Testosterone Treatment In Men Research Articles

Beyond T-Trials, T4DM and TRAVERSE: the next large testosterone randomized controlled trial.

Lower testosterone concentrations have been associated with poorer health outcomes in ageing men, but proving causality and demonstrating potential for therapeutic benefit requires randomized clinical trials (RCTs). This review discusses recent observational findings and results of major testosterone RCTs, to explore the need for another, larger trial. Evidence of Leydig cell impairment emerges in men above the age of 70 years. Lower testosterone is associated with diabetes risk, and also risk of incident dementia. An individual participant data meta-analysis found that below thresholds of testosterone of 7.4 nmol/L and 5.3 nmol/l respectively, risks of all-cause mortality and cardiovascular deaths in men increased. Testosterone for the Prevention of Type 2 Diabetes Mellitus (T4DM), a multicentre RCT, showed that testosterone treatment prevented or reverted type 2 diabetes in men at high risk. Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE), a cardiovascular safety trial, demonstrated cardiovascular and prostate safety of testosterone treatment in men with or at risk of cardiovascular disease. T4DM confirmed findings from the Testosterone Trials (T-Trials) that testosterone improved sexual function, and bone microarchitecture and density. However, in TRAVERSE, testosterone-treated men had a higher risk of clinical bone fractures, but not major osteoporotic fractures. Men with disorders of the hypothalamic-pituitary-testicular (HPT) axis causing androgen deficiency warrant consideration for testosterone therapy. In men with an intact HPT axis, testosterone treatment is a pharmacological intervention which requires justification from high quality RCT data. Currently, there is insufficient evidence to justify wider use of testosterone for prevention of cardiometabolic disease. However, there is scope for another large testosterone RCT to investigate whether testosterone treatment might, in older men, extend disability-free survival.

Prostate Risk and Monitoring During Testosterone Replacement Therapy.

Men with hypogonadism have reduced risk of prostate cancer mortality; whether testosterone treatment increases the risk of prostate safety events in men with hypogonadism remains controversial. Several studies including 4 larger randomized trials-the Testosterone Trials, TEstosterone and Atherosclerosis Progression in Aging Men (TEAAM) trial, Testosterone for Diabetes Mellitus trial, and Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) trial-treated men with testosterone or placebo for 1 year or longer and reported prospectively ascertained prostate safety data. The TRAVERSE Trial, because of its large size, longer duration, and adjudication of prostate events, has provided comprehensive data on the risk of adverse prostate events during testosterone replacement therapy (TRT). Among men with hypogonadism, carefully screened to exclude those at high risk of prostate cancer, the incidences of high-grade or any prostate cancer, acute urinary retention, surgical procedure for benign prostatic hyperplasia, prostate biopsy, or new pharmacologic therapy for lower urinary tract symptoms were low and did not differ between the testosterone and placebo groups. Testosterone did not worsen lower urinary tract symptoms. TRT was associated with a greater increase in prostate-specific antigen than placebo in the first year of treatment. Testosterone treatment of men with hypogonadism, screened to exclude those at high risk of prostate cancer, is associated with low risk of adverse prostate events. Baseline evaluation of prostate cancer risk and a standardized monitoring plan can minimize the risk of unnecessary prostate biopsy while enabling the detection of high-grade prostate cancers in men receiving TRT.

Testosterone Treatment of Men with Unequivocal Hypogonadism Following Treatment of Organ-Confined Prostate Cancer

