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Background: To date, there is a lack of a structured national plan of sexual education in Italy, with large interregional differences and poor uniformity in the promotion and learning of sexual health., Aim: The aim of this study was to evaluate the level of knowledge on sexuality and reproductive function among adolescents before and after a sexual education program, considering gender differences in the results., Methods: A longitudinal and interventional study was conducted on high school students. Six sessions for each class were carried out by a multidisciplinary team. Anonymous questionnaires were administered to investigate basic knowledge of human sexuality and reproduction before and after intervention., Outcomes: Participants were high school students who completed the questionnaires. Outcomes included pre and posttest answers on the knowledge questionnaire in study population., Results: We obtained data from 842 high school students (mean ± SD age, 16.11 ± 1.74 years). The main informative sources on sexuality were social media in 37.9% of participants; family, school, and scientific material were the main source in 15.1%, 5.2%, and 4.4%, respectively. A total score of 12.6 ± 3.4 (range, 1-20) was obtained on the knowledge questionnaire; specifically, the score was higher in females than males (12.8 ± 3.4 vs 11.9 ± 3.4, P = .0001). In males and females, a statistically significant increase in level of knowledge was found after the multidisciplinary intervention (14.5 ± 3.6, P = .0001)., Clinical Implications: The lack of sexual education programs in schools in Italy compels adolescents to refer to frequently unreliable sources, such as social media and peers, contributing to misinformation and adoption of risky sexual behaviors., Strengths and Limitations: This study is based on a large sample size and highlights the importance of sexual education programs. The main limitations are a greater representation of the female population and the inclusive nature of the school (ie, an artistic school), attracting students who identify with sexual minorities., Conclusions: Adolescents have limited knowledge about sexuality and reproduction, with a notable gender disparity; sexual education programs in schools, providing information from sexuality experts, led to a substantial increase in knowledge and a reduction in the gender gap., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of this review is to discuss the several interconnections between thyroid autoimmunity and type 1 diabetes in terms of epidemiology, immunoserology, genetic predisposition, and pathogenic mechanisms. We will also analyze the impact of these conditions on both male and female fertility. A literature search was carried out using the MEDLINE/PubMed, Scopus, Google Scholar, ResearchGate, and Clinical Trials Registry databases with a combination of keywords. It was found that the prevalence of thyroid autoantibodies in individuals with type 1 diabetes (T1DM) varied in different countries and ethnic groups from 7 to 35% in both sexes. There are several types of autoantibodies responsible for the immunoserological presentation of autoimmune thyroid diseases (AITDs) which can be either stimulating or inhibiting, which results in AITD being in the plus phase (thyrotoxicosis) or the minus phase (hypothyroidism). Different types of immune cells such as T cells, B cells, natural killer (NK) cells, antigen presenting cells (APCs), and other innate immune cells participate in the damage of the beta cells of the islets of Langerhans, which inevitably leads to T1D. Multiple genetic and environmental factors found in variable combinations are involved in the pathogenesis of AITD and T1D. In conclusion, although it is now well-known that both diabetes and thyroid diseases can affect fertility, only a few data are available on possible effects of autoimmune conditions. Recent findings nevertheless point to the importance of screening patients with immunologic infertility for AITDs and T1D, and vice versa., (© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods : This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia or azoospermia evaluated from January 2012 to January 2022. The genetic investigations consist of karyotype, CFTR gene mutations plus variant of the IVS8-5T polymorphic trait, Y chromosome microdeletion, and Next Generation Sequencing panel to analyze genes implicated in congenital hypogonadotropic hypogonadism (CHH). Results : Overall, 15.4% (72/466) of patients received a diagnosis of genetic cause of infertility. Specifically, 23 patients (31.9%) harbor mutations in the CFTR gene, 22 (30.6%) have a 47, XXY karyotype, 14 (19.4%) patients show a Y chromosome microdeletion, 7 (9.7%) have structural chromosomal anomalies, and 6 (8.3%) have CHH. Overall, 80.6% of patients were azoospermic and 19.4% oligozoospermic (sperm concentration 3.5 ± 3.8 million/mL). Almost all patients presented hormonal alterations related to the specific genotype, while the main ultrasound alterations were testicular hypoplasia, calcifications/microcalcifications, and enlarged/hyperechoic epididymis. Conclusions : The prevalence of genetic abnormalities in males of infertile couples was 15.4% in our Center. CFTR gene disease-causing variants resulted in more frequent, with various clinical features, highlighting the complexity and heterogeneity of the presentation. Other investigations are needed to understand if conditions like ring chromosomes and other translocations are related to infertility or are incidental factors.

