Testosterone Replacement Therapy Group Research Articles

Evaluation of the effect of testosterone replacement therapy with a transdermal testosterone on glycemic control in men with type 2 diabetes mellitus

BACKGROUND: It is important to evaluate the effect of androgen replacement therapy on glycemic control.AIMS: Assessment of the effect of transdermal testosterone therapy on glycemic control in men with hypogonadism and T2DM.MATERIALS AND METHODS: The prospective, comparative study included 300 men aged 55[49;61] years: men receiving both glucose-lowering therapy (GLT) and transdermal testosterone; and patients receiving only GLT. Observation period 1 year. A medical history, a questionnaire for symptoms of androgen deficiency, and measurement of total testosterone and glycated hemoglobin were carried out. Groups were compared using nonparametric methods.RESULTS: Patients receiving androgen replacement therapy in combination with GLT at both 6 and 12 months from the moment of inclusion in the study, they had a statistically significantly higher level of total testosterone and less severity of symptoms of androgen deficiency. When assessing the magnitude of changes in the studied parameters, it was found that patients receiving testosterone replacement therapy (TRT) were characterized by a statistically significantly more pronounced decrease in the level of glycated hemoglobin (average difference 0,3%). In 29 (20,4% (95% ДИ 13,8–27,0)) men who received only GLT, hypogonadism was eliminated. In 3 patients from the TRT group, a pathological increase in the level of total blood PSA was observed, and therefore TRT was discontinued. An increase in hemoglobin above the reference value (>172 g/l) was detected in 8% and 1,3% of men on TRT and without correction of hypogonadism, respectively, p=0,011.CONCLUSIONS: The combination of transdermal TRT and GLT has a positive effect on glycemic control, which is manifested by a decrease in glycated hemoglobin to a greater extent than when using GLT alone. Normalization of testosterone levels leads to a decrease in the symptoms of androgen deficiency, which is accompanied by an improvement in quality of life. Elimination of hypogonadism only with GLT is possible in a small number of cases.

Association between testosterone replacement therapy and cardiovascular outcomes: A meta-analysis of 30 randomized controlled trials.

The Cardiovascular safety of testosterone replacement therapy (TRT) among men with hypogonadism is not well established to date. Hence, we sought to evaluate the cardiovascular disease (CVD) outcomes among patients receiving testosterone therapy by using all recently published randomized controlled trials. We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until September 30th, 2023. A total of 30 randomized trials with 11,502 patients were included in the final analysis. The mean age was ranging from 61.61 to 61.82years. Pooled analysis of primary and secondary outcomes showed that the incidence of any CVD events (OR, 1.12 (95%CI: 0.77-1.62), P=0.55), stroke (OR, 1.01 (95%CI: 0.68-1.51), P=0.94), myocardial infarction (OR, 1.05 (95%CI: 0.76-1.45), P=0.77), all-cause mortality (OR, 0.94 (95%CI: 0.76-1.17), P=0.57), and CVD mortality (OR, 0.87 (95%CI: 0.65-1.15), P=0.31) was comparable between TRT and placebo groups. Our analysis indicates that for patients with hypogonadism, testosterone replacement therapy does not increase the CVD risk and all-cause mortality.

Increased risk of erythrocytosis in men with type 2 diabetes treated with combined sodium-glucose cotransporter-2 inhibitor and testosterone replacement therapy.

