Estimate and needs of the transgender adult population: the SPoT study.

BACKGROUND: Despite the increasing interest in transgender health research, to date little is known about the size of the transgender and gender diverse (TGD) population. METHODS: A web-based questionnaire survey was developed, including a collection of socio-demographic characteristics and disseminated online through social media. Gender incongruence was evaluated by using a 2-item approach assessing gender recorded at birth and gender identity. The primary objective of the present population-based study was to estimate the proportion of TGD people across ages among a large sample of people who answered a web-based survey. The secondary endpoints were to identify gender-affirming needs and possible barriers to healthcare access. RESULTS: A total of 19,572 individuals participated in the survey, of whom 7.7% reported a gender identity different from the sex recorded at birth. A significantly higher proportion of TGD people was observed in the youngest group of participants compared with older ones. Among TGD people who participated in the study, 58.4% were nonbinary, and 49.1% experienced discrimination in accessing health care services. Nonbinary TGD participants reported both the need for legal name and gender change, along with hormonal and surgical interventions less frequently compared to binary persons. CONCLUSIONS: Being TGD is not a marginal condition In Italy. A large proportion of TGD persons may not need medical and surgical treatments. TGD people often experience barriers to healthcare access relating to gender identity.

Improving the TIR3B oncological stratification: try to bridge the gap through a comprehensive presurgical algorithm.

PURPOSE: Indeterminate cytology still puzzles clinicians, due to its wide range of oncological risks. According to the Italian SIAPEC-IAP classification, TIR3B cytology holds up to 30% of thyroid cancer, which justifies the surgical indication, even if more than half of cases do not result in a positive histology. The study aim is to identify potential clinical, ultrasound or cytological features able to improve the surgical indication. METHODS: Retrospective analysis. A consecutive series of TIR3B nodules referred to the Endocrine Unit of Careggi Hospital from 1st May 2014 to 31st December 2021 was considered for the exploratory analysis (Phase 1). Thereafter, a smaller confirmatory sample of consecutive TIR3B diagnosed and referred to surgery from 1st January 2022 to 31st June 2022 was considered to verify the algorithm (Phase 2). The main clinical, ultrasound and cytological features have been collected. A comprehensive stepwise logistic regression was applied to build a prediction algorithm. The histological results represented the final outcome. RESULTS: Of 599 TIR3B nodules referred to surgery, 451 cases were included in the exploratory analysis. A final score > 14.5 corresponded to an OR = 4.98 (95% CI 3.24-7.65, p < 0.0001) and showed a PPV and NPV of 57% and 79%, respectively. The Phase 2 analysis on a confirmatory sample of 58 TIR3B cytology confirmed that a threshold of 14.5 points has a comparable PPV and NPV of 53% and 80%, respectively. CONCLUSIONS: A predictive algorithm which considers the main clinical, US and cytological features can significantly improve the oncological stratification of TIR3B cytology.

Hyponatremia, hypernatremia and impairment of functional, psychological and sexual domains.

OBJECTIVE: To determine the influence of serum sodium on physical, psychologic and sexual function. METHODS: This is a cross-sectional survey on 3340 community-dwelling men aged 40-79 years from a prospective cohort study in eight European countries, the European Male Ageing Study (EMAS). Participants filled-out the Short Form-36 (SF-36), the Physical Activity Scale for the Elderly (PASE), and the EMAS sexual function questionnaire. For all the analyses, serum sodium corrected for glycaemia ([Na+]G) was used. RESULTS: The relationship between [Na+]G and SF-36 physical function score (F = 3.99; p = 0.01), SF-36 mental health score (F = 7.69; p < 0.001), and PASE score (F = 14.95; p < 0.001) were best described by a quadratic equation, with worse scores for [Na+]G in either the lowest or the highest ends of the range. After dividing the sample into [Na+]G < 136 mmol/L (n = 81), 136-147 mmol/L (n = 3223) and > 147 mmol/L (n = 36), linear regression analyses with linear spline functions adjusted for confounders did not confirm these relationships. Similarly, erectile dysfunction and [Na+]G, were in a quadratic relationship (F = 9.00; p < 0.001). After adjusting for confounders, the linear regression with spline functions denoted a significantly worsened erectile function for increases in serum [Na+]G > 147 mmol/L (B = 0.15 [0.04;0.26], p < 0.01) but no relationship with [Na+]G < 136 mmol/L. Likewise, the relationship of [Na+]G with concerns about sexual dysfunction was confirmed only for men with serum [Na+]G > 147 mmol/L. CONCLUSIONS: This is the first study supporting an association between [Na+]G and sexual function. A worsening of erection and concerns about sexual function were observed for the highest values of [Na+]G, independently of other relevant factors.

