Search

Adult-onset cases of idiopathic hypogonadotropic hypogonadism (IHH) are characterized by partial or normal puberty development until adolescence and by the impairment of the hypothalamic–pituitary–gonadal (HPG) axis in adulthood. WDR11 and DCC genes are known to be involved in axonal development, particularly of hypothalamic GnRH neurons, and ciliogenesis. We report a female case of adult-onset hypogonadism and cerebellar ataxia, in which we identified two gene mutations. A panel of 48 genes was set up to search for variants in the causative genes of CHH. The variants found were analyzed following the American College of Medical Genetics and Genomics (ACMG) criteria to define their pathogenicity. We identified a missense heterozygous variant in the WDR11 gene NM_018117.12:c.2306T>G (p.Met769Arg) and a mutation in a second gene DCC resulting in amino acid substitutions NM_005215.4:c.3533C>T (p.Ser1178Phe). These variants were classified as being of uncertain clinical significance. We assume that there is a link between the variants found and the impairment of the gonadotrophic and neurological phenotype of the patient. Therefore, we propose the genetic test to identify the best therapeutic approach to identify infertility in female patients with IHH; we believe it is necessary to test WDR11 and DCC genes in larger populations with the same condition to introduce it in future protocols of assessment.

Gynecomastia in adolescence is a benign condition that mostly disappears spontaneously within approximately two years from onset. When it is associated with hypogonadism, it may suggest a disorder of sexual differentiation. We report the case of a young man (18 years old) with gynecomastia associated with azoospermia, small testes, hyperestrogenism and hypergonadotropic hypogonadism. A karyotype 46,XX was found, and searching for SRY (sex-determining region Y) by fluorescence in situ hybridization (FISH) highlighted the presence of the gene on the terminal region of the short arm, with breakpoints likely in Xp22.3 and Yp11.3. Implications of testosterone replacement therapy with respect to sex differentiation disorder and to physical performance are discussed.

IntroductionTo analyse the perspectives of healthcare professionals (HCPs) regarding the acceptance of digital health solutions for growth hormone (GH) deficiency care. This study identified factors impacting HCPs’ intent to use and recommend digital solutions supporting recombinant-human growth hormone (r-hGH) therapy in Italy and Korea with a use case of connected drug delivery system (Aluetta® with Smartdot™) integrated in a platform for GH treatment support (the Growzen™ digital health ecosystem).MethodsParticipatory workshops were conducted in Rome, Italy, and Seoul, Korea, to collect the perspectives of 22 HCPs on various predefined topics. HCPs were divided into two teams, each moderated by a facilitator. The workshops progressed in five phases: introduction of the project and experts, capturing views on the current context of digitalisation, perceived usefulness and ease of use of Aluetta® with Smartdot™, exploration of the perception of health technology evolution, and combined team recommendations. Data shared by HCPs on technology acceptance were independently analysed using thematic analysis, and relevant findings were shared and validated with experts.ResultsHCPs from both Italy and Korea perceived Aluetta® with Smartdot™ and the Growzen™ based digital health ecosystem as user-friendly, intuitive, and easy-to-use solutions. These solutions can result in increased adherence, a cost-effective healthcare system, and medication self-management. Although technology adoption and readiness may vary across countries, it was agreed that using digital solutions tailored to the needs of users may help in data-driven clinical decisions and strengthen HCP–patient relationships.ConclusionHCPs’ perspectives on the digitalisation in paediatric GH therapies suggested that digital solutions enable automatic, real-time injection data transmission to support adherence monitoring and evidence-based therapy, strengthen HCP–patient relationships, and empower patients throughout the GH treatment process.

We report a case of a 19-year-old male referred to the Endocrine Unit because of gynecomastia. Initial investigation revealed elevated levels of estradiol (E2) along with secondary hypogonadism (hypotestosteronemia and severe oligoasthenoteratozoospermia (OAT)) despite normal testicular volume (12 mL) and secondary sexual characteristics. Surprisingly, an ultrasound examination revealed a small hypoechoic mass (1.1 cm) with intense intralesional vascularization within the right testicle, even though tumor markers were normal. Surgical removal of testicular mass led to the identification of Leydigioma, and the patient showed regression of gynecomastia during the nine-month follow-up. Unexpectedly, hypergonadotropinemia manifested along with normal testosterone (T) levels and significant improvement in OAT. Magnetic resonance imaging (MRI) showed pituitary hyperplasia (PH). Gynecomastia represents an atypical manifestation of Leydig cell tumors and typically resolves after surgical removal. However, unilateral orchiectomy may determine compensatory PH. Currently, it is uncertain whether the shift from hypogonadotropic to permanent hypergonadotropinemia was the only factor responsible for the high sperm count occurring in our patient. Further research is needed to elucidate the underlying mechanisms.

Prostate cancer (PCa) is the third highest cause of cancer death in men. PCa is a very heterogeneous tumor form in terms of grade, phenotypes, and genetics, often accompanied by complex networks. PCa is characterized by slow growth that does not compromise the patient’s quality of life, unlike more aggressive forms showing rapid growth and progression. Early diagnosis, even for the most aggressive forms, increases the possibilities of cure with less aggressive treatments and fewer side effects. However, it is important to know how to decrease the exposure to modifiable risk factors, including diet, sedentary life, smoking and alcohol, can represent an effective tool to reduce the incidence of PCa. In addition, the chronic exposure to environmental factors, most of which act as endocrine disruptors, is the focus of recent studies for their potential role in promoting the onset and progression of PCa. Although molecular therapies and clinical trials for biomarker identification have been introduced into the management of PCa, these still lag behind research performed in other solid tumors. This review provides an overview of the modifiable factors of PCa, linked to lifestyle and environmental pollutants, which together with the development of new therapeutic targets, can reduce the incidence of PCa and improve the quality of life of patients.

