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INTRODUCTION: The role of dapagliflozin on erectile dysfunction (ED), a condition widely affecting patients with type 2 diabetes mellitus (T2DM), has not yet been studied. AIM: The aim of the study was to evaluate the effects of dapagliflozin alone or in combination with tadalafil on ED in patients with T2DM. METHODS: This was an open-label, non-randomized pilot study involving 30 Caucasian male patients with T2DM and severe ED. They were equally divided into three groups, assigned to treatment with tadalafil 5 mg/day (Group 1), tadalafil 5 mg/day plus dapagliflozin 10 mg/day (Group 2) and dapagliflozin 10 mg/day (Group 3) for 3 months. The presence and the severity of ED were evaluated at enrolment and after treatment, by the International Index of Erectile Function 5-item (IIEF-5) questionnaire and the dynamic penile echo colour Doppler ultrasound (PCDU) examination. RESULTS: At the end of treatment, the three groups showed a significant improvement in IIEF-5 score, by 294%, 375% and 197%, in Groups 1, 2 and 3, respectively. PCDU evaluation showed a significant increase in peak systolic velocity by 178.9%, 339% and 153%; acceleration time was significantly shortened in Group 2 (-26.2%) and was significantly lower than in Group 1 and 3 (-7.2% and -6.6%), while no significant difference was found in end-diastolic velocity after treatment. The greatest rates of improvement were observed in Group 2 for all the end points. CONCLUSIONS: Dapagliflozin improves ED in patients with T2DM and enhances the efficacy of tadalafil. Further studies are needed to confirm our results explain the mechanism(s) by which dapagliflozin exerts its effects on ED.
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Diabetes Mellitus Tipo 2 , Disfunción Eréctil , Humanos , Masculino , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/etiología , Tadalafilo/uso terapéutico , Proyectos Piloto , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Carbolinas , Resultado del TratamientoRESUMEN
INTRODUCTION: The long interspersed nuclear element-1 (LINE1) gene is a retrotransposon whose methylation status appears to play a role in spermatogenesis, the outcome of assisted reproductive techniques (ART), and even in recurrent pregnancy loss (RPL). Advanced paternal age appears associated with altered sperm parameters, RPL, poor ART outcomes, and compromised offspring health. The methylation status of LINE1 has been reported to be affected by age. The latest meta-analysis on the LINE1 methylation pattern in spermatozoa found no significant differences in methylation levels between infertile patients and fertile controls. However, to the best of our knowledge, no updated meta-analysis on this topic has been published recently. Furthermore, no comprehensive meta-regression analysis was performed to investigate the association between sperm LINE1 methylation pattern and age. OBJECTIVES: To provide an updated and comprehensive systematic review and meta-analysis on sperm LINE1 gene methylation degree in patients with abnormal sperm parameters compared to men with normal sperm parameters and to probe the association between sperm LINE1 methylation status and age and/or sperm concentration. METHODS: This meta-analysis was registered in PROSPERO (registration n. CRD42023397056). It was performed according to the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating LINE1 gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included. RESULTS: Of 192 abstracts evaluated for eligibility, only 5 studies were included in the quantitative synthesis, involving a total of 340 patients and 150 controls. Our analysis showed no significant difference in LINE1 gene methylation degree in patients with infertility and/or abnormal sperm parameters compared to fertile controls and/or men with normal sperm parameters, although there was significant heterogeneity across studies. No significant evidence of publication bias was found, and no study was sensitive enough to alter the results. In meta-regression analysis, we found that the results were independent of both ages and sperm concentration. A sub-analysis examining patients and controls separately was also conducted and we found a trend for a positive correlation between LINE1 methylation and sperm concentration in the control group only. CONCLUSIONS: The results of this systematic review and meta-analysis do not suggest a determining role of sperm LINE1 gene methylation degree in patients with infertility and/or abnormal sperm parameters. Therefore, we do not suggest including LINE1 in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART cycles.
