Lifestyle and sexual habits of students in a Southern Italian region.

BACKGROUND: Incorrect or harmful lifestyle during youth may impact negatively gonadal function later in life. To reduce the development of risky behaviors a series of health prevention and intervention campaigns have been conducted in Italy. The present study is part of a Sicily Region (Italy) health surveillance program that was carried out on a sample of late adolescents. METHODS: Between March 2022 to December 2022, we enrolled 718 adolescents (15-26 years old) attending the last two years of high school (278 males and 440 females) in the districts of Syracuse, Ragusa, Catania, and Agrigento (Sicily, Italy). All adolescents were invited to complete a questionnaire that explored their lifestyles and the student's knowledge of sexually transmitted diseases (STDs) and the main andrological diseases. RESULTS: Our analysis revealed that 43% of students smoke cigarettes, with a similar gender distribution; one-third of the students use illicit drugs, with a higher prevalence of males than females. More than two-thirds of youngsters reported drinking alcohol with a statistically significant difference between genders. 68.2% of students do not have sexual difficulties and males have a greater tendency to sexual promiscuity than females and only about half of them use condoms. 92% of students surf the Internet every day; boys tend to visit pornographic sites more often than girls. CONCLUSIONS: This survey revealed statistically significant differences between the two genders in terms of lifestyle and sexual habits. In particular, the survey shows that the prevalence of risky behaviour is still extremely high among late adolescents and young adults and that much still needs to be done in terms of prevention and information. Adequate prevention campaigns, to be proposed in the early years of adolescence, should be initiated in order to provide youngsters with adequate preparation in terms of healthy lifestyle habits.

Does the Ketogenic Diet Improve the Quality of Ovarian Function in Obese Women?

Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, the prevalence of which ranges from 8 to 13%. It is characterized by metabolic, reproductive, and psychological alterations. PCOS prevalence is related to body mass index (BMI). Women with BMI < 25 kg/m2 have a prevalence of 4.3%, whereas women with BMI > 30 kg/m2 have a prevalence of 14%. Moreover, women with PCOS have a risk of type 2 diabetes mellitus (T2DM) two-fold higher than controls, independently of BMI. Both PCOS and T2DM are also consequences of lower serum sex-hormone-binding globulin (SHBG) levels, which is currently considered a biomarker of metabolic disorders, in particular T2DM. Aim: To evaluate the effect of the very-low-calorie ketogenic diet (VLCKD) on markers suggested to be predictive of metabolic and ovulatory dysfunction. These comprehend SHBG, anti-Mullerian hormone (AMH), and progesterone levels on day 21 of the menstrual cycle in a cohort of obese non-diabetic women with PCOS and regular menses. Methods: Twenty-five patients (mean age 25.4 ± 3.44 years) with obesity and PCOS underwent VLCKD for 12 weeks. Each of them underwent measurements of anthropometric parameters (body weight, height, and waist circumference) and blood testing to evaluate serum levels of SHBG, AMH, and progesterone before and after 12 weeks of VLCKD. Results: At enrollment, all patients had high BMI, WC, and AMH, whereas SHBG and progesterone levels were low. After VLCKD, the patients showed a significant reduction in BMI, WC, and HOMA index. In particular, 76% of patients (19/25) switched from obesity to overweight, and the HOMA index normalized, reaching values lower than 2.5 in 96% (24/25) of patients. In addition, serum AMH levels significantly decreased, and progesterone and SHBG significantly increased after VLCKD. Conclusions: This is the first study documenting the effects of VLCKD on ovarian reserve and luteal function in women with PCOS. VLCKD could be used to improve metabolic and ovulatory dysfunction in women with PCOS. Further studies are needed to understand the reasons for the AMH reduction.

Beneficial Effects of the Very-Low-Calorie Ketogenic Diet on the Symptoms of Male Accessory Gland Inflammation.

