Testosterone Replacement Therapy In Hypogonadal Men Research Articles

(O-13) TESTOSTERONE REPLACEMENT THERAPY AND PROSTATE CANCER PROGRESSION IN HYPOGONADAL MEN ON ACTIVE SURVEILLANCE: A RETROSPECTIVE ANALYSIS

Abstract Introduction The use of testosterone replacement therapy (TRT) in hypogonadal men with prostate cancer (PC) on active surveillance (AS) has been controversial. However, recent studies have challenged this notion, warranting further investigation. We aim to assess the impact of TRT on PC progression in hypogonadal men on AS. Methods We conducted a retrospective chart review using data from a single hospital system between 2009 and 2022. The database included hypogonadal men with PC on AS who underwent TRT. Patients with prior PC treatment were excluded. PSA and total testosterone (TT) levels were recorded at various time points, including before and after TRT initiation. One-way ANOVA was used to analyze mean PSA and TT levels, and PC treatment progression was documented. Results A total of 25 men met the inclusion criteria. Mean PSA and TT levels at each time interval showed no significant difference in PSA (P = 0.283), while TT exhibited significant variation (P = 0.0052) throughout the 2-year study period. Mean TT before TRT initiation was 311.39 ng/dL, and after TRT, it increased to 773.04 ng/dL (P = 0.00011). Only one patient (4%) underwent radiation therapy for PC five years after starting TRT. Conclusions Initiating TRT in hypogonadal men on AS for PC did not result in a significant change in PSA levels, despite an increase in testosterone. As our database expands, we aim to strengthen the study's statistical power. These findings contribute to the growing evidence supporting the potential viability of TRT in hypogonadal men on AS. Financing No conflict.

Untreated hypogonadism and testosterone replacement therapy in hypogonadal men are associated with a decreased risk of subsequent prostate cancer: a population-based study.

We sought to understand the relationship between hypogonadism and testosterone replacement therapy (TRT) in hypogonadal men on the risk of developing localized and metastatic prostate cancer. We used the Merative MarketScan database of commercial claims encounters to identify men diagnosed with hypogonadism. These men were matched to eugonadal men who served as controls. Multivariate negative binomial regression analysis of prostate cancer diagnoses, hypogonadism, and TRT in hypogonadal men adjusting for various known confounding factors was used to understand the impact of hypogonadism and TRT on prostate cancer risk. We identified 3,222,904 men who met inclusion criteria, of which 50% were diagnosed with hypogonadism (1,611,452) and each were matched to a control (1,611,452). The incidence of prostate cancer was 2.16%, 1.55%, and 1.99% in eugonadal controls, hypogonadal men on TRT, and hypogonadal men without TRT, respectively (p < 0.001). Untreated hypogonadism was independently associated with a decreased risk of localized prostate cancer (IRR 0.46, 95% CI 0.43-0.50, p < 0.001) compared to eugonadal controls. Hypogonadal men on TRT also had a significantly decreased risk of localized prostate cancer (IRR 0.49, 95% CI 0.45-0.53, p < 0.001). Furthermore, hypogonadal men on TRT (IRR 0.21, 95% CI 0.19-0.24, p < 0.001) or without TRT (IRR 0.20, 95% CI 0.18-0.22, p < 0.001) both had significantly decreased risk of metastatic prostate cancer, respectively. Our population-based analysis suggests that untreated hypogonadism in men is associated with a 50% decreased incidence of localized prostate cancer and an 80% decreased incidence of metastatic prostate cancer. TRT in hypogonadal men was also associated with a decreased risk of subsequent prostate cancer. Further research is needed to better understand the relationship between hypogonadism and TRT in hypogonadal men on the riskof subsequent prostate cancer.

The complex relation between obstructive sleep apnoea syndrome, hypogonadism and testosterone replacement therapy.

