Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome: a double blind randomized controlled trial (original) (raw)
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The Aging Male, 2012
To determine the effect of long-term testosterone replacement therapy (TRT) on depression symptoms in hypogonadal men. Methods: Data were from TRiUS, a multicenter, 12-month observational registry (N = 849) of hypogonadal men prescribed 1% testosterone gel. Measures including total testosterone (TT) were assessed at baseline and months 3, 6, and 12. Depression symptoms were measured with Patient Health Questionnaire-9 (PHQ-9), a validated self-report questionnaire. A PHQ-9 score decrease of ≥5 represents clinical improvement. Results PHQ-9 scores were available for 762/849 TRiUS participants at baseline. Overall, 92.4% (704/762) demonstrated some level of depressive symptoms, with 17.3% (132/762) having moderately severe (score 15-19) to severe (score 20-27) symptoms. Subcohorts with significantly (p ≤ 0.03) more moderately severe to severe symptoms were: <60 years old, TT levels <250 ng/dl (<8.68 nmol/l), HIV/AIDS-positive, or used antidepressants or opioids. TT levels and PHQ-9 scores improved significantly (p < 0.01) by 3 months of TRT. At 12 months PHQ-9 scores showed a clinically meaningful mean improvement of 5.62 points, patients with moderately severe to severe symptoms decreased from 17.3% to 2.1% (5/233), and subcohorts, including those defined by age (<60 years) and antidepressant use, had improved PHQ-9 scores ≥5. Conclusion: TRT may reduce depression symptoms in hypogonadal men, including middle-aged men and those using antidepressants.
Does testosterone supplementation improve health and function in elderly men?
Nature Clinical Practice Endocrinology & Metabolism, 2008
BACKGROUND-Low serum testosterone levels are associated with age-related changes in physical and cognitive function. Replacement therapy could, therefore, help alleviate symptoms of aging. OBJECTIVE-To determine whether 6 months' supplementation with testosterone improved signs of aging in a population of elderly men with low-normal testosterone levels. DESIGN AND INTERVENTION-This was a double-blind, randomized, placebo-controlled trial of testosterone supplementation conducted at a single center in the Netherlands between January 2004 and April 2005. Participants were recruited by direct mailing. Inclusion criteria included age 60-80 years and a serum testosterone level below the 50 th percentile of the study population-based testosterone distribution (cutoff 13.7 nmol/l). Exclusion criteria included myocardial infarction, heart failure, malignancy, serious liver or renal disease, epilepsy, diabetes mellitus, elevated prostatespecific antigen, use of corticosteroids, and use of testosterone esters within the previous 60 days. Eligible participants were randomly allocated to receive either 80 mg oral testosterone undecenoate or placebo twice daily for 6 months. Functional ability was measured with the timed 'get up and go' test, the Stanford Health Assessment Questionnaire, an isometric handgrip strength test, and a maximal voluntary isometric leg strength test. Cognitive parameters assessed included verbal episodic memory, cognitive and perceptual speed, attention and mental flexibility, extrapersonal spatial perception, and visuospatial performance. BMD and total body composition were measured by dual-energy X-ray absorptiometry. Quality of life was assessed with the Short-Form 36 Health Survey (SF-36) and the Questions on Life Satisfaction Modules questionnaires. OUTCOME MEASURES-The main outcome measures were functional mobility, cognitive function, BMD, anthropometry, body composition, biochemical measures, quality of life, and safety parameters. RESULTS-The study enrolled 113 men in the testosterone group (mean age 67.1 years; mean serum testosterone level 11.0 nmol/l) and 110 men in the placebo group (mean age 67.4 years; mean serum testosterone level 10.4 nmol/l). Treatment adherence was >90% for both groups. When compared with the placebo group, treatment with testosterone was associated with increased lean body mass, decreased body fat mass and decreased body fat percentage (P <0.001 for all comparisons); however, no significant changes in parameters of functional ability were observed in either group. Total cholesterol and HDL cholesterol decreased in the testosterone group, whereas insulin and glucose concentrations and measures of insulin resistance increased in the placebo group.
Journal of Men's Health, 2010
To determine the effect of long-term testosterone replacement therapy (TRT) on depression symptoms in hypogonadal men. Methods: Data were from TRiUS, a multicenter, 12-month observational registry (N = 849) of hypogonadal men prescribed 1% testosterone gel. Measures including total testosterone (TT) were assessed at baseline and months 3, 6, and 12. Depression symptoms were measured with Patient Health Questionnaire-9 (PHQ-9), a validated self-report questionnaire. A PHQ-9 score decrease of ≥5 represents clinical improvement. Results PHQ-9 scores were available for 762/849 TRiUS participants at baseline. Overall, 92.4% (704/762) demonstrated some level of depressive symptoms, with 17.3% (132/762) having moderately severe (score 15-19) to severe (score 20-27) symptoms. Subcohorts with significantly (p ≤ 0.03) more moderately severe to severe symptoms were: <60 years old, TT levels <250 ng/dl (<8.68 nmol/l), HIV/AIDS-positive, or used antidepressants or opioids. TT levels and PHQ-9 scores improved significantly (p < 0.01) by 3 months of TRT. At 12 months PHQ-9 scores showed a clinically meaningful mean improvement of 5.62 points, patients with moderately severe to severe symptoms decreased from 17.3% to 2.1% (5/233), and subcohorts, including those defined by age (<60 years) and antidepressant use, had improved PHQ-9 scores ≥5. Conclusion: TRT may reduce depression symptoms in hypogonadal men, including middle-aged men and those using antidepressants.