Introduction. Obesity exposes individuals to the risk of chronic inflammation of the prostate gland. Aim and design of the study. A longitudinal clinical study was conducted on selected overweight/obese patients with male accessory gland inflammation (MAGI) to evaluate the effects of body weight loss on their urogenital symptoms. Materials and methods. One hundred patients were selected and assigned to two groups undergoing two different nutritional programs. The first group (n = 50) started a Mediterranean diet (MedDiet) and the second (n = 50) a very-low-calorie ketogenic diet (VLCKD). Before and after three months on the diet, each patient was evaluated for body weight, waist circumference, and MAGI symptoms. The MAGI was assessed using the Structured Interview about MAGI (SI-MAGI), a questionnaire previously designed to assess the symptoms of MAGI. The questionnaire explores four domains, including urinary symptoms, ejaculatory pain or discomfort, sexual dysfunction, and impaired quality of life. Finally, in the two groups, the frequency of an α-blocker used to treat urinary tract symptoms was also evaluated. Results. Patients on MedDiet experienced significant amelioration in urinary symptoms and quality of life. Patients under VLCKD reported not only significant improvement of the same parameters, but also in ejaculatory pain/discomfort and sexual dysfunction. Finally, the percentage of patients on VLCKD taking the α-blocker decreased significantly. Moreover, patients under VLCKD showed a greater loss of body weight than those following the MedDiet. Discussion. The results of this study support the effectiveness of VLCKD in improving the symptoms of patients with MAGI. This improvement involved all of the domains of the SI-MAGI questionnaire and became manifest in a relatively short time. We suggest that a ketogenic nutritional approach can be used in overweight/obese patients with MAGI.

Molecular Mechanisms Underlying the Relationship between Obesity and Male Infertility.

In recent decades, the worldwide prevalence of obesity has risen dramatically and is currently estimated to be around 20%. Obesity is linked to an increased risk of comorbidities and premature mortality. Several studies have shown that obesity negatively impacts male fertility through various mechanisms. This review aims to investigate the molecular mechanisms through which obesity impairs male reproduction, including obesity-associated hypogonadism and its effects on spermatogenesis, chronic inflammation, and oxidative stress. Obesity negatively impacts both conventional and biofunctional sperm parameters, and it also induces epigenetic changes that can be transferred to offspring. Moreover, obesity-related diseases are linked to a dysregulation of adipocyte function and micro-environmental inflammatory processes. The dysregulated adipokines significantly influence insulin signaling, and they may also have a detrimental effect on testicular function. Sirtuins can also play an important role in inflammatory and metabolic responses in obese patients. Understanding the molecular mechanisms that are involved in obesity-induced male infertility could increase our ability to identify novel targets for the prevention and treatment of obesity and its related consequences.

Very-low-calorie ketogenic diet: An alternative to a pharmacological approach to improve glycometabolic and gonadal profile in men with obesity.

Obesity and metabolic diseases have become a worrying reality, especially in more developed societies. They are associated with the development of many comorbidities, such as type 2 diabetes mellitus, hypogonadism, hypertension, cerebrovascular and cardiovascular diseases, neoplasia, obstructive sleep apnea, and non-alcoholic fatty liver disease. Therefore, weight loss is of paramount importance. A promising therapeutic option to achieve this goal is the very-low-calorie ketogenic diet. This review aims to summarize the main effects of very-low-calorie-ketogenic diet on the glycometabolic and gonadal profiles of men with overweight/obesity.

The Role of Resveratrol Administration in Human Obesity.

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.

GPR56 gene down-regulation in patients with Klinefelter Syndrome: a candidate for infertility?

BACKGROUND: The etiology of azoospermia in patients with Klinefelter Syndrome (KS) is still unknown. The protein codified by the G protein-couple receptor 56 (GPR56) belongs to the adhesion family of G protein-coupled receptors (GPRs). Its mutations are involved in the pathogenesis of intellectual disability and, according to animal studies, infertility. As the expression of GPR56 in patients with KS has not been investigated so far, this study was undertaken with the purpose of evaluating its expression in peripheral blood mononuclear cells (PBMCs) of patients with KS and normal controls. METHODS: This age-matched case-control study was performed in 10 patients with KS and 10 controls. Patients and controls underwent to blood sampling for next-generation sequencing (NGS) analysis, and differentially expressed mRNAs were identified using DESeq2 v.1.12. QRT-PCR was used to validate the results obtained by NGS analysis. TaqMan Gene Expression Assay primers were used to carry out the real-time PCR analysis for GPR56. RESULTS: GPR56 was down-regulated by -2081-fold (q-value <0.05) in PBMCs of patients with KS compared to controls. NGS data were confirmed by QRT-PCR. CONCLUSIONS: The possible contribution of the GPR56 gene down-regulation in the pathogenesis of spermatogenic failure in patients with KS is worthy to be further explored.