Purpose: The aim of this review is to evaluate the effects of new technology used in the management of diabetes mellitus (DM), including the use of continuous glucose monitoring (CGM) and the administration of insulin through continuous subcutaneous insulin infusion (CSII), on male and female sexual function., Methods: This narrative review was performed for all available prospective, retrospective and review articles, published up to June 2023 in PubMed. Data were extracted from the text and from the tables of the manuscript., Results: Sexual dysfunctions are an underestimated comorbidity of DM in both male and female. Although erectile dysfunction (ED) is recognized by the guidelines as a complication of DM, female sexual dysfunction (FSD) is poorly investigated in clinical setting. In addition to the complications of DM, the different types of therapies can also influence male and female sexual response. Furthermore, insulin therapy can be administered through multiple-daily injections (MDI) or a CSII. The new technologies in the field of DM allow better glycemic control which results in a reduction in the occurrence or aggravation of complications of DM. Despite this evidence, few data are available on the impact of new technologies on sexual dysfunctions., Conclusions: The use of DM technology might affect sexual function due to the risk of a worse body image, as well as discomfort related to CSII disconnection during sexual activity. However, the use is related to an improved metabolic control, which, in the long-term associates to a reduction in all diabetes complications, including sexual function., (© 2023. The Author(s).)

Purpose: The diagnosis of insulinoma can be challenging, requiring documentation of hypoglycaemia associated with non-suppressed insulin and C-peptide, often achieved during a prolonged 72 h fast performed in inpatient setting. Our goal is to predict weather a shorter outpatient fasting test initiated overnight and prolonged up until 24 h could be a sensitive method for diagnosing insulinoma., Methods: We conducted a retrospective monocentric study on subjects admitted to our Unit of Endocrinology from 2019 to 2022 for clinical suspicion of insulinoma and underwent the short fasting test. A comparison between the short test group and the group of subjects who underwent the standard prolonged fasting test (from 2003 to 2018) has also been performed. The short fasting test was initiated by the patient overnight at home and proceeded the following day in outpatient setting (Day Hospital). As in the standard protocol, symptoms and capillary blood glucose (CBG) were strictly monitored. Venous blood was drawn for glycaemia, insulin and C-peptide at admission and at established intervals, in case of symptoms of hypoglycaemia or if CBG ≤ 45 mg/dl, when the fast would be suspended., Results: The final sample consisted of 37 patients, with mean age of 44.5 ± 12.6 years (17-74). Short and standard tests were performed in 15 and 22 subjects, respectively. Diagnostic values for insulinoma were observed in 12 patients: in 5/15 who underwent the short fasting test, in 6/22 who underwent the prolonged test and in 1 patient who was initially negative on the short test and subsequently showed diagnostic values during the prolonged test. The diagnosis of insulinoma was achieved in 11/12 cases within 24 h of the beginning of the fast (91.7%)., Conclusions: A short fasting test could be a valid, sensitive and reliable first-line workup in diagnosing insulinoma., (© 2024. The Author(s).)

As the incidence of neuroendocrine tumors has been rising, gender differences in epidemiology and clinical behavior have emerged, and interest into a gender-driven management of these tumors has grown with the aim to improve survival and quality of life of these patients. Somatostatin Analogues represent the first line of systemic treatment of both functional and non-functional neuroendocrine tumors, through the expression of somatostatin receptors (SSTRs) in the tumor cells, and proved effective in controlling hormonal hypersecretion and inhibiting tumor growth, improving progression-free survival and overall survival of these patients. Aim of the present review is to investigate any differences by gender in efficacy and safety of SSTS-targeted therapies, that represent the mainstay treatment of neuroendocrine tumors, as they emerge from studies of varying design and intent. Although preclinical studies have provided evidence in favor of differences by gender in tumor expression of SSTR, as well as of the role of sex hormones and related receptors in modulating SSTRs expression and function, the clinical studies conducted so far have not shown substantial differences between males and females in either efficacy or toxicity of SSTR-targeted therapies, even if with sometimes inconsistent results. Moreover, in most studies gender was not a predictor of response to treatment. Studies specifically designed to address this issue are needed to develop gender-specific therapeutic algorithms, improving patients' prognosis and quality of life., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The incidence of neuroendocrine neoplasm (NEN) and related carcinoid syndrome (CaS) has increased markedly in recent decades, and women appear to be more at risk than men. As per other tumors, gender may be relevant in influencing the clinical and prognostic characteristics of NEN-associated CS. However, specific data on carcinoid syndrome (CaS) are still lacking., Purpose: To evaluate gender differences in clinical presentation and outcome of CaS., Methods: Retrospective analysis of 144 CaS patients from 20 Italian high-volume centers was conducted. Clinical presentation, tumor characteristics, therapies, and outcomes (progression-free survival, PFS, overall survival, OS) were correlated to gender., Results: Ninety (62.5%) CaS patients were male. There was no gender difference in the site of primary tumor, tumor grade and clinical stage, as well as in treatments. Men were more frequently smokers (37.2%) and alcohol drinkers (17.8%) than women (9.5%, p = 0.002, and 3.7%, p = 0.004, respectively). Concerning clinical presentation, women showed higher median number of symptoms (p = 0.0007), more frequent abdominal pain, tachycardia, and psychiatric disorders than men (53.3% vs 70.4%, p = 0.044; 6.7% vs 31.5%, p = 0.001; 50.9% vs. 26.7%, p = 0.003, respectively). Lymph node metastases at diagnosis were more frequent in men than in women (80% vs 64.8%; p = 0.04), but no differences in terms of PFS (p = 0.51) and OS (p = 0.64) were found between gender., Conclusions: In this Italian cohort, CaS was slightly more frequent in males than females. Gender-related differences emerged in the clinical presentation of CaS, as well as gender-specific risk factors for CaS development. A gender-driven clinical management of these patients should be advisable., (© 2023. The Author(s).)

