Long-term penile prosthesis couple's satisfaction: A systematic review and meta-analysis.

CONTEXT: Data supporting successful and satisfactory penile prosthesis (PP) implantation outcomes are mainly based on subjective, rather than objective, analysis. OBJECTIVE: To systematically review and objectively analyze, all available data related to patient and partner PP satisfaction. EVIDENCE ACQUISITION: An extensive search was performed, including the following key-words: ("penile prosthesis" and "satisfaction"). The search, which accrued data from January 1, 1969, up to July 31, 2023, was restricted to English-language articles including human participants. EVIDENCE SYNTHESIS: Out of 663 retrieved articles, 83 were considered including, 12,132 subjects with a mean age and mean follow-up of 58.6 [range 20; 77.1] years and 47.6 [range 6; 374] months, respectively. Overall, a high patient satisfaction rate was observed 83[80; 86]%. The satisfaction rate increased in subjects with three-piece PP and in those with a higher rate of cardiovascular or neurological diseases and was independent of the patient's age. Partner's satisfaction rate was lower when compared to that observed in men and it increased according to the use of inflatable devices and the presence of patient Peyronie's disease. The long-term complication rate was limited ranging from 3% for erosion to 4.6% when mechanical failure was considered. CONCLUSIONS: Patient and partner satisfaction is excellent and increases with time. The number of complications is limited and is strongly associated with the presence of diabetes mellitus. PATIENT SUMMARY: We found a high couple satisfaction score that was higher when reported by males compared to females. Patient satisfaction increased with time, and it was independent of age.

Targeted Next Generation Sequencing molecular profiling and its clinical application in adrenocortical cancer.

OBJECTIVE: Adrenal cortical carcinoma (ACC) is a rare malignancy with a generally poor but heterogeneous prognosis, especially depending on the tumour stage at diagnosis. Identification of somatic gene alterations combined with clinical/histopathological evaluation of the tumour can help improve prognostication. We applied a simplified targeted-Next-Generation Sequencing (NGS) panel to characterise the mutational profiles of ACCs, providing potentially relevant information for better patient management. DESIGN AND METHODS: Thirty frozen tumour specimens from a local ACC series were retrospectively analysed by a custom-NGS panel (CDKN2A, CTNNB1, DAXX, MED12, NF1, PRKAR1A, RB1, TERT, TP53, ZNRF3) to detect somatic prioritised single-nucleotide variants. This cohort was integrated with 86 patients from the ACC-TCGA series bearing point-mutations in the same genes and their combinations identified by our panel. Primary endpoints of the analysis on the total cohort (113 patients) were overall survival (OS) and progression-free survival (PFS), and hazard ratio (HR) for the different alterations grouped by the signalling pathways/combinations affected. RESULTS: Different PFS, OS, and HR were associated to the different pathways/combinations, being NF1 + TP53 and Wnt/ß-catenin + Rb/p53 combined mutations the most deleterious, with a statistical significance for progression HR which is retained only in low-(I/II) stages-NF1 + TP53 combination: HR = 2.96[1.01-8.69] and HR = 13.23[3.15-55.61], all and low stages, respectively; Wnt/ß-catenin + Rb/p53 combined pathways: HR = 6.47[2.54-16.49] and HR = 16.24[3.87-68.00], all and low-stages, respectively. CONCLUSIONS: A simplified targeted-NGS approach seems the best routinely applicable first step towards somatic genetic characterisation of ACC for prognostic assessment. This approach proved to be particularly promising in low-stage cases, suggesting the need for more stringent surveillance and personalised treatment.

Evidence-based definition of hypoprolactinemia in European men aged 40-86 years: the European male ageing study.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.

Pharmacological management of testosterone deficiency in men current advances and future directions.