ObjectiveTo determine if testosterone treatment of men with unequivocal hypogonadism and organ-confined prostate cancer is associated with recurrence of the cancer. The testosterone dependence of metastatic prostate cancer has made physicians reluctant to treat hypogonadal men with testosterone even after treatment of prostate cancer. Prior studies of testosterone treatment of men with treated prostate cancer have not documented that the men were unequivocally hypogonadal. MethodsA computerized search of electronic medical records from January 1, 2005, to September 20, 2021, identified 269 men aged ≥50 years who were diagnosed with prostate cancer and hypogonadism. We reviewed the individual records of these men and identified those treated by radical prostatectomy and had no evidence of extraprostatic extension. We then identified men who were hypogonadal prior to the diagnosis of prostate cancer based on at least 1 morning serum testosterone concentration of ≤220 ng/dL, discontinued testosterone treatment when the prostate cancer was diagnosed, resumed testosterone treatment within 2 years after treatment of the cancer, and were monitored for cancer recurrence, defined by a prostate-specific antigen level of ≥0.2 ng/mL. ResultsSixteen men met the inclusion criteria. Their baseline serum testosterone concentrations were 9-185 ng/dL. The median duration of testosterone treatment and monitoring was 5 years (range, 1-20 years). None of the 16 men had biochemical recurrence of prostate cancer during this period. ConclusionTestosterone treatment of men with unequivocal hypogonadism whose organ-confined prostate cancer is treated by radical prostatectomy may be safe.

Correlation Analysis between Hypogonadal Symptoms and Changes in Body Composition and Physical Fitness after Testosterone Treatment in Men with Testosterone Deficiency.

This study analyzed changes in body composition and physical fitness in men with testosterone deficiency (TD) after testosterone treatment (TT) and examined the correlations of body composition and physical fitness with serum testosterone levels and hypogonadal symptoms. Seventy patients with TD were divided into control (group I, n=23) and experimental (group II, n=47) groups. Patients in the experimental group were administered intramuscular testosterone enanthate (250 mg) for six months. The aging males symptom scale (AMS) score, international prostate symptom score (IPSS), body mass index, waist circumference, and serum laboratory values were measured at baseline and at the end of the study. Bioelectrical impedance analysis was used to assess the patients' body composition. Seven types of basic exercise tests were used to evaluate the patients' physical fitness. After six months, there were no significant differences in group I, while group II had significantly improved IPSS and AMS scores; increased hemoglobin, hematocrit, prostate-specific antigen, and testosterone levels and skeletal muscle mass; and waist circumference, and body fat mass. All elements of the physical fitness test were significantly improved in group II, with the exceptions of flexibility and endurance. Decreased waist circumference was correlated with changes in testosterone levels in group II, and the IPSS, cardiorespiratory fitness, and agility were correlated with improved hypogonadal symptoms. TT improved the hypogonadal and lower urinary tract symptoms in patients with TD and improved body composition, physical fitness, and metabolic syndrome parameters. Increased testosterone and improved hypogonadal symptoms were correlated with a decrease in waist circumference and an improvement in cardiorespiratory fitness and agility. As such, when implementing TT, we should consider whether these areas may be improved, as this can help to predict the effect.

PMON260 Cost-Effectiveness of Testosterone Treatment for Men with Hypogonadism

Abstract Background Testosterone replacement therapy is the standard treatment for male hypogonadism (MH). Prescribing rates of testosterone in the UK have risen between 2001 and 2010 without an observable increase in the prevalence of hypogonadism, which may reflect increasing media awareness among men about hypogonadism. Currently, there is uncertainty about the safety and efficacy of testosterone treatment for MH, especially regarding its impact on cardiovascular risk, which has led to mandatory safety labelling in some countries. Aim We conducted an economic evaluation of testosterone therapy in men with hypogonadism, using individual patient data (IPD) of safety and efficacy outcomes in over 3000 participants as part of an international collaboration of investigators of 17 existing placebo-controlled RCTs assessing the safety and efficacy of testosterone treatment for MH (TestES Consortium). Methods A cost-utility analysis of the use of testosterone treatment for MH was conducted using a cohort Markov model developed following best practice. The model care pathway was informed by existing clinical guidelines, the results of the TestES Consortium individual patient data (IPD) meta-analysis, and discussions with clinical and methodological experts. Five Markov states were included: no complications, post-Cardiac pathology, post-Peripheral Vascular System Pathology, post-Cerebrovascular System Pathology, and Death. All-cause mortality, cardiovascular and cerebrovascular complications, and utility weights were obtained from the TestES IPD analyses. The UK NHS and personal and social services perspective was adopted for costs. Ten-year and lifetime time horizons were considered with costs and effects discounted annually at 3.5% rate. The model was run probabilistically using 10,000 Monte Carlo simulations. Three starting ages were defined (40, 60, and 75 years). Mean total cost, mean QALYs and incremental cost-effectiveness ratios were calculated. Results Cost-effectiveness of testosterone treatment appears to be dependent on the relative risk (RR) of all-cause mortality - favouring TRT - and the methods used to derive health state utility scores (i.e., SF-6D or a mapping between Beck Depression Inventory -BDI- score and EQ-5D score) for testosterone treatment versus standard care. When the RR of mortality and the BDI utilities were used, ICERs remained below the £20,000 ($27,400) UK conventional threshold, irrespective of the cohort starting age. However, ICERs increased above the £20,000 threshold when the difference in all-cause mortality was dropped, and the SF-6D utility scores were used. Conclusions We report the most in-depth economic analysis of male hypogonadism treatment to date. There remains limited data for generating preference-based health-related quality of life (HRQoL) weights for economic evaluation. Further clarity on the long-term cardiovascular safety of testosterone treatment in men with hypogonadism, and more in-depth mapping of clinical outcomes to generic preference-based measures of HRQoL will be crucial to inform robust estimates of the cost-effectiveness of testosterone treatment for MH. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