The aim of this study is to evaluate the predictive role of specific clinical factors for the diagnosis of Multiple Endocrine Neoplasia type-1 (MEN1) and type-4 (MEN4) in patients with an initial diagnosis of gastrointestinal, bronchial, or thymic neuroendocrine tumor (NET)., Methods: Patients referred to the NET Unit between June 2021 and December 2022 with a diagnosis of NET and at least one clinical criterion of suspicion for MEN1 and MEN4 underwent molecular analysis of the MEN1 and CDKN1B genes. Phenotypic criteria were: (1) age ≤ 40 years; (2) NET multifocality; (3) MEN1/4-associated manifestations other than NETs; and (4) endocrine syndrome related to NETs or pituitary/adrenal tumors., Results: A total of 22 patients were studied. In 18 patients (81.8%), the first-level genetic test was negative (Group A), while four patients (25%) were positive for MEN1 (Group B). No patient was positive for MEN4 . In Group A, 10 cases had only one clinical criterion, and three patients met three criteria. In Group B, three patients had three criteria, and one met all criteria., Conclusion: These preliminary data show that a diagnosis of NET in patients with a negative family history is suggestive of MEN1 in the presence of ≥three positive phenotypic criteria, including early age, multifocality, multiple MEN-associated manifestations, and endocrine syndromes. This indication may allow optimization of the diagnosis of MEN in patients with NET.

Background: A basal serum calcitonin (Ct) increase >100 pg/mL in patients with a thyroid nodule is consistent with the diagnosis of medullary thyroid cancer (MTC). In cases where the CT test have a slight to moderate increase, the calcium gluconate stimulation test is helpful to increase diagnostic accuracy. However, reliable cut-offs for calcium-stimulated Ct are still lacking. The aim of this study was to evaluate the sex-specific calcium-stimulated Ct cutoffs for the diagnosis of MTC in a multicenter series. A comparison between different Ct assays has been also performed., Methods: 90 subjects undergone calcium-stimulated Ct for a suspected MTC in 5 Endocrine Units between 2010-2021 were retrospectively analyzed. Serum Ct concentrations were assessed by immunoradiometric (IRMA) or chemiluminescence (CLIA) assays., Results: MTC was diagnosed in 37 (41.1%) and excluded in 53 (58.9%) patients. The best calcium-stimulated Ct cut-off to identify MTC was 611 pg/mL in males (AUC =0.90, 95% CI (0.76;1) and 445 pg/mL in females (AUC=0.79, 95% CI (0.66;0.91). Logistic regression analysis showed that both basal (OR 1.01, P=0.003) and peak Ct after stimulation (OR 1.07, P=0.007) were significantly associated with MTC, together with sex (OR=0.06, P<0.001). The "Ct assay" variable was also considered in the logistic regression model, but it was not significantly associated with MTC (OR=0.93, P=0.919)., Conclusions: This study indicates that calcium test could be helpful to identify patients with early-stage MTC and those without MTC. A Ct value of 611 pg/mL in males and 445 pg/mL in females are proposed as the optimal Ct cut-offs at the stimulation test.

Purpose: To evaluate the association among andrological diseases at the first outpatient visit and the medications taken by patients for other comorbidities, as well as the differential impact between specific medication and relative comorbidities., Methods: This is a single-center retrospective study based on subjects who referred to the Andrology Unit with a well-defined andrological diagnosis., Results: A total of 3752 subjects were studied (mean age ± DS 46.2 ± 16.5 years). A total of 19 categories of andrological diseases and 110 type of medications for other comorbidities were identified. ED was the most frequent andrological pathology at the first andrological examination (28.7%), followed by infertility (12.4%). The couple of variables that were statistically significant in the univariate association analysis (p < 0.001) were: ED and (a) antihypertensives; (b) antihyperglycemics; (c) lipids-lowering; (d) psychotropics. The univariate and multivariate regression analyses confirmed the association. All the related comorbidities were also significantly associated with the univariate analysis, and all remained significantly associated with multivariate analysis. A multivariate analysis was also conducted to analyze the association between ED and the following pairs of variables "DM-antihyperglycemics", "dyslipidemia-lipids-lowering", and "hypertension-antihypertensives". In all cases, the pathology, but not the specific treatment, was significantly associated with ED., Conclusion: ED is significantly associated with antihypertensive, antihyperglycemic, lipid-lowering, psychotropic drugs' intake. Anyway, ED appears to be more related to the diseases than to the specific therapies. The definitive cause/effect relationship should be established based on future prospective studies., (© 2023. The Author(s).)