INTRODUCTION: Testosterone deficiency (TD) is relatively common in aging men, affecting around 2% of the general population. Testosterone replacement therapy (TRT) represents the most common medical approach for subjects who are not interested in fathering. AREAS COVERED: This review summarizes advances in TRT, including approved or non-approved pharmacological options to overcome TD. When possible, a meta-analytic approach was applied to minimize subjective and biased interpretations of the available data. EXPERT OPINION: During the last decade, several new TRT formulations have been introduced on the market, including oral, transdermal, and parenteral formulations. Possible advantages and limitations have been discussed appropriately. Anti-estrogens, including selective estrogen modulators or aromatase inhibitors still represent further possible off-label options. However, long-term side effects on sexual function and bone parameters constitute major limitations. Glucagon-like peptide 1 analogues can be an alternative option in particular for massive obesity-associated TD. Weight loss obtained through lifestyle modifications including diet and physical exercise should be encouraged in all overweight and obese patients. A combination of TRT and lifestyle changes can be considered in those subjects in whom a reversal of the condition cannot be expected in a reasonable time frame.

Early traumatic experiences are linked to hypersexual behavior and erectile dysfunction in men through the mediation of body uneasiness and general psychopathology.

BACKGROUND: Childhood traumatic experiences have been associated with hypersexuality and sexual dysfunctions. However, the mediators of the interactions between these variables should be clarified in men. AIM: This study aimed to investigate the interaction of early traumatic experiences, psychopathology, and sexuality with respect to erectile dysfunction (ED) and hypersexual behavior. The hypothesized model expected that traumatic experiences would be associated with hypersexual behavior and reduced sexual functioning through the mediation of body uneasiness and psychological distress. METHODS: The study was cross-sectional and observational. A total of 317 men were enrolled. Male patients with a primary complaint of ED and an indication for psychiatry referral represented the clinical sample (n = 116; mean ± SD age, 42.82 ± 16.89 years). Clinical classification was assessed with the Structured Interview on Erectile Dysfunction. The second sample (n = 201, 30.82 ± 11.94 years) was recruited from the general population. All participants were administered the following questionnaires: Brief Symptom Inventory, Childhood Trauma Questionnaire-Short Form, Hypersexual Behavior Inventory, Body Uneasiness Test-A, and 5-item International Index of Erectile Function. OUTCOMES: Psychopathology and sexual functioning were assessed by a dimensional approach, and a multivariate model was computed by structural equation model analysis. RESULTS: When compared with the sample from the general population, the clinical sample exhibited a higher prevalence of early traumatic experiences, as measured by scores on the Childhood Trauma Questionnaire-Short Form (45.08 ± 14.25 vs 39.03 ± 10.22, F = 17.63, P < .001), and a higher tendency to engage in hypersexual behaviors (34.63 ± 13.55 vs 30.79 ± 12.44, F = 6.97, P < .01). Structural equation model analysis showed excellent fit indices indicating that early traumatic experiences predicted hypersexual behaviors and ED through the exacerbating mediating effect of body uneasiness and psychopathology. CLINICAL IMPLICATIONS: Clinicians should not limit their attention to the behavioral level when assessing sexual dysfunction in men; rather, they should also consider the complex psychopathologic consequences of childhood trauma. Integrated treatments that address the potential presence of childhood trauma with its wider psychological correlates (eg, emotion dysregulation, body uneasiness) might improve treatment response. STRENGTHS AND LIMITATIONS: The study reports novel data on the relationship among childhood maltreatment, male sexuality, and psychopathologic mediators with a dimensional assessment. However, the assessment was cross-sectional, and causality was mainly derived from previous studies. CONCLUSION: The present study enriches the current literature, strengthening the hypothesis that childhood traumatic experiences significantly shape development and sexuality. Body uneasiness and psychopathology can both tax sexual functioning, as assessed by erectile functioning or hypersexuality.

Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold.

Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. <2 SD from the population mean) might serve as an additional biochemical marker in the assessment of functional hypogonadism (late-onset hypogonadism, LOH) where testosterone is in the borderline low range. Excluding individuals with low LCI (INSL3 ≤ 0.4 ng/ml) leads to an age-independent (> 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 - 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.

The 3D in vitro Adrenoid cell model recapitulates the complexity of the adrenal gland.