Obstructive sleep apnoea syndrome (OSAS) is an under-recognized medical disease. The main risk factors for OSAS are male sex, older age, obesity, and metabolic syndrome, that are also associated with male hypogonadism (MH). Therefore, obesity has been classically identified as the most evident link between OSAS and MH. However, OSAS is per se linked to the development of MH by a combined effect of hypoxia, increased night-time awakenings, reduced sleep efficiency and fragmented sleep. Similarly, MH might represent a risk factor for OSAS, mainly related to sleep disturbances that are frequently associated with low testosterone. Data on testosterone replacement therapy (TRT) in patients with OSAS are limited. Nevertheless, TRT is generally contraindicated by guidelines in the presence of untreated or severe OSAS. TRT might in fact worse OSAS symptoms in different ways. Furthermore, OSAS has been proposed to be a risk factor for secondary polycythaemia and TRT might exacerbate polycythaemia. Therefore, TRT in hypogonadal men affected by untreated OSAS or severe OSAS should be considered with caution and in a personalised way. Nevertheless, the type and dosage of TRT should be considered, as short-term high-dose TRT might worsen OSAS, whereas long-term lower doses could eventually determine a clinical improvement of symptoms of OSAS. Here we reviewed the data on the association between OSAS, MH and TRT, including the opportunity of assessment of patients who develop signs and symptoms of OSAS during TRT by polysomnography.

Testosterone Replacement Therapy and Cardiovascular Disease: Balancing Safety and Risks in Hypogonadal Men.

PURPOSEOF REVIEW: The purpose of this review is to analyze the link between testosterone replacement therapy (TRT) and adverse cardiovascular (CV) events. RECENT FINDINGS: A few published studies suggest a link between TRT and CV events. These studies contained flaws, and many other studies reveal a reduction in CV events. Hypogonadism is associated with increased mortality in men with CVD. TRT in hypogonadal men can improve many CVD risk factors, reduce QT interval prolongation, lead to better outcomes in heart failure patients, and slow the progression of atherosclerosis. The use of TRT to achieve physiologic testosterone concentrations in men does not pose a threat to CV health and has demonstrated a cardioprotective effect.

(065) The Impact of Testosterone-Replacement Therapy (TRT) on Benign Prostatic Hyperplasia (BPH) Incidence and Need for Interventions in Hypogonadal Men

Abstract Introduction Investigations on the application of testosterone-replacement therapy (TRT) in hypogonadal men with benign prostatic hyperplasia (BPH) show contrasting results. While some studies reported increased prostate-related events with TRT, recent evidence suggested that TRT can alleviate BPH symptoms in hypogonadal men. Objective Our main objective was to determine the impact of TRT on BPH incidence in a large cohort of hypogonadal men. We also evaluated the relationship between TRT in hypogonadal men and the need for BPH interventions. Methods This retrospective case-control study used the 2011-2020 IBM MarketScan database to identify males above 18 years old with a hypogonadism diagnosis, and determine if they received TRT. We used ICD-9, -10, CPT, HCPCS, and NDC codes to identify diagnoses, interventions, and medications. We excluded individuals who were diagnosed with congenital genetic disorders (e.g. chromosomal abnormalities), hypothalamic-pituitary disorders, or prostatic adenocarcinoma. BPH diagnosis was the primary outcome of this study, and BPH treatment was the secondary outcome. We ran cox proportional hazard (CPH) models from initial hypogonadism diagnosis to BPH occurrence to investigate the effect of TRT on the development of BPH. We also used CPH models from time of BPH diagnosis to first intervention, to evaluate the impact of TRT on BPH interventions. In all models we controlled for age, geographic region, population density, and comorbidities. We included TRT within the last 6 as a time-varying covariate in the models. For BPH occurrence there was non-proportionality in the effect of TRT. Thus, we ran two CPH models for BPH occurrence, one from first hypogonadism diagnosis to 912 days (2.5 years), and one from 2.5 years to the end of enrollment. Results In our total cohort of 882570 hypogonadal men, 157185 (17.8%) were diagnosed with BPH. Hyperlipidemia was the most common comorbidity detected in 84% and 68% of hypogonadal men with and without BPH respectively. For the first 2.5 years after hypogonadism diagnosis, there was no significant difference for development of BPH between patients on TRT and those who were not on TRT (HR 1.00, 95%CI 0.98-1.01, p=0.66). However, from 2.5 years onward, men who were on TRT had a 32% greater chance for development of BPH (HR 1.32, 95%CI 1.28-1.36, p&amp;lt;0.001). Hypogonadal men with BPH who received TRT showed no significant difference for BPH interventions compared to those who were not on TRT (HR 0.95, 95%CI 0.89-1, p=0.08). Conclusions In the long term, TRT can increase the risk of development of BPH in hypogonadal men. On the other hand, TRT in hypogonadal men with BPH does not change the need for BPH interventions. Our findings indicate that TRT should be used with caution in hypogonadal men who are at risk of developing BPH but further work is needed to clarify this relationship. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Educational/Research grant: Acerus, Coloplast, Endo, Boston Scientific; Consultant: Turtle Health; Hold equity: StreamDx, FirmTech, Maximus.