Background and Objectives : The aim of this study was to evaluate the impact of medications on oxidative stress, inflammatory biomarkers and semen characteristics in males with idiopathic infertility. Materials and Methods : In this observational case-control clinical study, 50 men with idiopathic infertility were enrolled, of whom 38 (the study group) were on pharmacological treatment and 12 made up the control group. The study group was clustered according to the medications (Group A: anti-hypertensive, n = 10; Group B: thyroxine, n = 6; Group C: non-steroidal anti-inflammatory drugs, n = 13; Group D: miscellaneous, n = 6; Group E: lipid-lowering drugs, n = 4). Semen analyses were performed according to WHO 2010 guidelines. Interleukins (IL)-10, IL-1 beta, IL-4, IL-6, Tumor Necrosis Factor- alpha (TNF-alpha) and IL-1 alpha were determined using a solid-phase sandwich immunoassay. The diacron reactive oxygen metabolites, d-ROMs test, was performed by means of a colorimetric determination of reactive oxygen metabolites and measured with a spectrophotometer. Beta-2-microglobulin and cystatin-C were measured with an immunoturbidimetric analyzer. Results : No differences between the study and control groups for age and macroscopic and microscopic semen characteristics were found, nor were any differences found after clustering according to the drug categories. IL-1 alpha and IL-10 were significantly lower in the study group compared with the control group; IL-10 was significantly lower in groups A, B, C and D compared with the control group. Furthermore, a direct correlation between IL-1 alpha, IL-10 and TNF-alpha and leukocytes was found. Conclusions : Despite the sample size limitations, the data suggest a correlation between drug use and activation of the inflammatory response. This could clarify the pathogenic mechanism of action for several pharmacological classes on male infertility.

Background: Erectile dysfunction is recognized as one of the complications of diabetes mellitus. To date, a wide gap of knowledge is present on the efficacy of pharmacological treatments of diabetes mellitus on erectile function, acting not only through metabolic control. Similarly, the effects of different diet regimens on erectile dysfunction are still debated., Objectives: We aimed to explore the effects of diet and antihyperglycemic drugs, considering both old and novel therapeutic approaches, on erectile function., Materials/methods: We performed a systematic review, following the PRISMA guidelines. The research was conducted on studies reporting erectile dysfunction assessment in subjects with diabetes and the relationship with diet and antihyperglycemic drugs., Results: The Mediterranean diet was effective in most studies for the protection of erectile function. Furthermore, antihyperglycemic drugs seem to show an overall protective role on erectile function., Discussion/conclusion: Although encouraging results are present for all classes of antihyperglycemic drugs, several studies are needed in humans, mainly on acarbose, pioglitazone, dipeptidyl-peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: The aim of this study was to evaluate (i) the prevalence of subjects with a positive sperm culture (SC) for bacteria in subjects with or without genitourinary tract inflammation (GTI); (ii) the actual distribution of the species analysed, according to Gram stain; (iii) the impact on sperm parameters; and (iv) the actual bacterial susceptibility to antibiotics., Methods: A total of 930 subjects (18-55) years, were retrospectively studied. All the patients underwent SC and in the case of positive tests (CFU > 10 6 ), a microbiological susceptibility analysis. The subjects studied were subdivided into group A (n = 452), with subjective signs of GTI; group B (n = 478), male partners of infertile couples; and group C, 30 healthy normospermic subjects. In group B and in the control group, a semen analysis was performed., Results: Overall, the prevalence of positive SC was 21.5% (200/930). The prevalence of positive SC in group A (113/200; 56.5%) was significantly higher vs. group B (87/200; 43.5%; p = 0.01) and control group (1/30; 3.3%; p = 0.0001). In subjects with GTI, the prevalence of asthenozoospermic (96/285; 33.7%) and oligo-asthenozoospermic (98/285; 34.4%) was significantly higher vs. normospermic, oligo-astheno-teratozoospermic, oligozoospermic and azoospermic subjects (22/285 (7.7%), 48/285 (16.8%), 15/285 (5.3%) and 6/285 (2.1%), respectively; p = 0.001). Finally, Enterococcus faecalis (Gram-positive) and Escherichia coli (Gram-negative) showed the highest prevalence of antibiotic resistance., Conclusions: The prevalence of positive SC is higher in GTI subjects; however, the SC could also be positive in subjects without GTI. Commonly used antibiotics have an increasing risk of being useless for the treatment of bacterial infections. Finally, the diagnosis of GTIs is important also for male fertility., (© 2022. The Author(s).)

Purpose: We herein aimed to review the new insights into the impact of impaired thyroid function on male and female fertility, spacing from spontaneous pregnancy to ART, with the objective of providing an updated narrative revision of the literature., Methods: This narrative review was performed for all available prospective, retrospective and review articles, published up to 2021 in PubMed. Data were extracted from the text and from the tables of the manuscript., Results: Thyroid dysfunction is frequently associated with female infertility, whereas its link with male infertility is debated. Female wise, impaired function is detrimental to obstetric and fetal outcomes both in spontaneous pregnancies and in those achieved thanks to assisted reproduction technologies (ART). Furthermore, the reference range of TSH in natural pregnancy and ART procedures has recently become a matter of debate following recent reports in this field. On the other hand, the impact of thyroid function on the male reproductive system is less clear, although a possible role is suggested via modulation of Sertoli and Leydig cells function and spermatogenesis., Conclusion: Thyroid function should be carefully monitored in both male and female, in couples seeking spontaneous pregnancy as well as ART, as treatment is generally immediate and likely to improve chances of success., (© 2022. The Author(s).)

