Seminological, Hormonal and Ultrasonographic Features of Male Factor Infertility Due to Genetic Causes: Results from a Large Monocentric Retrospective Study.

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.

The interlink between thyroid autoimmunity and type 1 diabetes and the impact on male and female fertility.

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.

Endocrine-metabolic assessment checklist for cancer patients treated with immunotherapy: A proposal by the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE) and Italian Society of Pharmacology (SIF) multidisciplinary group.

Immunotherapy with immune checkpoint inhibitors (ICI) is increasingly employed in oncology. National and international endocrine and oncologic scientific societies have provided guidelines for the management of endocrine immune-related adverse events. However, guidelines recommendations differ according to the specific filed, particularly pertaining to recommendations for the timing of endocrine testing. In this position paper, a panel of experts of the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) offers a critical multidisciplinary consensus for a clear, simple, useful, and easily applicable endocrine-metabolic assessment checklist for cancer patients on immunotherapy.

Short fasting test as a reliable and effective tool to diagnose insulinoma.

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.

Postbariatric surgery hypoglycemia: Nutritional, pharmacological and surgical perspectives.

Post-bariatric hypoglycaemia (PBH) is a metabolic complication of bariatric surgery (BS), consisting of low post-prandial glucose levels in patients having undergone bariatric procedures. While BS is currently the most effective and relatively safe treatment for obesity and its complications, the development of PBH can significantly impact patients' quality of life and mental health. The diagnosis of PBH is still challenging, considering the lack of definitive and reliable diagnostic tools, and the fact that this condition is frequently asymptomatic. However, PBH's prevalence is alarming, involving up to 88% of the post-bariatric population, depending on the diagnostic tool, and this may be underestimated. Given the prevalence of obesity soaring, and an increasing number of bariatric procedures being performed, it is crucial that physicians are skilled to diagnose PBH and promptly treat patients suffering from it. While the milestone of managing this condition is nutritional therapy, growing evidence suggests that old and new pharmacological approaches may be adopted as adjunct therapies for managing this complex condition.

Clinical Factors Predicting Multiple Endocrine Neoplasia Type 1 and Type 4 in Patients with Neuroendocrine Tumors.

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.

Polybrominated Diphenyl Ethers (PBDEs) and Human Health: Effects on Metabolism, Diabetes and Cancer.

There is increasing evidence of the role of endocrine disruptors (EDs) derived from commonly employed compounds for manufacturing and processing in altering hormonal signaling and function. Due to their prolonged half-life and persistence, EDs can usually be found not only in industrial products but also in households and in the environment, creating the premises for long-lasting exposure. Polybrominated diphenyl ethers (PBDEs) are common EDs used in industrial products such as flame retardants, and recent studies are increasingly showing that they may interfere with both metabolic and oncogenic pathways. In this article, a multidisciplinary panel of experts of the Italian Association of Medical Diabetologists (AMD), the Italian Society of Diabetology (SID), the Italian Association of Medical Oncology (AIOM), the Italian Society of Endocrinology (SIE) and the Italian Society of Pharmacology (SIF) provides a review on the potential role of PBDEs in human health and disease, exploring both molecular and clinical aspects and focusing on metabolic and oncogenic pathways.

The Impact of Non-Andrological Medications on Semen Characteristics, Oxidative Stress and Inflammatory Parameters.

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.

Women with type 1 diabetes gain more weight during pregnancy compared to age-matched healthy women despite a healthier diet: a prospective case-control observational study.

PURPOSE: Women with type 1 diabetes mellitus (T1D), especially those with suboptimal glucose control, have 3-4 greater chances of having babies with birth defects compared to healthy women. We aimed to evaluate glucose control and insulin regimen modifications during the pregnancy of women with T1D, comparing the offspring's weight and the mother's weight change and diet with those of non-diabetic, normal-weight pregnant women. METHODS: Women with T1D and age-matched healthy women controls (CTR) were consecutively enrolled among pregnant women with normal weight visiting our center. All patients underwent physical examination and diabetes and nutritional counseling, and completed lifestyle and food intake questionnaires. RESULTS: A total of 44 women with T1D and 34 healthy controls were enrolled. Women with T1D increased their insulin regimen during pregnancy, going from baseline 0.9 ± 0.3 IU/kg to 1.1 ± 0.4 IU/kg (p = 0.009), with a concomitant significant reduction in HbA1c (p = 0.009). Over 50% of T1D women were on a diet compared to < 20% of healthy women (p < 0.001). Women with T1D reported higher consumption of complex carbohydrates, milk, dairy foods, eggs, fruits, and vegetables, while 20% of healthy women never or rarely consumed them. Despite a better diet, women with T1D gained more weight (p = 0.044) and gave birth to babies with higher mean birth weight (p = 0.043), likely due to the daily increase in insulin regimen. CONCLUSION: A balance between achieving metabolic control and avoiding weight gain is crucial in the management of pregnant women with T1D, who should be encouraged to further improve lifestyle and eating habits with the aim of limiting upward insulin titration adjustments to a minimum.