The crosstalk between the chromaffin and adrenocortical cells is essential for the endocrine activity of the adrenal glands. This interaction is also likely important for tumorigenesis and progression of adrenocortical cancer and pheochromocytoma. We developed a unique in vitro 3D model of the whole adrenal gland called Adrenoid consisting in adrenocortical carcinoma H295R and pheochromocytoma MTT cell lines. Adrenoids showed a round compact morphology with a growth rate significantly higher compared to MTT-spheroids. Confocal analysis of differential fluorescence staining of H295R and MTT cells demonstrated that H295R organized into small clusters inside Adrenoids dispersed in a core of MTT cells. Transmission electron microscopy confirmed the strict cell-cell interaction occurring between H295R and MTT cells in Adrenoids, which displayed ultrastructural features of more functional cells compared to the single cell type monolayer cultures. Adrenoid maintenance of the dual endocrine activity was demonstrated by the expression not only of cortical and chromaffin markers (steroidogenic factor 1, and chromogranin) but also by protein detection of the main enzymes involved in steroidogenesis (steroidogenic acute regulatory protein, and CYP11B1) and in catecholamine production (tyrosine hydroxylase and phenylethanolamine N-methyltransferase). Mass spectrometry detection of steroid hormones and liquid chromatography measurement of catecholamines confirmed Adrenoid functional activity. In conclusion, Adrenoids represent an innovative in vitro 3D-model that mimics the spatial and functional complexity of the adrenal gland, thus being a useful tool to investigate the crosstalk between the two endocrine components in the pathophysiology of this endocrine organ.

Cardiovascular safety of testosterone replacement therapy in men: an updated systematic review and meta-analysis.

INTRODUCTION: The cardiovascular (CV) safety of testosterone (T) replacement therapy (TRT) is still conflicting. Recent data suggested a TRT-related increased risk of atrial fibrillation (AF). The aim of this study was to systematic review and meta-analyze CV risk related to TRT as derived from placebo controlled randomized trials (RCTs). AREAS COVERED: An extensive Medline, Embase, and Cochrane search was performed. All placebo-controlled RCTs reporting data on TRT-related CV safety were considered. To better analyze the role of T on AF, population-based studies investigating the relationship between endogenous circulating T levels and AF incidence were also included and analyzed. EXPERT OPINION: Out of 3.615, 106 studies were considered, including 8.126 subjects treated with TRT and 7.310 patients allocated to placebo. No difference between TRT and placebo was observed when major adverse CV events were considered. Whereas the incidence of non-fatal arrhythmias and AF was increased in the only trial considering CV safety as the primary endpoint, this was not confirmed when all other studies were considered (MH-OR 1.61[0.84;3.08] and 1.44[0.46;4.46]). Similarly, no relationship between endogenous T levels and AF incidence was observed after the adjustment for confounders Available data confirm that TRT is safe and it is not related to an increased CV risk.

Update on known and emergent viruses affecting human male genital tract and fertility.

Many viruses infect the male genital tract with harmful consequences at individual and population levels. In fact, viral infections may induce damage to different organs of the male genital tract (MGT), therefore compromising male fertility. The oxidative stress, induced during viral-mediated local and systemic inflammation, is responsible for testicular damage, compromising germinal and endocrine cell functions. A reduction in sperm count, motility, number of normal sperm and an increase in DNA fragmentation are all common findings in the course of viral infections that, however, generally regress after infection clearance. In some cases, however, viral shedding persists for a long time leading to unexpected sexual transmission, even after the disappearance of the viral load from the blood.The recent outbreak of Zika and Ebola Virus evidenced how the MGT could represent a reservoir of dangerous emergent viruses and how new modalities of surveillance of survivors are strongly needed to limit viral transmission among the general population.Here we reviewed the evidence concerning the presence of relevant viruses, including emergent and re-emergent, on the male genital tract, their route of entry, their adverse effects on male fertility and the pattern of viral shedding in the semen.We also described laboratory strategies to reduce the risk of horizontal or vertical cross-infection in serodiscordant couples undergoing assisted reproductive technologies.