In clinical trials, sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and testosterone replacement therapy (TRT) were shown to stimulate red blood cell production. Little is known if combination therapy poses risk of erythrocytosis in real world clinical practice. This was a retrospective nationwide cohort study of US Veterans with type 2 diabetes (T2D) and baseline hematocrit between 38 and 50% who were prescribed SGLT-2i and/or TRT between 3/2013 and 10/2022 and had adequate adherence based on the proportion of days covered > 80%. Patients were divided into 3 groups: SGLT-2i only, TRT only, or combination therapy. Odds Ratio (OR) of new erythrocytosis defined as hematocrit level > 54% within 365days of therapy initiation was calculated by logistic regression model adjusted for baseline hematocrit, age, BMI, obstructive sleep apnea, diuretic use, and smoking status. Of the entire cohort of 53,971 people with T2D, total of 756 (1.4%) patients developed erythrocytosis. In unadjusted analyses, the OR of new onset erythrocytosis was higher in the combined SGLT-2i and TRT group compared with the SGLT-2i or TRT group alone (4.99, 95% CI (3.10-7.71) and 2.91, 95% CI (1.87-4.31), respectively). In the models adjusted for baseline characteristics, patients on combination therapy had significantly higher odds of erythrocytosis compared to those on SGLT-2i (OR 3.80, 95% CI (2.27-6.11)) or TRT alone (OR 2.49, 95% CI (1.51-3.59)). Testosterone delivery route (topical vs injectable) did not modify increased odds of erythrocytosis. For the first time, we demonstrated that in large cohort of patients combined therapy with SGLT-2i and TRT is associated with increased erythrocytosis risk compared with either treatment alone. Given rising prevalence of SGLT-2i use, providers should consider periodic hematocrit assessment in persons receiving both SGLT-2i and TRT.

Depressive Syndromes in Men with Hypogonadism in the TRAVERSE Trial: Response to Testosterone Replacement Therapy.

The effect of testosterone on depressive symptoms in men with hypogonadism remains incompletely understood. We assessed the effects of testosterone replacement therapy (TRT) in improving depressive symptoms in hypogonadal men with and without depressive symptoms enrolled in the TRAVERSE cardiovascular safety trial. Randomized, placebo-controlled, double-blind. 316 trial sites. Men, 45 to 80 years, with two fasting testosterone levels <300 ng/dL, one or more hypogonadal symptoms, cardiovascular disease (CVD), or increased risk of CVD. We evaluated three subgroups of participants: 1) men with rigorously defined late-life-onset, low-grade persistent depressive disorder (LG-PDD, previously "dysthymia"); 2) all men with significant depressive symptoms (Patient Health Questionnaire-9 Score >4); and 3) all randomized men. 1.62% transdermal testosterone or placebo gel. Proportions of participants 1) meeting criteria for LG-PDD or 2) with significant depressive symptoms; changes in depressive symptoms, energy, sleep quality, and cognition in testosterone- vs. placebo-treated men in the three subgroups. Of 5,204 randomized participants, 2,643 (50.8%) had significant depressive symptoms, but only 49 (1.5%) met rigorous criteria for LG-PDD. Among those with LG-PDD, there was no significant difference in any outcome measure between the TRT and placebo groups, possibly reflecting low statistical power. In men with significant depressive symptoms n=2643) and in all randomized participants (n=5204), TRT was associated with modest but significantly greater improvements in mood and energy but not cognition or sleep quality. Depressive symptoms are common in middle-aged and older men with hypogonadism, but LG-PDD is uncommon. TRT is associated with small improvements in mood and energy in hypogonadal men with and without significant depressive symptoms. ClinicalTrials.gov Identifier: NCT03518034.

Blood pressure responses to testosterone therapy are amplified by hematocrit levels in opioid-induced androgen deficiency: a double-blind, randomized, placebo-controlled trial.

Our study aimed to examine the effect of testosterone replacement therapy (TRT) on blood pressure in opioid-treated men with relative hypogonadism, and whether the effect of TRT on blood pressure was modified by body composition, red blood cell levels, or carotid intima media thickness. Men (over 18 years old) receiving opioid treatment and total testosterone less than 12 nmol were randomly assigned to receive either TRT or placebo. Baseline and 6-month measurements included anthropometric measurements, office blood pressure (OBPM), 24-h ambulatory blood pressure, blood samples, and carotid ultrasound. The mean systolic OBPM increased by 6.2 mmHg (0.2-12.1) in the TRT group and decreased by 7.0 mmHg (1.0-15.1) in the placebo group, with a mean difference of 13.2 mmHg (3.4-23.1), P  = 0.01. In the TRT group, a 10 mmHg increase in systolic OBPM was associated with an increase in hematocrit of 0.3% points (0.1-0.5) ( P  = 0.01), whereas no association was observed in the placebo group ( P  = 0.266). Daytime SBP showed a nonsignificant increase of 5.2 mmHg (-1.7, 12.1) ( P  = 0.134) in the TRT group compared to that in the placebo group. However, the impact of TRT on the increase in daytime ambulatory blood pressure was significantly accentuated by baseline values of BMI, hematocrit, and hemoglobin. In conclusion, TRT was associated with higher OBPM compared to placebo, and the increase in blood pressure was linked to higher hematocrit during TRT. Our data suggest that men with opioid-induced androgen deficiency, particularly those with obesity or red blood cell levels in the upper normal range, are more susceptible to increased daytime SBP during TRT.

