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Introduction The counterfeit phenomenon is a largely under-reported issue, with potentially large burden for healthcare. The market for counterfeit drugs used in sexual medicine, most notably type 5 phosphodiesterase inhibitors (PDE5i), is rapidly growing. Aims To report the health risks associated with the use of counterfeit medications, the reasons driving their use, and the strategies enacted to contain this phenomenon. Methods A systematic scoping review of the literature regarding counterfeit PDE5i was carried between January and June 2021, then updated in August 2021. Main Outcome Measure We primarily aimed to clarify the main drivers for counterfeit PDE5i use, the health risks associated, and the currently available strategies to fight counterfeiters. Results One hundred thirty-one records were considered for the present scoping review. Production of fake PDE5i is highly lucrative and the lacking awareness of the potential health risks makes it a largely exploitable market by counterfeiters. Adulteration with other drugs, microbial contamination and unreliable dosages make counterfeit medications a cause of worry also outside of the sexual medicine scope. Several laboratory techniques have been devised to identify and quantify the presence of other compounds in counterfeit medications. Strategies aimed at improving awareness, providing antitampering packaging and producing non-falsifiable products, such as the orodispersible formulations, are also described. Clinical implications Improving our understanding of the PDE5i counterfeit phenomenon can be helpful to promote awareness of this issue and to improve patient care. Strengths & Limitations Despite the systematic approach, few clinical studies were retrieved, and data concerning the prevalence of counterfeit PDE5i use is not available on a global scale. Conclusion The counterfeit phenomenon is a steadily growing issue, with PDE5i being the most counterfeited medication with potentially large harmful effects on unaware consumers.

Background Vernal keratoconjunctivitis (VKC) is a bilateral, chronic, allergic condition mostly affecting children. Clinical evaluations may not necessarily reflect the impact of the disease on the patients' health-related quality of life (HRQoL). We aimed to evaluate HRQoL in children at VKC diagnosis and to analyze correlations between HRQoL and clinical and laboratory variables. Methods We studied 5- to 12-year-old patients with VKC. Data on clinical history, instrumental eye evaluations, blood examinations, and visual analog scale (VAS) for the subjective symptoms were collected. HRQoL was assessed through a disease-specific validated Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) questionnaire. Results Seventy subjects were included in the analysis (female/male: 10/60; tarsal/mixed VKC form: 36/34). Clinical severity of VKC according to the Bonini scale was as follows: 14, mild; 36, moderate; and 20, severe. No significant difference was found concerning the distribution of patient age, gender, and history of allergic manifestations between tarsal and mixed VKC. A significant positive correlation was found between all QUICK scores and VAS scores, including different VAS subscale, while no significant correlation was found between QUICK scores and total sign scores, Schirmer's test, and corneal thickness. The presence of active severe VKC was not associated with worse HRQoL. Conclusions Our evidence shows that VKC patients experience impairment of HRQoL, especially in relation to the perception of symptoms independently of the ophthalmologic changes found, and that the QUICK questionnaire could be a useful tool to evaluate HRQoL in children with VKC, which may improve patients' classification and management.

STUDY QUESTION Does pituitary response to a GnRH stimulation test differ according to the different FSHB-211 G/T genotypes? SUMMARY ANSWER The promoter polymorphism FSHB-211 G > T affects the pituitary response to exogenous GnRH stimulation by reducing FSH and increasing LH outputs. WHAT IS KNOWN ALREADY The FSHB-211 G > T single nucleotide polymorphism (SNP) is known to affect pituitary FSH output by impairing the transcriptional activity of FSHB. STUDY DESIGN, SIZE, DURATION This was a cross-sectional, retrospective study on 67 male subjects (mean age: 24.6 ± 10.3 years) undergoing a GnRH stimulation test for diagnostic purposes in cases of secondary hypogonadism. PARTICIPANTS/MATERIALS, SETTING, METHODS A GnRH stimulation test was performed by administering an i.v. bolus of 100 µg of the GnRH-analogue gonadorelin acetate to all patients, with blood samples drawn from the cubital vein immediately prior to injection (T0) and 30 (T1) and 45 minutes (T2) after. Clinical and genetic data were retrieved from a computerized database. Linear longitudinal mixed-effect models were used to assess the effects of SNP genotype on FSH and LH levels over time via additive and recessive models. MAIN RESULTS AND THE ROLE OF CHANCE An overall marked increase in serum FSH and LH following administration i.v. of 100 µg of an LHRH-analogue was found (P LIMITATIONS, REASONS FOR CAUTION Given the retrospective nature of the study and the small number of TT carriers, results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS The FSHB c.-211G>T polymorphism might result in an impaired response to endogenous, as well as exogenous, GnRH stimulation. This finding might contribute to the clinical phenotype of reduced testicular volume and sperm count for patients carrying one or two T alleles. STUDY FUNDING/COMPETING INTEREST(S) Parts of the study were supported by the German Research Foundation (CRU326 Male Germ Cells). On behalf of all authors, the corresponding author states that there is no conflict of interest. TRIAL REGISTRATION NUMBER NA.