12-Month Observation of Testosterone Replacement Effectiveness in a General Population of Men
Postgraduate Medicine, 2013
Background: Testosterone decline becomes more prevalent as men age and symptomatic testosterone deficiency is associated with potentially serious comorbidities. Despite limitations, registries can provide an opportunity to accumulate data regarding disease management in a typical patient population, including diagnosis, treatment, and outcomes. Materials and Methods: The Testim Registry in the United States (TRiUS) was a prospective, 12-month, observational cohort registry of men prescribed Testim ® (1% testosterone gel; Auxilium Pharmaceuticals, Inc.) for the first time; patients previously on other forms of testosterone replacement therapy (TRT) were eligible to participate in the study as well. The registry recorded total testosterone (TT) and free testosterone (FT) levels, prostate-specific antigen (PSA), sexual function, mood/depression, and cardiometabolic and anthropometric criteria before and after TRT. Changes over time were analyzed by analysis of variance, and linear regression and Pearson product-moment correlation coefficients were used to examine relationships between variables. Results: At baseline, 849 patients from 72 sites were enrolled, with 743 of 849 started on 5 g gel/day (50 mg testosterone/ day) and 106 of 849 started on 10 g gel/day (100 mg testosterone/day). Mean TT and FT levels increased significantly after 3 months of TRT (TT level, 16.8 ± 9.87 nmol/L [485 ± 284 ng/dL], P , 0.001; FT level, 286.3 ± 224.9 pmol/L [82.5 ± 64.8 pg/mL], P , 0.001) and were maintained at eugonadal levels. Mean PSA levels increased significantly (P = 0.004) from 1.12 ± 1.11 µg/L (1.12 ± 1.11 ng/mL) at baseline to 1.26 ± 1.22 µg/L (1.26 ± 1.22 ng/mL) after 12 months of TRT, although changes were well within guidelines (, 1.4 µg/L/year increase). Significant improvements were seen in sexual function and mood/depression at 3 months and in metabolic parameters at 12 months. Conclusion: Testosterone deficiency symptoms improved with TRT use in men; sexual function and mood/depression improvements were seen before metabolic improvements. Prostate-specific antigen levels increased, although increases were within guideline-determined safety limits.
The Burden of Testosterone Deficiency Syndrome in Adult Men: Economic and Quality-of-Life Impact
The Journal of Sexual Medicine, 2007
Testosterone deficiency syndrome (TDS) causes a wide range of symptoms that can lead to significant morbidity. Preliminary evidence has also linked TDS with premature mortality and with a number of co-morbid diseases including diabetes and metabolic syndrome. Such associations can lead to substantial economic and quality of life implications, the magnitude of which remains largely unknown. Despite the availability of effective treatment, TDS is a largely under-diagnosed and under-treated condition. Understanding the burden of TDS is impeded by a number of issues. First, there is a lack of clear universally accepted diagnostic criteria. Testosterone threshold levels below which a diagnosis of TDS should be made and treatment started differs between guidelines, countries and laboratories. Second, the link between TDS and some of the consequences that carry economic and quality of life implications are still unclear. The symptoms that potentially add to the economic burden include depression, sexual dysfunction, mild cognitive impairment, osteoporosis, cardiovascular disease and mortality. However, although good evidence exists demonstrating an association between TDS and sexual dysfunction and cognitive impairment, evidence is less strong for depression, the incidence of fractures and mortality and highly controversial for cardiovascular disease. The consequences that are likely to impact on patients' quality of life include sexual function, energy levels, body composition, mood and cognitive function. Understanding the burden is only the first step decision-makers need to take to decide whether to allocate scarce resources to treat the condition. To make informed decisions on when and who to treat information is also needed on the cost-effectiveness of available treatments. Such data would highlight the benefits of treatment of TDS to physicians, patients and to society as a whole.