The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study.

BACKGROUND: Overweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on ß-cell function and total testosterone (TT) levels are less clear. AIM: To evaluate the effects of VLCKD on markers suggested to be predictive of ß-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism. METHODS: Patients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks. RESULTS: Twenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment. CONCLUSIONS: This is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve ß-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from ß-cell failure and metabolic hypogonadism.

SOX13 gene downregulation in peripheral blood mononuclear cells of patients with Klinefelter syndrome.

Klinefelter syndrome (KS) is the most common sex chromosome disorder in men. It is characterized by germ cell loss and other variable clinical features, including autoimmunity. The sex-determining region of Y (SRY)-box 13 (Sox13) gene is expressed in mouse spermatogonia. In addition, it has been identified as islet cell autoantigen 12 (ICA12), which is involved in the pathogenesis of autoimmune diseases, including type 1 diabetes mellitus (DM) and primary biliary cirrhosis. Sox13 expression has never been investigated in patients with KS. In this age-matched, case-control study performed on ten patients with KS and ten controls, we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls. This finding might be consistent with the germ cell loss typical of patients with KS. However, the role of Sox13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.

Effectiveness of a Very Low Calorie Ketogenic Diet on Testicular Function in Overweight/Obese Men.

BACKGROUND: Obesity has become an increasingly worrisome reality. A very-low-calorie ketogenic diet (VLCKD) represents a promising option by which to achieve significant weight loss. This study sought to evaluate the effectiveness of VLCKD on metabolic parameters and hormonal profiles of obese male patients. METHODS: We enrolled 40 overweight/obese men who consumed VLCKD for at least eight weeks. Body weight, waist circumference, fasting glucose, insulin, total cholesterol, high-density lipoprotein, triglycerides, creatinine, uric acid, aspartate aminotransferase, alanine aminotransferase, vitamin D, luteinizing hormone (LH), total testosterone (TT), and prostate-specific antigen (PSA) were calculated before and after VLCKD consumption. We additionally determined the homeostasis model assessment index and low-density lipoprotein (LDL) values. RESULTS: After VLCKD (13.5 ± 0.83 weeks), the mean body weight loss was 21.05 ± 1.44 kg; the glucose homeostasis and lipid profile were improved significantly; serum vitamin D, LH, and TT levels were increased and the PSA levels were decreased significantly as compared with pretreatment values. These results are of interest since obesity can lead to hypogonadism and in turn, testosterone deficiency is associated with impaired glucose homeostasis, metabolic syndrome, and diabetes mellitus. Moreover, a close relationship between obesity, insulin resistance, and/or hyperinsulinemia and increased prostate volume has been reported, with a consequent greater risk of developing lower urinary tract symptoms. CONCLUSIONS: VLCKD is an effective tool against obesity and could be a noninvasive, rapid, and valid means to treat obese patients with metabolic hypogonadism and lower urinary tract symptoms.

Testosterone levels after treatment with urofollitropin in infertile patients with idiopathic mild reduction of testicular volume.

INTRODUCTION: A reduction of testicular volume (TV) represents an important clinical sign, which may hide sperm abnormalities and predispose to hypogonadism. AIM: The primary purpose of this study was to evaluate the serum levels of total testosterone after treatment with urofollitropin in selected patients with male infertility and idiopathic mild reduction of testicular volume. METHODS: In this 1-year-long prospective design, patients with abnormal sperm parameters, mild reduction in TV (8-12 mL) and normal gonadotropin, and total testosterone (TT) serum levels were recruited in this study. Patients treated for 4 months with urofollitropin were included in group A, those treated with intracytoplasmatic sperm injection due to a female-factor infertility were included in group B. Hormone values, sperm parameters, and TV were detected at baseline (T0), after 4 (T1) and 12 months (T2) in group A and at T0 and T2 in group B. RESULTS: Group A (n = 80) showed increased follicle-stimulating hormone (FSH) at T1 and sperm morphology at T1 and T2 compared to T0 (all p < 0.05). Group B (n = 50) had lower TT and higher FSH levels at T2 compared to T0 (all p < 0.05). At T2, TT, VT, total sperm count, progressive motility, total motility, and sperm morphology were higher in group A compared to group B (all p < 0.05). CONCLUSION: Reduced TV may predispose to infertility and hypogonadism. FSH treatment may improve Sertoli and Leydig cell function and prevent the development of hypogonadism.