Numerous animal models have demonstrated that caloric restriction (CR) is an excellent tool to delay aging and increase the quality of life, likely because it counteracts age-induced oxidative stress and inflammation. The aging process can affect the prostate in three ways: the onset of benign prostatic hyperplasia, prostatitis, and prostate cancer. In this study, we used 14 aged male Sprague Dawley rats, which were allocated into two groups, at the age of 18 months old. One group was fed ad libitum (a normal diet (ND)), and the other group followed a caloric restriction diet with a 60% decrease in intake. The rats were sacrificed at the age of 24 months. By immunohistochemical (IHC) and Western blot (WB) analyses, we studied the variations between the two groups in immune inflammation and fibrosis-related markers in aged prostate tissues. Morphological examinations showed lower levels of prostatic hyperplasia and fibrosis in the CR rats vs. the ND rats. The IHC results revealed that the prostates of the CR rats exhibited a lower immune proinflammatory infiltrate level and a reduced expression of the NLRP3 inflammasome pathway, together with significantly reduced expressions of mesenchymal markers and the profibrotic factor TGFβ1. Finally, by WB analysis, we observed a reduced expression of ERα, which is notoriously implicated in prostate stromal proliferation, and increased expressions of SOD1 and Hsp70, both exerting protective effects against oxidative stress. Overall, these data suggest that CR brings potential benefits to prostatic tissues as it reduces the physiological immune–inflammatory processes and the tissue remodeling caused by aging.

The coronavirus disease 2019 (COVID-19) is an emerging pandemic caused by a novel coronavirus (SARS-CoV-2). Since December 2019 the new virus has spread all over the world and has become a major health problem also because of the public measures that could affect people’s sexual activity. We report a case of a 35-year-old married male admitted to the andrology outpatient clinic in July 2021 because of sudden onset erectile dysfunction (ED). The diagnostic workup showed no risk factor for ED, normal levels of testosterone, increased levels of endothelial dysfunction markers, such as CRP (C-Reactive Protein) and Endothelin-1, and reduced Vitamin D (VD) levels. Dynamic penile duplex ultrasound (D-PDU) revealed dysfunctional penile arterial flow. The five-item International Index of Erectile Function (IIEF-5) and the Short-Form Health Survey (SF-36) showed a reduction in all domain scores. The patient, initially unresponsive to the high dose oral phosphodiesterase 5 inhibitors (PDE-5is), was treated with vitamin-D and then submitted to LI-SWT (low intensity shockwave treatment), with a progressive clinical benefit at the 12-month follow-up. After 18 months, hormone levels persisted in normal ranges, with a consistent reduction in CRP and Endothelin-1. Additionally, IIEF-5, SF-36 and arterial flow significantly improved over the follow-up period. Thus far, the erectile function was restored and the patient is no more treated with PDE-5i.

Aim: We aimed to evaluate the impact of seminal low-risk human Papillomavirus (LR-HPV) infection on sperm conventional parameters. Material and methods: This was a retrospective case–control study including patients attending to our center for infertility. Patients with evidence for high risk (HR)-HPV infection previously or at the time of enrollment, and/or with severe oligozoospermia (sperm concentration .05). Sperm concentration, total sperm count, sperm progressive motility, morphology, and leukocyte concentration did not differ between patients and controls. However, the prevalence of oligozoospermia was significantly higher in patients than controls (50% vs. 15%). No difference in the prevalence of astenozoospermia (30% vs. 40%) or teratozoospermia (15% vs. 15%) was found. Conclusion: We found no difference in sperm conventional parameters in LR-HPV infected patients than in controls. These data might prompt to research the impact on LR-HPV genotype on male fertility. Particularly, evidence on sperm DNA fragmentation (SDF) and pregnancy outcome is needed.

Metabolic reprogramming is an emerging hallmark of cancer, involving the overexpression of metabolism-related proteins, such as glucose and monocarboxylate transporters and intracellular glycolytic enzymes. The biology of testicular germ cell tumors (TGCTs) is very complex, and although their metabolic profile has been scantily explored, some authors have recently reported that the metabolic rewiring of cancer cells resulted in an association with aggressive clinicopathological characteristics. In this study we have investigated, by immunohistochemical analysis, the expression of key proteins sustaining the hyperglycolytic phenotype in pure seminoma (SE, nr. 35), pure embryonal carcinoma (EC, nr. 17) tissues samples, and normal testes (nr. 5). GLUT1, CD44, PFK-1, MCT1, MCT4, LDH-A, and PDH resulted in more expression in EC cells compared to SE cells. TOM20 was more expressed in SE than in EC. GLUT1, MCT1, and MCT4 expression showed a statistically significant association with SE histology, while for EC, the association resulted in being significant only for GLUT1 and MCT4. Finally, we observed that EC resulted as negative for p53, suggesting that the GLUT1 and MTC overexpression observed in EC could be also attributed to p53 downregulation. In conclusion, our findings evidenced that EC exhibits a higher expression of markers of active aerobic glycolysis compared to SE, suggesting that the aggressive phenotype is associated with a higher glycolytic rate. These data corroborate the emerging evidence on the involvement of metabolic reprogramming in testicular malignancies as well, highlighting that the metabolic players should be explored in the future as promising therapeutic targets.

The therapeutic management of premature lifelong ejaculation (PE) ranges from behavioral therapy to pharmacological and surgical treatments. Hyaluronic Acid (HA) injection into the glans penis is a non-surgical procedure, intended to reduce glans hypersensitivity, improving the intravaginal ejaculation latency time (IELT). HA injection can be performed through different techniques that, although safe and effective, rarely can cause local complications. In this pilot uncontrolled study, we tested the effectiveness of a new technique based on a single HA injection into the frenulum of the glans, to improve IELT in a sample of patients affected by PE. We observed a significant increase of the IELT after one (median 73.3, IQR 66.2–79.9 s) and two months (66.2, 63.1–73.9) that gradually decreased at three months, remaining still significantly higher than at baseline (34.8, 30.9–37.4). PEDT and IIEF questionnaires significantly improved compared to baseline in the first two months of follow-up (p < 0.001). In conclusion, the preliminary results emerging from this pilot uncontrolled study, highlight the effectiveness of this one-shot HA injection approach, although a larger sample and longer follow-up time are needed to standardize the procedure.

Introduction: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto’s thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. Methods: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. Results: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. Conclusions: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.