OR25-5 Adverse Cardiovascular Events and Cause Mortality in Men During Testosterone Treatment: Individual Patient and Aggregate Data Meta-Analyses

Abstract Background The cardiovascular safety of testosterone treatment in low testosterone is widely acknowledged to be unclear. Testosterone increases haematocrit, thereby potentially increasing venous thromboembolism risk. The FDA lists cardiovascular risk and stroke as adverse effects of testosterone. Systematic reviews and meta-analyses of published data have limited ability to confirm source data quality and categorisation. Some published meta-analyses have included participants with distinct risk profiles (e.g. cancer, HIV), with serum testosterone atypical for hypogonadism (>12nmol/L), short durations of testosterone treatment, and studies without placebo treatment. Furthermore, subtypes of cardiovascular or cerebrovascular events (e.g. stable angina) during testosterone treatment are seldom published, so have not been analysed previously. Objective Evaluate frequencies of all-cause mortality, and all cardiovascular or cerebrovascular event subtypes, and analyse efficacy of testosterone monotherapy compared to placebo for men with low testosterone, using individual patient data (IPD) and aggregate data meta-analyses. Methods MEDLINE, EMBASE, Science Citation Index, CENTRAL and clinical trial registries (PROSPERO CRD42018111005) were searched for placebo-controlled RCTs including men with serum testosterone <12nmol/L. One-stage meta-analyses were performed for studies providing IPD and two-stage meta-analyses were performed to integrate IPD and aggregated data. Primary outcomes were all-cause mortality and cardiovascular and/or cerebrovascular events at 12 months or nearest time point. Results IPD were obtained from 17 of 35 eligible RCTs (3431/5601 participants) in men with low testosterone. Most participants had functional hypogonadism. Risks of cardiovascular and/or cerebrovascular events were similar between the testosterone and placebo arms (testosterone 120/1601, 7.5%; placebo, 110/1519, 7.2% OR 1.07, 95% CI 0.81-1.42 p=0.62). Frequencies of all cardiovascular or cerebrovascular event subtypes were also similar between testosterone and placebo arms, but testosterone increased risks of oedema and erythrocytosis. No subgroups at higher cardiovascular and/or cerebrovascular event risk were identified. Fewer deaths were recorded in the testosterone arm, but this difference was non-significant (testosterone, 6/1621, 0.4%; placebo, 12/1537, 0.8% OR 0.46, 95% CI 0.17-1.24 p=0.13). Testosterone significantly reduced serum total cholesterol, high-density lipoprotein (HDL), and triglycerides versus placebo. No significant differences in serum low-density lipoprotein (LDL), blood pressure, glycaemic parameters, diabetes incidence or prostate outcomes were observed between groups. Testosterone had positive, albeit varied, effects on quality of life and sexual function. Conclusions This is the most comprehensive study to date interrogating the safety of testosterone treatment in men with low testosterone. We were unable to find evidence from our IPD meta-analyses that testosterone increases risks of mortality or cardiovascular and/or cerebrovascular events in the short- to medium-term in men with low testosterone, most of whom have various forms of functional hypogonadism. These data provide some reassurance to men with low testosterone and their clinicians about the safety of testosterone in the short-to-medium term although more long-term data are required.Acknowledgement: NIHR TestES Consortium. Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.