Poor Efficacy of L-Acetylcarnitine in the Treatment of Asthenozoospermia in Patients with Type 1 Diabetes.

Introduction. In recent years, research has focused on the impact that diabetes mellitus (DM) has on male reproductive function. The available evidence has mainly considered type 2 DM (DM2). However, we have previously shown that type 1 DM (DM1) also affects male reproductive health. Given the efficacy of carnitine in the treatment of male infertility, a topic that merits further investigation is its role in the treatment of infertile patients with DM1. Aim. To investigate the efficacy of carnitines for the treatment of asthenozoospermia in DM1 patients. Methods. This was a two-arm single-blind, randomized control trial. The patients enrolled in this study were assigned to the group receiving L-acetylcarnitine (LAC) (1.5 g daily for 4 months) or to the group receiving LAC (same dosage) plus L-carnitine (LC) (2 g daily for 4 months). Serum-glycated hemoglobin levels did not differ significantly after either of the two treatments given. Administration of LAC plus LC showed greater efficacy on progressive sperm motility than single therapy (increase 14% vs. 1% after treatment, respectively). Discussion. The results of this study showed that the administration of LAC plus LC is more effective than the administration of LAC alone. The lower efficacy of LAC alone could be due to the lower overall administered dosage. Alternatively, a selective defect of carnitine transporters at an epididymal level could be hypothesized in patients with DM1. Further studies are needed to clarify this point.

Early Identification of Isolated Sertoli Cell Dysfunction in Prepubertal and Transition Age: Is It Time?

The male transitional phase is of fundamental importance for future fertility. This aspect is largely neglected in clinical practice. This opinion aims to shed light on these issues. The children frequently complete the transition phase with a slight reduction of testicular volume. The system of detecting testicular volume is often inadequate. These patients evidently complete puberty in an incomplete way because they do not reach an adequate testicular volume, albeit in the presence of adequate height and regular secondary sexual characteristics.

Evidence for long noncoding RNA GAS5 up-regulationin patients with Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS) is characterized by the presence of at least one supernumerary X chromosome. KS typical symptoms include tall stature, gynecomastia, hypogonadism and azoospermia. KS patients show a higher risk of developing metabolic and cardiovascular diseases, inflammatory and autoimmune disorders, osteoporosis and cancer. Long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) has been shown to be involved in several biologic processes, including inflammatory and autoimmune diseases, vascular endothelial cells apoptosis and atherosclerosis, as well as cellular growth and proliferation, cellular development and cell-to-cell signaling and interaction. The lncRNA GAS5 expression profile in KS patients has never been evaluated so far. METHODS: To accomplish this, GAS5 mRNA levels were evaluated by Next Generation Sequencing (NGS) technology and qRT-PCR assay in 10 patients with KS and 10 age-matched controls. RESULTS: NGS results showed a significantly lncRNAGAS5up-regulation by 5.171-fold in patients with KS. Theresults of qRT-PCR confirmed the NGS data. CONCLUSIONS: These findings showed the occurrence of lncRNA GAS5 over-expression in KS patients. Whether this lncRNA is involved in the pathogenesis of inflammation and autoimmune diseases, atherogenesis or germ cell depletion in KS patients is not known. Further studies are needed.

Urogenital infections in patients with diabetes mellitus: Beyond the conventional aspects.

Diabetes mellitus (DM) is a widespread disease in our country. Urogenital infections, including urinary tract infections, vaginitis, balanitis, balanoposthitis, and male accessory gland infections, show a higher risk of occurrence in patients with DM that non-diabetic subjects. Both non-drug-related and drug-related mechanisms are involved in their pathogenesis. These conditions may impact on glucose control and islets function in DM and more likely develop into adverse complications. A throughout microbial characterization, including the drug-sensitivity test, is required for a proper management. To reduce the risk of recurrence, combined treatment, including antibiotic, anti-inflammatory, and fibrinolytic molecules, should be prescribed also to the sexual partner. The choice of the antidiabetic drug to prescribe should take into consideration the presence of urogenital infections. In conclusion, urogenital infections may more likely lead to complication in diabetic than non-diabetic patients, affect fertility and glucose control. Therefore, they need proper management.