Alpha-lipoic acid (ALA) is a natural antioxidant dithiol compound, exerting antiproliferative and antimetastatic effects in various cancer cell lines. In our study, we demonstrated that ALA reduces the cell growth of prostate cancer cells LNCaP and DU-145. Western blot results revealed that in both cancer cells, ALA, by upregulating pmTOR expression, reduced the protein content of two autophagy initiation markers, Beclin-1 and MAPLC3. Concomitantly, MTT assays showed that chloroquine (CQ) exposure, a well-known autophagy inhibitor, reduced cells’ viability. This was more evident for treatment using the combination ALA + CQ, suggesting that ALA can reduce cells’ viability by inhibiting autophagy. In addition, in DU-145 cells we observed that ALA affected the oxidative/redox balance system by deregulating the KEAP1/Nrf2/p62 signaling pathway. ALA decreased ROS production, SOD1 and GSTP1 protein expression, and significantly reduced the cytosolic and nuclear content of the transcription factor Nrf2, concomitantly downregulating p62, suggesting that ALA disrupted p62-Nrf2 feedback loop. Conversely, in LNCaP cells, ALA exposure upregulated both SOD1 and p62 protein expression, but did not affect the KEAP1/Nrf2/p62 signaling pathway. In addition, wound-healing, Western blot, and immunofluorescence assays evidenced that ALA significantly reduced the motility of LNCaP and DU-145 cells and downregulated the protein expression of TGFβ1 and vimentin and the deposition of fibronectin. Finally, a soft agar assay revealed that ALA decreased the colony formation of both the prostate cancer cells by affecting the anchorage independent growth. Collectively, our in vitro evidence demonstrated that in prostate cancer cells, ALA reduces cell growth and counteracts both migration and invasion. Further studies are needed in order to achieve a better understanding of the underlined molecular mechanisms.

Background: The American Joint Commission on Cancer on Tumor Node Metastasis (AJCC/TNM) staging system provides adequate information on the risk of differentiated thyroid cancer (DTC)-specific mortality in totally thyroidectomized patients, but its role in predicting persistence and relapse of disease is uncertain. The relatively new 2015 American Thyroid Association (ATA) guidelines recommend stratifying patients at the time of DTC diagnosis with its own risk classification system, in order to identify those at high risk of residual or recurrent morbidity who may benefit from post-operative radioiodine (RAI) administration and/or need additional work-up. Methods: To verify the prevalence proportion of persistence or relapse of disease, a consecutive cohort of 152 patients with a diagnosis of DTC, subjected to total thyroidectomy (+/− post-operative RAI administration as per guidelines indication) and to neck ultrasonography (US), as well as biochemical surveillance for a minimum of 2 years at the Endocrinology Unit of Mater-Domini Hospital (Catanzaro, Italy), was enrolled. The prognostic role of the AJCC/TNM stage and ATA risk classification system was analyzed by logistic regression. Results: At a mean of 9 years after surgical treatment, DTC was found to persist or relapse in 19 (12.5%) participants. The initial risk for these outcomes, based on the ATA classification, was mostly low (53.9%) or intermediate (39.5%). AJCC/TNM stages were predominantly stage I or stage II. Despite a small representation in this cohort, high-risk patients according to the ATA classification had 8-fold higher odds of persistence or relapse of disease than those of low-risk participants, while controlling for potential risk modifiers, including age at DTC diagnosis, male gender, and post-operative RAI administration (p = 0.008). In contrast, the AJCC/TNM stage was not associated with the disease status at the last follow-up visit (p = 0.068 for the 7th Edition; p = 0.165 for the 8th Edition). Furthermore, low-risk participants subjected to post-operative RAI administration had the same probability of persistence or relapse of DTC when compared to those who had undergone total thyroidectomy only. Conclusions: There is a need for the endocrine community to revise the current work-up of DTC. The initial ATA risk classification is a reliable tool for predicting the persistence or relapse of disease in long-term surveillance.

Objective: Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The purpose of this systematic review and meta-analysis is to summarize the main currently available evidence and analyze data on the relationship between ID and thyroid function. Methods: This study included all articles evaluating the relationship between ID and thyroid function. Quality assessment was performed using Cambridge Quality Checklists. The search strategy included the following combination of Medical Subjects Headings terms and keywords: “iron deficiency”, “thyroid function”, “thyroid disease”, “thyroid dysfunction”, and “hypothyroidism”. A meta-analysis was performed to evaluate whether thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels differed between patients with ID and healthy controls without ID. For statistical comparison between cases and controls, the mean difference (MD) was calculated, and a subgroup analysis of pregnant and non-pregnant women was performed. Cochran’s Q testing and heterogeneity indices (I2) were used to assess statistical heterogeneity. Sensitivity analysis and publication bias analyses were also performed, both qualitatively and quantitatively. Finally, a meta-regression analysis was performed to evaluate the correlation between serum TSH or FT4 levels and SF in the study population. Results: Ten cross-sectional studies were identified and reviewed. Patients with ID showed TSH (MD: −0.24 mIU/L; 95% CI −0.41, −0.07; I2 = 100%, p = 0.005), FT4 (MD: −1.18 pmol/L; 95% CI −1.43, −0.94; I2 = 99%, p < 0.000001), and FT3 (MD: −0.22 pmol/L; 95% CI −0.32, −0.12; I2 = 99%, p < 0.00001) levels that were significantly lower. Subgroup analysis confirmed significantly lower TSH, FT4, and FT3 levels in pregnant women. Non-pregnant women showed significantly lower serum FT4 and FT3 levels but no difference in TSH values. Meta-regression analysis showed that serum TSH and FT4 levels were positively correlated with SF levels. Our systematic review of the literature found that ID significantly increases the prevalence of thyroid autoantibody (anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies) positivity both individually and collectively. Conclusion: Studies currently published in the literature indicate a possible relationship between ID, thyroid function, and autoimmunity, especially in some patient groups. Data analysis shows that thyroid hormone levels are lower in patients with ID and, in particular, in pregnant women. Further studies are needed to understand the role played by iron in thyroid metabolism.

Abstract The authors describe a very rare case of an angiosarcoma originating from the petrous portion of the temporal bone that evolved as an indolent lesion until it became a giant retroauricular mass. A biopsy demonstrated that it was an angiosarcoma. A presurgical embolization from the left occipital and left parietal branches of the left middle meningeal artery was performed, followed by a total resection of the tumor. The patient developed a transient dysphasia during early follow-up, from which, subsequently, she fully recovered. There were no signs of recurrence in the current 3 years of follow-up. Free margins can be achieved even in some giant tumors and remain the most important prognostic factor for soft tissue malignant tumors with intracranial infiltration.