Accumulation of Adipocytes in Penile Corpus Cavernosum May Contribute to Venous Leakage and Veno-Occlusive Dysfunction in Patients with Testosterone Deficiency and Erectile Dysfunction

In 2005, we reported that, in the animal model, androgen deprivation resulted in significant changes in the structural elements of the penile corpus cavernosum (CC), including: (1) atrophy of the trabecular smooth muscle, (2) increased deposition of connective tissue, and (3) accumulation of adipocytes in the sub-tunical region. These structural alterations, together with reported decreases in the expression and activity of endothelial nitric oxide synthase (eNOS) and neural nitric oxide synthase (nNOS), are believed to contribute to reduced blood inflow and increased blood outflow, contributing to veno-occlusive dysfunction and erectile dysfunction (ED). More recently, several clinical studies have documented accumulation of adipocytes in the sub-tunical region of the corpora cavernosa from patients with ED, supporting findings reported in the animal models. Here, we summarize the observations from basic and clinical research and advance the hypothesis that testosterone deficiency contributes to significant changes in the structural integrity of the CC, resulting in atrophy of the trabecular smooth muscle and contributing to reduced vascular smooth muscle relaxation and diminished blood inflow into the penis, resulting in a failure to fill. In addition, atrophy of the trabecular smooth muscle, accumulation of adipocytes in the sub-tunical region, and increased deposition of connective tissue contribute to veno-occlusive dysfunction and a failure to maintain erection. It is postulated that testosterone treatment in men with testosterone deficiency may reverse the structural alterations in the CC and improve erectile function.

Testosterone, Hypogonadism, and Heart Failure

Male hypogonadism is defined as low circulating testosterone level associated with signs and symptoms of testosterone deficiency. Although the bidirectional link between hypogonadism and cardiovascular disease has been clarified, the association between testosterone and chronic heart failure (HF) is more controversial. Herein, we critically review published studies relating to testosterone, hypogonadism, and HF and provide practical clinical information on proper diagnosis and treatment of male hypogonadism in patients with HF. In general, published studies are extremely heterogeneous, frequently have not adhered to hypogonadism guidelines, and suffer from many intrinsic methodological inaccuracies; therefore, data provide only low-quality evidence. Nevertheless, by selecting the few methodologically robust studies, we show the prevalence of testosterone deficiency (30%-50%) and symptomatic hypogonadism (15%) in men with HF is significant. Low testosterone correlates with HF severity, New York Heart Association class, exercise functional capacity, and a worse clinical prognosis and mortality. Interventional studies on testosterone treatment in men with HF are inconclusive but do suggest beneficial effects on exercise capacity, New York Heart Association class, metabolic health, and cardiac prognosis. We suggest that clinicians should measure testosterone levels in men with HF who have symptoms of a testosterone deficiency and conditions that predispose to hypogonadism, such as obesity and diabetes. These patients-if diagnosed as hypogonadal-may benefit from the short- and long-term effects of testosterone replacement therapy, which include improvements in both cardiac prognosis and systemic outcomes. Further collaborative studies involving both cardiologists and endocrinologists are warranted.

Benefits and Risks of Testosterone Treatment in Men with Age-Related Decline in Testosterone.

The substantial increase in life expectancy of men has focused growing attention on quality-of-life issues associated with reproductive aging. Serum total and free testosterone levels in men, after reaching a peak in the second and third decade of life, decline gradually with advancing age. The trajectory of age-related decline is affected by comorbid conditions, adiposity, medications, and genetic factors. Testosterone treatment of older men with low testosterone levels improves overall sexual activity, sexual desire, and erectile function; improves areal and volumetric bone density, as well as estimated bone strength in the spine and the hip; corrects unexplained anemia of aging; increases skeletal muscle mass, strength and power, self-reported mobility, and some measures of physical function; and modestly improves depressive symptoms. The long-term effects of testosterone on major cardiovascular events and prostate cancer risk remain unclear. The Endocrine Society recommends against testosterone therapy of all older men with low testosterone levels but suggests consideration of treatment on an individualized basis in men who have consistently low testosterone levels and symptoms or conditions suggestive of testosterone deficiency.