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Aborto Habitual , Infertilidad Masculina , Infertilidad , Embarazo , Femenino , Humanos , Masculino , Estudios Prospectivos , Semen , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto , Espermatozoides/metabolismo , Infertilidad/genética , Metilación de ADN/genética , Aborto Habitual/genética , Análisis de Regresión , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismoRESUMEN
This systematic review and meta-analysis summarize the difference in the methylation of the H19 gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on H19 methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that H19 methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the H19 methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.
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Metilación de ADN , Infertilidad Masculina , Femenino , Humanos , Masculino , Embarazo , Impresión Genómica , Histonas/metabolismo , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Metaanálisis como Asunto , Semen , Espermatozoides/metabolismoRESUMEN
Congenital hypogonadotropic hypogonadism (cHH)/Kallmann syndrome (KS) is a rare genetic disorder with variable penetrance and a complex inheritance pattern. Consequently, it does not always follow Mendelian laws. More recently, digenic and oligogenic transmission has been recognized in 1.5-15% of cases. We report the results of a clinical and genetic investigation of five unrelated patients with cHH/KS analyzed using a customized gene panel. Patients were diagnosed according to the clinical, hormonal, and radiological criteria of the European Consensus Statement. DNA was analyzed using next-generation sequencing with a customized panel that included 31 genes. When available, first-degree relatives of the probands were also analyzed to assess genotype-phenotype segregation. The consequences of the identified variants on gene function were evaluated by analyzing the conservation of amino acids across species and by using molecular modeling. We found one new pathogenic variant of the CHD7 gene (c.576T>A, p.Tyr1928) and three new variants of unknown significance (VUSs) in IL17RD (c.960G>A, p.Met320Ile), FGF17 (c.208G>A, p.Gly70Arg), and DUSP6 (c.434T>G, p.Leu145Arg). All were present in the heterozygous state. Previously reported heterozygous variants were also found in the PROK2 (c.163del, p.Ile55*), CHD7 (c.c.2750C>T, p.Thr917Met and c.7891C>T, p.Arg2631*), FLRT3 (c.1106C>T, p.Ala369Val), and CCDC103 (c.461A>C, p.His154Pro) genes. Molecular modeling, molecular dynamics, and conservation analyses were performed on three out of the nine variants identified in our patients, namely, FGF17 (p.Gly70Arg), DUSP6 (p.Leu145Arg), and CHD7 p.(Thr917Met). Except for DUSP6, where the L145R variant was shown to disrupt the interaction between ß6 and ß3, needed for extracellular signal-regulated kinase 2 (ERK2) binding and recognition, no significant changes were identified between the wild-types and mutants of the other proteins. We found a new pathogenic variant of the CHD7 gene. The molecular modeling results suggest that the VUS of the DUSP6 (c.434T>G, p.Leu145Arg) gene may play a role in the pathogenesis of cHH. However, our analysis indicates that it is unlikely that the VUSs for the IL17RD (c.960G>A, p.Met320Ile) and FGF17 (c.208G>A, p.Gly70Arg) genes are involved in the pathogenesis of cHH. Functional studies are needed to confirm this hypothesis.