We report a case of a 50-year-old male admitted to the Endocrinology Unit because of persistent headaches, nausea, feeling tired, sudden weight loss, cold intolerance, decreased appetite, and lack of sex interest. Diagnostic workup showed a 6-millimeter pituitary tumor without signs of compression, and a condition of progressive panhypopituitarism. After 12 months of hormone replacement therapy, the patient was hospitalized because of sudden weight gain, periorbital-peripheral edema, severe dyslipidemia, hypertension, and proteinuria. Corticosteroid therapy was shifted from oral to continuous intravenous infusion, and once the diagnosis of “immune complex-mediated glomerulonephritis with mesangial deposits suggestive for membranoproliferative glomerulonephritis type IIIIgG4-positive” was made, the immunosuppressant mycophenolate (1500 mg/day) was started. After a 6-month follow-up, the complete resolution of renal symptoms was accompanied by the disappearance of a pituitary lesion and the patient was back to prior hormone replacement therapy. Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disease of the pituitary gland that can impair hormone secretion and function. IgG4-hypophysitis is rare and is usually associated with other IgG4-related diseases. Herein, we describe a rare case of AH associated with late renal disease, and without any other organ involvement.

The authors describe a rare case of abducens nerve schwannoma, manifested with headache and diplopia, associated to right side cerebellar syndrome. During surgery, the authors identified that the origin of the tumor was from the abducens nerve, and the histopathological diagnosis confirmed that it was a schwannoma. A gross total tumor resection was performed, and the patient recovered from her symptoms 1 month after surgery. The authors followed the Case Report guidelines (CARE) guideline and the patient authorized the authors to publish the present case report by signing an informed consent form.

The autosomal dominant familial form of neurohypophyseal diabetes insipidus (adFNDI) is a rare inherited endocrine disorder characterized by hypotonic polyuria, severe thirst and polydipsia, which results from a deficient neurosecretion of the antidiuretic hormone, also known as arginine vasopressin (AVP). To date, adFNDI has been linked to more than 70 different heterozygous point mutations of the 2.5 kb AVP gene, encoding the composite precursor protein of AVP. A minority of disease-causing mutations, such as the common c.55G>A variant, are predicted to affect amino acid residues close to the signal peptide (SP) cleavage site, and result in abnormal post-translational processing and intracellular trafficking of AVP precursors exerting neurotoxic activity on vasopressinergic magnocellular neurons. Generally, SP variants cause a gradual decline in the neurohypophyseal secretion of AVP in small children, although a wide variability in clinical onset and severity of manifestations has been reported. For the first time, we describe a kindred from Calabria (Southern Italy) with adFNDI and document a partial clinical phenotype in one female young adult member of the family. Methods: A young adult woman was subjected to clinical, neuroradiological and genetic assessments for a mild, adolescent-onset, polyuric state at our Endocrinology Unit. Her family medical history revealed an early-onset (A transition, predicting a p.Ala19Thr replacement in the C-terminal region of SP, was the cause of adFNDI in the investigated kindred. Conclusions: The identification of the genetic cause of aFNDI in this Calabrian kindred provides further information and confirms the wide variability of disease onset and severity of manifestations related to SP variants of the AVP gene, supporting the need for genetic testing in all patients with familial occurrence of polyuria, regardless of their clinical and radiological phenotype. Even though sexual differences in the antidiuretic responses are documented, it is unclear whether female gender would attenuate clinical disease progression in the presence of a pathogenic c.55G>A mutation.

Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, the prevalence of which ranges from 8 to 13%. It is characterized by metabolic, reproductive, and psychological alterations. PCOS prevalence is related to body mass index (BMI). Women with BMI < 25 kg/m2 have a prevalence of 4.3%, whereas women with BMI > 30 kg/m2 have a prevalence of 14%. Moreover, women with PCOS have a risk of type 2 diabetes mellitus (T2DM) two-fold higher than controls, independently of BMI. Both PCOS and T2DM are also consequences of lower serum sex-hormone-binding globulin (SHBG) levels, which is currently considered a biomarker of metabolic disorders, in particular T2DM. Aim: To evaluate the effect of the very-low-calorie ketogenic diet (VLCKD) on markers suggested to be predictive of metabolic and ovulatory dysfunction. These comprehend SHBG, anti-Mullerian hormone (AMH), and progesterone levels on day 21 of the menstrual cycle in a cohort of obese non-diabetic women with PCOS and regular menses. Methods: Twenty-five patients (mean age 25.4 ± 3.44 years) with obesity and PCOS underwent VLCKD for 12 weeks. Each of them underwent measurements of anthropometric parameters (body weight, height, and waist circumference) and blood testing to evaluate serum levels of SHBG, AMH, and progesterone before and after 12 weeks of VLCKD. Results: At enrollment, all patients had high BMI, WC, and AMH, whereas SHBG and progesterone levels were low. After VLCKD, the patients showed a significant reduction in BMI, WC, and HOMA index. In particular, 76% of patients (19/25) switched from obesity to overweight, and the HOMA index normalized, reaching values lower than 2.5 in 96% (24/25) of patients. In addition, serum AMH levels significantly decreased, and progesterone and SHBG significantly increased after VLCKD. Conclusions: This is the first study documenting the effects of VLCKD on ovarian reserve and luteal function in women with PCOS. VLCKD could be used to improve metabolic and ovulatory dysfunction in women with PCOS. Further studies are needed to understand the reasons for the AMH reduction.

Metformin appears to reduce TSH levels in untreated hypothyroid patients. In contrast, in euthyroid patients with type 2 diabetes mellitus (T2DM), metformin is initially devoid of effects on TSH. However, it is followed by a significant reduction in TSH level after twelve months of treatment. Additionally, some evidence suggests that metformin may also improve thyroid morphological abnormalities. This study aimed to evaluate the effects of metformin not only on TSH and thyroid hormone values, but also on thyroid volume and nodules. A total of 50 patients (mean age: 36.9 ± 12.8 years) with insulin resistance (homeostatic model assessment (HOMA) index ≥2.5) and with thyroid uninodular disease were recruited for this study. They were prescribed slow-acting metformin at a daily dose of 500 mg for six months. Treatment with metformin in euthyroid patients with uninodular thyroid disease and insulin resistance reduces TSH levels, increases FT4 and FT3 values, and decreases thyroid and nodule volumes. These data suggest that metformin may be an effective drug not only for the treatment of T2DM and metabolic syndrome, but also for thyroid disease.