Diabetes and erectile dysfunction: The relationships with health literacy, treatment adherence, unrealistic optimism, and glycaemic control.

PURPOSE: The aim of this study was to evaluate the relationships between health literacy, unrealistic optimism, and adherence to glycometabolic disease management related to erectile dysfunction (ED) in male patients with type 2 diabetes (T2D) or preDM. MATERIALS AND METHODS: This prospective observational study enroled 167 consecutive patients with T2D and ED. All patients underwent the following examinations: (a) medical history collection; (b) Body Mass Index (BMI) determination; (c) hormonal and biochemical assessment; (d) duration of T2D, complications and treatment; (e) International Index of Erectile Function-5 questionnaire to assess ED; and (f) validated questionnaire to evaluate health literacy, unrealistic optimism, and treatment adherence. RESULTS: Overall, mean age was 62.5 ± 9.4 years (range: 20-75) and mean BMI was 28.4 ± 4.8 kg/m2 (range: 18.4-46.6). The mean IIEF-5 score was 15.4 ± 5.2 (range: 5-25). The majority of patients showed high health literacy. However, low health literacy was found in patients with higher IIEF-5 scores and high BMI. Unrealistic optimism was low in most patients. Higher adherence to treatment was found in patients who reported regular physical activity, who followed a diet, and in patients with a family history of T2D. Regarding anti-diabetic treatment, patients treated with insulin showed higher health literacy than patients not treated with other medications, whereas higher adherence was found in patients using SGLT2-i. CONCLUSIONS: This study highlighted the close relationship between metabolic compensation, BMI, ED, and psychological attitudes, including health literacy and unrealistic optimism.

Effects of diet and antihyperglycemic drugs on erectile dysfunction: A systematic review.

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.

Sperm culture and bacterial susceptibility to antibiotics in a large andrological population: prevalence and impact on seminal parameters.

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 > 106), 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.

Female infertility in the era of obesity: The clash of two pandemics or inevitable consequence?

Obesity is an epidemic that has led to a rise in the incidence of many comorbidities: among others, reduced fertility is often under-evaluated in clinical practice. The mechanisms underlying the link between reduced fertility and obesity are numerous, with insulin resistance, hyperglycaemia and the frequent coexistence of polycystic ovary syndrome being the most acknowledged. However, several other factors concur, such as gut microbiome alterations, low-grade chronic inflammation and oxidative stress. Not only do women with obesity take longer to conceive, but in vitro fertilization (IVF) is also less likely to succeed. We herein provide an updated state-of-the-art regarding the molecular bases of what we could define as dysmetabolic infertility, focusing on the clinical aspects, as well as possible treatment.

Erectile Dysfunction Severity: The Role of Glycometabolic Compensation and Antihyperglycemic Drugs.

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.

Angioside: The role of Angiogenesis and Hypoxia in Lung Neuroendocrine Tumours According to Primary Tumour Location in Left or Right Parenchyma.

Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypical (AC) carcinoids, represent 30% of NETs. Angiogenesis plays an essential role in NET development and progression. A higher vascular network is a marker of differentiation, with positive prognostic implications. Materials and Methods: We retrospectively evaluated microvessel density (MVD) by CD34 immunohistochemical (IHC) staining and hypoxia by IHC staining for Hypoxia-inducible factor 1α (HIF-1α), comparing right- and left-lung parenchyma in 53 lung NETs. Results: The median age was 66 years (39−81), 56.6% males, 24.5% AC, 40.5% left-sided tumours and 69.8% TNM stage I. The mitotic count was <2/10 per 10 HPF in 79.2%, and the absence of necrosis in 81.1%, 39.6% with Ki67, was ≤2%. The MVD, the number of vessels and the average vessel area median values were significantly higher in the right than the left parenchyma (p: 0.025, p: 0.019, p: 0.016, respectively). Hypoxia resulted present in 14/19 (73.6%) left tumours and in 10/20 (50%) right tumours in the parenchyma (p: 0.129). Conclusions: This study suggests a biological rationale for a different angiogenesis and hypoxia according to the Lu-NETs' location. In our study, left primary tumours were less vascularized and most likely to present hypoxia than right primary tumours. This finding could have potentially useful prognostic and predictive implications for Lu-NETs.

Corticosteroids in oncology: Use, overuse, indications, contraindications. An Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) multidisciplinary consensus position paper.

Corticosteroids (CSs) are widely used in oncology, presenting several different indications. They are useful for induction of apoptosis in hematological neoplasms, for management of anaphylaxis and cytokine release/hypersensitivity reaction and for the symptomatic treatment of many tumour- and treatment-related complications. If the employment of CSs in the oncological setting results in several benefits for patients and satisfaction for clinicians, on the other hand, many potential adverse events (AEs), both during treatment and after withdrawal of CSs, as well as the duality of the effects of these compounds in oncology, recommend being cautious in clinical practice. To date, several gray zones remain about indications, contraindications, dose, and duration of treatment. In this article, a panel of experts provides a critical review on CSs therapy in oncology, focusing on mechanisms of action and pharmacological characteristics, current and emerging therapeutic indications/contraindications, AEs related to CSs treatment, and the impact on patient outcome.