Metabolic syndrome and erectile dysfunction: a systematic review and meta-analysis study.

PURPOSE: The clinical significance of metabolic syndrome (MetS) versus its single components in erectile dysfunction (ED) is conflicting. Thus, the purpose is to analyze the available evidence on the relationship between MetS-along with its components-and ED. METHODS: All prospective and retrospective observational studies reporting information on ED and MetS were included. In addition, we here reanalyzed preclinical and clinical data obtained from a previously published animal model of MetS and from a consecutive series of more than 2697 men (mean age: 52.7 ± 12), respectively. RESULTS: Data derived from this meta-analysis showed that MetS was associated with an up to fourfold increased risk of ED when either unadjusted or adjusted data were considered. Meta-regression analysis, performed using unadjusted statistics, showed that the MetS-related risk of ED was closely associated with all the MetS components. These associations were confirmed when unadjusted analyses from clinical models were considered. However, fully adjusted data showed that MetS-associated ED was more often due to morbidities included (or not) in the algorithm than to the MetS diagnostic category itself. MetS is also associated with low testosterone, but its contribution to MetS-associated ED-as derived from preclinical and clinical models-although independent, is marginal. CONCLUSIONS: The results of our analysis suggest that MetS is a useless diagnostic category for studying ED. However, treating the individual MetS components is important, because they play a pivotal role in determining ED.

Hyperprolactinemia and male sexual function: focus on erectile dysfunction and sexual desire.

The present paper aims to analyze and discuss the available evidence supporting the relationship between male sexual function and elevated prolactin (PRL) levels (HPRL). Two different sources of data were analyzed. Clinical data were derived from a series of patients seeking medical care for sexual dysfunction at our Unit. Out of 418 studies, 25 papers were used with a meta-analytic approach to evaluate the overall prevalence of HPRL in patients with erectile dysfunction (ED) and to study the influence of HPRL and its treatment on male sexual function. Among 4215 patients (mean age 51.6 ± 13.1 years) consulting for sexual dysfunction at our Unit, 176 (4.2%) showed PRL levels above the normal range. Meta-analytic data showed that HPRL is a rare condition among patients with ED (2 [1;3]%). Either clinical and meta-analytic data confirm a stepwise negative influence of PRL on male sexual desire (S = 0.00004 [0.00003; 0.00006]; I = -0.58915 [-0.78438; -0.39392]; both p < 0.0001 from meta-regression analysis). Normalization of PRL levels is able to improve libido. The role of HPRL in ED remains inconclusive. Data from a meta-analytic approach showed that either HPRL or reduced T levels were independently associated with ED rates. The normalization of PRL levels only partially restored ED. HPRL did not significantly contribute to ED severity, in our clinical setting. In conclusion, treating HPRL can restore normal sexual desire, whereas its effect on erection is limited.

Low prolactin level identifies hypoactive sexual desire disorder women with a reduced inhibition profile.

