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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 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 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: 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.

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.

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: 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.