Summary
Objectives The role of androgen decline in the sexual activity of adult males is controversial. To clarify whether sexual function would benefit from testosterone (T) treatment in men with ...partially or severely reduced serum T levels, we conducted a systematic review and meta‐analysis of placebo‐controlled studies published in the past 30 years. The aim of this study was to assess and compare the effects of T on the different domains of sexual life.
Data source A comprehensive search of all published randomized clinical trials was performed in MEDLINE, the Cochrane Library, EMBASE and Current Contents databases.
Review methods Guided by prespecified criteria, software‐assisted data ion and quality assessed by two independent reviewers, a total of 17 randomized placebo‐controlled trials were found to be eligible. For each domain of sexual function we calculated the standardized mean difference relative to T and reported the results of pooled estimates of T treatment using the random effect model of meta‐analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta‐regression analysis.
Results Overall, 656 subjects were evaluated: 284 were randomized to T, 284 to placebo (P) and 88 treated in cross‐over. The median study length was 3 months (range 1–36 months). Our meta‐analysis showed that in men with an average T level at baseline below 12 nmol/l, T treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourses, scores of erectile function and overall sexual satisfaction, whereas T had no effect on erectile function in eugonadal men compared to placebo. Heterogeneity was explored by grouping studies according to the characteristics of the study population. A cut‐off value of 10 nmol/l for the mean T of the study population failed to predict the effect of treatment, whereas the presence of risk factors for vasculogenic erectile dysfunction (ED), comorbidities and shorter evaluation periods were associated with greater treatment effects in the studies performed in hypogonadal, but not in eugonadal, men. Meta‐regression analysis showed that the effects of T on erectile function, but not libido, were inversely related to the mean baseline T concentration. The meta‐analysis of available studies indicates that T treatment might be useful for improving vasculogenic ED in selected subjects with low or low‐normal T levels. The evidence for a beneficial effect of T treatment on erectile function should be tempered with the caveats that the effect tends to decline over time, is progressively smaller with increasing baseline T levels, and long‐term safety data are not available. The present meta‐analysis highlights the need, and pitfalls, for large‐scale, long‐term, randomized controlled trials to formally investigate the efficacy of T replacement in symptomatic middle‐aged and elderly men with reduced T levels and ED.
Context:
Ectopic Cushing's Syndrome (ECS) can be a diagnostic challenge with the hormonal source difficult to find. This study analyzes the accuracy of imaging studies in ECS localization.
Evidence ...Acquisition:
Systematic review of medical literature for ECS case series providing individual patient data on at least one conventional imaging technique (computed tomography CT/magnetic resonance imaging) and one of the following: 111In-pentetreotide (OCT), 131I/123I-metaiodobenzylguanidine, 18F-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET), 18F-fluorodopa-PET (F-DOPA-PET), 68Ga-DOTATATE-PET/CT or 68Ga-DOTATOC-PET/CT scan (68Gallium-SSTR-PET/CT).
Evidence Summary:
The analysis comprised 231 patients (females, 50.2%; age, 42.6 ± 17 y). Overall, 52.4% (121/231) had “overt” ECS, 18.6% had “occult” ECS, and 29% had “covert” ECS. Tumors were located in the lung (55.3%), mediastinum-thymus (7.9%), pancreas (8.5%), adrenal glands (6.4%), gastrointestinal tract (5.4%), thyroid (3.7%), and other sites (12.8%), and primary tumors were mostly bronchial neuroendocrine tumors (NETs) (54.8%), pancreatic NETs (8%), mediastinum-thymus NETs (6.9%), gastrointestinal NETs (5.3%), pheochromocytoma (6.4%), neuroblastoma (3.2%), and medullary thyroid carcinoma (3.2%). Tumors were localized by CT in 66.2% (137/207), magnetic resonance imaging in 51.5% (53/103), OCT in 48.9% (84/172), FDG-PET in 51.7% (46/89), F-DOPA-PET in 57.1% (12/21), 131/123I-metaiodobenzylguanidine in 30.8% (4/13), and 68Gallium-SSTR-PET/CT in 81.8% (18/22) of cases. Molecular imaging discovered 79.1% (53/67) of tumors unidentified by conventional radiology, with OCT the most commonly used, revealing the tumor in 64%, followed by FDG-PET in 59.4%. F-DOPA-PET was used in only seven covert cases (sensitivity, 85.7%). Notably, 68Gallium-SSTR-PET/CT had 100% sensitivity among covert cases.
Conclusions:
Nuclear medicine improves the sensitivity of conventional radiology when tumor site identification is problematic. OCT offers a good availability/reliability ratio, and FDG-PET was proven useful. 68Gallium-SSTR-PET/CT use was infrequent, despite offering the highest sensitivity.
Summary
Objectives Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and ...increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle‐aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile.
Data source A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases.
Review methods Guided by prespecified criteria, software‐assisted data ion and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta‐analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta‐regression analysis.
