Role Of Testosterone Replacement Therapy Research Articles

Adult- and late-onset male hypogonadism: the clinical practice guidelines of the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE).

PurposeTo provide the evidence-based recommendations on the role of testosterone (T) on age-related symptoms and signs remains.MethodsThe Italian Society of Andrology and Sexual Medicine (SIAMS) and the and the Italian Society of Endocrinology (SIE) commissioned an expert task force to provide an updated guideline on adult-onset male hypogonadism. Derived recommendations were based on Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.ResultsClinical diagnosis of adult-onset hypogonadism should be based on a combination of clinical and biochemical parameters. Testosterone replacement therapy (TRT) should be offered to all symptomatic subjects with hypogonadism after the exclusion of possible contraindications. T gels and the long-acting injectable T are currently available preparations showing the best efficacy/safety profile. TRT can improve all aspects of sexual function, although its effect is limited in more complicated patients. Body composition (reducing fat mass and increasing lean mass) is improved after TRT, either in subjects with or without metabolic syndrome or type 2 diabetes. Conversely, the role of TRT in improving glycometabolic control is more conflicting. TRT can result in increasing bone mineral density, particularly at lumbar site, but no information on fracture risk is available. Limited data support the use of TRT for improving other outcomes, including mood frailty and mobility.ConclusionsTRT can improve sexual function and body composition particularly in less complicated adult and in aging subjects with hypogonadism. When hypogonadism is adequately diagnosed, T appropriately prescribed and subjects correctly followed up, no short-term increased risk of adverse events is observed. Longer and larger studies are advisable to better clarify TRT long-term efficacy/safety profile.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40618-022-01859-7.

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.

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.

Androgens and COVID-19: exploring the role of testosterone replacement therapy.

Androgens and COVID-19: exploring the role of testosterone replacement therapy.

The role of testosterone replacement therapy and statin use, and their combination, in prostate cancer

Previous studies have reported conflicting results in the associations of testosterone replacement therapy (TTh) and statins use with prostate cancer (PCa). However, the combination of these treatments with PCa stage and grade at diagnosis and prostate cancer-specific mortality (PCSM) and by race/ethnicity remains unclear.We identified non-Hispanic White (NHW, N = 58,576), non-Hispanic Black (NHB, n = 9,703) and Hispanic (n = 4,898) men diagnosed with PCa in SEER-Medicare data 2007-2011. Pre-diagnostic prescription of TTh and statins was ascertained for this analysis. Multivariable-adjusted logistic and Cox proportional hazards models were used to evaluate the association of TTh and statins use with PCa stage and grade and PCSM.22.5% used statins alone, 1.2% used TTh alone, and 0.8% used both. TTh and statins were independently, inversely associated with PCa advanced stage and high grade. TTh plus statins was associated with 44% lower odds of advanced stage PCa (OR 0.56, 95% CI 0.35-0.91). As expected, similar inverse associations were present in NHWs as the overall cohort is mostly comprised NHW men. In Hispanic men, statin use with or without TTh was inversely associated with aggressive PCa.Pre-diagnostic use of TTh or statins, independent or in combination, was inversely associated with aggressive PCa, including in NHW and Hispanics men, but was not with PCSM. The findings for use of statins with aggressive PCa are consistent with cohort studies. Future prospective studies are needed to explore the independent inverse association of TTh and the combined inverse association of TTh plus statins on fatal PCa.

Aging-related compensated hypogonadism: Role of metabolomic analysis in physiopathological and therapeutic evaluation

Aging is a complex process that increases the risk of chronic disease development. Hormonal and metabolic alterations occur with aging, such as androgen activity decrease. Studies aim to understand the role of testosterone replacement therapy (TRT) in males, however biomarkers and the metabolic responses to TRT are not well characterized. Therefore, the present study investigated TRT effect in young adult and aged rats by metabolomics. Male Wistar rats were divided into four groups: adult and adult + testo (6months), old and old + testo (25-27months). TRT animals received daily testosterone propionate (1 mg/kg/subcutaneous). TRT changed the testicular weight index decrease induced by aging but did not change the body weight and liver weight index. Sera were analyzed by liquid chromatograph high resolution mass spectrometry (LCMS/MS). Testosterone was quantified by target LCMS/MS. A total of 126 metabolites were detected with known identification altered by TRT by non-target metabolomics analysis. Multivariate statistics shows that all groups segregated individually after principal component analysis. The treatment with testosterone induced several metabolic alterations in adult and old rats that were summarized by variable importance on projection score, metabolite interaction and pathway analysis. Aging-related hypogonadism induces a pattern of systemic metabolic alterations that can be partially reversed by TRT, however, this treatment in aged rats induces novel alterations in some metabolites that are possible new targets for monitoring in patients submitted to TRT.