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Hipogonadismo , Síndrome de Kallmann , Humanos , Hipogonadismo/genética , Hipogonadismo/diagnóstico , Síndrome de Kallmann/genética , Fenotipo , Heterocigoto , Penetrancia , MutaciónRESUMEN
Gonadotropin-releasing hormone (GnRH) neurons are key neuroendocrine cells in the brain as they control reproduction by regulating hypothalamic-pituitary-gonadal axis function. In this context, anti-Müllerian hormone (AMH), growth hormone (GH), and insulin-like growth factor 1 (IGF1) were shown to improve GnRH neuron migration and function in vitro. Whether AMH, GH, and IGF1 signaling pathways participate in the development and function of GnRH neurons in vivo is, however, currently still unknown. To assess the role of AMH, GH, and IGF1 systems in the development of GnRH neuron, we evaluated the expression of AMH receptors (AMHR2), GH (GHR), and IGF1 (IGF1R) on sections of ex vivo mice at different development stages. The expression of AMHR2, GHR, and IGF1R was assessed by immunofluorescence using established protocols and commercial antibodies. The head sections of mice were analyzed at E12.5, E14.5, and E18.5. In particular, at E12.5, we focused on the neurogenic epithelium of the vomeronasal organ (VNO), where GnRH neurons, migratory mass cells, and the pioneering vomeronasal axon give rise. At E14.5, we focused on the VNO and nasal forebrain junction (NFJ), the two regions where GnRH neurons originate and migrate to the hypothalamus, respectively. At E18.5, the median eminence, which is the hypothalamic area where GnRH is released, was analyzed. At E12.5, double staining for the neuronal marker ß-tubulin III and AMHR2, GHR, or IGF1R revealed a signal in the neurogenic niches of the olfactory and VNO during early embryo development. Furthermore, IGF1R and GHR were expressed by VNO-emerging GnRH neurons. At E14.5, a similar expression pattern was found for the neuronal marker ß-tubulin III, while the expression of IGF1R and GHR began to decline, as also observed at E18.5. Of note, hypothalamic GnRH neurons labeled for PLXND1 tested positive for AMHR2 expression. Ex vivo experiments on mouse sections revealed differential protein expression patterns for AMHR2, GHR, and IGF1R at any time point in development between neurogenic areas and hypothalamic compartments. These findings suggest a differential functional role of related systems in the development of GnRH neurons.
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Células Neuroendocrinas , Hormonas Peptídicas , Animales , Ratones , Hormona Antimülleriana , Hormona Liberadora de Gonadotropina , Hormona del Crecimiento , Factor I del Crecimiento Similar a la Insulina , Neuronas , Hormonas Liberadoras de Hormona Hipofisaria , Tubulina (Proteína) , Células Neuroendocrinas/metabolismoRESUMEN
To evaluate whether the follicle-stimulating hormone (FSH) receptor (FSHR) is expressed in human spermatozoa and the effects of FSH incubation on sperm function. Twenty-four Caucasian men were recruited. Thirteen patients had asthenozoospermia, and the remaining 11 had normal sperm parameters (controls). After confirming FSHR expression, spermatozoa from patients and controls were incubated with increasing concentrations of human purified FSH (hpFSH) to reassess FSHR expression and localization and to evaluate progressive and total sperm motility, the mitochondrial membrane potential, and protein kinase B (AKT) 473 and 308 phosphorylation. FSHR is expressed in the post-acrosomal segment, neck, midpiece, and tail of human spermatozoa. Its localization does not differ between patients and controls. Incubation with hpFSH at a concentration of 30 mIU/mL appeared to increase FSHR expression mainly in patients. Incubation of human spermatozoa with hpFSH overall resulted in an overall deterioration of both progressive and total motility in patients and controls and worse mitochondrial function only in controls. Finally, incubation with FSH increased AKT473/tubulin phosphorylation to a greater extent than AKT308. FSHR is expressed in the post-acrosomal region, neck, midpiece, and tail of human spermatozoa. Contrary to a previous study, we report a negative effect of FSH on sperm motility and mitochondrial function. FSH also activates the AKT473 signaling pathway.
