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Background: Male hypogonadism (testosterone level < 300 ng/dl) is a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone. Most marketed testosterone replacement therapy products often require multiple dose adjustment clinic visits to achieve the desired, eugonadal testosterone levels. Objective: To evaluate the efficacy and safety of a novel oral testosterone undecanoate therapy for the treatment of hypogonadism. Material and methods: Ninety‐five (N = 95) hypogonadal men were enrolled in this open‐label, single‐arm, multicenter study in the United States (NCT03242590). Subjects received 225 mg of oral testosterone undecanoate (TLANDO) twice a day for 24 days without dose adjustment. Primary efficacy was percentages of subjects who achieved mean 24‐h testosterone levels within the eugonadal range and secondary efficacies were evaluated based on the upper limit of lab normal range of testosterone concentration. Results: Subjects enrolled were on average age of 56 years, with about 17% of subjects older than 65 years. The mean body mass index was 32.8 kg/m2. The baseline mean total testosterone values were below the normal range (202 ± 74 ng/dl). Post‐treatment with 450 mg testosterone undecanoate daily dose without dose adjustment, 80% of subjects (95% confidence interval of 72%–88%) achieved a testosterone Cavg in the normal range and restored testosterone levels to mean testosterone Cavg of 476 ± 184 ng/dl at steady state. Testosterone restoration was comparable to other approved testosterone replacement therapy products. TLANDO was well tolerated with no deaths, no drug‐related serious adverse events, and no hepatic adverse events. Discussion and conclusions: TLANDO restored testosterone levels to the normal range in the majority of hypogonadal males. This new oral testosterone replacement therapy can provide an option for no‐titration oral testosterone replacement therapy. This therapy has the potential to improve patient compliance in testosterone replacement therapy. [ABSTRACT FROM AUTHOR]

Background: Testosterone replacement therapy (TRT) prescriptions have increased several-fold in the last decade. There have been concerns regarding a possible increased incidence of DVT and pulmonary embolism (PE) with TRT. Few data support the association between TRT and DVT/PE. We evaluated the incidence of DVT and PE in men who were prescribed TRT for low serum total testosterone (sTT) levels.Methods: This is a retrospective cohort study, conducted using data obtained from the Veterans Affairs Informatics and Computing Infrastructure. We compared the incidence of DVT/PE between those who received TRT and subsequently had normal on-treatment sTT levels (Gp1), those who received TRT but continued to have low on-treatment sTT (Gp2), and those who did not receive TRT (Gp3). Those with prior history of DVT/PE, cancer, hypercoagulable state, and chronic anticoagulation were excluded.Results: The final cohort consisted of 71,407 subjects with low baseline sTT. Of these, 10,854 did not receive TRT (Gp3) and 60,553 received TRT. Of those who received TRT, 38,362 achieved normal sTT (Gp1) while 22,191 continued to have low sTT (Gp2). The incidence of DVT/PE was 0.5%, 0.4%, and 0.4% in Gp1, Gp2, and Gp3, respectively. Univariate, multivariate, and stabilized inverse probability of treatment weights analyses showed no statistically significant difference in DVT/PE-free survival between the various groups.Conclusions: This study did not detect a significant association between testosterone replacement therapy and risk of DVT/PE in adult men with low sTT who were at low to moderate baseline risk of DVT/PE. [ABSTRACT FROM AUTHOR]

Objective. Among patients with hypogonadism-associated comorbidities, opioid users have the highest incidence of hypogonadism. Data from the Testim Registry in the United States were analyzed to determine the efficacy of testosterone replacement therapy in opioid users vs nonusers. Design. Prospective, 12-month observational cohort registry. Subjects. Hypogonadal men (N = 849) prescribed Testim (but not necessarily testosterone replacement) for the first time. Interventions. Testim 1% testosterone gel (5-10 g/day). Outcome Measures. Total and free testosterone, sex hormone-binding globulin, prostate-specific antigen, sexual function, mood/depression, and anthropometric data were assessed. Changes from baseline were analyzed using repeated measures mixed-effects analysis of variance; multiple linear regressions of changes in testosterone levels with sexual function, mood, and opioid use were computed. Results. 90/849 patients (10.6%) reported opioid use at baseline; 75/90 (83%) used opioids for ≥30 days prior to baseline. Baseline total testosterone and prostate-specific antigen were not statistically different between opioid users and nonusers; there was a trend for higher sex hormone-binding globulin ( P = 0.08) and lower free testosterone ( P = 0.05) in opioid users. After 1 month, both opioid users and nonusers had significant ( P < 0.001) increases in total and free testosterone, which continued through 12 months. Sexual function and mood improved significantly in both opioid users and nonusers over 12 months, and significantly correlated with change in total testosterone. Conclusions. Testosterone replacement therapy increased serum testosterone in hypogonadal opioid users and nonusers alike. The data suggest that with testosterone replacement, hypogonadal opioid users might be expected to have similar improvements in sexual function and mood as opioid nonusers. [ABSTRACT FROM AUTHOR]