Background Erectile dysfunction (ED), as the hallmark of endothelial dysfunction, could be a short‐ or long‐term complication of COVID‐19. Additionally, being ED a clinical marker and predictor of non‐communicable chronic diseases, particularly cardiovascular, subjects with ED could potentially have a higher risk of contracting COVID‐19. Objectives To investigate the prevalence of ED among subjects with a reported diagnosis of COVID‐19 and to measure the association of COVID‐19 and ED. Materials and methods We reviewed data from the Sex@COVID online survey (performed between April 7 and May 4, 2020, in Italy) to retrieve a sample of Italian male sexually active subjects with reported SARS‐CoV‐2 infection. A matching sample of COVID‐19‐negative male sexually active subjects was also retrieved using propensity score matching in a 3:1 ratio. The survey used different standardized psychometric tools to measure effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of Italian subjects. Results One hundred subjects were included in the analysis (25 COVID‐positive; 75 COVID‐negative). The prevalence of ED, measured with the Sexual Health Inventory for Men, was significantly higher in the COVID+ group (28% vs. 9.33%; p = 0.027). Logistic regression models confirmed a significant effect of COVID‐19 on the development of ED, independently of other variables affecting erectile function, such as psychological status, age, and BMI [OR 5.66, 95% CI: 1.50–24.01]. Likewise, subjects with ED were more likely to have COVID‐19, once corrected for age and BMI [OR 5.27, 95% CI: 1.49–20.09]. Discussion and conclusion On top of well‐described pathophysiological mechanisms, there is preliminary evidence in a real‐life population of ED as a risk factor of developing COVID‐19 and possibly occurring as a consequence of COVID‐19. Universal vaccination against the COVID‐19 and the personal protective equipment could possibly have the added benefit of preventing sexual dysfunctions.

Long term complications of COVID-19, the disease caused by the SARS-CoV-2, involve many organ systems, dramatically worsening the quality of life, and finally contributing to impaired physical functioning. Despite the presence of well-identified pathogenetic mechanisms, the effect of "Long COVID" on sexual health has been only marginally addressed.To provide coverage of the current literature on long COVID, its epidemiology, pathophysiology, and relevance for erectile function.Comprehensive review of literature pertaining to the epidemiology and pathophysiology of long COVID, and its relevance for erectile function.Symptoms of long COVID are highly prevalent and involve almost all systems of the human body, with a plethora of clinical manifestations which range from minor nuisances to life-threatening conditions. "Brain fog" and fatigue are the most common complaints, although other neuropsychiatric complications, including sensory dysfunctions, anxiety, depression, and cerebrovascular events have also been reported. The respiratory and cardiovascular systems are also affected, with dyspnea, pulmonary fibrosis, endothelial dysfunction, and myocarditis occurring in some COVID long haulers. A subset of patients might develop endocrine manifestations, including onset of diabetes, thyroid dysfunction, and hypogonadism. Overall, long COVID features many complications which can impair erectile function by multiple pathogenetic mechanisms, and which could require tailored treatment: (i) careful investigation and management from the sexual medicine expert are therefore much needed, (ii) and future research on this topic is warranted.in COVID-19 long haulers, several complications can adversely affect erectile function which, upon future tailored studies, could be used as biomarker for the severity of the long COVID disease and for its follow-up. Sansone A, Mollaioli D, Limoncin E et al. The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers. Sex Med Rev 2022;10:271-285.

Aging is a natural phenomenon, affecting human behavior and functions alike. While there is no way to “turn back time,” it is generally acknowledged that there are several factors which can ease the transition through a “healthy” aging. The endocrine milieu is perhaps one of the clearest representations of how much organic factors are involved in the development of comorbidities of aging, especially in women. Menopause, and to a lesser extent its male counterpart, late-onset hypogonadism (LOH), are universally recognized to have detrimental effects on sexual, as well as general health. Hormone replacement therapy is often suggested in order to reduce the often-debilitating symptoms of aging; however, such treatments are not to be suggested indiscriminately, and adequate evaluation and follow-up are mandatory. LOH and menopause are however just the tip of the iceberg, as most of the endocrine axes are somehow affected by age: the inevitable effects of age reach most organs, including the thyroid, adrenal, and pituitary glands. Even when the endocrine production does not decline, receptor sensitivity could be decreased, therefore resulting in impaired endocrine function despite normal serum hormone levels. Aging and hormones are therefore closely intertwined: endocrine factors affect aging, and aging alters the hormonal status. Whether treatment of aging-related endocrine alterations would result in improved health is a matter largely open to debate, as current literature does not allow to provide clear, undeniable evidence of such benefits.

Purpose Infertility represents a peculiar social burden affecting more than 15% of couples, provoking it a real threat to the general quality of life and to the sexual health. The medicalization (diagnosis, therapy and follow up) of the lack of fertility is frequently a challenge in term of personal and couple’s involvement. In particular, while the Assisted Reproductive Technology (ART) has allowed many infertile couples to achieve pregnancy, the therapeutic process faced by the couple bears a strong psychological stress that can affect the couple's quality of life, relationship and sexuality. Despite infertility affects both female and male sexual health, only recently the interest in the effects of ART on the couple's sexuality has grown, especially for women. Methods A literature research on the sexual dysfunction in fertility care and particularly in ART setting was performed. Results Literature largely found that intimacy and sexuality appear specifically impaired by intrusiveness of treatments and medical prescriptions. Moreover, there is a close relationship between emotional, psychological and sexual aspects, which can be integrated in the new concept of Inferto-Sex Syndrome (ISS) that can impair the ART treatment outcomes. Evidence demonstrates that the assessment of sexual function is necessary in couples undergoing diagnosis of infertility and ART. Conclusion A close relationship between infertility and sexuality, both in the female and male partners, was detected. ART treatments may heavily impact on the couple's psychosexual health. A couple-centred program for the integrated management of psychological and sexual dysfunction should be considered in the context of ART programs.

The theory of sexuality by Sigmund Freud represents a landmark for all the studies about human sexology, and not only from a historical point of view. However, the development of sexuality is not limited to the infancy, but is a process lasting during the entire arc of life, and it is characterized by several bio-psycho-social systems and relational factors.