HP-03-004 The role of testosterone replacement therapy on metabolic disorders in patient with type 2 diabetes mellitus and androgen deficiency

HP-03-004 The role of testosterone replacement therapy on metabolic disorders in patient with type 2 diabetes mellitus and androgen deficiency

Is there a protective role of testosterone against high-grade prostate cancer? Incidence and severity of prostate cancer in 553 patients who underwent prostate biopsy: a prospective data register

This study investigated the role of testosterone replacement therapy (TRT) in prostate safety and cancer progression. A cohort of 553 patients, 42 treated and 162 untreated hypogonadal men, and 349 eugonadal men were included. Pathological analysis of prostate biopsies examining the incidence and severity of PCa revealed that: 16.7% of treated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 71.4% and >6 in 28.6% of men, a predominant score of 3 and tumour staging of II in 85.7% men; 51.9% of untreated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 40.5% and >6 in 59.5% men, a predominant score of 3 (77.4%) and tumour staging of II (41.7%) or III (40.5%); 37.8% of eugonadal men had a positive biopsy, a Gleason score of ≤6 in 42.4% and >6 in 57.6% of men, a predominant score of 3 (82.6%) and tumour staging of II (44.7%) or III (47.7%). The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TRT, with significantly lower severity of PCa in terms of staging and grading in the same group. These results suggest that TRT might have a protective effect against high-grade PCa.

Letter to the Editor regarding 'Treatment of Men for "Low Testosterone": A Systematic Review' by Huo et al.; Testosterone Replacement Therapy: Toward to the Robust Evidence and Facts.

We read with interest the systematic review (SR) by Huo et al [1] on the role of testosterone replacement therapy (TRT) for treating men with low testosterone, which suggests that there is no beneficial effect in most men. While we cannot rule out that the author's conclusions will ultimately be proven to be true, we believe that it is premature to make this determination based on the current study.

An update on the role of testosterone replacement therapy in the management of hypogonadism.

While US testosterone prescriptions have tripled in the last decade with lower trends in Europe, debate continues over the risks, benefits and appropriate use of testosterone replacement therapy (TRT). Some authors blame advertising and the availability of more convenient formulations whilst other have pointed out that the routine testing of men with erectile dysfunction (a significant marker of cardiovascular risk) and those with diabetes would inevitably increase the diagnosis of hypogonadism and lead to an increase in totally appropriate prescribing. They commented that this was merely an appropriate correction of previous underdiagnosis and undertreatment by adherence to evidence-based guidelines. Urologists and primary care physicians are the most frequent initiators of TRT, usually for erectile dysfunction. Benefits are clearly established for sexual function, increase in lean muscle mass and strength, mood and cognitive function, with possible reduction in frailty and osteoporosis. There remains no evidence that TRT is associated with increased risk of prostate cancer or symptomatic benign prostatic hyperplasia, yet the decision to initiate and continue therapy is often decided by urologists. The cardiovascular issues associated with TRT have been clarified by recent studies showing clearly that therapy associated with clear rise in testosterone levels are associated with reduced mortality. Studies reporting to show increased risk have been subject to flawed designs with inadequate baseline diagnosis and follow-up testing. Effectively they have compared nontreated patients with undertreated or on-compliant subjects involving a range of different therapy regimens. Recent evidence suggests long acting injections may be associated with decreased cardiovascular risk but the transdermal route may be associated with potentially relatively greater risk because of conversion to dihydrotestosterone by the effect of 5α reductase in skin. The multiple effects of TRT may add up to a considerable benefit to the patient that might be underestimated by the physician primarily concerned with his own specialty. This paper will attempt to identify who should be treated, and how they should be treated safely to achieve best outcomes, based on a comprehensive MEDLINE and EMBASE and Cochrane searches on hypogonadism, TRT and cardiovascular safety from May 2005 to May 2015. This revealed 1714 papers with 52 clinical trials and 32 placebo-controlled randomized, controlled trials.

Testosterone replacement therapy and the risk of prostate cancer.

Understanding the role of testosterone replacement therapy (TRT) in the development and progression of prostate cancer is an important concept in treating patients with symptoms of hypogonadism. This article revealed a small number of mostly retrospective, observational studies describing the use of TRT in the general population, in men with prostatic intraepithelial neoplasia (PIN), in men with a history of treated prostate cancer, and in men on active surveillance for prostate cancer. The current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism, and the prostate saturation theory provides a model explaining the basis for these results. The use of TRT in men with a history of prostate cancer is considered experimental, but future results from randomized controlled trials could lead to a change in our current treatment approach.