Introduction: Penile traction therapy (PTT) aims to non-surgically reduce curvature, enhance girth, and recover lost length. Available clinical practice guidelines however lack clear recommendations regarding their use. Aim: To present a comprehensive review and recommendation regarding the available evidence to the use of PTT in Peyronie's disease (PD). Methods: A systematic literature search was performed on Pubmed and Medline for relevant studies from all times until 2019. Studies of PTT (monotherapy and in combination) in patients with PD with any documented degree of curvature and in either the acute or chronic phase of the disease were included. Full texts not published in English language were excluded. Main outcomes measures: Several scenarios, including preclinical data have been investigated. For each topic covered evidence was analyzed and expert opinion was stated. Results: The paucity of high-level studies precluded any strong recommendations, however, specific statements on this topic, summarizing the ESSM position, were provided. The available data about the use of PTT in PD are still poor, and the impact of this therapy for the treatment of PD has not been clearly stablished. Available data in the clinical setting are still poor, and the impact of these devices on PD evolution has not been clearly established. Conclusion: PTT seems to be a valid treatment option for PD, although there is not enough evidence to give any definitive recommendation in any clinical scenario. García-Gómez B, Aversa A, Alonso-Isa M et al. The Use of Penile Traction Devices for Peyronie's Disease: Position Statements from the European Society for Sexual Medicine. Sex Med 2021;9:100387.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 19 (COVID-19), a respiratory infection that, starting from December 2019, has spread around the world in a few months, becoming a pandemic. The lack of initial knowledge on its management has led to a great effort in developing vaccines and in finding therapeutic weapons capable of improving the clinical outcome of the affected patients. In particular, the possible role of vitamin D status in the management of COVID-19 has been widely analysed, resulting in a great amount of data. This systematic review and meta-analysis aimed to assess whether hypovitaminosis D is a risk factor for developing SARS-CoV-2 infection and whether it affects the worsening of the clinical course of COVID-19. Methods: Data were extracted through extensive searches in the Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases from December 2019 to January 2021, using the keywords: “Vitamin D”, “25 hydroxy Vitamin D”, “25 hydroxycholecalciferol”, “cholecalciferol”, “COVID 19″, “SARS-CoV-2″. We included observational cohort, cross-sectional, and case-control studies that evaluated differences in serum levels of 25‑hydroxy-cholecalciferol [25(OH)D] in patients who were positive or negative for SARS-CoV-2, in patients with mild or severe forms of COVID-19, and in patients who died or were discharged from the hospital. Finally, studies that evaluated the risk of developing severe illness or death in patients with vitamin D deficiency (VDD), defined as levels of 25(OH)D

Endocrine diseases have a considerable impact on public health from an epidemiological point of view and because they may cause long-term disability, alteration of the quality-of-life of the affected patients, and are the fifth leading cause of death. In this extensive review of the literature, we have evaluated the prevalence of the different disorders of endocrine interest in the world and Italy, highlighting their epidemiological, clinical, and economic impact.

Background and Objectives: Thyroid dysfunction is associated with non-alcoholic fatty liver disease, but its role in the progression of liver damage in obese patients remains unclear. In addition, several case reports have suggested the existence of a levothyroxine-induced liver injury, which has been poorly investigated. Our aim was to verify whether a difference in the prevalence of liver fibrosis exists in a population of obese individuals taking Levothyroxine. Materials and Methods: We conducted a cross-sectional study on a population of 137 obese individuals, of which 49 were on replacement therapy with Levothyroxine. We excluded those who had hypertriglyceridemia and diabetes mellitus. All participants underwent a liver stiffness assessment by transient elastography as well as biochemical measurements. In subjects with liver fibrosis, other cause of liver fibrosis were ruled out. Results: Participants taking Levothyroxine had a higher prevalence of liver fibrosis than those not taking Levothyroxine (30.6% vs. 2.3%; p < 0.001), and these results were obtained after we made an adjustment for age (Exp(B) = 18.9; 95% CI = 4.1–87.4; p < 0.001). The liver stiffness value differed significantly between groups (6.0 ± 3.6 and 5.1 ± 1.2, p = 0.033). Of those subjects taking Levothyroxine, there were no significant differences in the dose of medication (1.21 ± 0.36 vs. 1.07 ± 0.42; p = 0.240) and treatment duration (13.7 ± 7.43 vs. 11.13 ± 6.23; p = 0.380) between those with and without liver fibrosis. Conclusions: We found, for the first time, a greater prevalence of liver fibrosis in obese individuals taking Levothyroxine than in those not taking this medication. This finding needs to be confirmed by longitudinal population studies as well as by cellular studies.

The evaluation of biofunctional sperm parameters can explain some cases of idiopathic male infertility. Among these, sperm DNA fragmentation (fDNA) is the most studied biofunctional sperm parameter. Mitochondrial membrane potential (MMP) correlates positively with sperm motility, the evaluation of sperm apoptosis by flow cytometry allows us to identify a population of spermatozoa not recognizable at the optical microscopy and finally, lipid peroxidation (LP) and mitochondrial superoxide levels measurements are rational oxidative stress indices. Male age seems to affect sperm concentration and sperm fDNA. For these reasons, this study was undertaken to evaluate the correlation, if any, between male age and biofunctional sperm parameters evaluating their possible impact on fDNA. To accomplish this, MMP, degree of chromatin compactness, sperm apoptosis/vitality, fDNA, LP, and mitochondrial superoxide levels were evaluated by flow cytometry in a cohort of 874 men. A significant negative correlation was found between age and the percentage of alive spermatozoa (r = -0.75, p < 0.05). The percentage of spermatozoa with low MMP (L-MMP) correlated positively with the percentage of spermatozoa with abnormal chromatin compactness (r = 0.24, p < 0.05). Spermatozoa with abnormal chromatin compactness and L-MMP correlated negatively with the percentage of alive spermatozoa (r = 0.83, p < 0.05) and positively with spermatozoa with PS externalization (r = 0.13, p < 0.01). The percentage of alive spermatozoa correlated negatively with both the percentage of spermatozoa with PS externalization (r = 0.24, p < 0.01) and of the spermatozoa with fDNA (r = 0.10, p < 0.05). Spermatozoa with PS externalization correlated positively with the percentage of spermatozoa with fDNA (r = 0.09, p < 0.05). Spermatozoa with LP correlated positively with the percentage of spermatozoa with increased mitochondrial superoxide (r = 0.11, p < 0.01) In conclusion, these findings in a large number of men suggest that age, mitochondrial damage, and alteration of chromatin compactness could activate the apoptotic cascade which could result in an increased fDNA rate.