Introduction . Hypersexuality is a clinical condition regarding the psychopathology of sexual behavior. In this study, we aimed to investigate the role of trauma, through the post-traumatic stress-disorder (PTSD), depression, shame and guilt on the hypersexual behavior. Methods . Through an online platform, a convenience sample of 1025 subjects was recruited (females: n=731; 71.3%; males: 294; 28.7%; age: 29.62±10.90). Recruited subjects compiled a psychometric protocol composed by the Hypersexual Behavior Inventory (HBI) to assess hypersexuality, the International Trauma Questionnaire (ITQ) for PTSD, the Patient Health Questionnaire (PHQ-9) to evaluate depression and the State Shame and Guilt Scale (SSGS) for shame and guilt. Then a mediation/moderation model was performed for the data analysis. Results . There was a statistically significant direct effect of post-traumatic symptoms (ITQTotal) on hypersexual behavior (HBTotal). Furthermore, indirect effects were also statistically significant, providing support to the hypothesis that depression and guilt would be serial mediators of trauma-hypersexual behavior relations. The paths through depression and guilt have been found to be the most significant with moderate and high indirect effects on hypersexuality. Moreover, male gender, as covariate variable, is a relevant risk factor for hypersexual behavior. Conclusion . We found the relationship between hypersexuality and trauma describing a possible etiological pathway mainly involving depression, shame and guilt. Hypersexuality can be considered as a reactive form of a major affective psychopathology representing a tip of the iceberg hiding the real issues of a suffering personality. Clinicians and researchers should therefore consider hypersexual behavior in the light of a symptomatic manifestation of a major psychopathology involving the affective aspects of personality.

Background Penis size is a highly sensitive topic, which has often raised concerns associated with human masculinity and male sexual health. Although data regarding penile dimensions have been published worldwide, little is known about these measurements in South-East Asian countries. Objective This study aimed to provide the reference range in penile length, circumference, and diameter of Vietnamese men and their variations among men with erectile dysfunction and other diseases. Materials and methods Information about flaccid length, stretched length, mid-shaft circumference, and glans diameter from the health records of 14,597 men attending the Andrology Consultation was collected. These men were classified into three groups being regular reproductive health screening group, sexual dysfunction group, and other disease groups. Results We found that penile dimensions follow a non-parametric distribution, as tested by Kolmogorov-Smirnov test. The median values are 9.03 cm for flaccid length, 14.67 cm for stretched length, 8.39 cm for mid-shaft circumference, and 2.86 cm for unaroused glans diameter. Length and girth of the penis also changed among the different groups, especially in flaccid state; specifically, men with erectile dysfunction had a greater value in all penile dimensions except for change ratio compared with other groups. Circumcision, which rarely occurs in Vietnam, was associated with a 2 mm reduced penis length. Discussion Findings on correlations between penile dimensions and somatometric parameters from previous studies are questionable and some measurements, such as glans dimension, have not been thoroughly investigated so far. Nevertheless, penile dimensions provide useful insight concerning conditions affecting sexual development and might be a valuable parameter in the assessment of erectile dysfunction. Conclusion Results of this study provide informative materials for the assessment of penile size, including reference values drawn from a large sample of Vietnamese men that can be useful in clinical practice and sexual health education.

Purpose Symptoms of hypogonadism are often reported by subjects with normal serum testosterone (T) levels. We aimed to assess the association between clinical symptoms in andrological outpatients and sex steroids levels. Methods This is a retrospective cross-sectional cohort study in an Academic clinic and research unit. International Index of Erectile Function (IIEF, EF domain) and Aging Males Symptoms scale (AMS) questionnaires were completed by 635 and 574 men, respectively (mean age: 47.3 ± 13.9 and 47.4 ± 13.8 years, p = 0.829), free of interfering medications with complaints possibly related to hypogonadism. Results Serum total/free T as well as dihydro-T (DHT) was associated with IIEF-EF and AMS scores in the overall population using univariate analyses. Multivariate approaches revealed DHT concentrations in subjects with normal T levels (n = 416, Total T > 12 nmol/L) to be significant predictors of AMS scores. A 0.1 nmol/l serum DHT increase within the eugonadal range was associated with a 4.67% decrease in odds of having worse symptoms (p = 0.011). In men with biochemical hypogonadism (Total T Conclusion DHT can be associated with symptoms of hypogonadism in biochemically eugonadal men. Serum DHT measurement might be helpful once the diagnosis of hypogonadism has been ruled out but should not be routinely included in the primary diagnostic process.

Premature ejaculation (PE) is the most prevalent male sexual dysfunction, and the most recently defined. PE is often mistakenly considered a purely psychosexological symptom by patients: the lacking awareness in regards to the pathophysiology and treatments often lead to resignation from the patients' side, making PE the most underdiagnosed sexual complaint. However, an ever-growing body of evidence supporting several organic factors has been developed in the last decades and several definitions have been suggested to encompass all defining features of PE. In the present document by the Italian Society of Andrology and Sexual Medicine (SIAMS), we propose 33 recommendations concerning the definition, pathophysiology, treatment and management of PE aimed to improve patient care. These evidence-based clinical guidelines provide the necessary up-to-date guidance in the context of PE secondary to organic and psychosexological conditions, such as prostate inflammation, endocrine disorders, and other sexual dysfunctions, and suggest how to associate pharmacotherapies and cognitive-behavioral therapy in a couple-centered approach. New therapeutic options, as well as combination and off-label treatments, are also described.

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, &ldquo, responders&rdquo, and &ldquo, non-responders&rdquo, were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of &ldquo, aiming to organize surveillance and eventual revaccination strategy.