ODP412 High Frequency of Erythrocytosis in Hypogonadal Men on Testosterone Replacement Therapy

Abstract Introduction Erythrocytosis is a frequent side effect of testosterone replacement therapy (TRT) in hypogonadal males and can be deleterious by increasing blood viscosity, which can lead to headaches, hypertension, and thromboembolic complications. Main causes of erythrocytosis are short-acting testosterone injections, smoking habit and obesity. Aim Study the frequency of erythrocytosis induced by TRT and its predictive factors in hypogonadal men in our setting. Subjects and methods: A retrospective study in hypogonadal males on TRT for at least 3 months was conducted. Age, age at treatment onset, months on treatment, initial hematocrit (IHt), highest hematocrit during follow-up (MaxHt), hematocrit on last visit (FHt), hematocrit increase (HtIn), maximum hematocrit increase (HtMaxIn), anthropometric measures, sex hormones and biochemical parameters on the last visit were recorded. In addition, testosterone formulation, smoking status, dyslipidemia, hypertension, diabetes, type of hypogonadism and presence of cardiovascular disease (CVD) were also documented. A hematocrit ≥ 50% (Ht≥50) was considered erythrocytosis and one ≥ 53% was indication for phlebotomy (Ht≥53). Results 108 patients were included, age 54 ± 19 years, age at THT onset 44 ± 18 years, BMI 30 ± 5 Kg/m 2 . On the last visit, 29% had FHt≥50 and 11% had FHt≥53, while during follow-up 58% had MaxHt≥50 and 35% had MaxHt≥53. Moreover, 18% were smokers, 61% had dyslipidemia, 48% had hypertension, 36% were diabetic, 59% were on short acting IM testosterone injections (cypionate), 25% were on extended-release IM testosterone injections (undecanoate) and 16% were on transdermal testosterone. On the other hand, 13% had CVD at onset and 6% developed CVD during follow-up. None of the hematocrit or hematocrit increase values was related to the type of testosterone formulation, smoking habit or appearance of CVD during follow-up. They also did not correlate with serum total testosterone, other sexual hormones and lipids levels or BMI. Interestingly, there was no difference in total testosterone levels between the three testosterone preparations groups. FHt (44 vs 48%, p=0,018) and HtIn values (1.86 vs 5.31%, p=0,036) were lower in those with previous CVD disease. This fact cannot be explained by BMI since there was no difference between patients with and without CVD. Although it could be due to a lower percentage of smokers in the group of patients with CVD, that could not be demonstrated. Discussion The occurrence of erythrocytosis secondary to TRT in hypogonadal men in our setting was very common and higher than reported previously: 58% of patients during follow-up and 35% required phlebotomy. Hematocrit and hematocrit increase values were independent of BMI, smoking status, type of testosterone formulation and presence of CVD. This lack of association could be due in part to the small number of individuals in some of the subgroups. Presentation: No date and time listed

Testosterone Replacement Therapy in Hypogonadal Men and Myocardial Infarction Risk: Systematic Review & Meta-Analysis.