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Hormona Folículo Estimulante , Proteínas Proto-Oncogénicas c-akt , Humanos , Masculino , Hormona Folículo Estimulante/farmacología , Motilidad Espermática , Semen/metabolismo , Hormona Folículo Estimulante Humana/farmacología , Receptores de HFE/metabolismo , Espermatozoides/metabolismoRESUMEN
Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and fertilization processes. However, the impact of sperm lipid composition on male fertility remains under-investigated. The aim of the present study was to perform a lipidomic analysis of human sperm membranes: we performed an untargeted analysis of membrane lipid composition in fertile (N = 33) and infertile subjects (N = 29). In parallel, we evaluated their serum lipid levels. Twenty-one lipids were identified by their mass/charge ratio and post-source decay spectra. Sulfogalactosylglycerolipid (SGG, seminolipid) was the most abundant lipid component in the membranes. In addition, we observed a significant proportion of PUFAs. Important differences have emerged between the fertile and infertile groups, leading to the identification of a lipid cluster that was associated with semen parameters. Among these, cholesterol sulfate, SGG, and PUFAs represented the most important predictors of semen quality. No association was found between the serum and sperm lipids. Dietary PUFAs and SGG have acknowledged antioxidant functions and could, therefore, represent sensitive markers of sperm quality and testicular function. Altogether, these results underline the important role of sperm membrane lipids, which act independently of serum lipids levels and may rather represent an independent marker of reproductive function.
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Astenozoospermia , Análisis de Semen , Humanos , Masculino , Semen , Lipidómica , Motilidad Espermática , Espermatozoides , Lípidos de la Membrana , Análisis por ConglomeradosRESUMEN
Aim: We aimed to evaluate the impact of seminal low-risk human Papillomavirus (LR-HPV) infection on sperm conventional parameters.Material and methods: This was a retrospective case-control study including patients attending to our center for infertility. Patients with evidence for high risk (HR)-HPV infection previously or at the time of enrollment, and/or with severe oligozoospermia (sperm concentration <5 mil/ml) were ruled out. Twenty selected patients positive for a LR-HPV and 20 control subjects with no evidence of HPV DNA and with available results of sperm analysis were consecutively enrolled.Results: Patients positive for LR-HPV had a mean age of 31.0 + 11.0 years, while controls were 35.0 + 8.0-year-old (p > .05). Sperm concentration, total sperm count, sperm progressive motility, morphology, and leukocyte concentration did not differ between patients and controls. However, the prevalence of oligozoospermia was significantly higher in patients than controls (50% vs. 15%). No difference in the prevalence of astenozoospermia (30% vs. 40%) or teratozoospermia (15% vs. 15%) was found.Conclusion: We found no difference in sperm conventional parameters in LR-HPV infected patients than in controls. These data might prompt to research the impact on LR-HPV genotype on male fertility. Particularly, evidence on sperm DNA fragmentation (SDF) and pregnancy outcome is needed.
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Infecciones por Papillomavirus , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Infecciones por Papillomavirus/epidemiología , Embarazo , Estudios Retrospectivos , Motilidad Espermática , EspermatozoidesRESUMEN
Meat consumption has represented an important evolutionary step for humans. However, modern patterns of consumption, including excess intake, type of meat and cooking method have been the focus of attention as a potential cause of rise in non-communicable diseases. The aim of this study was to investigate the association between total, red and processed meat with health outcomes and to assess the level of evidence by performing a systematic search of meta-analyses of prospective cohort studies. Convincing evidence of the association between increased risk of (i) colorectal adenoma, lung cancer, CHD and stroke, (ii) colorectal adenoma, ovarian, prostate, renal and stomach cancers, CHD and stroke and (iii) colon and bladder cancer was found for excess intake of total, red and processed meat, respectively. Possible negative associations with other health outcomes have been reported. Excess meat consumption may be detrimental to health, with a major impact on cardiometabolic and cancer risk.