Sentiment analysis (SA) is a technique aimed at extracting opinions and sentiments through the analysis of text, often used in healthcare research to understand patients&rsquo, needs and interests. Data from social networks, such as Twitter, can provide useful insights on sexual behavior. We aimed to assess the perception of Valentine&rsquo, s Day by performing SA on tweets we collected between 28 January and 13 February 2019. Analysis was done using ad hoc software. A total of 883,615 unique tweets containing the word &ldquo, valentine&rdquo, in their text were collected. Geo-localization was available for 48,918 tweets, most the tweets came from the US (36,889, 75.41%), the UK (2605, 5.33%) and Canada (1661, 3.4%). The number of tweets increased approaching February 14. &ldquo, Love&rdquo, was the most recurring word, appearing in 111,981 tweets, followed by &ldquo, gift&rdquo, (55,136), &ldquo, special&rdquo, (34,518) and &ldquo, happy&rdquo, (33,913). Overall, 7318 tweets mentioned &ldquo, sex&rdquo, among these tweets, the most recurring words were &ldquo, sexy&rdquo, (2317 tweets), &ldquo, love&rdquo, (1394) and &ldquo, (679), words pertaining to intimacy and sexual activity, such as &ldquo, lingerie&rdquo, &ldquo, porn&rdquo, and &ldquo, date&rdquo, were less common. In conclusion, tweets about Valentine&rsquo, s Day mostly focus on the emotions, or on the material aspect of the celebration, and the sexual aspect of Valentine&rsquo, s Day is rarely mentioned.

Background.: Diabetes mellitus (DM), one of the worldwide leading causes of death, is associated with a plethora of micro- and macro-vascular complications which should be carefully investigated and, in case, treated in order to improve quality of life and reduce the risk of premature mortality. Objective: The study aimed to investigate and report current evidence with regard to the association between sexual dysfunction and diabetes. Methods: A detailed analysis of current literature has been performed on PubMed and Scholar in order to retrieve the most relevant findings pertaining to the study topic. Results: Female and male sexual dysfunction often occurs in diabetes; while cardiovascular complications are clearly involved, psychosexological factors, endocrine complications, and endothelial dysfunction all contribute to the pathogenesis of sexual dysfunctions. Psychological symptoms are seldom investigated, yet they should not be overlooked by the clinician; in fact, an interplay between sexual dysfunctions and depressive symptoms has been reported, and beneficial effects in both conditions might be obtained by adequate psychological support. Sexual dysfunctions can also act as early biomarkers of cardiovascular disease, a phenomenon frequently reported in men, in which erectile dysfunction predicts the development of coronary artery disease. Additionally, drug therapies can act in both directions, with treatments for diabetes possibly improving male sexual function and exerting beneficial effects for cardiovascular health being reported for pro-erectile drugs. Conclusion: Sexual dysfunctions often occur in men and women with diabetes. Investigating micro- and macro-vascular complications might not be enough to prevent the development or worsening of any sexual dysfunction; endocrine and psychological assessments are therefore needed to provide the best chances for adequate treatment.

BACKGROUND: The COVID-19-related lockdown has profoundly changed human behaviors and habits, impairing general and psychological well-being. Along with psychosocial consequences, it is possible that sexual behavior was also affected. AIMS: With the present study, we evaluated the impact of the community-wide containment and consequent social distancing on the intrapsychic, relational, and sexual health through standardized psychometric tools. METHODS: A case-control study was performed through a web-based survey and comparing subjects of both genders with (group A, N = 2,608) and without (group B, N = 4,213) sexual activity during lockdown. The Welch and chi-square tests were used to assess differences between groups. Univariate analysis of covariance, logistic regression models, and structural equation modeling were performed to measure influence and mediation effects of sexual activity on psychological, relational, and sexual outcomes. OUTCOMES: Main outcome measures were General Anxiety Disorder-7 for anxiety, Patient Health Questionnaire-9 for depression, Dyadic Adjustment Scale for quality of relationship and a set of well-validated sexological inventories (International Index of Erectile Function, Female Sexual Function Index, and male-female versions of the Orgasmometer). RESULTS: Anxiety and depression scores were significantly lower in subjects sexually active during lockdown. Analysis of covariance identified gender, sexual activity, and living without partner during lockdown as significantly affecting anxiety and depression scores (P

The present study aims to evaluate the relationship in women between a history of physical/sexual abuse and the preferences regarding the choice of a partner for a short/long-term relationship in terms of male facial dimorphism, and to assess their sexual functioning. We enrolled 48 abused women and 60 non-abused women. Facial preferences were evaluated with the Morphing test. Sexual functioning was measured with the Female Sexual Function Index (FSFI). Regarding the choice for a short-term partner, abused and non-abused women did not show any differences, and both groups chose a less masculine male face. On the other hand, regarding the choice for a long-term partner, abused women showed a preference for an average male face, whilst non-abused women preferred a less masculine face. The sexual functioning of abused women was found significantly dysfunctional in all domains of the FSFI. These data, generated from a small but highly selected cohort, demonstrated that physical/sexual abuse may be associated with a more rational and conscious choice of a male partner for a long-term relationship, but not with an instinctive one, as the choice of an occasional partner. In addition, the sexual functioning of abused women appears to be compromised by the traumatic experience.

Purpose The COVID-19 pandemic, caused by the SARS-CoV-2, represents an unprecedented challenge for healthcare. COVID-19 features a state of hyperinflammation resulting in a “cytokine storm”, which leads to severe complications, such as the development of micro-thrombosis and disseminated intravascular coagulation (DIC). Despite isolation measures, the number of affected patients is growing daily: as of June 12th, over 7.5 million cases have been confirmed worldwide, with more than 420,000 global deaths. Over 3.5 million patients have recovered from COVID-19; although this number is increasing by the day, great attention should be directed towards the possible long-term outcomes of the disease. Despite being a trivial matter for patients in intensive care units (ICUs), erectile dysfunction (ED) is a likely consequence of COVID-19 for survivors, and considering the high transmissibility of the infection and the higher contagion rates among elderly men, a worrying phenomenon for a large part of affected patients. Methods A literature research on the possible mechanisms involved in the development of ED in COVID-19 survivors was performed. Results Endothelial dysfunction, subclinical hypogonadism, psychological distress and impaired pulmonary hemodynamics all contribute to the potential onset of ED. Additionally, COVID-19 might exacerbate cardiovascular conditions; therefore, further increasing the risk of ED. Testicular function in COVID-19 patients requires careful investigation for the unclear association with testosterone deficiency and the possible consequences for reproductive health. Treatment with phosphodiesterase-5 (PDE5) inhibitors might be beneficial for both COVID-19 and ED. Conclusion COVID-19 survivors might develop sexual and reproductive health issues. Andrological assessment and tailored treatments should be considered in the follow-up.