PURPOSE: Data on the role of prolactin (PRL) in the physiologic range in the female sexual response are scanty. We aimed at investigating the association between PRL and sexual function as assessed by the Female Sexual Function Index (FSFI). We explored the presence of a cut-off level of PRL able to identify Hypoactive Sexual Desire Disorder (HSDD). METHODS: 277 pre- and post-menopausal women consulting for Female Sexual Dysfunction (FSD) and sexually active were enrolled in an observational, retrospective study. 42 women were used as no-FSD controls. A clinical, biochemical and psychosexual evaluation was performed. The main outcome measures were: FSFI, Female Sexual Distress Scale-Revised, Middlesex Hospital Questionnaire and Sexual excitation/sexual inhibition scale (SIS/SES). RESULTS: Normo-PRL FSD women (n = 264) showed lower FSFI Desire score than controls (n = 42), and higher than hyper-PRL FSD women (n = 13). These differences emerged both in pre-menopausal and post-menopausal subjects. In the normo-PRL FSD group, those with PRL in the higher quintile reported higher FSFI Desire scores than those with PRL in the lowest quintile. Women with HSDD presented a lower PRL level than those without (p = 0.032). A ROC curve analysis for PRL showed an accuracy of 0.610 ± 0.044 (p = 0.014) in predicting HSDD. With a threshold of < 9.83 µg/L, sensitivity and specificity for HSDD were 63% and 56%, respectively. Subjects with PRL < 9.83 µg/L also reported lower sexual inhibition (p = 0.006) and lower cortisol levels (p = 0.003) than those with PRL > = 9.83 µg/L. CONCLUSIONS: Hyper-PRL is associated with low desire; however, among normo-PRL FSD women, those with the lowest levels demonstrated a poorer desire than those with the highest levels. PRL < 9.83 µg/L predicted HSDD and a lower sexual inhibitory trait.

Carbonic anhydrases III and IX are new players in the crosstalk between adrenocortical carcinoma and its altered adipose microenvironment.

PURPOSE: Adrenocortical carcinoma (ACC), a rare malignancy of the adrenocortex, is characterized by a crosstalk between the adipose microenvironment and tumor. Here, we assessed the involvement of carbonic anhydrase (CA) enzymes III and IX (CAIII and CAIX), in the metabolic alterations of the adipose tissue characterizing obesity and in the local crosstalk between the tumor adipose microenvironment and ACC. RESULTS/METHODS: CAIII and CAIX expression is altered in visceral adipose tissue (VAT) in obesity and in ACC. A significant CAIX upregulation was present in ACC at advanced stages (n = 14) (fold increase FI = 7.4 ± 0.1, P < 0.05) associated with lower CAIII levels (FI = 0.25 ± 0.06, P < 0.001), compared with lower stages (n = 9). In vitro coculture between visceral adipose stem cells (ASCs) and ACC cell lines, H295R and MUC-1, mimicking the interaction occurring between VAT and advanced ACC, showed a significant CAIX upregulation in H295R but not in MUC-1 cells, and a decreased expression of CAIII. The effect on adipose cells was different when cocultured with H295R or MUC-1 cells. Coculture did not modulate CAIII expression in ASCs, which, however, was significantly downregulated with H295R (FI = 0.34 ± 0.11, P < 0.05) and upregulated by MUC-1 when cocultured ASCs were induced to differentiate toward adipocytes, with an expression profile similar to what found in VAT of obese subjects. CAIX expression was markedly increased in ASCs cocultured with H295R and to a less extent following adipogenesis induction (FI = 150.9 ± 46.5 and FI = 4.6 ± 1.1, P < 0.01, respectively). CONCLUSION: Our findings highlight a modulation of CAIII and CAIX in the metabolic crosstalk between ACC and its local adipose microenvironment, suggesting that CAs might represent a potential target for novel anticancer therapies.

The Italian Society of Andrology and Sexual Medicine (SIAMS), along with ten other Italian Scientific Societies, guidelines on the diagnosis and management of erectile dysfunction.

PURPOSE: Erectile dysfunction (ED) is one of the most prevalent male sexual dysfunctions. ED has been in the past mistakenly considered a purely psycho-sexological symptom by patients and doctors. However, an ever-growing body of evidence supporting the role of several organic factors in the pathophysiological mechanisms underlying ED has been recognized. METHODS: The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving several other National Societies to provide an updated guideline on the diagnosis and management of ED. Derived recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Several evidence-based statements were released providing the necessary up-to-date guidance in the context of ED with organic and psychosexual comorbidities. Many of them were related to incorrect lifestyle habits suggesting how to associate pharmacotherapies and counseling, in a couple-centered approach. Having the oral therapy with phosphodiesterase type 5 inhibitors as the gold standard along with several other medical and surgical therapies, new therapeutic or controversial options were also discussed. CONCLUSIONS: These are the first guidelines based on a multidisciplinary approach that involves the most important Societies related to the field of sexual medicine. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving couple sexual satisfaction and overall general health.