Cardiovascular Outcomes of Hypogonadal Men Receiving Testosterone Replacement Therapy: A Meta-analysis of Randomized Controlled Trials

ObjectiveTo investigate the impact of testosterone replacement therapy (TRT) on cardiovascular outcomes in hypogonadal men. MethodsA meta-analysis of 26 randomized controlled trials involving 10 941 participants was conducted. Various clinical outcomes, including all-cause mortality, cardiovascular-related mortality, myocardial infarction, stroke, congestive heart failure, atrial fibrillation, pulmonary embolism, and venous thrombosis, were assessed. ResultsNo statistically significant differences were observed between the TRT group and the control group in terms of these clinical outcomes. Sensitivity analysis and publication bias assessment supported the robustness of the findings. Meta-regression analysis found no significant associations between clinical outcomes and potential covariates, including age, diabetes, hypertension, dyslipidemia, and smoking. DiscussionPrevious research on TRT and cardiovascular events, with comparisons to studies like the Testosterone Trials and the studies conducted by Vigen et al, Finkle et al, Layton et al, and Wallis et al, is provided. The significance of the systematic review and meta-analysis approach is emphasized, particularly its exclusive focus on hypogonadal patients. ConclusionThis study offers reassurance that TRT does not increase mortality risk or worsen cardiovascular outcomes in hypogonadal men. However, further research, especially long-term studies involving diverse populations, is essential to strengthen the evidence base and broaden the applicability of these findings.

Does testosterone replacement therapy increase the risk of conversion to treatment in patients with prostate cancer on active surveillance?

PurposeWe aimed to evaluate the impact of testosterone replacement therapy (TRT) in patients with localized prostate cancer (CaP) who elected active surveillance (AS). MethodsA retrospective review of our CaP database was performed. Patients who received TRT while on AS were identified and were matched to a cohort of patient on AS while not on TRT (1:3) using propensity score matching. Treatment-free survival (TFS) was computed using Kaplan Meier method. Multivariable Cox regression model was used to evaluate variables associated with treatment. ResultsTwenty-four patients in the TRT group were matched to 72 patients without TRT. Median follow-up was 5.82 years (IQR 3.27–9.30). There was no significant difference in conversion to treatment (24% vs. 21%, P = 1.00) There was no significant difference in TFS (log rank P = 0.87). Prostate specific antigen (PSA) density was the only variable associated TFS (HR 1.08, 95%CI 1.03–1.13, P = 0.001). ConclusionTRT was not associated with conversion to treatment in this matched analysis among patients with localized prostate cancer on AS.

MP38-16 DOES TESTOSTERONE REPLACEMENT THERAPY INCREASE THE RISK OF CONVERSION TO TREATMENT IN PATIENTS WITH PROSTATE CANCER ON ACTIVE SURVEILLANCE?