RéSUMé: De nombreux virus infectent l'appareil génital masculin avec des conséquences néfastes au niveau individuel et de la population. En fait, les infections virales peuvent induire des dommages à différents organes de l'appareil génital masculin (AGM), compromettant ainsi la fertilité masculine. Le stress oxydatif, induit lors de l'inflammation locale et systémique à médiation virale, est responsable de lésions testiculaires, compromettant les fonctions des cellules germinales et endocrines. Une réduction de la concentration et de la motilité des spermatozoïdes, du nombre de spermatozoïdes normaux ainsi qu'une augmentation de la fragmentation de l'ADN, sont les résultats habituels retrouvés au cours des infections virales qui, cependant, régressent généralement après la clairance de l'infection. Dans certains cas, cependant, l'excrétion virale persiste pendant une longue période, ce qui entraîne une transmission sexuelle inattendue, même après la disparition de la charge virale sanguine.La récente épidémie de Zika et d'Ebola a montré à quel point l'AGM pouvait représenter un réservoir de virus émergents dangereux, et à quel point de nouvelles modalités de surveillance des survivants sont fortement nécessaires pour limiter la transmission virale au sein de la population générale. Dans la présente revue, nous avons examiné les preuves concernant la présence de virus pertinents, y compris émergents et réémergents, dans l'appareil génital masculin, leur voie d'entrée, leurs effets néfastes sur la fertilité masculine et le modèle d'excrétion virale dans le sperme.Nous avons également décrit des stratégies de laboratoire pour réduire le risque d'infection croisée horizontale ou verticale chez les couples sérodifférents qui ont recours à des techniques de procréation assistée.Mots-clés Voies génitales masculines, Virus, Fertilité masculine, Transmission sexuelle, Paramètres du Sperme.

Is marijuana a foe of male sexuality? Data from a large cohort of men with sexual dysfunction.

BACKGROUND: Although it has been assumed that chronic cannabis use may have an unfavorable impact on male sexual function and its metabolic correlates, evidence from clinical studies remains inconclusive. OBJECTIVE: To investigate the relationship between cannabis use and sexual behavior, anthropometrics and metabolic/vascular profiles in a large series of men evaluated for sexual dysfunction. METHODS: A total of 4800 men (mean age 50.8 years) attending an andrology outpatient clinic for sexual dysfunction were studied. Sexual symptoms, hormonal, metabolic, and instrumental (penile color Doppler ultrasound, PCDU) parameters were evaluated according to the reported habitual use of recreational substances (no use, 1-2 joints/week, >2 joints/week, and use of illicit drugs other than cannabis). RESULTS: When compared with non-users, cannabis users were younger and exhibited a lower prevalence of comorbidities as well as better PCDU parameters, despite reporting higher alcohol and tobacco consumption. After adjustment for confounders, cannabis use was associated with a greater instability in the couple's relationship and a higher frequency of masturbation. In addition, the group smoking >2 joints/week showed a significantly lower body mass index than both controls and users of substances other than cannabis. Men who reported using recreational drugs (either cannabis or other) exhibited significantly lower levels of both total and low-density lipoprotein cholesterol than non-users. At the PCDU, smoking 1-2 joints/week was associated with significantly higher dynamic peak systolic velocity than both non-drug use and use of >2 joints/week. Prolactin levels were significantly higher in individuals smoking 1-2 joints/week and in those who used substances other than cannabis when compared with controls, whereas no difference in total testosterone levels was observed. DISCUSSION: In men with sexual dysfunction, mild cannabis consumption may be associated with a more favorable anthropometric and lipid profile and with a better penile arterial vascular response to intracavernous prostaglandin injection.

Tip-microVapour Fast Freezing: A novel easy method for cryopreserving severe oligozoospermic samples.

BACKGROUND: Sperm cryopreservation is an important procedure for oligozoospermic subjects at risk of azoospermia and after surgical recovery of spermatozoa in non-obstructive azoospermic men. Conventional procedures for sperm cryopreservation might be, however, not suitable for samples with a very low sperm number. OBJECTIVES: In this pilot study, we investigated the recoveries of sperm motility and viability in severe oligozoospermic subjects (n = 39) after cryopreservation with a tip-microVapour Fast Freezing, a procedure previously developed by our group for men with good semen quality. Sperm DNA fragmentation was also evaluated in a second group of oligozoospermic samples (n = 16). MATERIALS AND METHODS: We used a Vapour Fast Freezing procedure using 10 µL tips as carrier, and Test Yolk Buffer as freezing medium (tip-microVapour Fast Freezing). In a subset of samples (n = 22), we compared recovery of motility and viability as obtained with tip-microVapour Fast Freezing and with a Vapour Fast Freezing procedure using 500 µL straws. Sperm DNA fragmentation was evaluated by the sperm chromatin dispersion test. RESULTS: We found a recovery rate (median [interquartile range]) of 0.29 (0.13-0.41) for progressive motility, 0.30 (0.21-0.52) for total motility and 0.48 (0.29-0.60) for viability. Interestingly, we observed that samples with the poorest motility were apparently less damaged by freezing/thawing. In a subset of samples (n = 22), we directly compared values of viability, progressive motility and total motility by freezing/thawing with tip-microVapour Fast Freezing and Vapour Fast Freezing conducted with 500 µL straws. We found much better values of all sperm parameters in samples after freezing/thawing with tip-microVapour Fast Freezing than with Vapour Fast Freezing in 500 µL straws: that is, progressive motility: 7.00 (3.00-8.50)% versus 2.00 (0.00-4.25)%, p < 0.001; total motility: 12.00 (8.00-16.25)% versus 6.50 (1.00-9.25)%, p < 0.001; viability: 29.75 (23.75-45.25) versus 22.50 (13.75-28.13), p < 0.001, respectively. In the second group of oligozoospermic samples, we found that tip-microVapour Fast Freezing produced lower levels of sperm DNA fragmentation than straws (33.00 [19.75-36.00]% vs. 36.00 [22.75-41.87]%, p < 0.001). DISCUSSION AND CONCLUSION: Tip-microVapour Fast Freezing appears to be a very promising method to cryopreserve semen samples from severe oligozoospermic patients.