Background and Aims. Neurotensin (NT) is a gut hormone secreted by specific endocrine cells scattered throughout the epithelial layer of the small intestine, which has been identified as an important mediator in several gastrointestinal functions and disease conditions. Its potential involvement in celiac disease (CD) has been investigated, but there are conflicting findings. The aim of this study was to evaluate serum NT levels in children with CD at diagnosis, compared to a control group, and to investigate whether NT correlated in CD patients with symptoms, antibody response, and intestinal mucosal damage.Materials and Methods. Children (1-16 years old) undergoing gastrointestinal endoscopy for CD or for other clinical reasons were included in this study. Patients with CD diagnosed according to the 2012 European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines without biopsy were also recruited. Fasting serum samples were analyzed for NT levels using ELISA. Logistic regression, Wilcoxon rank sum, and Spearman’s rank tests were used for statistical analysis.Results. Thirty children (18 females, 2.2-15.9 years old) were enrolled. Of 25 patients who underwent endoscopy, 9 were CD patients, 13 were controls, and 3 were excluded due to nonspecific inflammation at duodenal biopsy. CD was diagnosed in 5 patients without biopsy. NT median was higher in CD patients compared to controls (13.25 (IQR 9.4-17.5) pg/ml vs. 7.8 (IQR 7.6-10) pg/ml;p=0.02). No statistically significant association between NT and clinical, serological, or histological data of CD was observed in this CD cohort.Conclusions. To our knowledge, this is the first study that evaluates NT in CD children from Italy. Results show that NT is higher in the serum of CD children at diagnosis compared to controls. However, larger-scale studies are required to validate these findings. Whether serum NT levels can be an adjunctive marker for pediatric CD remains currently elusive.

Cancer therapy and conditioning treatments of non-malignant diseases affect spermatogonial function and may lead to male infertility. Data on the molecular properties of spermatogonia and the influence of disease and/or treatment on spermatogonial subpopulations remain limited. Here, we assessed if the density and percentage of spermatogonial subpopulation changes during development (n = 13) and due to disease and/or treatment (n = 18) in tissues stored in fertility preservation programs, using markers for spermatogonia (MAGEA4), undifferentiated spermatogonia (UTF1), proliferation (PCNA), and global DNA methylation (5mC). Throughout normal prepubertal testicular development, only the density of 5mC-positive spermatogonia significantly increased with age. In comparison, patients affected by disease and/or treatment showed a reduced density of UTF1-, PCNA- and 5mC-positive spermatogonia, whereas the percentage of spermatogonial subpopulations remained unchanged. As an exception, sickle cell disease patients treated with hydroxyurea displayed a reduction in both density and percentage of 5mC- positive spermatogonia. Our results demonstrate that, in general, a reduction in spermatogonial density does not alter the percentages of undifferentiated and proliferating spermatogonia, nor the establishment of global methylation. However, in sickle cell disease patients’, establishment of spermatogonial DNA methylation is impaired, which may be of importance for the potential use of this tissues in fertility preservation programs.

PurposeIn males, AMH is secreted by immature Sertoli cells; following exposure to endogenous androgens, Sertoli cells undergo a process of maturation which ultimately inhibits AMH expression to undetectable levels in the serum. However, expression of AMH receptor (AMHR-2) has never been studied in human testes, and high intratubular concentrations of AMH have been reported in recent literature. We therefore assessed expression of AMHR-2 in several testicular tissue samples by immunohistochemistry (IHC).MethodsThe IHC method was first validated on tissue samples from healthy human testis (n = 2) and from marmoset ovary (n = 1). The same method was then used for assessment on testicular histopathology specimens from patients with mixed atrophy (MA,n = 2), spermatogenetic arrest (SA,n = 2), Sertoli cell-only syndrome (SCO,n = 1), Klinefelter syndrome (KS,n = 1), and nonseminomatous germ cell tumors (NSGCT,n = 1). Tissue samples from two subjects at different pubertal stages (AndroProtect (AP), aged 5 and 14 years) with hematological malignancies were also retrieved.ResultsIn adult men, AMHR-2 was expressed on peritubular mesenchymal cells, with patterns closely mirroring α-smooth muscle actin expression. Similar patterns were preserved in almost all conditions; however, in nonseminomatous germ cell tumors the tissue architecture was lost, including AMHR-2 expression. More positive and diffuse staining was observed in tissue samples from prepubertal testes.ConclusionsIn specimens from both healthy and affected testes, AMHR-2 expression appears weaker in adult than in prepubertal tissue sections. The persistence of AMHR-2 expression seemingly hints at a possible effect of intratesticular AMH on the tubular walls.

Background Opportunities and pitfalls of e-health have been described and assessed in various health domains, but in the field of sexual health, the respective literature is limited. Aim The aim of this document is to present the European Society of Sexual Medicine’s (ESSM) current position statement on e-sexual health. Methods This statement article is an expert opinion–based proposal that was developed under the auspices of the ESSM with input from the e-sexual health subcommittee of the ESSM Scientific Committee. Outcomes ESSM statements were provided on four domains: health information for patients, e-learning for professionals, health interventions, and health research. Results e-Sexual health is the use of information and communication technologies for sexual health including sexual health care, surveillance, education, knowledge, and research. Quality indicators have to be applied on Web pages that provide sexual health information, e-learning can increase educational opportunities for professionals, online treatment interventions can be effective but needs to be available to the public, and online health research can provide access to difficult to reach populations. Clinical Implications The ESSM acknowledges the necessity for the use of information and communication technologies to meet the sexual health needs of citizens and patients and also the professional needs of sexual healthcare providers, in an evidence-based manner. Strengths & Limitations ESSM statements on this topic were provided based on expert opinion and summarize the ESSM position in this field. Conclusion The ESSM believes that e-sexual health can provide opportunities for the improvement of the sexual health of the population.