Background: Testosterone levels naturally decline with age in men, often resulting in testosterone deficiency (hypogonadism). However, few studies have examined hypogonadal characteristics and treatment in older (⩾65 years) men. Objective: To compare data at baseline and after 12 months of testosterone replacement therapy (TRT) in hypogonadal men ⩾65 vs ,65 years old. Data for participants 65-74 vs ⩾75 years old were also compared. Methods: Data were from TRiUS (Testim Registry in the United States), which enrolled 849 hypogonadal men treated with Testim® 1% (50-100 mg testosterone gel/day) for the first time. Anthropometric, laboratory, and clinical measures were taken at baseline and 12 months, including primary outcomes of total testosterone (TT), free testosterone (FT), and prostate-specific antigen (PSA) levels. Comparisons of parameters were made using Fisher's exact test or analysis of variance. Nonparametric Spearman's ρ and first-order partial correlation coefficients adjusted for the effect of age were used to examine bivariate correlations among parameters. Results: Of the registry participants at baseline with available age information, 16% (133/845) were ⩾65 years old. They were similar to men ,65 years old in the duration of hypogonadism prior to enrollment (∼1 year), TT and FT levels at baseline, TT and FT levels at 12-month follow-up, and in reported compliance with treatment. Older patients were more likely to receive lower doses of TRT. PSA levels did not statistically differ between groups after 12 months of TRT (2.18 ± 2.18 ng/mL for ⩾65 vs 1.14 ± 0.84 ng/mL for ,65 years old, P = 0.1). Baseline values for the .75-year-old subcohort were not significantly different from subcohorts aged 65-74 years and ,65 years. Conclusion: Hypogonadal men ⩾65 years old showed significant benefit from TRT over 12 months, similar to that found for hypogonadal men ,65 years old. TRT was well tolerated in older patients, successfully increased testosterone level regardless of age, and did not significantly increase PSA levels in older men [ABSTRACT FROM AUTHOR]

• Clinical trials have shown presence and absence of correlation between cardiovascular risks and testosterone therapy. • Such contradictions have reduced certainty in predicting cardiovascular risks during testosterone replacement therapy. • The cardiovascular risk of such therapy was found to be associated with age. • The risk was even more severe in patients who had a previous history of myocardial infarction or stroke. Since the male secondary sex characters, libido and fertility are attributed to their major androgen hormone testosterone, the sub-optimum levels of testosterone in young adults may cause infertility and irregularities in their sexual behaviour. Such deficiency is often secondary to maladies involving testes, pituitary or hypothalamus that could be treated with an administration of exogenous testosterone. In the last few decades, the number of testosterone prescriptions has markedly increased to treat sub-optimal serum levels even though its administration in such conditions is not yet approved. On account of its associated cardiovascular hazards, the food and drug authority in the United States has issued safety alerts on testosterone replacement therapy (TRT). Owing to a great degree of conflict among their findings, the published clinical trials seem struggling in presenting a decisive opinion on the matter. Hence, the clinicians remain uncertain about the possible cardiovascular adversities while prescribing TRT in hypogonadal men. The uncertainty escalates even further while prescribing such therapy in older men with a previous history of cardiovascular ailments. In the current review, we analysed the pre-clinical and clinical studies to evaluate the physiological impact of testosterone on cardiovascular and related parameters. We have enlisted studies on the association of cardiovascular health and endogenous testosterone levels with a comprehensive analysis of epidemiological studies, clinical trials, and meta-analyses on the cardiovascular risk of TRT. The review is aimed to assist clinicians in making smart decisions regarding TRT in their patients. [ABSTRACT FROM AUTHOR]

Testosterone deficiency is common in men with chronic obstructive pulmonary disease (COPD) and may exacerbate their condition. Research suggests that testosterone replacement therapy (TRT) may have a beneficial effect on respiratory outcomes in men with COPD. To date, however, no large-scale nationally representative studies have examined this association. The objective of the study was to assess whether TRT reduced the risk of respiratory hospitalizations in middle-aged and older men with COPD. We conducted two retrospective cohort studies. First, using the Clinformatics Data Mart-a database of one of the largest commercially insured populations in the United States-we examined 450 men, aged 40-63 years, with COPD who initiated TRT between 2005 and 2014. Second, using the national 5% Medicare database, we examined 253 men, aged ≥66 years, with COPD who initiated TRT between 2008 and 2013. We used difference-in-differences (DID) statistical modeling to compare pre- versus post-respiratory hospitalization rates in TRT users versus matched TRT nonusers over a parallel time period. DID analyses showed that TRT users had a greater relative decrease in respiratory hospitalizations compared with nonusers. Specifically, middle-aged TRT users had a 4.2% greater decrease in respiratory hospitalizations compared with nonusers (-2.4 decrease vs. 1.8 increase; p = 0.03); and older TRT users had a 9.1% greater decrease in respiratory hospitalizations compared with nonusers (-0.8 decrease vs. 8.3 increase; p = 0.04). These findings suggest that TRT may slow disease progression in patients with COPD. Future studies should examine this association in larger cohorts of patients, with particular attention to specific biological pathways.

Aims: There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke., Methods and Results: We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42-0.46], risk of MI (HR: 0.76, CI 0.63-0.93), and stroke (HR: 0.64, CI 0.43-0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50-0.55), risk of MI (HR: 0.82, CI 0.71-0.95), and stroke (HR: 0.70, CI 0.51-0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3., Conclusion: In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke., (Published by Oxford University Press on behalf of the European Society of Cardiology 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)