Does an increase in adipose tissue 'weight' affect male fertility? A systematic review and meta-analysis based on semen analysis performed using the WHO 2010 criteria.

INTRODUCTION: Obesity negatively impact on the metabolism of sex hormones, leading to reduced testosterone serum levels. However, how the obesity could negatively impact on the overall gonadal function, particularly on male fertility, remained unclear so far. OBJECTIVE: To systematically review evidences regarding the influence of body weight excess on the sperm production. METHODS: A meta-analysis was conducted, searching all prospective and retrospective observational studies reporting male subjects older than 18 years old, with body weight excess from overweight to severe obesity were considered. Only studies using the V edition of the World Health Organization (WHO) manual for semen analysis interpretation were considered. No specific interventions were considered. Search was focused on studies comparing overweight/obese to normal weight subjects. RESULTS: Twenty-eight studies were considered. Total sperm count and sperm progressive motility were significantly lower in overweight compared to normal weight subjects. Meta-regression analyses demonstrated that patients' age impacted on sperm parameters. Similarly, obese men showed lower sperm concentration, total sperm number, progressive and total motilities, and normal morphology lower than normal weight subjects. Reduced sperm concentration in obese men was influenced by age, smoking habit, varicocele, and total testosterone serum levels at meta-regression analyses. CONCLUSIONS: The male potential fertility is reduced in subjects with increased body weight, compared to normal weight men. The higher was the increased body weight, the worst was the sperm quantity/quality. This result comprehensively included obesity among non-communicable risk factor for male infertility, shedding new lights on the negative impact of increased body weight on overall gonadal function.

Visceral adipose tissue adiponectin predicts excess weight loss after bariatric surgery in females with severe obesity.

OBJECTIVE: Bariatric surgery not always results in satisfactory excess weight loss (EWL) in severe obesity. Given the economic and clinical costs of bariatric surgery failure, defining predictors of successful EWL represents a relevant clinical issue for the health system to select patients benefiting from operation. METHODS: By ELISA and Western blot analyses, we assessed the predicting value of pre-operative adiponectin (APN) locally produced in abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue versus plasma levels as a novel sex-linked biomarker of EWL at different time points of follow up (6-24 months) after bariatric surgery in 43 patients (56% females) affected by severe obesity undergoing a small pilot observational study. RESULTS: VAT-APN was lower in females and represented the only marker significantly correlated with EWL. In females, VAT-APN in the distribution upper quartile but not baseline BMI retained a statistically significant correlation with EWL at any time points (6-24 months) at multivariate analysis. The best VAT-APN cut-off value to predict 95% EWL at 12 months from surgery (98% accuracy, 100% sensitivity, 94% specificity, p = 0.010) was 5.1 µg/mg. CONCLUSIONS: In this very preliminary study, APN in VAT rather than its circulating or subcutaneous levels predicts EWL after bariatric surgery as an independent factor in the female sex only, thus contributing to identify those patients who could much benefit from surgery.

Cabozantinib for different endocrine tumours: killing two birds with one stone. A systematic review of the literature.