You have accessJournal of UrologyCME1 Apr 2023MP38-16 DOES TESTOSTERONE REPLACEMENT THERAPY INCREASE THE RISK OF CONVERSION TO TREATMENT IN PATIENTS WITH PROSTATE CANCER ON ACTIVE SURVEILLANCE? Jorge Daza, Usma Shabir, Zhe Jing, Mohsin Sheikh, Eric Kauffman, Khurshid Guru, Ahmed A Hussein, and Buffalo NY Jorge DazaJorge Daza More articles by this author , Usma ShabirUsma Shabir More articles by this author , Zhe JingZhe Jing More articles by this author , Mohsin SheikhMohsin Sheikh More articles by this author , Eric KauffmanEric Kauffman More articles by this author , Khurshid GuruKhurshid Guru More articles by this author , Ahmed A HusseinAhmed A Hussein More articles by this author , and Buffalo NYBuffalo NY More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003276.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We aimed to evaluate the impact of testosterone replacement therapy (TRT) in patients with localized prostate cancer who elected active surveillance (AS). METHODS: A retrospective review of our AS database was performed. Patients who received TRT while on AS were identified. A cohort of patients who underwent AS while not on TRT was matched in a ratio of 1:2. Both groups were compared. Kaplan Meier analysis and log-rank test were performed to compare treatment-free survival. Statistical significance was defined as p≤0.05. RESULTS: 23 (2%) patients who underwent TRT while on AS were identified. Two patients elected discontinuation of TRT and 2 were lost to follow up. Median follow-up was 91 months. Nineteen patients in the TRT group were matched to 40 patients without TRT. There was no significant difference in conversion to treatment (21% vs 22%, p=1.00), time to conversion to treatment (56 vs 42 months, p=0.09) or the change in PSA while on AS (-0.05 vs 1.45, p=0.56) (Table 1). Kaplan Meier analysis showed no significant difference in treatment-free survival between the 2 groups (log rank p>0.05) (Figure 1). Univariate analysis showed that Age, CCI, receipt of TRT, Gleason grade at initiation of AS or history of fusion biopsy were not associated with conversion to treatment. CONCLUSIONS: TRT was not associated with conversion to treatment in this matched analysis among patients with localized prostate cancer on AS. Despite limitations, to our knowledge, this study has the longest follow-up in patients receiving TRT while on AS. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e530 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jorge Daza More articles by this author Usma Shabir More articles by this author Zhe Jing More articles by this author Mohsin Sheikh More articles by this author Eric Kauffman More articles by this author Khurshid Guru More articles by this author Ahmed A Hussein More articles by this author Buffalo NY More articles by this author Expand All Advertisement PDF downloadLoading ...

Testosterone therapy increases the anticoagulant potential in men with opioid-induced hypogonadism: a randomized, placebo-controlled study.

Hypogonadism is prevalent during opioid treatment, and low testosterone concentrations are associated with cardiovascular disease. The effect of testosterone replacement therapy (TRT) on the coagulation system in men with hypogonadism is not clarified. We investigate the effects of TRT on the tissue factor (TF) and contact activation pathways of coagulation in opioid-treated men. This was a double-blinded, placebo-controlled study in 37 men with total testosterone < 12 nmol/L randomized to 24 weeks of testosterone injections (n = 17) or placebo (n = 20). Variables of the coagulation system were analysed at baseline and after 24 weeks. Measurements included the TF pathway (endogenous thrombin potential (ETP) and peak thrombin), the contact activation pathway (endogenous kallikrein potential (EKP) and peak kallikrein), coagulation factors (FVII, FX, prothrombin, and FXII), and inhibitors (tissue factor pathway inhibitor (TFPI), protein C, protein S, antithrombin, and C1 esterase inhibitor (C1inh)). Between-group differences at 24 weeks were determined with analysis of covariance. Within-group changes in TRT and placebo were analysed with paired t-test. Between-group differences at 24 weeks were observed for ETP (P = 0.036), FVII (P = 0.044), FX (P = 0.015), prothrombin (P = 0.003), protein C (P = 0.004), and protein S (P = 0.038). Within the TRT group, ETP, peak thrombin, FVII, FX, prothrombin, TFPI, protein C, FXII, and C1inh decreased and protein S increased (all P < 0.05). Within the placebo group, coagulation outcomes were unchanged. TRT affects the coagulation system in an anticoagulant direction through suppressed TF pathway in men with opioid-induced hypogonadism.