Purpose: To systematically review the impact of smoking habits on cardiovascular (CV) as well as on male sexual and reproductive function and to provide updated evidence on the role of electronic cigarettes (e-Cig) on the same topics. Methods: A comprehensive Medline, Embase, and Cochrane search was performed including the following words: smoking, CV system, CV risk, erectile dysfunction (ED), and male fertility. Publications from January 1, 1969 up to February 29, 2020 were included. Results: Smoking has a tremendous negative impact on CV mortality and morbidity. Current smoking behavior is also negatively associated with erectile dysfunction (ED) and impaired sperm parameters. E-Cig can release significantly lower concentrations of harmful substances when compared to regular combustible cigarettes. Whether or not the latter can result in positive CV, sexual, and fertility outcomes is still under study. Preliminary studies showed that exposure to e-Cig leads to lower vascular damage when compared to the traditional cigarette use. However, data on the long-term effects of e-Cig are lacking. Similarly, preliminary data, obtained in animal models, have suggested a milder effect of e-Cig on erectile function and sperm parameters. Conclusion: Available evidence showed that e-Cig are much less dangerous when compared to the traditional tobacco use. However, it should be recognized that the risk related to e-Cig is still higher when compared to that observed in non-smoking patients. Hence, e-Cig should be considered as a potential tool, in the logic of harm reduction, to reduce the CV, sexual and fertility risk in patients refractory to the fundamental, healthy choice to definitively quit smoking.

Despite several studies showing an inverse correlation of total testosterone with endothelial damage, the effect of testosterone replacement therapy (TTh) on endothelial function has been scarcely investigated. In order to systematically assess the relationship between endothelial dysfunction and TTh, we performed a review and meta-analysis of available prospective and cross-sectional studies. A thorough research was performed on MEDLINE for hypogonadism and endothelial dysfunction. We retrieved 28 papers, among which 23 were excluded for different reasons: five papers accounting for six studies (two crossover randomized clinical trial (RCT), three observational, one placebo controlled RCT) were therefore included in analysis. Overall, 86 patients with hypogonadism were included in analysis (mean age 49.57 ± 8.85 years). Baseline total testosterone serum levels were 8.11 ± 2.42 nmol/L and significantly increased while undergoing TTh (standard mean difference (SMD) 2.93 nmol/L, 95% confidence interval (CI) 1.89:3.97, p

Negli adolescenti e nei giovani adulti, la salute sessuale e riproduttiva e un bene prezioso, da tutelare e proteggere; tuttavia, sin troppo spesso la letteratura scientifica trascura questa importante fase della vita. Scopo di questa rassegna e discutere delle principali problematiche della sessualita dei giovani, identificando i fattori di rischio, approfondendo il ruolo di Internet e le possibili ricadute sulla salute sessuale.

We develop an algorithm that relates the incubation time for flash initiation to the workpiece velocity as it is pulled through stationary electrodes in a continuous flash sintering experiment. Experiments with a whiteware green body that is sintered in this way are compared with the model. A processing map when the workpiece is drawn at a constant velocity is developed. The parameter space for the map is given by the speed and the current flowing through the workpiece. It distinguishes between the regimes for uniform and inhomogeneous sintering. All experiments were carried out at a furnace temperature of 900°C. The study shows the viability of continuous flash sintering of ceramics at speeds of up to 3 mm s−1 with electrodes that form a line contact with the workpiece. Remarkably, higher velocities and higher currents yield better sintering.

Introduction Tinder is the most popular and used meeting application for dating. However, its impact on sexual behavior and sexual health has not yet been thoroughly investigated. Objectives To review the current empirical knowledge on the sexual health and sexual behavior effects related to Tinder use. Methods A literature review was conducted based on empirical studies published in the last 5 years. A computerized search was performed to identify all relevant studies in PubMed and Google Scholar. The following search terms were used: “Tinder” AND “Sexuality” OR “Tinder” AND “Sexual Behavior” OR “Tinder” AND “Sexual Dysfunctions” OR “Tinder” AND “Sexual Health.” 34 articles fully satisfied the established criteria. Results We found sociosexuality, that is, sexual activities outside a committed relationship, to be the main predictor for casual sex in the Tinder users. The sexual aims appeared gender-influenced: men used Tinder mostly for casual sex compared with women. With respect to other dating apps, it has been also found that the Tinder use is less related to the risk of sexually transmitted infections. However, specific personality traits related to dark personality (ie, the association of Machiavellianism, narcissism, and psychopathy) were more frequently reported among male Tinder users. Conclusion Existing literature concerning Tinder use shows the advantages and disadvantages of this dating technology. Casual sex might be a risk for sexual health, but Tinder users have also been committed to romantic relationships. Moreover, some pathological aspects of personality characterize some Tinder users. From an evolutionary perspective, sociosexuality partially explains the reasons of the Tinder user's interest for casual sex. Finally, this review highlights the need of further studies on Tinder as a new, pivotal virtual place to promote sex education and sexual health. Ciocca G, Robilotta A, Fontanesi L, et al. Sexological Aspects Related to Tinder Use: A Comprehensive Review of the Literature. Sex Med Rev 2020;8:367–378.