PURPOSE: Cabozantinib is an oral multi-tyrosine kinase inhibitor (TKI) that has been approved in Europe for advanced renal cell carcinoma, hepatocellular carcinoma, locally advanced and metastatic medullary thyroid carcinoma (MTC) and radioiodine-refractory differentiated thyroid cancer. Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous malignant neuroendocrine tumour that usually presents in sun-exposed skin areas of immunosuppressed patients. Conflicting data exist about cabozantinib for MCC and this TKI is currently under investigation in several onco-endocrine frameworks. METHODS: We herein report a case of an 83-year-old man who was diagnosed with MCC during the treatment of an advanced metastatic MTC. The diagnosis of MCC was established based on clinical, histopathologic evaluation and immunohistochemistry. A systematic review of the literature on cabozantinib use for advanced endocrine and neuroendocrine tumours has been performed. RESULTS: The patient was initially treated with surgery and adjuvant radiotherapy. Cabozantinib was therefore started to control both MTC and MCC. After 24 months, no sign of local or metastatic MCC relapse was evidenced. CONCLUSION: Promising data on cabozantinib treatment for endocrine and neuroendocrine neoplasms is recently emerging in the literature. In our clinical case, we reported that, besides the good response for the MTC, cabozantinib also seems to effectively control metastatic MCC, along with efficient surgery and adjuvant radiotherapy. Further investigations are needed to determine the efficacy and safety of cabozantinib in MCC patients and in off-label endocrine tumours.

Effect of antioxidants on semen parameters in men with oligo-astheno-teratozoospermia: a network meta-analysis.

BACKGROUND: Although antioxidants are largely used in subfertile men with oligo-astheno-teratozoospermia (OAT), the choice among different molecules is challenged by the lack of comparative head-to-head studies. The network meta-analysis (NMA) can overcome limitations of pairwise meta-analyses, since it incorporates direct and indirect evidence into a single model generating an effectiveness hierarchy. OBJECTIVE: To assess with a NMA the effects of antioxidants in improving seminal parameters in idiopathic OAT. MATERIALS AND METHODS: PubMed, Scopus, Cinahl, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing any antioxidant treatment to each other or placebo in men with at least one idiopathic seminal abnormality. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). RESULTS: 29 RCTs provided information on 2045 men (mean age: 33.5 years) with idiopathic OAT and 19 antioxidant preparations. Compared to placebo, l-carnitine, especially in combination with l-acetyl-carnitine (LAC), had the highest SUCRA for sperm concentration, progressive motility, and morphology. Folate was the only other compound effective on sperm concentration. Vitamin E+selenium or zinc had the highest SUCRA for total motility. A contribution on progressive motility was revealed for pentoxifylline and vitamin E+CoQ10.

Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?

CONTEXT: The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated. OBJECTIVE: The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time. METHODS: This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by triptorelin prescription after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2. RESULTS: The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid levels, height and body mass index percentiles, waist-hip ratio, and acne severity) observed during triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety, and body image concerns. CONCLUSION: Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDAs whose puberty has already progressed.

Advances in the treatment of functional male hypogonadism.

INTRODUCTION: Functional hypogonadism is frequently found in obese men, particularly those with metabolic complications. Several possible therapeutic approaches could be considered. AREAS COVERED: An extensive search on Medline, Embase, and Cochrane databases was performed to retrieve the available studies assessing the change of testosterone (T) and sexual function upon dieting or physical activity programs, as well as glucagon-like peptide 1 analogues. The role of lifestyle interventions associated with T replacement therapy (TRT) was also evaluated. The expert opinion provided here has been corroborated by meta-analyzing the results of the retrieved studies. EXPERT OPINION: Current evidence supports the beneficial role of lifestyle modifications in increasing T and improving sexual function as a function of weight loss. While dieting programs are associated with greater effects in younger populations, physical exercise has major effects in older ones. Among the dieting programs, a very low-calorie ketogenic diet shows the best results; aerobic or endurance physical exercise perform similarly. The advantages of functional hypogonadism in lifestyle modifications are empowered by the association with TRT. Therefore, TRT may be a valuable complementary strategy to increase muscle mass and facilitate physical exercise while improving sexual symptoms, thus favoring the motivation and compliance for lifestyle interventions.