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Neoplasias Colorrectales , Carne Roja , Accidente Cerebrovascular , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Culinaria , Dieta/efectos adversos , Humanos , Masculino , Carne/efectos adversos , Estudios Observacionales como Asunto , Estudios Prospectivos , Carne Roja/efectos adversos , Factores de Riesgo , Accidente Cerebrovascular/complicacionesRESUMEN
Fish represents one of the most important dietary sources of omega-3 polyunsaturated fatty acids, which are known to be associated with various health benefits. This study aimed to systematically review existing meta-analyses of observational studies exploring the association between fish intake and various health outcomes. A systematic search of electronic databases was conducted to retrieve a total of 63 studies. Evidence was deemed as possible for the association between higher fish intake and decreased risk of the acute coronary syndrome, liver cancer, and depression, and limited for other outcomes (including age-related macular degeneration, Alzheimer's disease, heart failure, all-cause and coronary heart disease mortality, total and ischaemic stroke) due to heterogeneity between results and potential otherwise inexplicable confounding factors. In conclusion, results from epidemiological studies support the mechanistic effects associated with omega-3 fatty acids from high fish consumption, but evidence needs to be further corroborated with more reliable results.
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Isquemia Encefálica , Ácidos Grasos Omega-3 , Accidente Cerebrovascular , Animales , Humanos , Peces , DietaRESUMEN
Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.
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Infertilidad Masculina/metabolismo , Obesidad/metabolismo , Sirtuinas/metabolismo , Humanos , Infertilidad Masculina/etiología , Masculino , Obesidad/complicaciones , Análisis de Semen , Transducción de SeñalRESUMEN
The aim of the study is to describe the clinical features of two unrelated patients with resistance to thyroid hormones (RTH), the first, a total thyroidectomized patient, and the second, a pregnant woman. We report the features found in her newborn who also showed RTH. Patient 1 is a 38-year-old man with total thyroidectomy managed for excessive thyroid stimulating hormone (TSH) production, which poorly responded to the replacement therapy. He was found with a THRß c.1378G>A p.(Glu460Lys) heterozygous mutation, which was also present in other members of his family (son, brother, and father). Interestingly, Patient 1 had hypertension, dyslipidemia, and hepatic steatosis, which have been recently suggested as RTH-related comorbidities. Patient 2 is a 32-year-old pregnant woman with multinodular goiter, and the THRß heterozygous variant c.959G>C, that, to the best of our knowledge, has been reported in literature only once. Her newborn had tachycardia and increased thyroid hormone levels, and showed the same mutation. After delivery, high parathyroid hormone (PTH) and calcium serum levels were found in Patient 2 and the scintigraphy showed the presence of adenoma of a parathyroid gland. This case-series study provides a practical example of the management of RTH in a thyroidectomized patient, a pregnant woman, and a newborn. A novel RTH pathogenic mutation is described for the second time in literature. Furthermore, the importance of metabolic assessment in patients with RTHß has been highlighted and the possible correlation between RTH and primary hyperparathyroidism is discussed.
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Receptores beta de Hormona Tiroidea , Síndrome de Resistencia a Hormonas Tiroideas , Adulto , Calcio , Femenino , Humanos , Recién Nacido , Masculino , Mutación , Hormona Paratiroidea/genética , Embarazo , Receptores beta de Hormona Tiroidea/genética , Síndrome de Resistencia a Hormonas Tiroideas/diagnóstico , Síndrome de Resistencia a Hormonas Tiroideas/genética , Hormonas Tiroideas , Tirotropina/genéticaRESUMEN
BACKGROUND: Only few studies have assessed sexual dysfunction in men with Klinefelter syndrome (KS). AIM: To define pooled prevalence estimates and correlates of erectile dysfunction (ED) and decreased libido (DL) in KS. METHODS: A thorough search of Medline, Embase and Web of Science was performed to identify suitable studies. Quality of the articles was scored using the Assessment Tool for Prevalence Studies. Data were combined using random effect models and the between-studies heterogeneity was assessed by the Cochrane's Q and I2. The sources of heterogeneity were investigated by meta-regression and sub-group analyses. Funnel plot, Begg's rank correlation and trim-and-fill test were used to assess publication bias. MAIN OUTCOME MEASURE: The pooled prevalence of ED and DL in KS as well as 95% confidence intervals (CIs) were estimated from the proportion of cases of