Background: The aim of this study was to evaluate the prevalence of DM among patients with ED and the impact of glycometabolic compensation and antihyperglycemic treatment on ED severity. Methods: In total, 1332 patients with ED were enrolled. The diagnosis was performed through the International-Index-of-Erectile-Function questionnaire. ED severity was considered according to presence/absence of spontaneous erections, maintenance/achievement deficiency and response to PDE5-i. DM patients were clustered according to antihyperglycemic treatment: “metformin”/“insulin”/“old antihyperglycemic drugs”/“new antihyperglycemic drugs”. Results: The prevalence of DM patients was 15.8% (Group A, patients with ED and DM). Among these, the prevalence of spontaneous erections (21.0%) was lower than in the remaining patients (Group B, patients with ED without DM) (32.0%, p < 0.001). The prevalence of poor response to PDE5-i was lower in Group B (10.0%) than in Group A (35.0%, p < 0.001). Patients with good response to PDE5-i therapy showed lower HbA1c values than patients with poor/no response (6.6 ± 1.1% vs. 7.7 ± 1.9%, p = 0.02). The prevalence of absent response to PDE5-i was higher in patients treated with old antidiabetic drugs than in the population treated with new drugs (p = 0.03). Conclusion: The severity of ED and lower response to PDE5-i were higher in DM patients. A better glycometabolic profile, as well as new antihyperglycemic drugs, seem to have a positive effect on ED.

Background: The effects of an mRNA COVID-19 vaccine on spermatozoa parameters are not known. The aim of this study was to evaluate the effect of the BNT162b2 mRNA COVID-19 vaccine on human semen, comparing spermatozoa parameters before and after vaccine inoculation., Materials and Methods: In this single-center prospective study, voluntary subjects who received mRNA vaccines from February to July 2021 were enrolled. The study population included male subjects aged between 18 and 45 years who completed the BNT162b2 mRNA COVID-19 vaccine cycle. All subjects were evaluated before the first dose of vaccine (T0) and after 3 months (T1) with semen analysis and further analysis of seminal plasma, including colorimetric determination of reactive oxygen metabolites (d-ROM test), electrolytes, and interleukin 6 (IL-6) assessment by enzyme-linked immunosorbent assay technology., Results: The experimental sample included 47 subjects (age: 29.3 ± 6.0 years, range 24-32; body mass index: 23.15 ± 2.5 kg/m 2 , range 19.2-28.0). All the subjects reported no systemic side effects. No significant differences were observed in any spermatozoa parameter between T0 and T1. A subanalysis was performed in oligoazoospermic and asthenozoospermic subjects, confirming the same results. Electrolyte analysis also showed no significant differences before and after vaccine inoculation. Finally, no significant differences were observed in T0, compared to T1 for the d-ROM test and IL-6., Discussion and Conclusion: In this study, no significant differences in spermatozoa parameters before and after vaccine inoculations were found. Furthermore, oxidative stress analysis,, the activity of the cell membrane, and IL-6, as a marker of inflammation, was not affected by the mRNA COVID-19 vaccine. These results suggest that this vaccine is safe for male semen quality., (© 2022 American Society of Andrology and European Academy of Andrology.)

Purpose: The aim of this study was to evaluate in a population of patients with erectile dysfunction (ED): (a) the prevalence of a previously unknown endocrine/glycemic disorders; (b) the correlation between ED severity and endocrine/glycemic disorders., Methods: 1332 patients referred for ED from 2013 to 2020 were included. The ED diagnosis was made using the International-Erectile-Function-Index-5 questionnaire. ED severity was considered according to presence/absence of spontaneous erections, maintenance/achievement deficiency. All patients were subjected to search for sociodemographic and clinical characteristics: age, ethnicity, marital status, previous use of PDE5i, previous prostatectomy, diabetes mellitus (DM), prediabetes, endocrine dysfunctions., Results: The mean ± SD age was 54.3 ± 13.7 years. The 19.1% (255/1332) of patients were already in treatment for prediabetes/diabetes or endocrine dysfunctions. Among the remaining 1077, the prevalence of previously unknown endocrine and glycemic disorders was 30% (323/1077). Among them, 190/323 subjects (58.8%) were affected by hypogonadism, with high estradiol level observed in 8/190 (4.2%). The prevalence of new glycemic alterations was 17.3% (56/323) [specifically, 32/56 (57.1%) DM, and 24/56 (42.9%) prediabetes]. A thyroid dysfunction was observed in 40/323 subjects (12.3%) and hyperprolactinemia in 37/323 (11.5%). Patients with new diagnosis of DM showed more severe form of ED compared to the total group {difficulty in the achievement of erection: 46/56 [82.2%, vs 265/1332 (19.9%), p < 0.05]; absence of spontaneous erection 23/56 [41.1%, vs 321/1332 (24.1%), p < 0.05]}., Conclusion: ED is an early marker of endocrine/glycemic disorder, and a previously unknown dysfunction was found in more than a quarter of patients. A newly diagnosed DM is associated with ED severity, especially in elderly man and in presence of hypertension., (© 2022. The Author(s).)