Hyponatremia-related liver steatofibrosis and impaired spermatogenesis: evidence from a mouse model of the syndrome of inappropriate antidiuresis.

PURPOSE: Hyponatremia is the most frequent electrolytic disorder in clinical practice. In addition to neurological symptoms, hyponatremia, even when mild/moderate and chronic, has been related to other manifestations, such as bone demineralization and increased risk of fractures. To better elucidate tissue alterations associated with reduced serum sodium concentration [Na+], we developed an in vivo model of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. METHODS AND RESULTS: Hyponatremia was induced in Foxn1nu/nu mice by subcutaneous infusion of the vasopressin analog 1-deamino [8-D-arginine] vasopressin (dDAVP) for 14 days via osmotic mini-pumps. Mice in the control group were infused with isotonic saline solution. Serum [Na+] progressively decreased, with a nadir of 123.4 ± 2.3 mEq/L (mean ± SD, dDAVP 0.3 ng/h) and 111.6 ± 4.7 mEq/L (mean ± SD, dDAVP 0.5 ng/h). Evident signs of liver steatofibrosis were observed at histology in hyponatremic mice. Accordingly, the expression of proteins involved in lipid metabolism (SREBP-1, PPARα and PPARγ) and in myofibroblast formation (αSMA and CTGF) significantly increased. Furthermore, heme oxygenase 1 expression was up-regulated in Kupffer and hepatic stellate cells in the liver of hyponatremic mice. Testis alterations were also observed. In particular, the thickness of the seminiferous epithelium appeared reduced. The expression levels of PCNA and PTMA, which are involved in DNA replication and germ cells maturation, were markedly reduced in the testis of hyponatremic mice. CONCLUSION: Overall, these findings shed new light on the possible consequences of chronic hyponatremia and prompt a more thorough evaluation of hyponatremic patients.

Aquatic plants entrap different size of plastics in indoor flume experiments.

Plastics accumulate in the environment affecting biota and ecosystems. Although rivers are vectors of land-based plastics to the sea, macroplastics and microplastics in rivers are recently studied. Most studies focused on floating plastic transport to the sea through rivers considering only abiotic hydromorphological factors. In this view, among biotic factors, vegetation has recently been found to entrap plastics. Indeed, the role of vegetation is pivotal in affecting riverine plastic transport. While marine vegetation blocking plastics has been studied, research in freshwater ecosystems is neglected. Since hydrological factors have a pivotal role in riverine plastic transport and few is known on plant entrapment, the interaction between hydrological variables and plastic entrapment by vegetation has not yet been investigated. Given that the composition, transport, and fate of "submerged" plastics in the water column are neglected, we aimed at investigating the behaviour of plants in entrapping plastics within a specific laboratory flume tank. Specifically, we assessed whether (i) aquatic plants block different plastic sizes within the water column and (ii) different factors (e.g. water level, density of plants) affect plastic entrapment. Our results showed that, according to plant density, the higher the plant density the higher the entrapment of plastics by plants - independently of plastic size. Considering the water level, macro-, meso-, and microplastics were trapped similarly. Moreover, Potamogeton crispus blocked fewer microplastics compared with Myriophyllum spicatum. Our results might have impact as plants acted as temporary plastic trappers and can be used as tools for mitigating plastic pollution. Future research might investigate if this laboratory approach can be applied in field for recollecting plastics and consequently mitigating the problem. In conclusion, good management of plants in watercourses, canals, and rivers should be ideal for enhancing river functionality and ecosystem services for human well-being (i.e. the plastic entrapment service by plants).

Relationship between hyponatremia at hospital admission and cardiopulmonary profile at follow-up in patients with SARS-CoV-2 (COVID-19) infection.