Neuroendocrine Tumors: A Comprehensive Review on Nutritional Approaches.

Neuroendocrine neoplasms are a heterogeneous group of neoplasms with increasing incidence, high prevalence, and survival worldwide. About 90% of cases are well differentiated forms, the so-called neuroendocrine tumors (NETs), with slow proliferation rates and prolonged survival but frequent development of liver metastases and endocrine syndromes. Both the tumor itself and systemic therapy may have an impact on patient nutrition. Malnutrition has a negative impact on outcome in patients with NETs, as well as obesity. In addition, obesity and metabolic syndrome have been shown to be risk factors for both the development and prognosis of NET. Therefore, dietary assessment based on body composition and lifestyle modifications should be an integral part of the treatment of NET patients. Nutrition plans, properly formulated by a dietician, are an integral part of the multidisciplinary treatment team for patients with NETs because they allow an improvement in quality of life, providing a tailored approach based on nutritional needs and nutritional manageable signs and/or symptoms related to pharmacological treatment. The aim of this review is to condense the latest evidence on the role of the most used dietary models, the Mediterranean diet, the ketogenic diet, and intermittent fasting, in the context of NETs, while considering the clinical and molecular mechanisms by which these dietary models act.

Glycemic Variability in Subjects with Diabetes and Hypogonadism during Testosterone Replacement Treatment: A Pilot Study.

BACKGROUND: This is a proof of concept, as a pilot study, with the aim to evaluate continuous glucose monitoring metrics (CGM) in subjects with type 2 diabetes (T2DM), treated with nutritional therapy and metformin, before and after testosterone replacement therapy (TRT). METHODS: In this longitudinal observational study, subjects affected by T2DM and starting TRT for documented ED and hypogonadism were enrolled. All subjects mounted a CGM system during the v0 visit, one week before the beginning of the TRT (week-1), during v2, four weeks after the start of TRT (week 4), and v4 (week 12). CGM was worn for about 144 h after each visit. RESULTS: A total of seven patients, referring to our clinic for erectile dysfunction (ED), were studied (aged 63.3 ± 2.3 years). Mean (± standard deviation) total testosterone level was 2.3 ± 0.6 ng/mL at baseline. After TRT, total testosterone level was 4.6 ± 3.04 ng/mL at week 4 and 3.93 ± 4.67 ng/mL at week 12. No significant differences were observed in TIR, TAR, TBR, estimated HbA1c, AUC below, and AUC above limit during the intervention period. CONCLUSIONS: This is the first study evaluating the effects of TRT on daily glucose excursions in subjects with T2DM and hypogonadism. Though we did not find any significant difference in key CGM metrics during the 12 weeks of TRT, this study confirms the glycometabolic safety of the TRT even on the most novel standardized glycemic targets.

Effect of Neuroendocrine Neoplasm Treatment on Human Reproductive Health and Sexual Function.

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 Role of Antihyperglycemic Drugs and Diet on Erectile Function: Results from a Perspective Study on a Population with Prediabetes and Diabetes.

BACKGROUND: The purpose of this study was to evaluate the effect of diet and antihyperglycemic drugs on erectile dysfunction (ED) in a setting of subjects affected by diabetes mellitus (DM) or preDM. METHODS: This is a prospective observational study on 163 consecutive subjects with preDM or DM. All patients have undergone a medical evaluation (age, Body Mass Index (BMI), family history of DM, duration of DM, smoking, physical activity, dyslipidemia, cardiovascular comorbidities, and testosterone and HbA1c levels) and the International Index of Erectile Function (IIEF)-5 questionnaire. RESULTS: Overall, the mean age was 62.8 ± 9.3 years, and the mean BMI was 28.4 ± 4.6 kg/m2. The IIEF-5 score mean value was 14.4 ± 6.2 (range 4-25). Among all confounders investigated for their association with the IIEF-5 score, only age and the duration of DM among diabetic patients showed a significant trend. The IIEF-5 score was higher in patients using GLP-1a compared to insulin (16.7 ± 4.7 vs. 12.9 ± 6.2; p = 0.02). This association was confirmed after adjustment for age and duration of DM (p = 0.01). All other treatments were similar (14.9 ± 6.2, 14.8 ± 9.2, 15.3 ± 5.4, and 13.6 ± 6.8 for metformin, sulfonylureas (SU), dipeptidyl-peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) treatment, respectively). CONCLUSIONS: This prospective observational study increases attention and focus on the effect of antihyperglycemic drugs and diet on ED, above all about the role of new classes, showing a significant higher IIEF-5 mean value in patients using GLP-1a compared to patients on insulin treatment.