Neuroendocrine neoplasms (NEN) are characterized by a wide clinical heterogeneity and biological variability, with slow progression and long survival in most cases. Although these tumors can affect young adults, there are few studies that focus on the sexual and reproductive system. The aim of this review was to evaluate the effect of NEN treatment, including somatostatin analogues (SSA), targeted therapy (Everolimus and Sunitinib), radiolabeled-SSA and chemotherapy, on male and female reproductive systems and sexual function. This narrative review was performed for all available prospective and retrospective studies, case reports and review articles published up to March 2022 in PubMed. To date, few data are available on the impact of SSA on human fertility and most of studies come from acromegalic patients. However, SSAs seem to cross the blood-placental barrier; therefore, pregnancy planning is strongly recommended. Furthermore, the effect of targeted therapy on reproductive function is still undefined. Conversely, chemotherapy has a well-known negative impact on male and female fertility. The effect of temozolomide on reproductive function is still undefined, even if changes in semen parameters after the treatment have been described. Finally, very few data are available on the sexual function of NEN treatment.

The incidence of neuroendocrine neoplasms and related carcinoid syndrome (CS) has markedly increased over the last decades and women seem to be more at risk than men for developing CS. Nevertheless, very few studies have investigated sex differences in clinical presentation and outcomes of CS. However, as per other tumours, sex might be relevant in influencing tumour localization, delay in diagnosis, clinical outcomes, prognosis and overall survival in CS. The present review was aimed at evaluating sex differences in CS, as they emerge from an extensive search of the recent literature. It emerged that CS occurs more frequently in female than in male patients with NENs and women seem to have a better prognosis and a slight advantage in overall survival and response to therapy. Moreover, the disease likely impacts differently the quality of life of men and women, with different psychological and social consequences. Nevertheless, sex differences, even if partially known, are deeply underestimated in clinical practice and data from clinical trials are lacking. There is urgent need to increase our understanding of the sex-related differences of CS, in order to define tailored strategies of management of the disease, improving both the quality of life and the prognosis of affected patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetes mellitus (DM), a chronic metabolic disease characterised by elevated levels of blood glucose, is among the most common chronic diseases. The incidence and prevalence of DM have been increasing over the years. The complications of DM represent a serious health problem. The long-term complications include macroangiopathy, microangiopathy and neuropathy as well as sexual dysfunction (SD) in both men and women. Erectile dysfunction (ED) has been considered the most important SD in men with DM. The prevalence of ED is approximately 3.5-fold higher in men with DM than in those without DM. Common risk factors for the development of DM and its complications include sedentary lifestyle, overweight/obesity and increased caloric consumption. Although lifestyle changes may help improve sexual function, specific treatments are often needed. This study aims to review the definition and prevalence of ED in DM, the impact of DM complications and DM treatment on ED and, finally, the current and emerging therapies for ED in patients with DM., (© 2021 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

The aim of the present literature review is to describe the influence of sex hormones on the human voice in physiological conditions. As a secondary sexual organ, the larynx is affected by sex hormones and may change considerably over the lifespan. In the current review, sex hormone-related voice modifications occurring during childhood, puberty, the menstrual cycle, pregnancy and senescence are described. The roles of sex hormones (including gonadotropins, testosterone, estrogen, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone-sulfate) underlying physiological voice changes are discussed, the main differences between males and females are explained and clinical implications are taken into account., (© 2021. The Author(s).)

Purpose: No data are currently available on female sexual dysfunction (FSD) in primary adrenal insufficiency (PAI) and the possible impact of replacement therapy. The aim of this study was to evaluate the prevalence of FSD and sexual distress (SD), and to evaluate the possible impact of replacement therapy on sexuality in women with PAI., Methods: Female Sexual Function Index-6 (FSFI-6) and Sexual Distress Scale (SDS) questionnaires were administered to 22 women with PAI and 23 healthy women matched for age as controls., Results: The prevalence of sexual symptoms measured by FSFI-6 (total score < 19) was significantly higher in women with PAI (15/22; 68.2%) compared to the controls (2/23; 8.7%; p = 0.001). Regarding the questionnaire items, significantly different scores were found for desire ( p < 0.001), arousal ( p = 0.0006), lubrication ( p = 0.046) and overall sexual satisfaction ( p < 0.0001) in women with PAI compared to the controls. The rate of FSD (FSFI < 19 with SDS >15) was 60% in patients with PAI. A significant inverse correlation was found between FSFI-6 total scores and SD (r = -0.65; p = 0.0011), while a significant direct correlation was found between FSFI-6 total scores and serum cortisol levels (r = 0.55; p = 0.035)., Conclusions: A higher prevalence of FSD was found in women affected by PAI compared to healthy women. Desire seems to be the most impaired aspect of sexual function. Moreover, sexual dysfunction in this population seems to be related to sexual distress and cortisol levels.