The Relationship Between Testosterone Therapy and Rotator Cuff Tears, Repairs, and Revision Repairs.

The purpose of this study was to evaluate rates of rotator cuff tears (RCTs), repairs (RCRs), and revision RCR in patients who were prescribed testosterone replacement therapy (TRT) and compare these patients with a control group. The PearlDiver database was queried for patients who were prescribed testosterone for at least 90 days between 2011 and 2018 to evaluate the incidence of RCTs in this population. A second analysis evaluated patients who sustained RCTs using International Classification of Diseases, 9th/10th codes to evaluate these patients for rates of RCR and revision RCR. Chi square analysis and multivariate regression analyses were used to compare rates of RCTs, RCR, and subsequent or revision RCR between the testosterone and control groups, with a P -value of 0.05 representing statistical significance. A total of 673,862 patients with RCT were included for analysis, and 9,168 of these patients were prescribed testosterone for at least 90 days before their RCT. The TRT group had a 3.6 times greater risk of sustaining an RCT (1.14% versus 0.19%; adjusted odds ratio (OR) 3.57; 95% confidence interval (CI) 3.57 to 3.96). A 1.6 times greater rate of RCR was observed in the TRT cohort (TRT, 46.4% RCR rate and control, 34.0% RCR rate; adjusted OR 1.60; 95% CI 1.54 to 1.67). The TRT cohort had a 26.7 times greater risk of undergoing a subsequent RCR, irrespective of laterality, within 1 year of undergoing a primary RCR when compared with the control group (TRT, 47.1% and control, 4.0%; adjusted OR 26.4; 95% CI 25.0 to 27.9, P < 0.001). There is increased risk of RCTs, RCRs, and subsequent RCRs in patients prescribed testosterone. This finding may represent a musculoskeletal consequence of TRT and is important for patients and clinicians to understand. Additional research into the science of tendon injury in the setting of exogenous anabolic steroids remains of interest. Level Ⅲ, retrospective cohort study.

PS-BPC08-4: IMPACT OF TESTOSTERONE REPLACEMENT THERAPY ON 24-HOUR AMBULATORY BLOOD PRESSUR E MEASUREMENTS IN MALES WITH OPIOID-INDUCED ANDROGEN DEFICIENCY. A PLACEBO-CONTROLLED RCT

Objective: The primary aim was to investigate the effects of testosterone replacement therapy (TRT) on 24-hour ambulatory blood pressure (24hABPM) in opioid-treated men with relative hypogonadism. The secondary aim was to evaluate potential effect modification of baseline body composition and red blood cell measurements on the impact of TRT on 24hABPM. Design and methods: This was a double blinded and placebo controlled study. Men aged &gt; 18 years, treated with an opioid dosage &gt; 50 mg opioid/day were eligible for inclusion if total testosterone (TT) was &lt; 12 nmol/L. Participants were randomized to TRT (1,000 mg testosterone undecanoate) or placebo at 0, 6 and 18 weeks. Participants were examined before and during 24 weeks of TRT/placebo. Results: The two groups (TRT, n = 15 and placebo, n = 20) were comparable at baseline. TRT was associated with numerical increase in 24hABPM. The difference in changes from baseline of daytime systolic blood pressure (SBP) was 5.2 mmHg (P = 0.134) between the TRT group and the placebo group. In subgroup analysis, baseline values of body mass index (BMI), hematocrit (Hct) and hemoglobin (Hgb) levels displayed significant positive interaction on the effect of TRT on change in SBP compared to placebo. In participants with BMI above the study median (30.7 m2/kg), daytime SBP change from baseline was 17.6 mmHg [10.6, 24.6] (P = 0.002) in the TRT group and 0.4 mmHg [-5.5, 4.7] (P = 0.864) in the placebo group. In participants with Hct levels above the study median (0.43%), daytime SBP increased 8.4 mmHg [-1.9, 18.8] (P = 0.09) in the TRT group and decreased -2.3 mmHg [-11.3, 6.8] (P = 0.564) in the placebo group. Similarly, in participants with Hgb&gt; 8.7 mmol/L daytime, SBP change was 11.2mmHg [0.6–21.7] (P = 0.041) in the TRT group and -2.9 mmHg [-4.1, 9.9] (P = 0.367) in the placebo group. Baseline cIMT also increased the strength of association between TRT and change in SBP. After adjusting for delta-BMI, delta-Hct remained significantly associated with increase in daytime SBP. An increase in 1 mmHg SBP was associated with an increase in Hct of 0.11% [0.10–0.22] (P = 0.032). Conclusions: Baseline levels of BMI, Hct, Hgb and cIMT, influence the effect of TRT on BP. The magnitude of BP increase is associated with increase in Hct levels.