sexual dysfunction and the sample size. Variables that could affect the estimates were identified by linear meta-regression models. RESULTS: Sixteen studies included collectively gave information about ED and DL in 482 and 368 KS men, respectively, resulting in a pooled prevalence of 28% (95% CI: 19%-36%) for ED and 51% (95% CI: 36%-66%) for DL, with a large heterogeneity. The trim-and-fill adjustment for publication bias produced a negligible effect on the pooled estimates. At the meta-regression analyses, a higher prevalence of ED was significantly associated with an older age but not with lower testosterone levels. In series with a mean age >35 years, the ED prevalence estimate increased up to 38% (95% CI: 31%-44%) with no heterogeneity (I2=0.0%, P=0.6). On the contrary, the prevalence of DL increased significantly as testosterone levels decreased, without a significant relationship with age. CLINICAL IMPLICATIONS: While DL would largely reflect an androgen deficiency, in older men with KS, erectile function should be assessed irrespective of testosterone levels. STRENGTH & LIMITATIONS: This is the first meta-analysis defining pooled prevalence estimates and correlates of ED and DL in KS. Nevertheless, caution is required when interpreting results, due to the high risk of bias in many studies, as well as the dearth of data about psychosocial and/or psychosexological variables and age at the diagnosis. CONCLUSIONS: ED and DL represent common clinical complaints in KS. While the prevalence of ED would increase with age, DL gets more common as serum testosterone decreases. Further studies are warranted to elucidate the pathogenetic mechanism(s) underlying the age-dependent increase in the prevalence of ED, apparently unrelated to the androgenic status. A Barbonetti, S D'Andrea, W Vena, et al. Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study. J Sex Med 2021;18:1054-1064.
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Disfunción Eréctil , Síndrome de Klinefelter , Adulto , Anciano , Disfunción Eréctil/epidemiología , Humanos , Libido , Masculino , Erección Peniana , PrevalenciaRESUMEN
Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus, cardiovascular-cerebrovascular disease, hypertension, obstructive sleep apnea syndrome, cancer, and sexual and hormonal disorders. The treatment of obesity has therefore become a goal of great clinical and social relevance. Among the therapeutic strategies against obesity, resveratrol has aroused great interest. This polyphenol has anticancer and antioxidant properties and cytoprotective and anti-inflammatory effects. Other favorable effects attributed to resveratrol are anti-lipid, anti-aging, anti-bacterial, anti-viral, and neuroprotective actions. Administration of resveratrol appears to improve the metabolic profile in obese and/or insulin-resistant patients. This article aims to review the main results of clinical studies evaluating the effects of administering resveratrol alone in overweight/obese patients.
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Fármacos Antiobesidad/uso terapéutico , Antioxidantes/uso terapéutico , Obesidad/tratamiento farmacológico , Resveratrol/uso terapéutico , Humanos , Obesidad/metabolismo , Obesidad/patologíaRESUMEN
Anti-Müllerian hormone (AMH) is secreted by Sertoli or granulosa cells. Recent evidence suggests that AMH may play a role in the pathogenesis of hypogonadotropic hypogonadism (HH) and that its serum levels could help to discriminate HH from delayed puberty. Moreover, the growth hormone (GH)/insulin-like growth factor 1 (IGF1) system may be involved in the function of gonadotropin-releasing hormone (GnRH) neurons, as delayed puberty is commonly found in patients with GH deficiency (GHD) or with Laron syndrome, a genetic form of GH resistance. The comprehension of the stimuli enhancing the migration and secretory activity of GnRH neurons might shed light on the causes of delay of puberty or HH. With these premises, we aimed to better clarify the role of the AMH, GH, and IGF1 on GnRH neuron migration and GnRH secretion, by taking advantage of previously established models of immature (GN11 cell line) and mature (GT1-7 cell line) GnRH neurons. Expression of Amhr, Ghr, and Igf1r genes was confirmed in both cell lines. Cells were then incubated with increasing concentrations of AMH (1.5-150 ng/mL), GH (3-1000 ng/mL), or IGF1 (1.5-150 ng/mL). All hormones were able to support GN11 cell chemomigration. AMH, GH, and IGF1 significantly stimulated GnRH secretion by GT1-7 cells after a 90-min incubation. To the best of our knowledge, this is the first study investigating the direct effects of GH and IGF1 in GnRH neuron migration and of GH in the GnRH secreting pattern. Taken together with previous basic and clinical studies, these findings may provide explanatory mechanisms for data, suggesting that AMH and the GH-IGF1 system play a role in HH or the onset of puberty.