There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has alarming adverse health effects through both hormone-direct and hormone-indirect pathways. Non-chemical agents, including physical agents such as artificial light, radiation, temperature, and stress exposure, are currently poorly investigated, even though they can seriously affect the endocrine system, by modulation of hormonal action. Several mechanisms have been suggested to explain the interference of EDCs with hormonal activity. However, difficulty in quantifying the exposure, low standardization of studies, and the presence of confounding factors do not allow the establishment of a causal relationship between endocrine disorders and exposure to specific toxic agents. In this review, we focus on recent findings on the effects of EDCs and hormone system modulators on the endocrine system, including the thyroid, parathyroid glands, adrenal steroidogenesis, beta-cell function, and male and female reproductive function.

Recent and growing literature has reported that oleuropein (OLE), the main polyphenol in olive leaf extract, inhibits tumor cell proliferation and reduces the invasiveness properties of cancer cells; therefore, OLE may play a significant role in the development of new drugs for cancer treatment. These antineoplastic properties have been reported in many experimental cancer models, but the effect of OLE on seminoma cells is yet to be evaluated. In the present study, we demonstrate, for the first time, that OLE reduces cell viability in both intra- and extragonadal TCAM-2 and SEM-1 seminoma cells, respectively, in a dose-dependent manner. As shown by Western-blot analysis, OLE exposure reduced cyclin-D1 expression and upregulated p21Cip/WAF1, concomitantly affecting the upstream pathway of NF-κB, leading to the reduction of its nuclear content, thereby suggesting that OLE could modulate cell-cycle regulators by inhibiting NF-κB. Moreover, Annexin V staining revealed that OLE induced apoptosis in cancer cells and upregulated the pro-apoptotic factor BAX. Through wound-healing scratch and transmigration assays, we also demonstrated that OLE significantly reduced the migration and motility of TCAM-2 and SEM-1 cells, and downregulated the expression of TGFβ-1, which is known to be the main pro-fibrotic factor involved in the acquisition of the migratory and invasive properties of cancer cells. Collectively, our results indicate that OLE reduces seminoma cell proliferation, promotes apoptosis, and counteracts cell migration and motility. Further studies are needed to explore the molecular mechanisms underlying these observed effects.

Tadalafil is a selective phosphodiesterase type-5 (PDE5) inhibitor that is approved for the treatment of men with erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH) -associated symptoms. Besides its classical actions on PDE5 within the genitourinary tract, where the specific enzyme expression is maximal, it may exert different systemic effects. This is mainly due to the pleiotropic distribution of PDE5 enzyme throughout the human (and animal) body, where it can exert protective effects in different clinical conditions. Recently, it has been demonstrated that tadalafil may display novel actions on androgen receptor (AR) expression and activity and cytochrome P19a1 (Cyp19a1) and estrogen receptor β (ERβ) expression in different in vitro systems, such as adipose, bone and prostate cancer cells, where it can act as a selective modulator of steroid hormone production. This may determine novel potential mechanism(s) of control in pathophysiologic pathways. In this review, we summarize basic research and translational results applicable to the use of tadalafil in the treatment of obesity, bone loss and prostate cancer.

Introduction. Obesity exposes individuals to the risk of chronic inflammation of the prostate gland. Aim and design of the study. A longitudinal clinical study was conducted on selected overweight/obese patients with male accessory gland inflammation (MAGI) to evaluate the effects of body weight loss on their urogenital symptoms. Materials and methods. One hundred patients were selected and assigned to two groups undergoing two different nutritional programs. The first group (n = 50) started a Mediterranean diet (MedDiet) and the second (n = 50) a very-low-calorie ketogenic diet (VLCKD). Before and after three months on the diet, each patient was evaluated for body weight, waist circumference, and MAGI symptoms. The MAGI was assessed using the Structured Interview about MAGI (SI-MAGI), a questionnaire previously designed to assess the symptoms of MAGI. The questionnaire explores four domains, including urinary symptoms, ejaculatory pain or discomfort, sexual dysfunction, and impaired quality of life. Finally, in the two groups, the frequency of an α-blocker used to treat urinary tract symptoms was also evaluated. Results. Patients on MedDiet experienced significant amelioration in urinary symptoms and quality of life. Patients under VLCKD reported not only significant improvement of the same parameters, but also in ejaculatory pain/discomfort and sexual dysfunction. Finally, the percentage of patients on VLCKD taking the α-blocker decreased significantly. Moreover, patients under VLCKD showed a greater loss of body weight than those following the MedDiet. Discussion. The results of this study support the effectiveness of VLCKD in improving the symptoms of patients with MAGI. This improvement involved all of the domains of the SI-MAGI questionnaire and became manifest in a relatively short time. We suggest that a ketogenic nutritional approach can be used in overweight/obese patients with MAGI.

Male hypogonadism, defined as an inadequate production of testosterone (T), is associated with a greater morbidity and mortality. Epidemiological studies identified T deficiency as a risk factor for cardiovascular disease. Also, low serum T levels impact on glucose homeostasis through a worse glucose uptake, utilization, and disposal, and the general negative impact on metabolism. The aim of this review is to provide a comprehensive and updated overview of the effects of T replacement therapy on metabolic and cardiovascular systems and prostate tissue in patients with hypogonadism, including molecular mechanisms through which T exerts its actions. Furthermore, recent findings on novel coronavirus disease (COVID-19) epidemiology have shown a greater mortality in male compared with female patients and a role of T in promoting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection of the host cells has been demonstrated. Hence, the secondary aim of this review is to provide preliminary indications on the management in patients with COVID-19.

Polycystic ovary syndrome (PCOS) is a very common endocrine and metabolic disorder with the involvement of both genetic and environmental factors. Although much has been clarified on its pathogenesis, diagnosis, clinical manifestations, and therapy, there are still areas of uncertainty. To address fundamental concepts, novel aspects and hypotheses, and future perspectives, including the possible additional benefits of treatment with nutraceuticals, an expert consensus panel formed by endocrinologists and gynecologists was established. After an independent review of the literature, the panel convened electronically on February 3, 2020, and six resolutions were created, debated, and agreed upon discussion, and finally approved in their final form in a consensus livestream meeting held on April 15. The summary of the resolutions are: (1) PCOS is a well-established medical condition that negatively affects reproduction, general health, sexual health, and quality of life; (2) the symptoms and signs of PCOS appear early in life especially in female newborns from PCOS carriers; (3) women with PCOS have significantly increased risk of pregnancy-related complications including gestational diabetes mellitus; (4) a male PCOS equivalent exists, and it may impact on metabolic health and probably on reproduction; (5) the evidence supports that medical therapy for PCOS is effective, rational, and evidence-based; (6) the evidence supports a major research initiative to explore possible benefits of nutraceutical therapy for PCOS. The proposed resolutions may be regarded as points of agreement based on the current scientific evidence available.