Clinical characteristics and comorbidities associated with testosterone prescribing in men.

Testosterone replacement therapy (TRT) is recommended for the treatment of symptomatic hypogonadism in men. Data on prescription behaviours are, however, limited and conflicting. The objective of this study was to investigate clinical characteristics associated with the likelihood of being prescribed TRT by general practitioners (GP) in North-West London (NWL). Retrospective cohort study using Discover database of GP-registered patients in NWL between 2015 and 2019. We identified 20,299 men aged ≥18 years with serum total testosterone measurement (TT) and without prior TRT prescription records. We determined whether TRT was subsequently commenced, while analysing clinical characteristics related to hypogonadism. Of all men having TT measurement, 19,583 (96.4%) were not commenced on TRT (Group A) and 716 (3.5%) men were commenced on TRT (Group B). Men prescribed TRT (Group B) had higher mean age, body mass index (BMI) and higher risks of hypertension, depression type 2 diabetes and ischaemic heart disease; conversely, men in Group B had lower mean pretreatment TT and were less likely to have prostate cancer. Four-hundred and thirty-six men (24.3%) with TT < 8 nmol/L and symptoms of low libido were not prescribed TRT. Our study highlights several factors which may influence the decisions made by clinicians when initiating TRT in primary care. Clearer guidance for clinicians may help to improve the consistency of treatment of men with hypogonadism.

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.

Efficacy of testosterone replacement therapy for treating metabolic disturbances in late-onset hypogonadism: a systematic review and meta-analysis.

Late onset hypogonadism (LOH) is an age-dependent reduction of testosterone associated with alterations of metabolic profile, including glucose control, insulin sensitivity, and lipid profile. The purpose of this study was to investigate the efficacy of testosterone replacement therapy (TRT) for treating metabolic disturbances through a meta-analysis of randomized clinical trials (RCTs). A systematic review of literature published from 1964 to November, 2019 was performed using the PubMed/Medline, Embase, and Cochrane databases. Among the 1562 articles screened, 17 articles were selected for qualitative analysis and 16 articles (n = 1373) were included for data synthesis following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Criteria for final inclusion were RCTs. Sixteen studies were finally included (TRT group, n = 709; placebo group, n = 664). Among the metabolic markers, HbA1C [Mean difference (MD) = - 0.172, 95% CI - 0.329, - 0.015], HOMA IR (MD = - 0.514, 95% CI - 0.863, - 0.165), serum insulin (MD = - 12.622, 95% CI - 19.660, - 5.585), and leptin (MD = - 2.381, 95% CI - 2.952, - 1.810) showed significant improvement after TRT versus placebo. Among the lipid profiles, total cholesterol showed significant improvement (MD = - 0.433, 95% CI - 0.761, - 0.105) after TRT. However, HDL showed a decrease (MD = - 0.069, 95% CI - 0.121, - 0.018) after TRT. Among anthropometric markers, waist circumference showed significant improvement (MD = - 0.1640, 95% CI - 2.857, - 0.423). This study demonstrated greater improvement in metabolic profiles for patients given TRT versus placebo. Further well-designed trials are needed to verify our findings and further elucidate effects of TRT on lipid profiles. This systematic review demonstrates that TRT can exert a net beneficial effect on metabolic profiles.

Evaluation of the Efficacy of Transdermal and Injection Testosterone Therapy in Klinefelter Syndrome: A Real-Life Study.