1057-P: Long-Term Testosterone Therapy Results in Remission of Type 2 Diabetes (T2DM) in 34.3% (61 of 178) Men with Hypogonadism and T2DM in a Real-World Registry Study

Background: In 2018, ADA Standards of Medical Care in Diabetes added measurement of testosterone levels in men with T2DM as new recommendation. Methods: A registry of men with hypogonadism (testosterone ≤12.1 nmol/L) was initiated in 2004 in a urological practice setting. 356 of 858 patients (41.5%) had T2DM diagnosed and treated in a diabetes center. Of these men, 178 received testosterone undecanoate (TU) injections 1000 mg/12 weeks (T-group) following an initial 6-week interval. Anthropometric and metabolic parameters were measured at least twice a year. Fasting insulin was used to calculate HOMA-IR. Results: After a mean follow-up of 7.7±3.0 (minimum 2, maximum 11 years), 61 patients (34.3%) were in remission, defined as discontinuation of all diabetes medications and stable HbA1c <6.5%. In men who went into remission, HbA1c dropped from 8.7±1.0% at baseline to 5.4±0.1% at the last measurement, HOMA-IR from 10.2±2.5 to 1.7±0.5. In men who never received insulin, HOMA%S increased from 11.1±1.5 to 15.8±2.4. Anthropometric parameters: Body weight declined progressively from 113.6±13.8 to 90.9±8.4 kg by 22.6±8.0 kg, waist circumference from 111.1±7.5 to 98.3±4.6 cm by 12.6±4.3 cm. All patients were on metformin at baseline. 22 patients were on insulin. The average observation time was 130.7±25.9 months (10.9±2.2 years). The average time to discontinuation of diabetes medication was 8.6±2.9 years, average follow-up after achieving remission 2.5±2.3 years. Medication adherence to TU was 100% as all injections were administered in the office and documented. PSA and hematocrit stayed within normal range during the entire observation period. Discussion: The effects of testosterone were likely mediated by sustained weight loss, increased lean body mass and a profound and sustained reduction of insulin resistance. Conclusions: Long-term testosterone treatment in men with hypogonadism may result in remission of T2DM. Disclosure K.S. Haider: None. A. Haider: None. F. Saad: Consultant; Self; Bayer AG. Stock/Shareholder; Self; AbbVie Inc., Bayer AG. Funding Bayer AG

Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians.

The American College of Physicians (ACP) developed this guideline to provide clinical recommendations based on the current evidence of the benefits and harms of testosterone treatment in adult men with age-related low testosterone. This guideline is endorsed by the American Academy of Family Physicians. The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of testosterone treatment in adult men with age-related low testosterone. Clinical outcomes were evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and included sexual function, physical function, quality of life, energy and vitality, depression, cognition, serious adverse events, major adverse cardiovascular events, and other adverse events. The target audience includes all clinicians, and the target patient population includes adult men with age-related low testosterone. ACP suggests that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function (conditional recommendation; low-certainty evidence). The discussion should include the potential benefits, harms, costs, and patient's preferences. ACP suggests that clinicians should reevaluate symptoms within 12 months and periodically thereafter. Clinicians should discontinue testosterone treatment in men with age-related low testosterone with sexual dysfunction in whom there is no improvement in sexual function (conditional recommendation; low-certainty evidence). ACP suggests that clinicians consider intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function in men with age-related low testosterone, as costs are considerably lower for the intramuscular formulation and clinical effectiveness and harms are similar. ACP suggests that clinicians not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition (conditional recommendation; low-certainty evidence).

Age-Related Low Testosterone.

The American College of Physicians Clinical Guidelines Committee provides recommendations for the use of testosterone treatment in men with age-related low testosterone. The editorialist discusses ...