In recent years, endocrine disrupting chemicals have gained interest in human physiopathology and more and more studies aimed to explain how these chemicals compounds affect endocrine system. In human populations, the majority of the studies point toward an association between exposure to endocrine disrupting chemicals and the disorders affecting endocrine axis. A great number of endocrine disrupting chemicals seem to be able to interfere with the physiology of hypothalamus-pituitary-gonadal axis; however, every endocrine axis may be a target for each EDCs and their action is not limited to a single axis or organ. Several compounds may also have a negative impact on energy metabolic homeostasis altering adipose tissue and promoting obesity, metabolic syndrome, and diabetes. Different mechanism have been proposed to explain these associations but their complexity together with the degree of occupational or environmental exposure, the low standardization of the studies, and the presence of confounding factors have prevented to establish causal relationship between the endocrine disorders and exposure to specific toxicants so far. This manuscript aims to review the state of art of scientific literature regarding the effects of endocrine-disrupting chemicals (EDCs) on endocrine system.

Background It is commonly accepted that testicular function is prevalently regulated by the hypothalamic-pituitary-gonadal axis: The pulsatile secretion of GnRH by the hypothalamus induces pituitary expression of the two gonadotropins FSH and LH, which then stimulate Sertoli and Leydig cells, respectively, therefore regulating steroidogenesis and spermatogenesis. However, a growing body of evidence has recently suggested that other hormones act on the reproductive tract since the early phases of fetal development. Anti-Mullerian hormone and INSL3 are still largely used only for research purposes despite being increasingly recognized as markers of Sertoli and Leydig cells function, respectively. Objectives Provide an up-to-date review of the role of anti-Mullerian hormone and INSL3 in human pathophysiology according to current evidence. Materials and methods A thorough literature review was performed on PubMed, OVID MEDLINE/EMBASE and Google Scholar for papers concerning anti-Mullerian hormone and INSL3 in human males. Results INSL3 is not acutely regulated by the hypothalamic-pituitary axis but is constitutively secreted by Leydig cells, therefore representing a valid marker for their number and status. Anti-Mullerian hormone expression, on the other hand, is downregulated by androgens, therefore occurring mostly at the early stages of testicular differentiation and before the onset of puberty. Several conditions affecting testicular development, such as male hypogonadotropic hypogonadism, and their treatment have been associated to specific pattern of INSL3 and anti-Mullerian hormone expression, proving a role for both hormones in the diagnostic and therapeutic management. Recent reports suggest a role for both anti-Mullerian hormone and INSL3 in extra gonadal physiology, such as cardiovascular and bone health. Conclusion Anti-Mullerian hormone and INSL3 are markers of Sertoli and Leydig cells maturation, respectively, usually involved in the pathogenesis of disorders of sexual differentiation. However, their role in testicular pathology has only been hinted at in the last decades. Recent evidence supports an involvement of both anti-Mullerian hormone and INSL3 in extragonadal pathophysiology as well.

Background Risk factors established during adolescence affect health outcomes in adulthood, although little is known about how adolescent health risk behaviours (HRBs) affect testicular development and reproductive health. Objectives To assess prevalence of HRBs among last year high school students; to describe the most prevalent andrological disorders in this cohort; to explore HRBs associated with andrological disorders and investigate factors possibly associated with impaired testicular development in puberty. Materials and methods The Amico-Andrologo Survey is a permanent nationwide surveillance programme conducted by the Italian Society of Andrology and Sexual Medicine and supported by the Ministry of Health. A nationally representative survey of final-year male high school students was conducted using a validated structured interview (n = 10124) and medical examination (n = 3816). Results Smoking (32.6%), drinking (80.6%) and use of illegal drugs (46.5%) are common in adolescence. 16.6% of subjects were overweight, 3.1% were underweight and 2.3% were obese. Among sexually active students (60.3%), unprotected sex was very common (48.3%). Only 11.6% had been treated for andrological disorders, despite an abnormal clinical examination in 34.6%. Bilateral testicular hypotrophy (14.0%), varicocoele (27.1%) and phimosis (7.1%) were the most prevalent disorders; 5.1% complained of premature ejaculation and 4.7% had an STI. Underweight and heavy alcohol or drug use were associated with testicular hypotrophy. HRBs emerged as significant predictors of testicular hypotrophy, explaining up to 9.6% of its variance. Limitations include risk of selection bias for voluntary physical examination and recall bias for the self-compiled questionnaire. Discussion There is an emerging global adverse trend of HRBs in male high school students. A significant proportion of adolescent males with unsuspected andrological disorders engage in behaviours that could impair testicular development. Conclusion Greater attention to the prevention of andrological health in adolescence is needed.

Varicocele is a common finding in men. Varicocele correction has been advocated for young patients with testicular hypotrophy, but there is a lack of morphofunctional follow-up data. We assessed whether percutaneous treatment of left varicocele is associated with testicular “catch-up growth” in the following 12 months by retrospectively reviewing data from an electronic database of 10 656 patients followed up in our clinic between 2006 and 2016. We selected all young adults (

The diagnosis of neuroendocrine tumors (NETs) is a challenging task: Symptoms are rarely specific, and clinical manifestations are often evident only when metastases are already present. However, several bioactive substances secreted by NETs can be included for diagnostic, prognostic, and predictive purposes. Expression of these substances differs between different NETs according to the tumor hormone production. Gastroenteropancreatic (GEP) NETs originate from the diffuse neuroendocrine system of the gastrointestinal tract and pancreatic islets cells: These tumors may produce many non-specific and specific substances, such as chromogranin A, insulin, gastrin, glucagon, and serotonin, which shape the clinical manifestations of the NETs. To provide an up-to-date reference concerning the different biomarkers, as well as their main limitations, we reviewed and summarized existing literature.