Next Generation Sequencing expression profiling of mitochondrial subunits in men with Klinefelter syndrome.

Objectives: Klinefelter syndrome (KS) is one of the most common sex-chromosome disorders as it affects up to 1 in every 600-1000 newborn males. Men with KS carry one extra X chromosome and they usually present a 47,XXY karyotype, but less frequent variants have also been reported in literature. KS typical symptoms include tall stature, gynecomastia, broad hips, hypogonadism and absent spermatogenesis. The syndrome is also related to a wide range of cognitive deficits, among which language-based learning disabilities and verbal cognition impairment are frequently diagnosed. The present study was carried out to investigate the role of mitochondrial subunits in KS, since the molecular mechanisms underlying KS pathogenesis are not fully understood. Methods: The study was performed by the next generation sequencing analysis and qRT-PCR assay. Results: We were able to identify a significant down-expression of mitochondrial encoded NADH: ubiquinone oxidoreductase core subunit 6 (MT-ND6) in men with KS. Conclusion: It is known that defects of the mtDNA encoding mitochondrial subunits are responsible for the malfunction of Complex I, which will eventually lead to the Complex I deficiency, the most common respiratory chain defect in human disorders. Since it has been shown that decreased Complex I protein levels could induce apoptosis, wehypothesizethat the above-mentioned MT-ND6 down-expression contributes to the wide range of phenotypes observed in men with KS.

Decreased miRNA expression in Klinefelter syndrome.

The widelyvariable phenotypic spectrum and the different severity of symptoms in men with Klinefelter syndrome (KS) suggest a role for epigenetic mediators. Therefore, the aim of this study is to evaluate the possible involvement of miRNAs in the clinical manifestations of KS. To accomplish this, we performed a transcriptome analysis in peripheral blood mononuclear cells (PBMCs) of 10 non-mosaic KS patients, 10 aged-matched healthy men and 10 aged-matched healthy female controls with normal karyotype. After RNA extraction from PBMC and the preparation of RNA libraries, the samples were sequenced using next generation high-throughput sequencing technology. Expression profiling analysis revealed a significant differential expression of 2 miRNAs in KS compared to male controls. In particular, MIR3648 resulted significantly (q-value < 0.0001) down-regulated by -19.084- fold, while MIR3687was strongly down-regulated (q-value < 0.0001) considering KS patients. These results were confirmed by qRT-PCR. The functional analysis of the two transcripts showed that they seem to play a role in breast cancer, hemopoietic abnormalities, immune defects and adipocyte differentiation and fat cell maturation. Therefore, we speculate that both miRNAs may play a role in the immune and metabolic disorders and in the risk of breast cancer development in men with KS.

Late-onset hypogonadism: the advantages of treatment with human chorionic gonadotropin rather than testosterone.

The traditional pharmacological treatment of patients with late onset hypogonadism (LOH) is represented by different formulations of testosterone (T) or alternatively by the extractive human chorionic gonadotropin (HCG). The hormone replacement treatment (HRT) is associated with the potential increase of hematocrit, serum concentrations of prostate-specific antigen (PSA) and prostate volume. Moreover, the gynecomastia represent a condition frequently associated with HRT. Recent evidences showed the role of leydig cells in the 25-hydroxylation of vitamin D and the elevated frequency of hypovitaminosis D among LOH patients. Finally, another important aspect of LOH is represented by the frequency of secondary infertility due to age or to traditional HRT. This study evaluated 40 LOH patients treated for 6 months with extractive HCG (n = 10 patients) and three different formulations of T: transdermal (n = 10 patients), undecaonate (n = 10 patients) and enantate (n = 10 patients). Hormonal, anthropometric, metabolic and sperm parameters were evaluated and compared. Moreover, the main safety parameters and the results of the main questionnaires were evaluated. After treatment, HCG group showed serum concentrations of 25-OH-vitamin D significantly higher (p < 0.05) and serum concentrations of oestrogens significantly lower (p < 0.05) compared with other groups. Moreover, they showed a mean value of hematocrit, PSA and prostate volume significantly lower (p < 0.05) compared with other groups. Finally, all the groups treated with T showed a significant reduction (p < 0.05) of sperm density and of percentage of spermatozoa with progressive motility compared with HCG group.