Baseline Data From the TRiUS Registry: Symptoms and Comorbidities of Testosterone Deficiency
Postgraduate Medicine, 2011
Background: Testosterone defi ciency (TD) is prevalent among men seeking medical attention and may be associated with other comorbidities. Objective: The Testim ® Registry in the United States (TRiUS), a large, multicenter, prospective, 12-month observational cohort registry, was established to quantify symptoms and comorbidities of hypogonadal men in realworld clinical settings and to evaluate the effect of testosterone replacement therapy (TRT). Methods: Eligible TRiUS participants were hypogonadal men prescribed Testim ® (1% testosterone gel) for the fi rst time. Evaluated baseline parameters included: total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), prostate-specifi c antigen (PSA), anthropometrics (height, weight, waist, hip, and body mass index [BMI]), lipids, blood glucose, sexual dysfunction, mood/depression, and cardiovascular and metabolic risk factors. Parameters were correlated to TT and age using bivariate correlation and to the combination of TT and age using multiple linear regression. Results: TRiUS had 849 registrants (baseline TT: 286.5 ± 151.8 ng/dL; FT: 40.8 ± 62.1 pg/mL; SHBG: 28.2 ± 15.0 nmol/L; PSA: 1.12 ± 1.11 ng/mL). Eighty-six percent were overweight/obese, with a BMI Ն 25 kg/m 2 , and 57% were aged 40 to 59 years, with a mean (± standard deviation) age of 52.1 ± 12.3 years. Total testosterone levels were signifi cantly lower in men aged Ն 65 years. The most common comorbid conditions and cardiovascular risk factors included: smoking, metabolic syndrome, hypertension, dyslipidemia, and coronary artery disease. Weak but statistically signifi cant inverse correlations were noted between TT and sexual dysfunction, fasting glucose, systolic blood pressure, BMI, and Framingham risk scores. Patients with obesity or metabolic syndrome had signifi cantly lower TT levels, particularly among younger and middle-aged patients. Conclusions: Untreated hypogonadal middle-aged men exhibited a high prevalence of cardiometabolic risk factors that were correlated to TT levels. This suggests that TD is associated with adverse medical conditions that pose serious health risks, especially in a younger age demographic than previously thought. Clinicians may want to consider TT testing in unhealthy, middle-aged patients with symptoms of TD.
The journal of sexual medicine, 2017
The benefits and risks of long-term testosterone administration have been a topic of much scientific and regulatory interest in recent years. To assess long-term quality of life (QOL) and sexual function benefits of testosterone replacement therapy (TRT) prospectively in a diverse, multinational cohort of men with hypogonadism. A multinational patient registry was used to assess long-term changes associated with TRT in middle-age and older men with hypogonadism. Comprehensive evaluations were conducted at 6, 12, 24, and 36 months after enrollment into the registry. QOL and sexual function were evaluated by validated measures, including the Aging Males' Symptom (AMS) Scale and the International Index of Erectile Function (IIEF). A total of 999 previously untreated men with hypogonadism were enrolled at 25 European centers, 750 of whom received TRT at at least one visit during the period of observation. Patients on TRT reported rapid and sustained improvements in QOL, with fewer s...
Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men
JAMA Psychiatry, 2018
IMPORTANCE Countering depressive disorders is a public health priority. Currently, antidepressants are the first-line treatment, although they show modest effects. In men, testosterone treatment is a controversial alternative or adjunct treatment option. OBJECTIVES To examine the association of testosterone treatment with alleviation of depressive symptoms in men and to clarify moderating effects of testosterone status, depression status, age, treatment duration, and dosage. DATA SOURCES English-language studies published in peer-reviewed journals identified from PubMed/Medline, Embase, Scopus, PsychINFO, and the Cochrane Controlled Trials Register from database inception to March 5, 2018, using the search terms testosterone, mood, administration, dosage, adverse effects, deficiency, standards, therapeutic use, therapy, treatment, and supplementation. STUDY SELECTION Randomized placebo-controlled clinical trials (RCTs) of testosterone treatment that together cover a broad age range and hypogonadal or eugonadal men reporting depressive symptoms on psychometrically validated depression scales. DATA EXTRACTION AND SYNTHESIS Of 7690 identified records, 469 were evaluated against full study inclusion criteria after removing duplicates, reviews, and studies that did not examine male patients or testosterone. Quality assessment and data extraction from the remaining 27 RCTs were performed. MAIN OUTCOMES AND MEASURES Primary outcomes were testosterone treatment effectiveness (standardized score difference after treatment), efficacy (proportion of patients who responded to testosterone treatment with a score reduction of 50% or greater), and acceptability (proportion of patients who withdrew for any reason). RESULTS Random-effects meta-analysis of 27 RCTs including 1890 men suggested that testosterone treatment is associated with a significant reduction in depressive symptoms compared with placebo (Hedges g, 0.21; 95% CI, 0.10-0.32), showing an efficacy of odds ratio (OR), 2.30 (95% CI, 1.30-4.06). There was no significant difference between acceptability of testosterone treatment and placebo (OR, 0.79; 95% CI, 0.61-1.01). Meta-regression models suggested significant interactions for testosterone treatment with dosage and symptom variability at baseline. In the most conservative bias scenario, testosterone treatment remained significant whenever dosages greater than 0.5 g/wk were administered and symptom variability was kept low. CONCLUSIONS AND RELEVANCE Testosterone treatment appears to be effective and efficacious in reducing depressive symptoms in men, particularly when higher-dosage regimens were applied in carefully selected samples. However, given the heterogeneity of the included RCTs, more preregistered trials are needed that explicitly examine depression as the primary end point and consider relevant moderators.