Hyponatremia Promotes Cancer Growth in a Murine Xenograft Model of Neuroblastoma.

In cancer patients, hyponatremia is detected in about 40% of cases at hospital admission and has been associated to a worse outcome. We have previously observed that cancer cells from different tissues show a significantly increased proliferation rate and invasion potential, when cultured in low extracellular [Na+]. We have recently developed an animal model of hyponatremia using Foxn1nu/nu mice. The aim of the present study was to compare tumor growth and invasivity of the neuroblastoma cell line SK-N-AS in hyponatremic vs. normonatremic mice. Animals were subcutaneously implanted with luciferase-expressing SK-N-AS cells. When masses reached about 100 mm3, hyponatremia was induced in a subgroup of animals via desmopressin infusion. Tumor masses were significantly greater in hyponatremic mice, starting from day 14 and until the day of sacrifice (day 28). Immunohistochemical analysis showed a more intense vascularization and higher levels of expression of the proliferating cell nuclear antigen, chromogranin A and heme oxigenase-1 gene in hyponatremic mice. Finally, metalloproteases were also more abundantly expressed in hyponatremic animals compared to control ones. To our knowledge, this is the first demonstration in an experimental animal model that hyponatremia is associated to increased cancer growth by activating molecular mechanisms that promote proliferation, angiogenesis and invasivity.

Does testosterone influence the association between sleep and frailty in men: results from the European Male Aging Study.

BACKGROUND: Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, although it has been suggested that hormonal factors may play a role. METHODS: The aim was to determine the association between sleep duration, sleep quality and frailty, and to determine whether testosterone influenced this association. Males aged 40-79 years were recruited from eight European centres to the European Male Aging Study (EMAS). Subjects completed an interviewer-assisted questionnaire including questions regarding sleep quality and duration. Sleep quality was scored 0-20 and categorised as 0-4, 5-9, 10-14, and 15-20, with higher scores indicating poorer quality. A 39-component frailty index (FI) was constructed. Total testosterone levels were measured. The association between sleep duration, sleep quality and the FI was assessed using negative binomial regression, with adjustment for putative confounders including testosterone level. RESULTS: Two thousand three hundred ninety-three participants contributed data to the analysis. The mean age was 63.3 years and mean sleep duration was 7.01 h. The mean frailty index was 0.15. Mean testosterone levels declined with decreasing sleep quality. After adjustment, compared to those with a sleep score of 0-4, the FI was 57% (95% CI 38%, 78%) higher among those with a sleep score of 15-20. After adjustment compared to those with normal sleep duration (6-9 h), those with a short (< 6 h) and long (≥ 9 h) sleep duration had a 16% (95% CI 6%, 28%) and 11% (95% CI 0%, 23%) higher FI, respectively. Adjustment for testosterone did not influence the strength of either association. CONCLUSION: Frailty is associated with impaired sleep quality and sleep duration. The association cannot, however, be explained by variation in testosterone levels.

Multiparametric Ultrasound for Diagnosing Testicular Lesions: Everything You Need to Know in Daily Clinical Practice.

BACKGROUND: Ultrasonography (US) represents the gold standard imaging method for the assessment of testicular lesions (TL). The gray-scale (GSUS) and color-Doppler (CDUS) ultrasound examination allow sonographers to investigate the size, margins, echotexture, and vascular features of TLs with the aim to differentiate benign from malignant lesions. Recently, the use of contrast-enhanced US (CEUS) and sonoelastography (SE) has led to further improvements in the differential diagnosis of TL. Although GSUS and CDUS are often sufficient to suggest the benign or malignant nature of the TL, CEUS can be decisive in the differential diagnosis of unclear findings, while SE can help to strengthen the diagnosis. The contemporary combination of GSUS, CDUS, CEUS, and SE has led to a new diagnostic paradigm named multiparametric US (mp-US), which is able to provide a more detailed characterization of TLs than single techniques alone. This narrative and pictorial review aimed to describe the mp-US appearance of several TLs. METHODS: An extensive Medline search was performed to identify studies in the English language focusing on the mp-US evaluation of TLs. RESULTS: A practical mp-US "identity card" and iconographic characterization of several benign and malignant TLs is provided herein. CONCLUSIONS: The mp-US characterization of TL reported herein can be useful in daily clinical practice.