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MicroRNAs are small, non-coding, single-strand oligonucleotides which regulate gene expression. There is little evidence in the literature about their role in azoospermia and no studies have investigated their presence in the seminal plasma of men with Klinefelter syndrome. This retrospective study investigated if there were any differences in microRNA expression (miR-509-5p, miR-122-5p, miR-34b-3p, miR-34c-5p) in the seminal plasma of patients with obstructive azoospermia, non-obstructive azoospermia and Klinefelter syndrome. Hormone levels were also investigated to identify any correlations with microRNA expression. We analysed 200 subjects (40 Klinefelter syndrome, 60 non-obstructive azoospermia with a normal karyotype, 60 obstructive azoospermia and 40 who were normozoospermic). All subjects underwent semen examination. Total RNA was obtained from seminal plasma and microRNA expression was analysed by RT-qPCR. There was a significant reduction in the expression of all investigated miRNAs in the seminal plasma of all patient categories in comparison with controls. There was a weak negative correlation between FSH values and miR-509-5p expression in non-obstructive azoospermic patients (r = - 0.391; p = 0.014). We hypothesize that in non-obstructive azoospermia and Klinefelter syndrome patients, the downregulation of microRNAs may be caused by damage to the germ cells and aberrant spermatogenesis. In our opinion the identification of seminal plasma microRNAs deriving almost exclusively from the testes could be essential for the development of specific biomarkers for male infertility. The expression of such microRNAs, in combination with hormone values, could comprise testicular markers of abnormal spermatogenesis and failed mature sperm production.

Background: The management of male idiopathic infertility is heterogeneous. Although meta-analyses reported the effectiveness on pregnancy rate, the real clinical impact of follicle-stimulating hormone (FSH) was not evaluated so far. In Italy, FSH is approved by the National Medicines Agency (AIFA) for idiopathic infertile patients with FSH < 8 IU/L, independently of semen parameters., Aim: Primary endpoint was to record the therapeutic approach to the male partner of infertile couples. Secondary aim was to assess changes of semen parameters during FSH treatment., Methods: A multicentre, prospective, observational, clinical practice survey was carried out, enrolling the male partner of infertile couples attending ten Italian participating centres. Inclusion criteria were as follows: couple infertility, age >18 years and FSH serum levels <8 IU/L. Thus, all men in which AIFA allowed the FSH prescription were enrolled. Primary endpoint was the number of infertile patients treated with FSH. Secondary outcomes were semen parameters. The treating physician decided whether to offer FSH therapy and whether to re-evaluate the male partner., Results: A total of 718 infertile couples were enrolled, and 241 patients were re-evaluated (median follow-up: 4.5 months). In 64.9% (466 patients), a treatment was prescribed. FSH was prescribed in 397 patients (85.2% of treated men). Sperm concentration (P = .002) and normal form percentage (P < .001) significantly improved during FSH administration. No correlation was found between these parameters and FSH duration (P = .545 and P = .627, respectively) or dosage (P = .455 and P = .533, respectively). Among patients treated with FSH, the incidence of oligozoospermia decreased from 73.0% to 56.0% (P < .001) and teratozoospermia from 43.6% to 27.7% (P < .001)., Discussion: This first nation-wide survey reveals a FSH prescription rate of 55% in patients qualifying for treatment according to AIFA. Although the study was not designed to highlight FSH efficacy in male infertility, a slight increase in semen parameters was demonstrated in about half of the treated men without adverse events., (© 2019 American Society of Andrology and European Academy of Andrology.)