Testosterone replacement therapy (TRT) has become increasingly popular over the years and there has been an increasing debate on whether testosterone replacement should be offered to older men due to its association with cardiovascular events. In this study, we evaluated the risk of myocardial infarction (MI) associated with TRT in hypogonadal men through a meta-analysis. We carried out the analysis by following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: Google Scholar, PubMed, Science Direct, Cochrane Library trials, and ClinicalTrials.gov. The search strategy resulted in a total of 782 articles, after applying our inclusion and exclusion criteria. Six observational studies and two randomized controlled trials (RCTs) were included for the analysis. A total of 55,806 hypogonadal men with baseline testosterone levels <300ng/mL were included in the analysis. The intervention group received testosterone in various routes including transdermal patches, gels, mouth patches, testosterone injections, and deposits. The incidence of MI was taken to be the primary measure outcomes. The pooled data from eight studies showed MI incidence in 249 out of 11,720 (2.1%) in the TRT group and 1420 out of 33,086 (4.3%) in the control group. The pooled OD showed no statistically significant association of TRT and MI compared to the control group (OR = 0.76, 95% CI 0.36-1.31; p=0.48). The model revealed high heterogeneity with I2 =79%. With sensitivity analysis and, excluding two studies out of the eight, the pooled data was able to achieve low heterogeneity with I2 = 0%. The newly pooled data from six studies showed MI incidence in 226 out of 10,137 (2.2%) in the TRT group and 969 out of 36,304 (2.7%) in the control group. The pooled OD shows no statistical significance in the association between TRT treatment and MI compared to the control group. (OR =0.87, 95% CI 0.75-1.01; P =0.08). It appears that TRT does not increase the risk of MI as compared to the non-intervention group. Further RCTs with greater population size are needed that could produce more solid results, allowing more definitive conclusions to be made on this topic.

039 Testosterone Replacement Therapy and Prostate Cancer

It has been well established that male hypogonadism has a significant impact on patient quality of life and that replacement of testosterone can markedly improve symptoms and potentially offer protective effect. The connection between testosterone replacement therapy (TRT) and prostate cancer (CaP) risk has long been a contentious subject among urologists. With the relatively recent introduction of the saturation model hypothesis by Morgentaler to explain androgen binding in CaP along with a growing body of retrospective studies, there has been a mounting challenge to the entrenched paradigm that TRT in hypogonadal men stimulates CaP. This review is a relevant update for the practicing urologist seeking to gain a better understanding regarding the risk and benefit profile to TRT in a variety of CaP settings.

SAT-001 Supra-Physiological Testosterone Treatment Reduces Aortic Atheroma but Increases Markers of Cardiac Hypertrophy

Supra-physiological Testosterone Treatment Reduces Aortic Atheroma but Increases Markers of Cardiac Hypertrophy The impact of testosterone on the cardiovascular system is controversial and concerns have been raised in regard to the safety of testosterone replacement therapy (TTh) in hypogonadal men with cardiovascular disease. We have examined the effects of supra-physiological concentrations of testosterone upon aortic fatty streak formation in high-fat diet-fed testicular feminized (Tfm) mice, which exhibit non-functional androgen receptors (AR) and low circulating testosterone levels. Tfm mice were fed a high-cholesterol diet ad libitum for 28 weeks and received fortnightly intramuscular injections of either saline (Tfm, n=8, XY, n=8), 10uL of 250mg/mL testosterone alone (Tfm, n=8, XY, n=8), or in conjunction with either a 30uL intramuscular injection of 50mg/ml estrogen receptor-alpha antagonist fulvestrant (Tfm, n=8), or with 10mg/kg/day of aromatase inhibitor anastrazole in drinking water (Tfm, n=7). Cardiac tissue mRNA was analysed by qPCR for markers of hypertrophy (ANP, BNP, alpha-actin, MYH7, Gsk3-beta, SM22-alpha). A significant reduction in aortic fatty streak formation was observed in Tfm mice receiving supra-physiological testosterone compared to those receiving saline; 1.25+0.36% versus 2.85+0.37% respectively (p<0.01). No significant increase in aortic lipid deposition was observed in XY littermates administered supra-physiological testosterone compared to those receiving saline; 0.22+0.13% versus 0.32+0.12% respectively (p=ns). Aortic fatty streak formation in Tfm mice receiving supra-physiological testosterone in conjunction with fulvestrant or anastrazole was similar to that observed in Tfm mice receiving supra-physiological testosterone therapy alone; 0.71+0.18% and 1.09+0.81% respectively versus 1.25+0.36% (both p=ns) indicating non-genomic actions of testosterone. Hypertrophic markers and heart weights were elevated in XY littermates receiving supra-physiological testosterone but not in Tfm mice compared to placebo suggesting AR-dependent actions. This evidence suggests that supra-physiological levels of testosterone protect against diet induced aortic atheroma formation, at least in part, via non-genomic mechanisms but incur increased cardiovascular risk by potentially inducing cardiac hypertrophy via AR-dependent actions. Dose titration to physiological levels and careful monitoring of patients throughout treatment is key to eliciting the beneficial cardiovascular effects of TTh in hypogonadal men.