PURPOSE: Hyponatremia occurs in about 30% of patients with pneumonia, including those with SARS-CoV-2 (COVID-19) infection. Hyponatremia predicts a worse outcome in several pathologic conditions and in COVID-19 has been associated with a higher risk of non-invasive ventilation, ICU transfer and death. The main objective of this study was to determine whether early hyponatremia is also a predictor of long-term sequelae at follow-up. METHODS: In this observational study, we collected 6-month follow-up data from 189 laboratory-confirmed COVID-19 patients previously admitted to a University Hospital. About 25% of the patients (n = 47) had hyponatremia at the time of hospital admission. RESULTS: Serum [Na+] was significantly increased in the whole group of 189 patients at 6 months, compared to the value at hospital admission (141.4 ± 2.2 vs 137 ± 3.5 mEq/L, p < 0.001). In addition, IL-6 levels decreased and the PaO2/FiO2 increased. Accordingly, pulmonary involvement, evaluated at the chest X-ray by the RALE score, decreased. However, in patients with hyponatremia at hospital admission, higher levels of LDH, fibrinogen, troponin T and NT-ProBNP were detected at follow-up, compared to patients with normonatremia at admission. In addition, hyponatremia at admission was associated with worse echocardiography parameters related to right ventricular function, together with a higher RALE score. CONCLUSION: These results suggest that early hyponatremia in COVID-19 patients is associated with the presence of laboratory and imaging parameters indicating a greater pulmonary and right-sided heart involvement at follow-up.

Effects of hormonal treatment on dermatological outcome in transgender people: a multicentric prospective study (ENIGI).

PURPOSE: The aim of our study was to assess dermatological changes in transgender people after the start of gender-affirming hormonal treatment (GAHT) and to investigate whether various hormonal preparations differently affect dermatological changes in trans AFAB (assigned female at birth) people. METHODS: In a multicenter prospective study, 484 participants (193 assigned male at birth/AMAB and 291 AFAB) were evaluated at baseline (T0), 6 (T1) and 12 months (T2) after the start of GAHT. Hair growth was assessed by the Ferriman-Gallwey (FG) score, acne by the Global Acne Grading Scale (GAGS), and alopecia by the Norwood Hamilton (NH) score. RESULTS: In AFAB people, a significant increase in FG score and NH grade was observed across time, as well as in GAGS score in a subsample of 71 individuals (p < 0.001). Testosterone (T) undecanoate and esters showed a higher increase in hair distribution at T2 vs. T1 as compared to T gel (p < 0.01). T esters showed a significantly higher impact in GAGS score modifications at T1 and at T2 vs. T0 compared to T gel (p = 0.021 and p = 0.003, respectively). In trans AMAB people, a significant decrease of FG score was observed across time (p < 0.001), although 51.3% of individuals still reported an FG score higher than eight after 12 months. CONCLUSION: T treatment increased hair growth, acne and alopecia prevalence in AFAB people, with T undecanoate and esters influencing hair growth more than T gel. Opposite dermatological changes were observed in AMAB people.

Adult- and late-onset male hypogonadism: the clinical practice guidelines of the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE).

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.

Adult- and late-onset male hypogonadism: the clinical practice guidelines of the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE)

To provide the evidence-based recommendations on the role of testosterone (T) on age-related symptoms and signs remains. 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. 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. 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.

Apparent autistic traits in transgender people: a prospective study of the impact of gender-affirming hormonal treatment.

PURPOSE: We evaluated differences in Autism Spectrum Quotient (AQ) scores between a sample of hormone-naïve transgender and cisgender people and the impact of gender-affirming hormonal treatment (GAHT) on AQ scores across time. Furthermore, we assessed alexithymia and social anxiety as possible mediators of changes in AQ scores. METHODS: A cross-sectional comparison between cisgender and transgender people before GAHT and a prospective study on the effects of GAHT over time were performed. Transgender and cisgender people completed several psychometric tests. A total sample of 789 persons (n = 229 cismen; n = 172 ciswomen; n = 206 transmen; n = 182 transwomen) referring to the Florence and Rome Gender Clinics between 2018 and 2020 was enrolled. Of these, 62 participants referring to the Florence Gender Clinic were evaluated in a prospective study at baseline and 12 months after GAHT. RESULTS: Groups showed significant differences in terms of autistic traits: ciswomen showed lower scores of AQ, while cismen reported higher scores of AQ than all other groups. Transgender individuals showed significant higher levels of Gender Dysphoria (GD), body uneasiness, alexithymia and social anxiety, compared to cisgender ones. No significant differences in general psychopathology were found between groups. Across time, transmen and transwomen showed a significant reduction in AQ scores. The decrease in alexithymia and social anxiety after GAHT did not predict the change in AQ scores. CONCLUSIONS: The autistic traits in our sample may represent an epiphenomenon of GD rather than being part of an Autism Spectrum Disorder (ASD) condition, since they significantly decreased after 12 months of GAHT.