The aim of this observational study was to develop a new quantitative liquid chromatography-mass spectrometry (LC-MS/MS) method for Therapeutic-Drug-Monitoring (TDM) of psychotropic drugs in seminal fluid to investigate potential gonadotoxic effects in patients with reduced fertility. After the validation of the LC-MS/MS method for psychotropics' levels determination in seminal fluid, we included 20 male partners of infertile couples with idiopathic and/or unexplained male infertility, treated with psychotropic medications for more than 3 months and 10 untreated fertile controls. General and andrological clinical examination, semen analysis and seminal drugs, and metabolites levels determination were performed for each subject. Of the 20 patients included, 6 were treated with antidepressants; 4 with benzodiazepines and 10 with antipsychotics. Seminal drugs and metabolites levels were detectable in all samples. In particular, alprazolam, olanzapine, and levetiracetam showed seminal and serum similar concentrations, while fluoxetine, quetiapine, and aripiprazole were detectable, but seminal levels were significantly lower than the serum therapeutic range. Sperm progressive motility was significantly reduced in subjects treated with psychotropic drugs compared to the untreated controls (p = 0.03). Sperm concentration and progressive motility were significantly reduced in subjects treated with antipsychotics compared to the untreated controls and to the other classes of psychotropics (p < 0.05). In conclusion, this study reports a validated LC-MS/MS method for the detection of seminal psychotropic levels and preliminary data suggesting a potential correlation of seminal psychotropics with alterations of sperm concentration and motility. Pending larger studies, semen TDM might represent a new pivotal tool in the clinical management of reduced fertility in males treated with psychotropic medications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mazzilli, Curto, De Bernardini, Olana, Capi, Salerno, Cipolla, Zamponi, Santi, Mazzilli, Simmaco and Lionetto.)

Background: The aim of this study was to evaluate: 1) the prevalence of male infertility due to ejaculatory dysfunction (premature ejaculation-PE, intravaginal ejaculatory dysfunction-IVEjD, anejaculation-AE, and retrograde ejaculation-RE); and 2) the hormonal profile and semen characteristics of such subjects., Methods: N.3280 subjects who were referred to our andrology unit for infertility were studied. Exclusion criteria: the presence of known causes of male infertility and erectile dysfunction. In all subjects were performed: medical history and andrological physical examination; hormonal profile; semen analysis or centrifugation/resuspension of post-orgasmic urine; IIEF-5 questionnaire for the diagnosis of ED; PEDT questionnaire for the diagnosis of EP., Results: the prevalence of ejaculatory dysfunctions in infertile males was 1.8% (59/3280). The causes were: a) absence of ejaculation in 37/3280 subjects (1.1%); among them, 23/3280 (0.7%) subjects showed a condition of RE and 14/3280 (0.4%) of AE; b) PE in 16/3280 subjects (0.5%); and c) IVEjD in 6/3280 subjects (0.2%). Hormonal values and seminal parameters (when semen analysis was possible) were within the normal ranges in all the cases. In subjects with RE, sperm recovery was possible in 69.9% (16/23) subjects after centrifugation and resuspension of post-orgasmic urine., Conclusions: The prevalence of male infertility due to ejaculatory dysfunctions is overall just under 2%. The main cause is retrograde ejaculation; psychogenic origins could also have an important role. It is important to identify the cause of ejaculatory dysfunction in order to decide upon correct management (PE treatment, centrifugation and resuspension of post-orgasmic urine, penile vibratory stimulation, and psychological counselling).

Background: This study aims to evaluate: 1) the prevalence of Female Sexual Dysfunction (FSD) in women affected by type 1 Diabetes Mellitus (DM) and the control group; 2) the correlation between duration of DM, HbA1C levels and sexual life quality; 3) the relationship between different methods of insulin administration and sexual life quality; 4) the correlation between FSD and diabetes complications., Methods: We selected 33 women with type 1 DM and 39 healthy women as controls. Each participant underwent a detailed medical history and physical examination and completed the 6-item Female Sexual Function Index questionnaire (FSFI-6). In patients affected by type 1 DM, the different methods of insulin administration (Multi Drug Injection - MDI or Continuous Subcutaneous Insulin Infusion - CSII) and the presence of DM complications were also investigated., Results: The prevalence of FSD (total score ≤ 19) was significantly higher in the type 1 DM group than in the control group (12/33, 36.4% and 2/39, 5.2%, respectively; p = 0.010). No statistically significant differences were found regarding FSD according to the presence of complications, method of insulin administration or previous pregnancies., Conclusions: This study underlined that FSD is higher in women affected by type 1 DM than in healthy controls. This could be due to the diabetic neuropathy/angiopathy and the type of insulin administration. Therefore, it is important to investigate FSD in diabetic women, as well as erectile dysfunction in diabetic men.