Cardiovascular benefits and risks of testosterone replacement therapy in hypogonadal men with type 2 diabetes mellitus and/or the metabolic syndrome: a systematic review

Background: Because of the paucity of large randomised controlled trials (RCTs) in men with type 2 diabetes mellitus (T2DM) and/or the metabolic syndrome (MS), the majority of evidence for use of testosterone replacement therapy (TRT) on the cardiovascular (CV) system in such men is derived from observational studies and systematic reviews.Methods: We carried out an extensive retrospective review of the literature, comparing the major comparative trials that involved TRT in hypogonadal men with T2DM and/or MS and focused on CV outcomes.Results: Of 311 studies initially identified, 25 studies (12 RCTs and 13 non-RCTs) with a total number of 729,927 participants were deemed eligible for further review. Three RCTs and one non-RCT were excluded as these had not measured all-cause mortality and CV events as primary outcomes. Benefits of TRT on myocardial infarction were observed in two RCTs which were reviewed, while the rest demonstrated a neutral effect on CV events. In the non-RCTs, seven studies observed reduced all-cause mortality and/or major adverse CV events in the TRT group compared with the placebo group.Conclusions: This retrospective and systematic review of the literature suggests protective effects of TRT against all-cause mortality and major adverse cardiac events in hypogonadal men with T2DM and/or MS, although these results need to be interpreted cautiously.

Evidence-based Medicine Update on Testosterone Replacement Therapy (TRT) in Male Hypogonadism: Focus on New Formulations

Until the 2000s Testosterone (T) Replacement Therapy (TRT) wasn't very satisfactory for male hypogonadic patients because the available T formulations weren't able to reproduce the physiological pattern of T secretion in man. In fact, oral formulations (oral undecanoate T) showed very short half-life (<24 hours), requiring the administration of several daily doses, whereas the old injection products (T esters) were characterized by very long half-life (>7 days) because of their adipose tissue storage, requiring to be administered every 2-3 weeks but determining remarkable and quick fluctuations (in 2-3 weeks) of the testosteronemia with variations in a few days from over-physiological levels (> 2000 ng/dl) to very low levels (< 200 ng/dl). Nowadays, several compounds can attain the standards of suitability and effectiveness of TRT in hypogonadal men. Both transcutaneous (gel) T and long-acting injectable formulations are the most modern preparations that can satisfy the criteria of an ideal chronic replacement therapy. In fact, they keep the serum T levels in the physiological range imitating its circadian rhythm, leading to the development and/or the preservation of male sexual characteristics and, finally, positively influencing bone mass, skeletal muscle and adipose tissue distribution. In particular, the availability and use of long-acting injectable undecanoate T can really improve the patients' compliance as requested for a life-long treatment. However, definitive and conclusive evidence regarding the main end-points, such as the diminished recurrence of falls in elderly men, the decrease in fractures in osteoporotic subjects, the reduction in disabling conditions and the extension of life, have not been reached so far. Therefore, the aim of this review is to sum up the most important evidence that has been collected regarding TRT, highlighting in particular those concerning both transcutaneous and long-acting injectable T compounds.