Results Overall, 1083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64·5 years (range 49·9–77·6) and mean serum testosterone was 10·9 nmol/l (range 7·8–19). Testosterone treatment produced: (i) a reduction of 1·6 kg (CI: 2·5–0·6) of total body fat, corresponding to −6·2% (CI: 9·2–3·3) variation of initial body fat, (ii) an increase in fat free mass of 1·6 kg (CI: 0·6–2·6), corresponding to +2·7% (CI: 1·1–4·4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size = 0·3 standard mean difference (SMD), CI: −0·0 to 0·6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3·7% (CI: 1·0–6·4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = −0·6 SMD, CI: −1·0 to −0·2). Testosterone also reduced total cholesterol by 0·23 mmol/l (CI: −0·37 to −0·10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)‐cholesterol. A significant reduction of high density lipoprotein (HDL)‐cholesterol was found only in studies with higher mean T‐values at baseline (−0·085 mmol/l, CI: −0·017 to −0·003). Sensitivity and meta‐regression analysis revealed that the dose/type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL‐cholesterol among studies.
Conclusion The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle‐aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems.
The morbidity and mortality of diabetes mellitus are mostly attributed to cardiovascular complications. Despite tremendous advancement in glycemic control, anti-diabetic medications have failed to ...revert vascular impairment once triggered by the metabolic disorder. The angiogenic growth factors, Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2), are crucial regulators of vessel formation and maintenance starting with embryonic development and continuing through life. In mature vessels, angiopoietins control vascular permeability, inflammation and remodeling. A crucial role of angiopoietins is to drive vascular inflammation from the active to the quiescent state, enabling restoration of tissue homeostasis. The mechanism is of particular importance for healing and repair after damage, two conditions typically impaired in metabolic disorders. There is an emerging body of evidences suggesting that the imbalance of Ang1 and Ang2 regulation, leading to an increased Ang2/Ang1 ratio, represents a culprit of the vascular alterations of patients with type-2 diabetes mellitus. Pharmacological modulation of Ang1 or Ang2 actions may help prevent or delay the onset of diabetic vascular complications by restoring vessel function, favoring tissue repair and maintaining endothelial quiescence. In this review, we present a summary of the role of Ang1 and Ang2, their involvement in diabetic complications, and novel therapeutic strategies targeting angiopoietins to ameliorate vascular health in metabolic disorders.
Introduction: A large body of evidence has clearly documented that erectile dysfunction (ED) represents not only a complication of cardiovascular (CV) diseases (CVD) but often an early sign of ...forthcoming CVD.
Areas covered: All the available data from meta-analyses evaluating the association between ED and CV risk were collected and discussed. Similarly, all available meta-analyses investigating the significance of ED as a possible early marker for major adverse cardiovascular events (MACE) were analyzed. In addition, data originally obtained in a Florence cohort, dealing with a large series of patients seeking medical care for sexual dysfunction, will be also reported.
Expert opinion: Available evidence indicates that ED represents a risk factor of CV mortality and morbidity. Not only conventional CV risk factors but also unconventional ones, derived from a perturbation of the relational and intrapsychic domains of ED, might play a possible role in CV risk stratification of ED subjects. Finally, penile doppler ultrasound can give important information on CV risk, especially in younger and low risk subjects. The presence of ED should become an opportunity - for the patient and for the physician - to screen for the presence of comorbidities improving not only sexual health but, more importantly, men's overall health.
Abstract Purpose Andrological pathologies in the adulthood are often the results of conditions that originate during childhood and adolescence and sometimes even during gestation and neonatal period. ...Unfortunately, the reports in the literature concerning pediatric andrological diseases are scares and mainly concerning single issues. Furthermore, no shared position statement are so far available. Methods The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP) to provide an updated guideline on the diagnosis and management of andrological disorders from childhood and adolescence to transition age. Derived recommendations were based on the grading of recommendations, assessment, development, and evaluation (GRADE) system. Results A literature search of articles in English for the term “varicoceles”, “gynecomastia”, “fertility preservation”, “macroorchidism”, “precocious puberty” and “pubertal delay” has been performed. Three major aspects for each considered disorder were assessed including diagnosis, clinical management, and treatment. Recommendations and suggestions have been provided for each of the mentioned andrological disorders. Conclusions These are the first guidelines based on a multidisciplinary approach that involves important societies related to the field of andrological medicine from pediatric to transition and adult ages. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving andrological and general health of the transitional age.
Purpose
To provide the evidence-based recommendations on the role of testosterone (T) on age-related symptoms and signs remains.
Methods
The Italian Society of Andrology and Sexual Medicine (SIAMS) ...and the and the Italian Society of Endocrinology (SIE) commissioned an expert task force to provide an updated guideline on adult-onset male hypogonadism. Derived recommendations were based on Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.
Results
Clinical diagnosis of adult-onset hypogonadism should be based on a combination of clinical and biochemical parameters. Testosterone replacement therapy (TRT) should be offered to all symptomatic subjects with hypogonadism after the exclusion of possible contraindications. T gels and the long-acting injectable T are currently available preparations showing the best efficacy/safety profile. TRT can improve all aspects of sexual function, although its effect is limited in more complicated patients. Body composition (reducing fat mass and increasing lean mass) is improved after TRT, either in subjects with or without metabolic syndrome or type 2 diabetes. Conversely, the role of TRT in improving glycometabolic control is more conflicting. TRT can result in increasing bone mineral density, particularly at lumbar site, but no information on fracture risk is available. Limited data support the use of TRT for improving other outcomes, including mood frailty and mobility.
Conclusions
TRT can improve sexual function and body composition particularly in less complicated adult and in aging subjects with hypogonadism. When hypogonadism is adequately diagnosed, T appropriately prescribed and subjects correctly followed up, no short-term increased risk of adverse events is observed. Longer and larger studies are advisable to better clarify TRT long-term efficacy/safety profile.
PDF