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Hormona Antimülleriana/farmacología , Hormona Liberadora de Gonadotropina/metabolismo , Hormona de Crecimiento Humana/farmacología , Factor I del Crecimiento Similar a la Insulina/farmacología , Neuronas/fisiología , Animales , Movimiento Celular , Células Cultivadas , Ratones , Neuronas/citología , Neuronas/efectos de los fármacosRESUMEN
Resveratrol (RSV) (3,4',5 trihydroxystilbene) is a natural non-flavonoid polyphenol widely present in the Mediterranean diet. In particular, RSV is found in grapes, peanuts, berries, and red wine. Many beneficial effects of this molecule on human health have been reported. In fact, it improves some clinical aspects of various diseases, such as obesity, tumors, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, and diabetes mellitus. However, little is known about the relationship between this compound and male fertility and the few available results are often controversial. Therefore, this review evaluated the effects of RSV on human male fertility and the mechanisms through which this polyphenol could act on human spermatozoa.
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Fármacos para la Fertilidad Masculina/química , Fertilidad/efectos de los fármacos , Polifenoles/química , Resveratrol/química , Arachis/química , Dieta Mediterránea , Fertilidad/fisiología , Fármacos para la Fertilidad Masculina/uso terapéutico , Frutas/química , Humanos , Masculino , Polifenoles/uso terapéutico , Resveratrol/uso terapéutico , Espermatozoides/efectos de los fármacos , Vitis/química , VinoRESUMEN
Introduction: Androgen insensitivity syndrome (AIS), an X-linked recessive disorder of sex development (DSD), is caused by variants of the androgen receptor (AR) gene, mapping in the long arm of the X chromosome, which cause a complete loss of function of the receptor. Case presentation: We report a patient diagnosed with complete AIS (CAIS) at birth due to swelling in the bilateral inguinal region. Transabdominal ultrasound revealed the absence of the uterus and ovaries and the presence of bilateral testes in the inguinal region. The karyotype was 46,XY. She underwent bilateral orchiectomy at 9 months and was given estrogen substitutive therapy at the age of 11 years. Genetic analysis of the AR gene variants was requested when, at the age of 20, the patient came to our observation. Methods: The genetic testing was performed by next-generation sequence (NGS) analysis. Results: The genetic analysis showed the presence of the c.2242T>A, p.(Phe748Ile) variant in the AR gene. To the best of our knowledge, this variant has not been published so far. Furthermore, the patient has a heterozygous c.317A>G, p.(Gln106Arg) variation of the gonadotropin-releasing hormone receptor (GNRHR) gene, a heterozygous c.2273G>A, p.Arg758His variation of the chromodomain helicase DNA binding protein 7 (CHD7) gene, and compound heterozygous c.875A>G, p.Tyr292Cys, and c.8023A>G, p.Ile2675Val variations of the Dynein Axonemal Heavy Chain 11 (DNAH11) gene. Conclusions: The case herein reported underlines the importance of an accurate genetic analysis that has to include karyotype and AR gene variant analysis. This is useful to confirm a clinical diagnosis and establish the proper management of patients with CAIS. Numerous variants of the AR gene have not yet been identified. Moreover, several pitfalls are still present in the management of these patients. More studies are needed to answer unresolved questions, and common protocols are required for the clinical follow-up of patients with CAIS.