Purpose: The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, iatrogenic hypogonadism and acquired hypogonadotropic hypogonadism after surgical removal of pituitary adenomas) called non-KS. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients., Methods: This is a case-control multicentre study from KING group: Endocrinology clinics in university-affiliated medical centres. One hundred and seventy four KS, and sixty-two non-KS hypogonadal men were enrolled. The primary outcome was the prevalence of thyroid diseases in KS and in non-KS. Changes in hormonal parameters were evaluated. Exclusion criterion was secondary hypothyroidism. Analyses were performed using Student's t test. Mann-Whitney test and Chi-square test., Results: FT4 was significantly lower in KS vs non-KS. KS and non-KS presented similar TSH and testosterone levels. Hashimoto's thyroiditis (HT) was diagnosed in 7% of KS. Five KS developed hypothyroidism. The ratio FT3/FT4 was similar in both groups. TSH index was 1.9 in KS and 2.3 in non-KS. Adjustment for differences in age, sample size and concomitant disease in multivariate models did not alter the results., Conclusions: We demonstrated in KS no etiopathogenic link to hypogonadism or change in the set point of thyrotrophic control in the altered FT4 production. The prevalence of HT in KS was similar to normal male population, showing absence of increased risk of HT associated with the XXY karyotype.

Erectile dysfunction (ED) is risk factor for cardiovascular (CV) events. The relationship between sexual activity and incident major adverse cardiovascular events (MACE) in subjects at high CV risk is conflicting and never investigated in ED subjects. The aim of this study was to investigate relationships between frequency of sexual attempts and incident MACE and to retrospectively explore its main determinants in subjects with sexual dysfunction. A consecutive series of 2187 subjects (mean age 49.9 ± 11.6 years old) attending the Outpatient Clinic for sexual dysfunction was retrospectively studied. A subset of the previous sample (N = 1687) was enrolled in a longitudinal study. Frequency of sexual intercourse (coital and non-coital) was assessed using a standard question ('During the last 3 months how many sexual attempts per month did you have?'). In the whole sample, sexual attempts were an age- and testosterone-dependent phenomenon, while no association between frequency of sexual intercourse and ED or premature and delayed ejaculation, was observed. However, when the same analysis was performed according to age tertiles (I = 17-46, II = 47-59, III = 60-88 years old), ED was significantly associated with a higher risk of reduced sexual intercourse in younger (hazard ratio = 1.857 [1.066-3.234]; p = 0.029), but not in middle-aged or older individuals. The marital component, as assessed by SIEDY Scale 2, played a major role in regulating sexual frequency in all age bands. Depressive symptoms represent another independent risk factor for reduced sexual activity (adj r = -0.139; p < 0.0001), in an age-dependent manner. When longitudinal data were analysed, a higher frequency of sexual intercourse significantly reduced the risk of MACE even after adjusting for known CV risk factors for this cohort. Identifying among mild-to-moderate ED subjects those with lower frequency of sexual activity might provide an opportunity to modify their behaviour and to discover subthreshold comorbidities, possibly preventing forthcoming CV events., (© 2013 American Society of Andrology and European Academy of Andrology.)

Background: The relationship between cardiovascular (CV) diseases (CVD) and testosterone (T) levels in men has not been completely clarified., Aim: To evaluate the association between T levels and CV risk in subjects with erectile dysfunction (ED) and to verify whether their body mass index might (BMI) represents a possible confounder in T-related CV stratification., Material and Methods: A consecutive series of 2269 male patients attending the Outpatient Clinic for ED was studied. The assessment of CV risk was evaluated using the engine derived from the Progetto Cuore study., Results: After adjustment and for BMI and associated morbidities, SHBG-bound and -unbound T levels decreased as a function of CV risk assessed thorough Progetto Cuore risk engine. In addition, a higher prevalence of hypogonadism related symptoms and signs was associated with a higher CV risk. Among factors included in the Progetto Cuore risk engine age, total and HDL cholesterol and diabetes were all significantly associated with CV risk-dependent modification of total and calculated free-T levels. When the relationship between SHBG bound and unbound T and CV risk was evaluated as a function of obesity (BMI>30 kg/m(2)), all the aforementioned associations were confirmed only in non obese patients., Conclusions: Hypogonadism could be associated either with an increased or reduced CV risk, depending on the characteristics of subjects. Low T observed in obese patients might represent the result of higher CV risk rather than a direct pathogenetic mechanism.