Thinking outside the square: considering gender in Klinefelter syndrome and 47, XXY

Thinking outside the square: considering gender in Klinefelter syndrome and 47, XXY

Testosterone and Metabolic Syndrome: A Meta‐Analysis Study

Metabolic syndrome (MetS) is often associated with male hypogonadism. Despite the well-known link, the role of testosterone replacement therapy (TRT) in MetS has not been completely clarified. To systematically analyse the relationship between androgen levels and MetS we performed a review and meta-analyses of available prospective and cross-sectional studies. In addition, a specific meta-analysis on the metabolic effects of TRT in available randomized clinical trials (RCTs) was also performed. An extensive Medline search was performed including the following words "testosterone,""metabolic syndrome," and "males". Out of 323 retrieved articles, 302 articles were excluded for different reasons. Among the 20 published studies included, 13, 3, and 4 were cross-sectional, longitudinal, and RCTs, respectively. Another unpublished RCT was retrieved on http://www.clinicaltrials.gov. MetS patients showed significantly lower T plasma levels, as compared with healthy individuals. Similar results were obtained when MetS subjects with and without erectile dysfunction were analyzed separately or when NCEP-ATPIII MetS criteria were compared with other definitions. Meta-regression analysis demonstrated that type 2 diabetes (T2DM) increased the MetS-associated T fall. In a multiple regression model, after adjusting for age and BMI, both T2DM and MetS independently predicted low testosterone (adj. r = -0.752; P < 0.001 and -0.271; P < 0.05, respectively). Analysis of longitudinal studies demonstrated that baseline testosterone was significantly lower among patients with incident MetS in comparison with controls (2.17 [-2.41;-1.94] nmol/L; P < 0.0001). Combining the results of RCTs, TRT was associated with a significant reduction of fasting plasma glucose, homeostatic model assessment index, triglycerides, and waist circumference. In addition, an increase of high-density lipoprotein cholesterol was also observed. The meta-analysis of the available cross-sectional data suggests that MetS can be considered an independent association of male hypogonadism. Although only few RCTs have been reported, TRT seems to improve metabolic control, as well as central obesity.

Type 2 diabetes mellitus and testosterone: a meta-analysis study

Several studies suggest that type 2 diabetes mellitus (T2DM) is often associated with male hypogonadism. Despite the well-known link, the role of testosterone replacement therapy (TRT) in T2DM has not been completely clarified. The aim of the present study was to analyse systematically the relationship between androgen levels and T2DM by reviewing and meta-analysing available prospective and cross-sectional studies. In addition, a specific meta-analysis on the metabolic effects of TRT in available randomized clinical trials (RCTs) was performed. An extensive Medline search was performed including the following words: 'testosterone', 'type 2 diabetes mellitus' and 'males'. Of 742 retrieved articles, 37 were included in the study. In particular 28, 5 and 3 were cross-sectional, longitudinal and interventional studies, respectively. A further unpublished RCT was retrieved from http://www.clinicaltrials.gov. T2DM patients showed significantly lower testosterone plasma levels in comparison with non-diabetic individuals. Similar results were obtained when T2DM subjects with and without erectile dysfunction were analysed separately. Meta-regression analysis demonstrated that ageing reduced, while obesity increased, these differences. However, in a multiple regression model, after adjusting for age and body mass index (BMI), T2DM was still associated with lower total testosterone (TT) levels (adjusted r = -0.568; p < 0.0001). Analysis of longitudinal studies demonstrated that baseline TT was significantly lower among patients with incident diabetes in comparison with controls (HR = -2.08[-3.57;-0.59]; p < 0.001). Combining the results of RCTs, TRT was associated with a significant reduction in fasting plasma glucose, HbA1c, fat mass and triglycerides. Conversely, no significant difference was observed for total and high-density lipoprotein cholesterol, blood pressure and BMI. The meta-analysis of the available cross-sectional data suggests that T2DM can be considered independently associated with male hypogonadism. Although only few RCTs have been reported, TRT seems to improve glycometabolic control as well as fat mass in T2DM subjects.