Efficacy and Safety of Testosterone Treatment in Men: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

Testosterone treatment rates in adult men have increased in the United States over the past 2 decades. To assess the benefits and harms of testosterone treatment for men without underlying organic causes of hypogonadism. English-language searches of multiple electronic databases (January 1980 to May 2019) and reference lists from systematic reviews. 38 randomized controlled trials (RCTs) of at least 6 months' duration that evaluated transdermal or intramuscular testosterone therapies versus placebo or no treatment and reported prespecified patient-centered outcomes, as well as 20 long-term observational studies, U.S. Food and Drug Administration review data, and product labels that reported harms information. Data extraction by a single investigator was confirmed by a second, 2 investigators assessed risk of bias, and evidence certainty was determined by consensus. Studies enrolled mostly older men who varied in age, symptoms, and testosterone eligibility criteria. Testosterone therapy improved sexual functioning and quality of life in men with low testosterone levels, although effect sizes were small (low- to moderate-certainty evidence). Testosterone therapy had little to no effect on physical functioning, depressive symptoms, energy and vitality, or cognition. Harms evidence reported in trials was judged to be insufficient or of low certainty for most harm outcomes. No trials were powered to assess cardiovascular events or prostate cancer, and trials often excluded men at increased risk for these conditions. Observational studies were limited by confounding by indication and contraindication. Few trials exceeded a 1-year duration, minimum important outcome differences were often not established or reported, RCTs were not powered to assess important harms, few data were available in men aged 18 to 50 years, definitions of low testosterone varied, and study entry criteria varied. In older men with low testosterone levels without well-established medical conditions known to cause hypogonadism, testosterone therapy may provide small improvements in sexual functioning and quality of life but little to no benefit for other common symptoms of aging. Long-term efficacy and safety are unknown. American College of Physicians. (PROSPERO: CRD42018096585).

SUN-222 Testosterone Treatment in Men with Classical vs. Functional Hypogonadism: A 9-Year Registry

Introduction and Objective Longterm data of Testosterone (T) substitution in hypogonadal men are scarce and clinical value of this treatment is especially debated in men with functional (so called “late-onset”) hypogonadism. A long-term registry comprising various groups of patients provides an efficient tool to approach this issue. Methods Registry data of max. 9 years comprising 650 patients with hypogonadism including 266 men with primary forms (mean age 34.0±11.7 years), 196 with secondary origin (mean age 31.9±12.0 years) and 188 with functional hypogonadism (mean age 42.3±11.3 years) all receiving uniform treatment using intramuscular T undecanoate (1000 mg). Results The registry contained 8358 time points with a subset of metabolic and safety parameters each. Serum T concentrations increased from 5.7±2.3 nmol/L to 19.4±2.8 nmol/L in men with classical hypogonadism and from 7.8±2.4 nmol/L to 19.2±3.1 nmol/L in men with functional hypogonadism (difference in delta T: p<0.0001). There was an initial difference in the distribution of body mass index (BMI): 35.6% of men with classical hypogonadism and 51.6% of men with functional hypogonadism were obese (BMI>30 kg/m2, p=0.0006). Changes over time using Kaplan-Meier models revealed fundamental differences in inter-individual effects: men with functional hypogonadism were more likely to lose 10% weight and 5% of waist circumference (WC) than men with classical hypogonadism (hazard ratio 1.3 [1.1-1.4], p=0.008 and hazard ratio 1.4 [1.3-1.5], p=0.001). There was no difference for increase in hematocrit. Changes in PSA levels were more likely to occur in functional hypogonadism (hazard ratio 1.3 [1.1-1.6], p=0.003). Significantly more pronounced effects of T substitution in functional hypogonadism could also be attributed to changes in parameters of lipid metabolism (levels of total cholesterol, triglycerides, LDL- and HDL-cholesterol and glucose metabolism). Stepwise multiple Cox regression models could attribute these differences to the initial higher values in BMI, WC, lipids, glucose and age found in functional hypogonadism. The condition as such rather attenuated the effects of testosterone treatment compared to those seen in classical forms of hypogonadism, due to the lower increase of testosterone concentrations during treatment. Conclusions Major new findings regarding effects and safety of T substitution in different groups of hypogonadal men are provided. Effects on factors influencing cardiovascular health are modulated by diagnosis and age. Patients with functional hypogonadism seem to benefit to a larger extent from T substitution, this being a function of their initially worse status in cardiovascular risk factors compared to men with classical forms of hypogonadism.