Gynecomastia-the enlargement of male breast tissue in men-is a common finding, frequently observed in newborns, adolescents, and old men. Physiological gynecomastia, occurring in almost 25 % of cases, is benign and self-limited; on the other hand, several conditions and drugs may induce proliferation of male breast tissue. True gynecomastia is a common feature often related to estrogen excess and/or androgen deficiency as a consequence of different endocrine disorders. Biochemical evaluation should be performed once physiological or iatrogenic gynecomastia has been ruled out. Non-endocrine illnesses, including liver failure and chronic kidney disease, are another cause of gynecomastia which should be considered. Treating the underlying disease or discontinuing medications might resolve gynecomastia, although the psychosocial burden of this condition might require different and careful consideration.

Sexual function is an important component of either general health and quality of life in both genders. Many studies have focused on the different risk factors for sexual dysfunctions, proving an association with several medical conditions. Endocrine disorders have been often mentioned in the pathogenesis of female and male sexual dysfunctions; however, particularly in women, sexual function is rarely addressed during clinical, in general, and endocrinological, in particular, consultations. As a thorough diagnosis is required in order to provide an adequately tailored treatment, knowing how each endocrine dysfunction can impair sexual health is of the utmost importance, considering the high prevalence of conditions such as disorders of pituitary, thyroid, adrenal, gonads, as well as metabolic disorders. We performed a thorough review of existing literature on the different mechanisms involved in the pathogenesis of female sexual dysfunctions secondary to endocrine disorders in order to provide an up-to-date reference.

Priorities for every athlete include improving endurance performance, optimizing training, nutrition, and recovery. Nutritional strategies are crucial to support athletes to perform at the highest level, and considering that muscular and hepatic glycogen stores are limited, alternative strategies to maximize fat metabolism have been suggested. A ketogenic diet has been proposed as a possible method of providing metabolic fuel during prolonged periods of exercise. However, clinical trials and empirical experience have produced contrasting results regarding the ergogenic value of a ketogenic diet. For this reason, using ketone esters and/or salts have been proposed to obtain nutritional ketosis without limiting carbohydrate intake. Exogenous ketones should not only represent an alternative metabolic fuel source, sparing carbohydrates, but they also may increase postexercise glycogen replenishment, decrease proteolysis, and act as metabolic modulators and signaling metabolites. While there are some encouraging results showing an increase in endurance performance, contrasting evidence regarding the efficacy of exogenous ketones for endurance performance is present and further studies should be performed to make a definitive statement.

Among behavioral addictions, problematic Internet use and online pornography consumption are often cited as possible risk factors for sexual dysfunction, often with no definite boundary between the two phenomena. Online users are attracted to Internet pornography because of its anonymity, affordability, and accessibility, and in many cases its usage could lead users through a cybersex addiction: in these cases, users are more likely to forget the “evolutionary” role of sex, finding more excitement in self-selected sexually explicit material than in intercourse.

In recent decades, the decline in human fertility has become increasingly more worrying: while therapeutic interventions might help, they are vexing for the couple and often burdened with high failure rates and costs. Prevention is the most successful approach to fertility disorders in males and females alike. We performed a literature review on three of the most common unhealthy habits – tobacco, alcohol and drug addiction – and their reported effects on male fertility. Tobacco smoking is remarkably common in most first-world countries; despite a progressive decline in the US, recent reports suggest a prevalence of more than 30% in subjects of reproductive age – a disturbing perspective, given the well-known ill-effects on reproductive and sexual function as well as general health. Alcohol consumption is often considered socially acceptable, but its negative effects on gonadal function have been consistently reported in the last 30 years. Several studies have reported a variety of negative effects on male fertility following drug abuse – a worrying phenomenon, as illicit drug consumption is on the rise, most notably in younger subjects. While evidence in these regards is still far from solid, mostly as a result of several confounding factors, it is safe to assume that cessation of tobacco smoking, alcohol consumption and recreational drug addiction might represent the best course of action for any couple trying to achieve pregnancy.

A growing body of evidence suggests a role for homocysteine (Hcys) and folate (FA) in erectile function (EF): Hcys appears to impair EF affecting endothelium via several mechanism whereas the role of FA remains to be elucidated, besides decreasing Hcys. To assess correlation between erectile dysfunction (ED) and serum levels of FA, Hcys, and B12, we enrolled 31 patients affected by ED (Group A; age 52.83 ± 11.89 years) and 31 healthy adults (Group B; age 49.14 ± 13.63 years). Fasting blood samples were taken for each subject. ED was assessed by the International Index of Erectile Function-5 (IIEF-5). IIEF-5 mean score was significantly lower in Group A than in Group B (10.71 ± 4.24 versus 23.32 ± 1.33, p .001). Compared to Group B, Group A also showed significantly lower serum FA levels (5.11 ± 1.79 versus 7.9 ± 3.55 ng/ml, p .001) and significantly higher serum Hcys levels (13.61 ± 3.55 versus 9.17 ± 2.32 µmol/L, p .001). No significant correlation was observed between Hcys and FA both groups. Our results showed a significant association among ED, FA deficiency and hyperomocisteinemia. Lack of correlation between FA and Hcys suggests that FA deficit may directly impair EF.

The present review provides a comprehensive overview on the erythropoietic and non-erythropoietic effects of rHuEpo on human sport performance, paying attention to quantifying numerically how rHuEpo affects exercise performance and describing physiological changes regarding the most important exercise variables. Much attention has been paid to treatment schedules, in particular, to assess the effects of microdoses of rHuEpo and the prolonged effects on sport performance following withdrawal. Moreover, the review takes into account non-erythropoietic ergogenic effects of rHuEpo, including cognitive benefits of rHuEpo. A significant increase in both Vo2max and maximal cycling power was evidenced in studies taken into account for this review. rHuEpo, administered at clinical dosage, may have significant effects on haematological values, maximal and submaximal physiological variables, whereas few reports show positive effects on exercise perfomance. However, the influence of micro-dose rHuEpo on endurance performance in athletes is still unclear and further studies are warranted.