against TRT if patients experienced a cardiovascular event within the past 3-6 months, while the EAU guideline states that TRT is contraindicated in patients with NYHA Class IV heart failure. In contrast, the CMAJ guideline recommends TRT in patients with stable cardiovascular disease.

234 Testosterone-Replacement Therapy in Patients with Baseline Low-normal to Normal Testosterone Levels and Hypogonadal Symptoms

234 Testosterone-Replacement Therapy in Patients with Baseline Low-normal to Normal Testosterone Levels and Hypogonadal Symptoms