Over the last decades, the adverse effects of human exposure to the so-called “endocrine disruptors” have been a matter of scientific debate and public attention. Bisphenols are synthetic chemicals, widely used in the manufacture of hard plastic products. Bisphenol A (BPA) is one of the best-known environmental toxicants proven to alter the reproductive function in men and to cause other health problems. Consumer concern resulted in “BPA free” products and in the development of bisphenol analogs (BPA-A) to replace BPA in many applications. However, these other bisphenol derivatives seem to have effects similar to those of BPA. Although a number of reviews have summarized the effects of BPA on human reproduction, the purpose of this article is to review the effects of bisphenols on testicular steroidogenesis and to explore their mechanisms of action. Testicular steroidogenesis is a fine-regulated process, and its main product, testosterone (T), has a crucial role in fetal development and maturation and in adulthood for the maintenance of secondary sexual function and spermatogenesis. Contradictory outcomes of both human and animal studies on the effects of BPA on steroid hormone levels may be related to various factors that include study design, dosage of BPA used in in vitro studies, timing and route of exposure, and other confounding factors. We described the main possible molecular target of bisphenols on this complex pathway. We report that Leydig cells (LCs), the steroidogenic testicular component, are highly sensitive to BPA and several mechanisms concur to the functional impairment of these cells.

Ageing is associated with declines in cognitive functions and physical fitness (PF). Physical exercise training and physical activity (PA) have been shown to have positive effects on cognitive functions and brain plasticity. This study aims to establish a practical equation for evaluating cognitive functions using PF parameters in healthy older adults. One-hundred and two older subjects were physically and clinically evaluated. Participants performed the Short Physical Performance Battery (SPPB) and handgrip test (HG); general cognitive functions were examined using the Mini Mental State Examination (MMSE). For all of them, a multiple regression analysis was used to predict MMSE from age, SPPB and HG variables. The new equation was cross validated to determine its prediction accuracy. Considering that SPPB and MMSE reference score are not different between genders, only one equation was developed for females and males. Age, SPPB and HG correlated significantly (p

Abstract Background Male infertility is a widespread condition among couples. In about 50% of cases, couple infertility is attributable to the male partner, mainly due to a failure in spermatogenesis. In recent times, the crucial role that modifiable lifestyle factors play in the development of infertility have generated a growing interest in this field of study, i.e. aging, psychological stress, nutrition, physical activity, caffeine, high scrotal temperature, hot water, mobile telephone use. Several studies have investigated associations between semen quality and the presence of lifestyle stressors i.e. occupational, life events (war, earthquake, etc.) or couple infertility; overall, these studies provide evidence that semen quality is impaired by psychological stress. In this review, we will discuss the impact of quality of life (modifiable lifestyle factors) and psychological stress on male fertility. In addition, the role that increased scrotal temperature along with inappropriate nutritional and physical exercise attitudes exert on male fertility will be presented. Conclusion The decline of male fertility, particularly associated with advancing age, incorrect lifestyles and environmental factors plays an important role on natality, and its consequences on the future on human population makes this an important public health issue in this century. Thus, modification of lifestyle through a structured program of educational, environmental, nutritional/physical exercise and psychological support, combined with the use of nutraceutical antioxidants can prevent infertility and therefore, may help couples to obtain better quality of life and improved possibility to conceive spontaneously or optimize their chances of conception.

Insulin resistance (IR) is a condition which refers to individuals whose cells and tissues become insensitive to the peptide hormone, insulin. Over the recent years, a wealth of data has made it clear that a synergistic relationship exists between IR, type 2 diabetes mellitus, and cancer. Although the underlying mechanism(s) for this association remain unclear, it is well established that hyperinsulinemia, a hallmark of IR, may play a role in tumorigenesis. On the other hand, IR is strongly associated with visceral adiposity dysfunction and systemic inflammation, two conditions which favor the establishment of a pro-tumorigenic environment. Similarly, epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA, in IR states, have been often associated with tumorigenesis in numerous types of human cancer. In addition to these observations, it is also broadly accepted that gut microbiota may play an intriguing role in the development of IR-related diseases, including type 2 diabetes and cancer, whereas potential chemopreventive properties have been attributed to some of the most commonly used antidiabetic medications. Herein we provide a concise overview of the most recent literature in this field and discuss how different but interrelated molecular pathways may impact on tumor development.

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs.

Abstract Objective The aim of this paper is to describe our surgical strategy and technique and to identify the best management for posterior fossa dermoid and epidermoid tumors (PFDETs). Methods We retrospectively identified 21 consecutive patients (11 males and 10 females), with a mean age of 33.2 years, a mean follow-up of 6.1 years, and pathologically confirmed PFDETs. Total 17 patients were submitted to the extended retrosigmoid approach. This approach incorporates transverse sigmoid sinus exposure and a generous mastoidectomy. Results Gross total tumor removal was achieved in 16 (76.1%) cases, with no surgical mortality and a recurrence rate of 9.5%. Conclusions The surgical strategies used in this group of patients enabled the total removal of most tumors without surgical mortality and with minimal morbidity and recurrence rates. The extended retrosigmoid approach used is an alternative path regarding cranial base approaches. This approach is quick, simple and safe, and decreases the retraction of the cerebellum.