Introduction: The aims of this study were to determine the prevalence of testicular-adrenal rest tumors (T-ARTs) in patients with congenital adrenal hyperplasia (CAH) and to evaluate the related ultrasound (US) features, hormonal profiles, and semen parameters. Therefore, we attempted to understand the potential impact of adrenocorticotropic hormone (ACTH) on the persistence or disappearance of T-ART. Methods: We conducted a longitudinal cohort study including patients with CAH who were undergoing treatment with cortisone and, when indicated, fludrocortisone replacement therapy. We performed andrological examinations, US of the testis, hormone profiling, and semen analysis. Results: Of the 25 patients (mean ± SD age, 32.2 ± 7.5 years), T-ARTs were detected by US in 14 (56.0%) patients. The mean ± SD diameter of the lesions was 13.2 ± 6.8 mm. Among 3 (21.4%) patients, the lesions were observed in one testis, whereas both testes were affected in the remaining 11 (78.6%) patients. The lesions were hypoechoic in 12 (85.7%) patients and hyperechoic in 2 (14.3%). Plasma ACTH and 17-hydroxyprogesterone (17-OHP) levels were significantly higher in patients with T-ART than in patients without lesions (319.4 ± 307.0 pg/ml and 12.4 ± 2.7 ng/ml vs. 33.5 ± 10.7 pg/ml and 8.2 ± 1.8 ng/ml, respectively; p < 0.01). The mean values of sperm concentration and motility were significantly lower in patients with T-ART than in patients without lesions (12.1 ± 12.4 × 10 6 cells/ml and 18.4 ± 11.1% vs. 41.5 ± 23.2 × 10 6 cells/ml and 30.8 ± 15.4%, respectively; p < 0.05). Logistic regression analysis showed ACTH level as a significant predictor of T-ART ( p < 0.05). In patients with T-ART, the dose of hydrocortisone was increased by ~25-30%, while the fludrocortisone treatment remained unchanged. After 6 months of steroid treatment, patients underwent US and hormonal evaluation. Disappearance and a reduction in T-ART were observed in 6 (42.9%) and 5 (35.7%) patients, respectively; a reduction in ACTH levels (from 319.4 ± 307.0 to 48.1 ± 5.1 pg/ml; p < 0.01) was reported. A significant correlation between ACTH level reduction and T-ART diameter reduction was observed ( p < 0.5; r = 0.55). Conclusions: T-ARTs were detected in 56% of patients with CAH and were associated with impaired semen parameters. However, these lesions are potentially reversible, as demonstrated by the disappearance/reduction after adjustment of cortisone therapy and by the reduction in plasma ACTH level. Our study supports the importance of periodic US evaluation and maintenance of plasma ACTH levels within the normal range in men with CAH.

Objective: The aims of this research were to study: a) the prevalence of male adolescents, aged between 10 and 19 years of age, referred to our Unit for an andrological assessment; b) the reasons (stated and subsequently modified) for referral; c) the prevalence of clinically diagnosed diseases., Materials and Methods: A total of 2.855 subjects, referred to the Andrology Unit for a first examination, were retrospectively studied. For each adolescent, a medical history was taken and an andrological physical examination was carried out., Results: Prevalence was found to be 6.9% (197/2855). Subjects were divided into two groups according to age (A: ≤ 14 and B: ≥ 15 years). The original reason stated for their consultation was corrected by 11.7% of the subjects (23/197); this correction concerned almost all the Group B subjects (21/23 (91.3%) vs 2/23 (8.7%) of Group A; p < 0.01). Regarding sexual dysfunctions, a simple explanation of certain conditions reassured the subject in about 15% of the cases. Furthermore, the physical examination proved extremely useful, revealing clinical alterations in more than 60% of subjects., Conclusions: In conclusion, to date in Italy, the prevalence of adolescents among males referred to an Andrology Unit for assessment is very low. It is important to encourage adolescents to undergo andrological examination to enable identification of reproductive function and psycho-sexual disorders.

Objectives: The aim of this study was to assess the prevalence of patients with Erectile Dysfunction (ED) receiving psychotropic drugs, the impact of these drugs on hormonal profile, and the efficacy of PDE5-i in these patients., Materials and Methods: We recruited 1872 patients referring for ED to our Andrology Unit. Assessment included serum testosterone, gonadotropins, TSH, prolactin, and PSA, and the IIEF-5 questionnaire for ED diagnosis. Inclusion criteria were age 21-75 years and IIEF-5 total score ≤ 21; exclusion criteria included hypogonadism, diabetes mellitus, previous prostatectomy, other medication intake, and ED diagnosis prior to psychotropic drug treatment. Efficacy was rated with the IIEF-5 (remission: total score ≥ 22)., Results: The prevalence of ED patients treated with psychotropic drugs since ≥ 3 months was 9.5% (178/1872), subdivided according to the drugs used into: Group A, 16 patients treated with atypical antipsychotics (9.0%); Group B, 55 patients with benzodiazepines (30.9%); Group C, 33 patients with antidepressant drugs (18.5%); and Group D, 74 patients with multiple psychotropic drugs (41.6%). Patients in Group A were significantly younger than other groups (p < 0.05). The hormonal profile presented only higher prolactin level in patients treated with antipsychotics, alone or in combination (p < 0.05). Overall, 146 patients received PDE5-i. Remission rate, after three months of treatment, was significantly higher in Group B compared to C and D groups (p < 0.05)., Conclusions: A substantial portion of patients receiving psychotropic drugs show ED. Sexual performance in these patients benefits from PDE5-i. Age, effects of psychiatric disorders, psychotropic drugs, and PDE5-i treatment modality accounted for variability of response in this sample.