First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy.

BACKGROUND: Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify.  OBJECTIVE: We describe KS clinical presentation in a large Italian cohort. DESIGN: This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Primary outcomes were to describe the basic clinical features and the actual phenotype of KS in Italy. Secondary outcomes were to determine age at diagnosis and geographical distribution. METHODS: We performed a basic phenotyping and evaluation of the hormonal values of 609 adult KS patients. RESULTS: Mean age at diagnosis was 37.4 ± 13.4 years. The overall mean testicular size was 3 ml, and 2.5 ml in both testes in untreated KS group. BMI was 26.6 ± 5.8 kg/m2, and 25.5% of KS had metabolic syndrome (MetS). LH and FSH were increased, and mean total testosterone were 350 ± 9.1 ng/dl. A descriptive analysis showed that 329 KS patients were evaluated in Northern Italy, 76 in Central and 204 in Southern Italy. Analysis of variance demonstrated significant statistical differences (p < 0001) between the age at diagnosis of the three geographical groups. Compared with the expected number among male patients matched for age in Italy, only 16% of KS patients received a diagnosis. CONCLUSIONS: These data are the results of the only national database available that collects the clinical and hormonal data of the KS patients, currently referred at the KING centers. In Italy the typical KS patient is overweight, with small testes, and elevated LH and FSH. Only 25.5% of them are diagnosed with MetS. Early detection and timely treatment are mandatory.

Andrological effects of SARS-Cov-2 infection: a systematic review and meta-analysis.

PURPOSE: The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated. METHODS: All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (n = 19), as well as those reporting data on semen analysis (n = 5) and hormonal parameters (n = 11) in infected/recovered patients without any arbitrary restriction were included. RESULTS: Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1 ± 12.6 years, and mean follow-up 24.3 ± 18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological effects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality. CONCLUSIONS: The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specific contribution of reduced T levels during the acute phase of the infection needs to be better clarified.

The V2 receptor antagonist tolvaptan counteracts proliferation and invasivity in human cancer cells.

PURPOSE: Hyponatremia, the most frequent electrolyte alteration in clinical practice, has been associated with a worse prognosis in cancer patients. On the other hand, a better outcome has been related to serum sodium normalization. In vitro studies have shown that low extracellular sodium promotes cancer cells proliferation and invasiveness. Tolvaptan, a selective vasopressin receptor type 2 (V2) antagonist, has been effectively used in the last decade for the treatment of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. A few in vitro data suggested a direct role of tolvaptan in counteracting cancer progression, so far. The aim of this study was to evaluate the effect and the mechanism of action of tolvaptan in cell lines from different tumours [i.e. colon cancer (HCT-8), hepatocarcinoma (HepG2), neuroblastoma (SK-N-AS)]. METHODS AND RESULTS: First, we showed that these cell lines express the V2 receptor. Tolvaptan significantly reduced cell proliferation with an IC50 in the micromolar range. Accordingly, reduced levels of cAMP, of the catalytic α subunit of PKA, and a reduced pAKT/AKT ratio were observed. Tolvaptan effectively inhibited cell cycle progression, whereas it induced apoptotis. Furthermore, it reduced cell invasiveness. In particular, anchorage-independent growth and the activity of collagenases type IV were blunted in the three cell lines. Accordingly, tolvaptan counteracted the RhoA/ROCK1-2 pathway, which has a pivotal role in regulating cell movement. CONCLUSIONS: Overall, these findings indicate that tolvaptan effectively inhibits tumour progression in vitro. Further studies should clarify whether the V2 receptor might be considered a possible target in anti-cancer strategies in the future.