The age-related decline of serum T occurs in ~20–30% of adult men and it is today defined as late-onset hypogonadism (LOH). In the elderly, such decline becomes more prevalent (up to 60%) and shows-up with erectile dysfunction (ED) and hypoactive sexual desire. A large body of experimental evidences have shown that the combination of T replacement therapy (TRT) and phosphodiesterase type 5 inhibitors (PDE5i) is, usually, effective in restoring erectile function in patients with LOH and ED who have not responded to monotherapy for sexual disturbances. In fact, PDE5is potentiate the action of nitric oxide (NO) produced by endothelial cells, resulting in a vasodilator effect, while T facilitates PDE5i effects by increasing the expression of PDE5 in corpora cavernosa. Meta-analytic data have recognized to PDE5i a protective role on the cardiovascular health in patients with decreased left ventricular ejection fraction. In addition, several studies have shown pleiotropic beneficial effects of these drugs throughout the body (i.e., on bones, urogenital tract and cerebral, metabolic, and cardiovascular levels). TRT itself is able to decrease endothelial dysfunction, oxidative stress and inflammation, thus lowering the cardiovascular risk. Furthermore, untreated hypogonadism could be the cause of PDE5i ineffectiveness especially in the elderly. For these reasons, aging men complaining ED who have LOH should undergo TRT before or at the moment when PDE5i treatment is started.

Aging is accompanied by a decline in multiple domains. Positive effects of dance practice on several health issues have been evaluated in young adults, while the effects of regular social dance practice on physical fitness, sexual health, and cognitive functions have not been studied yet in older experienced dancers. Thus, the aim of this study has been to investigate whether a 6-month social dance practice might influence fitness performance, sexual health, and specific cognitive functions and/or mood characteristics in older experienced dancers. Thirty experienced dancers (age: 71.2±5.1 years, 18 females/12 males) were enrolled from the dance school “NonSoloLiscio” of Catanzaro. Body composition, physical fitness, sexual health, and cognitive functions were assessed before (T0) and after (T6) intervention. After 6 months of dance practice, percent of fat mass (%FM) significantly decreased (p

Background: The androgen receptor (AR) plays a key role in normal prostate homeostasis and in prostate cancer (PCa) development, while the role of aromatase (Cyp19a1) is still unclear. We evaluated the effects of a treatment with Tadalafil (TAD) on both these proteins. Methods: Androgen-sensitive human PCa cell line (LnCAP) was incubated with/without TAD (10−6 M) and bicalutamide (BCT) (10−4 M) to evaluate a potential modulation on cell proliferation, protein and mRNA expression of Cyp19a, AR and estrogen receptor-β (ERβ), respectively. Results: TAD increased early AR nuclear translocation (p < 0.05, after 15 min of exposure), and increased AR transcriptional activity (p < 0.05) and protein expression (p < 0.05) after 24 h. Moreover, after 24 h this treatment upregulated Cyp19a1 and ERβ mRNA (p < 0.05 and p < 0.005 respectively) and led to an increase in protein expression of both after 48 h (p < 0.05). Interestingly, TAD counteracted Cyp19a1 stimulation induced by BCT (p < 0.05) but did not alter the effect induced by BCT on the AR protein expression. Conclusion: We demonstrate for the first time that TAD can significantly modulate AR expression and activity, Cyp19a1 and ERβ expression in PCa cells, suggesting a specific effect of these proteins. In addition, TAD potentiates the antiproliferative activity of BCT, opening a new clinical scenario in the treatment of PCa.

The prevalence of idiopathic male infertility is high, up to 75% of patients with abnormal sperm parameters. Hence, the research of its causes is mandatory. Oxidative stress (OS) can be responsible for male infertility in 30–80% of cases. In recent years, seminal plasma (SP) proteomics has developed as a useful tool to provide biomarkers of specific diseases. This systematic review aims to collect the available evidence on the changes of SP proteome in patients exposed to OS to provide possible SP biomarkers of sperm OS. To accomplish this, the following keyterms “seminal fluid proteome”, “seminal plasma proteome”, “oxidative stress”, and “sperm oxidative stress” were used and 137 records were found. Among these, 17 were finally included. Nine proteins involved with OS were found overexpressed in patients with OS. Twenty-three proteins were found differentially expressed in patients with clinical conditions associated with OS, such as varicocele, male accessory gland infection/inflammation, cigarette smoke, and obesity. These proteins do not seem to overlap among the clinical conditions taken into account. We speculate that specific SP proteins may mediate OS in different clinical conditions. Altogether, these results suggest that proteomics could help to better understand some of the molecular mechanisms involved in the pathogenesis of infertility. However, further studies are needed to identify potential biomarkers of male infertility with valuable clinical significance.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease (COVID-19) appears to have a higher mortality rate in presence of comorbidities and in men. The latter suggests the presence of a possible sex-dependent susceptibility. An enzymatic system involved in this different predisposition could be represented by angiotensin converting enzyme 2 (ACE2). ACE2 is activated and down-regulated by the spike protein of the virus and allows the penetration of SARS-CoV-2 into epithelial cells and myocardium. Data on the experimental animal have shown that 17ß-estradiol increases the expression and activity of ACE2 in both adipose tissue and kidney. Spontaneously hypertensive male mice have a higher myocardial ACE2 expression than females and its levels decrease after orchiectomy. In addition to this first aspect, the recent evidence of an increased frequency of venous thromboembolism in patients with COVID-19 (a clinical element associated with a worse prognosis) calls the attention on the safety of treatment with testosterone, in particular in hypogonadal men with greater genetic predisposition. Evidence that sex hormones are able to modulate the expression of ACE2 could help in interpreting epidemiological results and in designing more appropriate intervention strategies. Moreover, the vitamin D deficiency in elderly men may be worthy of further study regarding the epidemiological aspects of this different susceptibility and lethality between sexes.

The relationship between testosterone deficiency (TD) syndrome and surgical resilience has a great impact in the modern approach to male elderly patients. There is good evidence that low levels of T are a strong marker for cardiovascular risk; also, TD is frequently associated with increased cardiovascular and all-cause mortality especially in cardiac older frail men. Screening for low T should be mandatory in high risk groups candidate to surgery including those with diabetes, metabolic syndrome and obesity, even though benefits from T-treatment on survival rates are unclear. The low-T3 syndrome, named non-thyroidal illness (NTI) that occurs during critical illness refers to a syndrome with different faces in both sexes. The acute stress or critical illness-induced alterations within the thyroid axis occur in the first days of critical illness i.e. post-surgery and are brought about at least in part by the concomitant macronutrient deficit. The NTI that occurs in prolonged critically ill patients or in post-surgical resilience patients who continue to be dependent on intensive medical care for weeks or months, may have an impact on surgical outcomes because of frequent occurrence of cardiac arrhythmias. Future directions should better routinely investigate circulating thyroid hormones in population at risk before surgery after excluding iatrogenic drug interferences, and investigate the effect of possible treatments on survival rates after surgery.