1498 TESTOSTERONE REPLACEMENT THERAPY IN HIGH RISK PATIENTS FOLLOWING RADICAL PROSTATECTOMY

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Medical and Non-Surgical Therapy II1 Apr 20101498 TESTOSTERONE REPLACEMENT THERAPY IN HIGH RISK PATIENTS FOLLOWING RADICAL PROSTATECTOMY Kumaran Sathyamoorthy, Marshall Stein, Osama Mohammed, Larry Lipshultz, and Mohit Khera Kumaran SathyamoorthyKumaran Sathyamoorthy Houston, TX More articles by this author , Marshall SteinMarshall Stein New Orleans, LA More articles by this author , Osama MohammedOsama Mohammed Houston, TX More articles by this author , Larry LipshultzLarry Lipshultz Houston, TX More articles by this author , and Mohit KheraMohit Khera Houston, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1235AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Testosterone replacement therapy (TRT) is the main treatment for symptomatic hypogonadism, and can help mitigate the sequelae of hypogonadism such as increased cardiovascular disease, erectile dysfunction and osteoporosis. However, significant controversy exists regarding the role of TRT in patients with a history of prostate cancer. Several series have demonstrated the low risk of PSA biochemical recurrence with TRT in radical prostatectomy (RP) patients. We present the largest series in the literature of post RP patients receiving TRT, and the first data on the risk of TRT in a series of high risk patients following RP. METHODS A total of 133 hypogonadal patients with history of RP were treated with TRT. Of these patients, 21 were classified as high risk (Gleason greater than or equal to 8, positive margins or node positive disease). Patients were all started on TRT for symptomatic hypogonadism following RP. Serum prostate specific antigen (PSA) and testosterone levels were measured every three months. Data analysis was completed with SPSS. RESULTS Mean patient age was 64.9 years. Patients were followed for a mean of 363 days. There were no PSA recurrences, and there was no statistically significant increase in PSA over the course of treatment. Among high risk patients, eight patients had a Gleason 8 or greater, 16 had positive margins and 1 patient had a positive lymph node. Mean PSA was .003 ng/mL (+/- .001) at the start of therapy, .016 (+/- .027) at three months, .011 (+/- .008) at six months, .010 (+/- .01) at 9 months, .010 (+/- .01) at 12 months and .01 (+/-.008) at 15 months. Testosterone increased from 262 to 418 ng/dL. There was no significant change in PSA during the duration of treatment (p > .05 at all intervals). CONCLUSIONS These data demonstrate that there was no statistically significant change in PSA among men placed on TRT with a history of RP and high risk characteristics. Although these results are encouraging, randomized clinical trials are needed to validate these findings. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e577 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kumaran Sathyamoorthy Houston, TX More articles by this author Marshall Stein New Orleans, LA More articles by this author Osama Mohammed Houston, TX More articles by this author Larry Lipshultz Houston, TX More articles by this author Mohit Khera Houston, TX More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Role of Testosterone Replacement Therapy on Plasma Ghrelin Level before and after Orchiectomy in Male Albino Rats

The aim of the present study is to investigate whether testosterone replacement therapy play a role on plasma ghrelin level before and after orchiectomy in male albino rats. Four groups of animals were studied, control group, control group received testosterone propionate (T.P) 300 µg/Kg subcutaneously (s.c) daily for 4 weeks, orchiectomized group and lastly orchiectomized group receiving T.P by the same regimen as group two. Blood samples were taken at the end of the experimental period for carrying out the hormonal investigations; also body weight was measured from all studied animals.The results of this work showed that subcutaneous administration of T.P to sham operated and orchiectomy rats produces significant decrease in FSH and LH, however it produces significant increase in total testosterone, free testosterone, ghrelin, insulin-like growth factor-I (IGF-I) and total body weight when these results compared to group one and three respectively. Conclusions:We can conclude that plasma ghrelin level significantly increase after testosterone supplementation in both sham operated and orchiectomy rats, also there are +ve correlation between ghrelin level and testosterone level (both total and free), IGF-1 and body weight & negative correlation between ghrelin and FSH & LH.

Androgen Deficiency as a Predictor of Metabolic Syndrome in Aging Men

The prevalence of metabolic syndrome is increasing globally and is an important risk factor for the development of cardiovascular disease. Longitudinal population studies have found that low testosterone status in men is a risk factor for the later development of metabolic syndrome. Men with metabolic syndrome and type 2 diabetes mellitus have a higher incidence of hypotestosteronaemia. Furthermore, in men, testosterone levels are inversely associated with the degree of carotid and aortic atherosclerosis. Early interventional, short-term studies have shown that testosterone replacement therapy has a beneficial effect on visceral obesity, insulin sensitivity, glycaemic control and lipid profiles in men with diagnosed hypogonadism with and without diabetes. The effect of testosterone therapy on atherogenesis in men is unknown; however, animal studies have shown that testosterone is atheroprotective and can ameliorate the degree of atherosclerosis. Testosterone is an arterial vasodilator and has been shown to improve myocardial ischaemia in men with coronary artery disease. This review discusses the role that testosterone may play in the pathogenesis of metabolic syndrome in men and also examines the potential role of testosterone replacement therapy in this condition.

A novel therapy with testosterone and sildenafil for erectile dysfunction in patients on renal dialysis or after renal transplantation

BackgroundWe undertook a prospective pilot study in a small cohort of patients with renal replacement therapy to determine the cause of erectile dysfunction (ED) and evaluate the role of testosterone...

Androgen deficiency in aging men: Role of testosterone replacement therapy

Physiology and Normal Pathology 1889;1:719 If the degenerations of the senile alterations are diseases, a day will come when it is possible to cure them. The question is certainly not whether the injections (of aqueous testicular extracts) rejuvenate, the question is to know if one can approximate the strength of a younger person, and to me that appears certain.C. E. BROWN-SEQUARD