How relevant are the complications associated with testosterone treatment in men with hypogonadism?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

SLEEP APNEA IN ENDOCRINE DISORDERS

In the recent years, an association between sleep apnea and a number of endocrine diseases has been established. The secretion of many hormones after falling asleep is considerably changed, compared to the period of wakefulness. In patients with endocrine disorders, abnormal hormonal secretion and its pathological consequences may contribute to sleep apnea. Sleep fragmentation and intermittent hypoxia arising in sleep apnea result in a decrease in insulin sensitivity, which contributes to the development of type 2 diabetes mellitus. The prevalence of sleep apnea increases in acromegaly, which may affect the risk of cardio-pulmonary complications. There is an association between sleep apnea and testosterone treatment in men, as well as in postmenopausal women. Sleep apnea in hypothyroidism is most frequently related to the development of hypothyroidism per se and can therefore be reversed with thyroid hormone replacement therapy. Timely detection and treatment of sleep apnea in patients with endocrine disorders can improve their survival prognosis and quality of life.

Testosterone treatment and risk of venous thromboembolism: population based case-control study

Objective To determine the risk of venous thromboembolism associated with use of testosterone treatment in men, focusing particularly on the timing of the risk.Design Population based case-control studySetting 370 general...

Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes.

One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH. A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks. Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (-3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P < 0.01) compared with placebo. Visceral and hepatic fat did not change. The expression of insulin signaling genes (IR-β, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower in men with HH and was upregulated after testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1β, tumor necrosis factor-α, and leptin (P < 0.05 for all). Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat.

Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials.

The effects of testosterone treatment on glucose metabolism and other outcomes in men with type 2 diabetes (T2D) and/or the metabolic syndrome are controversial. To perform a systematic review and meta-analysis of placebo-controlled double-blind randomized controlled clinical trials (RCT) of testosterone treatment in men with T2D and/or the metabolic syndrome. A systematic search of RCTs was conducted using Medline, Embase and the Cochrane Register of controlled trials from inception to July 2014 followed by a manual review of the literature. Eligible studies were published placebo-controlled double-blind RCTs published in English. Two reviewers independently selected studies, determined study quality and extracted outcome and descriptive data. Of the 112 identified studies, seven RCTs including 833 men were eligible for the meta-analysis. In studies using a simple linear equation to calculate the homeostatic model assessment of insulin resistance (HOMA1), testosterone treatment modestly improved insulin resistance, compared to placebo, pooled mean difference (MD) -1·58 [-2·25, -0·91], P < 0·001. The treatment effect was nonsignificant for RCTs using a more stringent computer-based equation (HOMA2), MD -0·19 [-0·86, 0·49], P = 0·58). Testosterone treatment did not improve glycaemic (HbA1c) control, MD -0·15 [-0·39, 0·10], P = 0·25, or constitutional symptoms, Aging Male Symptom score, MD -2·49 [-5·81, 0·83], P = 0·14). This meta-analysis does not support the routine use of testosterone treatment in men with T2D and/or the metabolic syndrome without classical hypogonadism. Additional studies are needed to determine whether hormonal interventions are warranted in selected men with T2D and/or the metabolic syndrome.

Testosterone treatment of men with mild cognitive impairment and low testosterone levels.

This study investigated the effects of testosterone (T) treatment on cognition, mood, and quality of life in men with mild cognitive impairment (MCI) and low serum T levels. A total of 351 community-dwelling men were screened, and 37 men evidenced both MCI and low T of whom 27 agreed for further screening. Twenty-two met all the study inclusion/exclusion criteria and enrolled in a 6-month randomized, double-blind, placebo-controlled study. Total T levels significantly increased in the T treatment group. No significant changes were observed in measures of cognition, mood, or quality of life other than improvement in 1 objective measure of verbal memory (P < .05) and decreased depression symptoms (P < .02) in the treatment group. Testosterone treatment may modestly improve verbal memory and depression symptoms in men with both MCI and low T.