Objective: To characterize the expression pattern of constitutive and inducible nitric oxide synthase (NOS) in spermatozoa isolated from normospermic fertile donors and asthenozoospermic infertile patients, by means of immunohistochemistry. Also to evaluate the immunohistochemical expression of citrulline, a marker of NOS activity, and nitrotyrosine, which indicates the formation of peroxynitrite, which may affect sperm functionality through its cytotoxic action., Design: Prospective study., Setting: Academic male infertility center., Patient(s): Twenty-nine infertile patients affected by idiopathic asthenozoospermia and 26 age-matched normospermic fertile donors., Intervention(s): Sperm parameters were evaluated, and immunohistochemical analysis was performed in isolated spermatozoa., Main Outcome Measure(s): Semen analyses, to ascertain volume, sperm count, motility, and morphology. Immunohistochemical expression of NOS isoforms, citrulline, and nitrotyrosine., Result(s): Constitutive NOS expression was greater in spermatozoa isolated from normospermic fertile donors. In contrast, the immunohistochemical expression of inducible NOS and nitrotyrosine was higher in asthenozoospermic samples. Our data concerning citrulline indicated enhanced NOS activity in sperm from idiopathic asthenozoospermic patients., Conclusion(s): Our results support the hypothesis that increased NOS activity and an excess of tyrosine nitration may affect the functional characteristics of spermatozoa in idiopathic asthenozoospermia., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the prevalence of major depressive disorder (MDD) and other selected axis-I disorders among women with newly diagnosed, untreated endocrine disorders., Methods: Two hundred and eighteen consecutive women, aged 18-65, with newly diagnosed, untreated endocrine disorders were referred for potential diagnosis of co-morbid axis-I disorders with the use of the Structured Clinical Interview for Axis I-Patient Edition (SCID-P). The SCID-P was re-administered after 12 weeks., Results: At baseline, 64 (29.3%) women met criteria for at least one axis-I disorder. Women who were diagnosed with hyperthyroidism were more likely to meet criteria for generalized anxiety disorder and panic disorder than women without hyperthyroidism. Nine of 154 (5.8 %) women who did not meet criteria for an axis-I disorder at baseline met criteria for at least one axis-I disorder during follow-up. Among them, the presence of diabetes mellitus was statistically correlated with a higher probability of developing major depressive disorder at follow-up., Conclusions: Although preliminary, our findings are consistent with previous studies and suggest an increased prevalence of MDD and other axis-I disorders among women with newly diagnosed endocrine disorders, providing further evidence suggesting that women with endocrine abnormalities may be at increased risk of depression and/or anxiety disorders.

The role of partial AZFc deletions of the Y chromosome in spermatogenic impairment is currently debated. Recently, it was also reported that duplications of the same region are associated with oligozoospermia in Han-Chinese men. The aims of this study were (1) to evaluate the clinical significance of partial AZFc deletions in a large study population and (2) to define if partial AZFc duplications are a risk factor for spermatogenic failure also in a Caucasian population such as the Italian. We screened 556 infertile patients and 487 normozoospermic controls for partial AZFc deletions with a combined method based on STS+/- followed by CDY1-DAZ gene dosage and copy analysis. For the second aim, we performed CDY1-DAZ gene dosage in 229 infertile patients and 263 normozoospermic controls. The frequency of gr/gr deletions in patients was significantly different from the controls (3.2 vs. 0.4%, respectively; P < 0.001), with an OR = 7.9 (95% CI 1.8-33.8). b2/b3 deletions were rare in both groups (0.5% in patients, 0.2% in controls). Concerning gr/gr duplications, we observed no significant differences in their frequency between cases (2.6%) and controls (3.8%). This is the largest study population in the literature in which all potential methodological and selection biases were carefully avoided to detect the clinical significance of partial AZFc deletions and duplications. Our study provides strong evidence that gr/gr deletion is a risk factor for impaired spermatogenesis, whereas we did not detect a significant effect of b2/b3 deletions and partial AZFc duplications on spermatogenesis in this Caucasian ethnic group.