ContextKlinefelter Syndrome (KS) is the most frequent sex chromosome disorder in males. Due to hypergonadotropic hypogonadism, treatment with testosterone replacement therapy (TRT) is commonly indicated. There are no international guidelines for the most appropriate TRT in KS.ObjectiveWe aimed to evaluate how different routes of testosterone administration impact testosterone-responsive variables, as well as the development of later metabolic diseases and other complications.MethodsWe conducted a retrospective study covering 5 years from 2015 to 2020. Data on TRT, biochemical parameters, bone mineral density (BMD), medications, comorbidity, and karyotyping were derived from electronic patient records and The Danish Cytogenetic Register.ResultsA total of 147 KS males were included: 81 received injection TRT, 61 received transdermal TRT, and 5 did not receive TRT. Testosterone levels were similar in the 2 TRT groups (P = 0.9), while luteinizing hormone and follicle-stimulating hormone levels were higher in the group receiving transdermal TRT (P = 0.002). Levels of cholesterol, blood glucose, hemoglobin A1c, hemoglobin, hematocrit, liver parameters, prostate-specific antigen, and spine and hip BMD were similar in the 2 treatment groups (Ps > 0.05).ConclusionTRT, irrespective of route of administration, affects androgen-responsive variables similarly in males with KS. Neither long-acting injection nor transdermal gel seem to reduce the risk of metabolic diseases significantly. These results should encourage clinicians in seeking the route of administration resulting in the highest degree of adhesion to treatment based on individual patient preferences. Implementation of shared decision-making with patients may be important when choosing TRT.

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).

Oncological safety and functional outcomes of testosterone replacement therapy in symptomatic adult-onset hypogonadal prostate cancer patients following robot-assisted radical prostatectomy.

Testosterone replacement therapy (TRT) remains controversial in men with treated prostate cancer. We assessed its safety and functional impacts in patients after definitive surgical treatment with robotic-assisted radical prostatectomy (RARP). We performed a retrospective analysis of 1303 patients who underwent RARP during the years 2006-2019. We identified men with symptoms of andropause and low serum testosterone who received TRT post-RARP; then we divided the cohort into two groups accordingly for comparison. Biochemical recurrence (BCR) was the primary endpoint. Secondary endpoints included functional outcomes. Predictors of BCR, including the effect of TRT on BCR, were evaluated using univariable and multivariable logistic regression. Among the forty-seven men who received TRT, the mean age was 60.83years with a median follow-up of 48months. Three (6.4%) and 157 (12.56%) patients experienced BCR in TRT and non-TRT groups, respectively. Baseline characteristics were similar between both groups except for higher mean BMI in the TRT group (p = 0.03). In the multivariate analysis (MVA), higher pre-RARP prostate-specific antigen (PSA) (p = 0.043), higher International Society of Urological Pathology score (p < 0.001), seminal vesical invasion (p = 0.018) and positive surgical margin (p < 0.001) were predictors of BCR. However, TRT was not (p = 0.389). In addition, there was a significant change in the Sexual Health Inventory for Men (p = 0.022), and serum testosterone level (p < 0.001) before and 6months after initiation of TRT. Our findings suggest that TRT, in well-selected, closely followed, symptomatic men post-RARP is an oncologically safe and functionally effective treatment in prostate cancer patients post-RARP.

Efficacy of testosterone replacement therapy on pain in hypogonadal men with chronic pain syndrome: A subanalysis of a prospective randomised controlled study in Japan (EARTH study).