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Síndrome de Resistencia Androgénica , Cadherinas/genética , Dineínas/genética , Receptores Androgénicos/genética , Receptores LHRH/genética , Síndrome de Resistencia Androgénica/diagnóstico , Síndrome de Resistencia Androgénica/genética , Niño , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Recién Nacido , Masculino , Mutación , UltrasonografíaRESUMEN
INTRODUCTION: Charcot-Marie-Tooth (CMT) is the most common inherited polyneuropathy. Polyneuropathies are likely to affect the urogenital system. Urogenital dysfunction is rarely investigated and may be underestimated in CMT patients. AIM: The aim of the present study was to perform a systematic review of the literature to collect all the available evidence on the presence of urogenital dysfunction and in patients with CMT. METHODS: Data sources were MEDLINE, Pubmed, Scopus, and Google Scholar. All types of studies describing the presence of lower urinary tract dysfunction, erectile dysfunction (ED), anejaculation, and other sexual disorders in male patients with CMT were included. RESULTS: Among 131 records identified, five articles were included in the qualitative synthesis. Lower urinary tract dysfunction, neurogenic bladder, ED, and other sexual dysfunctions have been reported in patients with CMT. One case of anejaculation has been described. CONCLUSION: Urogenital dysfunction occurs in patients with CMT. Therefore, uro-andrologic counseling should be performed in the aging male with CMT. This might positively impact on his quality of life.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth , Disfunciones Sexuales Fisiológicas , Enfermedad de Charcot-Marie-Tooth/complicaciones , Humanos , Masculino , Calidad de Vida , Disfunciones Sexuales Fisiológicas/etiología , Sistema UrogenitalRESUMEN
Background: There is growing evidence showing a putative association between high-risk human papillomavirus (HR-HPV) infection and an increased risk of PCa.Objective: The aim of the current meta-analysis was to evaluate the association between HPV infection and PCa risk.Methods: This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We included all studies on HPV DNA or antibodies detected in biopsy tissues or sera. Available data were extracted from the article, including means and standard deviations in all case-control groups.Results: Thirty studies that investigated the link between HPV-16 and -18 were identified as eligible for this systematic review and meta-analysis, including a total of 6321 participants. The pooled OR showed increased risk of PCa (OR =1.37; p < .01) in men positive for HPV-16. There were seven studies with 2391 PCa cases and 4059 controls investigating the association between HPV-18 infection and PCa risk. Significant heterogeneity between study was found in the pooled analyzes. The pooled OR did not show increased risk of PCa (OR =0.80; p = .49) in men positive for HPV-18.Conclusions: This meta-analysis suggests that HPV-16 infection could represent a risk factor for PCa, whereas we found no such association for HPV-18. Further well-conducted studies could be useful to confirm this conclusion.
Asunto(s)
Infecciones por Papillomavirus/complicaciones , Neoplasias de la Próstata/virología , Humanos , Masculino , Factores de RiesgoRESUMEN
The Italian law 40/2004 allows the use of assisted reproduction techniques only if there are no other effective therapeutic approaches to overcome infertility. According to article 4 paragraph 1, the impossibility of removing the otherwise impeding causes to achieve a pregnancy must be ascertained before the couple undergoes assisted reproduction techniques. On this premises, we sought to evaluate the percentage of couples who underwent or were addressed to assisted reproduction techniques despite a known and potentially treatable male infertility factor in fertility centers in the city of Catania, Italy. To accomplish this, andrologists, urologists and endocrinologists were asked to report the number of couples already addressed to assisted reproduction techniques which they counseled in the trimester April-June 2018 having a under 35-year-old female partner and at least one among the following untreated conditions: (A) oligoasthenoteratozoospermia and FSH <8 mIU/ml, (B) third-degree varicocele (mono or bilateral form), and (C) leukocytospermia or urogenital infections. Of the 320 enrolled couples, 75 (23%) met the criterion A, 45 (14%) the criterion B, and 62 (19%) the criterion C. More than a half couples were addressed to assisted reproduction techniques despite a potentially treatable male infertility factor.