Introduction: The relationship between obesity and erectile dysfunction (ED) has not been completely clarified., Aim: The aim of this study is to investigate the association between different obesity class (the World Health Organization definition) with several hormonal and instrumental parameters, in a large sample of patients with ED., Methods: A consecutive series of 2,435 (mean age 52.1 +/- 13.0 years) male patients with ED was investigated., Main Outcome Measures: Several hormonal and biochemical parameters were studied, along with a structured interview on erectile dysfunction (SIEDY), a psychometric questionnaire (Middle Hospital Questionnaire), and penile doppler ultrasound (PDU)., Results: Among patients studied, 41.5% were normal weight, while 42.4%, 12.1% and 4.0% showed a BMI of 25-29.9, 30-34.9 and 35 kg/m(2 )or higher, respectively. Androgen levels (including sex hormone-binding globuline bound and unbound testosterone) decreased as a function of obesity class, while luteinising hormone levels did not show any significant change. Obesity was significantly associated with a higher organic contribution to ED (as assessed by SIEDY scale 1 score), and worse PDU parameters. At multivariate linear regression analysis, after adjustment for confounders (including metabolic syndrome), low androgens remained associated with BMI, while both basal and dynamic (after prostaglandin E1 [PGE1] stimulation) peak systolic velocity (PSV) at PDU resulted significantly associated with age and elevated blood pressure (Adj. r = -0.179, -0.285 and -0.094, -0.071 for age, hypertension and for basal and dynamic PSV, respectively; all P < 0.05)., Conclusions: Obesity is characterized by low levels of androgens in men with ED, after adjustment for comorbidities. Obesity associated comorbidities, particularly hypertension, are the most important determinants of arteriogenic obesity-associated ED.

Introduction: Erectile dysfunction (ED) is often associated with a wide array of psychiatric symptoms, although few studies systematically address their specific association with ED determinants., Aim: The aim of this study is to explore the relationship between ED (as assessed by SIEDY Structured Interview, a 13-item tool which identifies and quantifies the contribution of organic, relational, and intrapsychic domains of ED) and different psychopathological symptoms (as assessed by the Middlesex Hospital Questionnaire, a self-reported test for the screening of mental disorders in a nonpsychiatric setting)., Methods: A consecutive series of 1,388 (mean age 51 +/- 13 years) male patients with ED was studied., Main Outcome Measures: Several hormonal and biochemical parameters were investigated, along with SIEDY Interview and the Middlesex Hospital Questionnaire., Results: Psychiatric symptoms resulted differentially associated with SIEDY domains. Depressive and phobic-anxiety symptoms were associated with the relational domain, somatization with the organic one, while free-floating anxiety, obsessive-compulsive, and phobic symptoms were significantly related with higher intrapsychic SIEDY scores. In addition, relevant depressive symptomatology was associated with hypogonadism, the presence of low frequency of intercourse, hypoactive sexual desire (HSD), and conflictual relationships within the couple and the family. Patients with high free-floating anxiety symptoms were younger, and complained of an unsatisfactory work and a conflictual relationship within family. Conversely, subjects with higher phobic anxious symptoms displayed a more robust relational functioning. Similar results were observed in subjects with obsessive-compulsive symptoms, who also reported a lower prevalence of HSD. Finally, subjects with somatization symptoms showed the worst erectile function., Conclusions: The main value of this study is that it alters various clinicians' belief that many psychiatric symptoms can be found among ED patients. Systematic testing of patients with ED, through psychiatric questionnaires, is recommended to detect even slight or moderate psychopathological distresses, which specifically associate and exacerbate sexual disturbances.