The present study investigated the efficacy of 6months of testosterone replacement therapy (TRT) on chronic pain syndrome in late-onset hypogonadal (LOH) men. Sixty hypogonadal patients with chronic pain syndrome (31 patients in TRT group and 29 controls) were extracted from a previous randomised controlled study in Japan. Chronic pain was evaluated based on bodily pain (BP) subscale of Short-form (36) Health Survey (SF-36), and patients with a score of 50.0 or less were defined as suffering from chronic pain. SF-36 scores, Aging Male Symptoms (AMS) scale, international prostatic symptoms score (IPSS) and prostate-specific antigen (PSA) levels at baseline and a 6-month visit for the two groups were collected and compared. There were no statistically significant differences in baseline backgrounds between the two groups. Six-month TRT could contribute to significant improvements in BP, mental health of SF-36 and sleep disturbance (AMS question 4). Though the PSA level in the TRT group also significantly elevated at 6months, the increase was not clinically significant. No significant improvements were evident in any characteristics in the controls. In conclusion, 6-month TRT can improve pain and some aspects of quality of life in LOH men with chronic pain.

Testosterone replacement therapy: Pre‐treatment sex hormone‐binding globulin levels and age may identify clinical subgroups

Testosterone replacement therapy (TRT) improves health in some but not all men with type 2 diabetes (T2DM) and adult-onset testosterone deficiency (TD). Such heterogeneity is compatible with the concept of patient subgroups that respond differently to therapy. Use baseline SHBG and age to identify putative subgroups that demonstrate different responses in variables such as waist circumference and HbA1c following TRT. A randomized double-blind trial approach was used to recruit and randomize men with T2DM and adult-onset TD into placebo and TRT-treated groups. Multiple regression was used to study differences between groups. Baseline SHBG and change in SHBG (∆SHBG) were inversely related in the TRT group. Both median values of SHBG and age mediated the effect of TRT on ∆SHBG depending on whether baseline values were≤or>median (28.1 nmol/L, 63years, respectively). In men with both SHBG≤28.1nmol/L and age≤63years (subgroup 1), TRT was positively associated with ∆SHBG (c=4.67, 95%CI 1.17-8.16, P=.010) while in those with SHBG>28.1nmol/L and age>63.1years (subgroup 4) the association was inverse (c = -7.07, 95%CI -11.64 to -2.49, P=.003). The association between TRT and change (∆) in waist circumference, HbA1c and International Index of Erectile Function (IIEF) score differed between subgroups; in subgroup 4 but not subgroup 1, the therapy was significantly associated with ∆waist circumference, ∆HbA1c and ∆IIEF. Though the mechanism remains unclear, our finding of different responses to TRT in terms of change in waist circumference, HbA1c and IIEF score supports the concept of subgroups in men with T2DM and adult-onset TD. Our approach may provide a basis for identifying men who will or will not derive benefit from TRT though a larger study is required.

Testosterone replacement therapy reduces biochemical recurrence after radical prostatectomy

To evaluate risk of prostate cancer biochemical recurrence (BCR) after radical prostatectomy (RP) in men receiving vs not receiving testosterone replacement therapy (TRT). A total of 850 patients underwent RP by a single surgeon. All patients had preoperative testosterone and sex hormone-binding globulin levels determined; free testosterone was calculated prospectively. In all, 152 (18%) patients with low preoperative calculated free testosterone (cFT) levels and delayed postoperative sexual function recovery were placed on TRT and proportionately matched to 419 control patients by pathological Gleason Grade Group (GGG) and stage. Rates and time to BCR [two consecutive prostate-specific antigen (PSA) levels of ≥0.2ng/mL] were compared in univariate and multivariate regression; Cox regression was used to generate a survival function at the mean of covariates. The median follow-up was 3.5years. There were no statistically significant differences in demographics or general health complications between groups. BCR occurred in 11/152 (7.2%) and 53/419 (12.6%) patients in the TRT and control groups, respectively. In adjusted time-to-event analysis, TRT was an independent predictor of recurrence-free survival. After accounting for GGG, pathological stage, preoperative PSA level, and cFT, patients on TRT were ~54% less likely to recur (hazard ratio 0.54, 95% confidence interval 0.292-0.997). In men destined to recur, TRT delayed time to recurrence by an average of 1.5years. In our experience, TRT after RP significantly reduced BCR and delayed time to BCR. There was no identifiable general health complications associated with TRT. These findings are hypothesis-generating and require confirmation with multi-centred, prospective randomised controlled trials.