The Italian Society of Andrology and Sexual Medicine (SIAMS), along with ten other Italian Scientific Societies, guidelines on the diagnosis and management of erectile dysfunction.

PURPOSE: Erectile dysfunction (ED) is one of the most prevalent male sexual dysfunctions. ED has been in the past mistakenly considered a purely psycho-sexological symptom by patients and doctors. However, an ever-growing body of evidence supporting the role of several organic factors in the pathophysiological mechanisms underlying ED has been recognized. METHODS: The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving several other National Societies to provide an updated guideline on the diagnosis and management of ED. Derived recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Several evidence-based statements were released providing the necessary up-to-date guidance in the context of ED with organic and psychosexual comorbidities. Many of them were related to incorrect lifestyle habits suggesting how to associate pharmacotherapies and counseling, in a couple-centered approach. Having the oral therapy with phosphodiesterase type 5 inhibitors as the gold standard along with several other medical and surgical therapies, new therapeutic or controversial options were also discussed. CONCLUSIONS: These are the first guidelines based on a multidisciplinary approach that involves the most important Societies related to the field of sexual medicine. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving couple sexual satisfaction and overall general health.

Hypersexuality as a tip of the iceberg of a primary psychopathology: a joined position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) and of the Italian Society of Psychopathology (SOPSI).

In the last years, hypersexual behavior has been broadly scientifically studied. The interest in this topic, belonging to psycho-sexology and sexual medicine, has been due to its still unclear aetiology, nature, and its manifestation in relationship with several organic and psychopathological conditions. So, the specialist (the psychologist, psychiatrist, endocrinologist, neurologist) may encounter some difficulties in diagnosing and managing this symptom. The first main objective of this position statement, which has been developed in collaboration between the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Psychopathology (SOPSI) is to give to the reader evidence about the necessity to consider hypersexuality as a symptom related to another underlying condition. Following this consideration, the second main objective is to give specific statements, for the biopsychosocial assessment and the diagnosis of hypersexual behavior, developed on the basis of the most recent literature evidence. To develop a psycho-pharmacological treatment tailored on patients' needs, our suggestion is to assess the presence of specific comorbid psychopathological and organic conditions, and the impact of pharmacological treatments on the presence of an excess of sexual behavior. Finally, a suggestion of a standardized psychometric evaluation of hypersexuality will be given.

First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy.

BACKGROUND: Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify.  OBJECTIVE: We describe KS clinical presentation in a large Italian cohort. DESIGN: This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Primary outcomes were to describe the basic clinical features and the actual phenotype of KS in Italy. Secondary outcomes were to determine age at diagnosis and geographical distribution. METHODS: We performed a basic phenotyping and evaluation of the hormonal values of 609 adult KS patients. RESULTS: Mean age at diagnosis was 37.4 ± 13.4 years. The overall mean testicular size was 3 ml, and 2.5 ml in both testes in untreated KS group. BMI was 26.6 ± 5.8 kg/m2, and 25.5% of KS had metabolic syndrome (MetS). LH and FSH were increased, and mean total testosterone were 350 ± 9.1 ng/dl. A descriptive analysis showed that 329 KS patients were evaluated in Northern Italy, 76 in Central and 204 in Southern Italy. Analysis of variance demonstrated significant statistical differences (p < 0001) between the age at diagnosis of the three geographical groups. Compared with the expected number among male patients matched for age in Italy, only 16% of KS patients received a diagnosis. CONCLUSIONS: These data are the results of the only national database available that collects the clinical and hormonal data of the KS patients, currently referred at the KING centers. In Italy the typical KS patient is overweight, with small testes, and elevated LH and FSH. Only 25.5% of them are diagnosed with MetS. Early detection and timely treatment are mandatory.

Relationship between hyperuricemia with deposition and sexual dysfunction in males and females.

PURPOSE: The association between gout, the most common crystal arthropathy, and sexual dysfunctions has often been investigated by studies in the last decades. Despite the presence of shared risk factors and comorbidities and the possible effects on sexual health of long-term gout complications, awareness of this association is severely lacking and the pathogenetic mechanisms have only partially been identified. In the present review, we aimed to investigate the current evidence regarding the potential mechanisms linking sexual dysfunctions and gout. METHODS: A comprehensive literature search within PubMed was performed to provide a summary of currently available evidence regarding the association between gout and sexual dysfunctions. RESULTS: Gout and sexual dysfunctions share several risk factors, including diabesity, chronic kidney disease, hypertension, metabolic syndrome, and peripheral vascular disease. Gout flares triggered by intense inflammatory responses feature severe pain and disability, resulting in worse sexual function, and some, but not all, treatments can also impair sexual health. Long-term gout complications can result in persistent pain and disability due to joint deformity, fractures, or nerve compression, with negative bearing on sexual function. The presence of low-grade inflammation impairs both sex steroids synthesis and endothelial function, further advancing sexual dysfunctions. The psychological burden of gout is another issue negatively affecting sexual health. CONCLUSIONS: According to currently available evidence, several biological and psychological mechanisms link sexual dysfunctions and gout. Addressing risk factors and providing adequate treatment could potentially have beneficial effects on both conditions. Appropriate clinical evaluation and multidisciplinary approach are recommended to improve patient care.

Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction.

PURPOSE: To explore the effects of 6-month systemic testosterone (T) administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD). METHODS: 81 women with FSD were retrospectively recruited. Data on CDU parameters at baseline and after 6 months with four different treatments were available and thus further longitudinally analyzed: local non-hormonal moisturizers (NH group), n = 37; transdermal 2% T gel 300 mcg/day (T group), n = 23; local estrogens (E group), n = 12; combined therapy (T + E group), n = 9. Patients underwent physical, laboratory, and genital CDU examinations at both visits and completed different validated questionnaires, including the Female Sexual Function Index (FSFI). RESULTS: At 6-month visit, T therapy significantly increased clitoral artery peak systolic velocity (PSV) when compared to both NH (p < 0.0001) and E (p < 0.0001) groups. A similar increase was found in the T + E group (p = 0.039 vs. E). In addition, T treatment was associated with significantly higher FSFI desire, pain, arousal, lubrication, orgasm, and total scores at 6-month visit vs. baseline. Similar findings were observed in the T + E group. No significant differences in the variations of total and high-density lipoprotein-cholesterol, triglycerides, fasting glycemia, insulin and glycated hemoglobin levels were found among the four groups. No adverse events were observed. CONCLUSION: In women complaining for FSD, systemic T administration, either alone or combined with local estrogens, was associated with a positive effect on clitoral blood flow and a clinical improvement in sexual function, showing a good safety profile. TRIAL REGISTRATION NUMBER: NCT04336891; date of registration: April 7, 2020.

The Inferto-Sex Syndrome (ISS): sexual dysfunction in fertility care setting and assisted reproduction.

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.

Addressing male sexual and reproductive health in the wake of COVID-19 outbreak.

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.

Management of premature ejaculation: a clinical guideline from the Italian Society of Andrology and Sexual Medicine (SIAMS).

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.

Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis.

PURPOSE: Low testosterone (T) in Klinefelter's syndrome (KS) can contribute to typical features of the syndrome such as reduced bone mineral density, obesity, metabolic disturbances and increased cardiovascular risk. The aim of the present study is to review and meta-analyze all available information regarding possible differences in metabolic and bone homeostasis profile between T treated (TRT) or untreated KS and age-matched controls. METHODS: We conducted a random effect meta-analysis considering all the available data from observational or randomized controlled studies comparing TRT-treated and untreated KS and age-matched controls. Data were derived from an extensive MEDLINE, Embase, and Cochrane search. RESULTS: Out of 799 retrieved articles, 21 observational and 22 interventional studies were included in the study. Retrieved trials included 1144 KS subjects and 1284 healthy controls. Not-treated KS patients showed worse metabolic profiles (including higher fasting glycemia and HOMA index as well as reduced HDL-cholesterol and higher LDL-cholesterol) and body composition (higher body mass index and waist circumference) and reduced bone mineral density (BMD) when compared to age-matched controls. TRT in hypogonadal KS subjects was able to improve body composition and BMD at spinal levels but it was ineffective in ameliorating lipid and glycemic profile. Accordingly, TRT-treated KS subjects still present worse metabolic parameters when compared to age-matched controls. CONCLUSION: TRT outcomes observed in KS regarding BMD, body composition and glyco-metabolic control, are similar to those observed in male with hypogonadism not related to KS. Moreover, body composition and BMD are better in treated than untreated hypogonadal KS. Larger and longer randomized placebo-controlled trials are advisable to better confirm the present data, mainly derived from observational studies.

Correction to: Vitamin D protects endothelial cells from irradiation-induced senescence and apoptosis by modulating MAPK/SirT1 axis.

Unfortunately, the 5th author name has been publisehd incorrectly in the original publication. The complete correct name is given below.

SARS-CoV-2 infection, male fertility and sperm cryopreservation: a position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) (Società Italiana di Andrologia e Medicina della Sessualità).

PURPOSE: The recent pandemic of severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has raised several concerns in reproductive medicine. The aim of this review is to summarize available evidence providing an official position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) METHODS: A comprehensive Pubmed, Web of Science, Embase, Medline and Cochrane library search was performed. Due to the limited evidence and the lack of studies, it was not possible to formulate recommendations according to the Oxford 2011 Levels of Evidence criteria. RESULTS: Several molecular characteristics of the SARS-CoV-2 can justify the presence of virus within the testis and possible alterations of spermatogenesis and endocrine function. Orchitis has been reported as a possible complication of SARS-CoV infection, but similar findings have not been reported for SARS-CoV-2. Alternatively, the orchitis could be the result of a vasculitis as COVID-19 has been associated with abnormalities in coagulation and the segmental vascularization of the testis could account for an orchitis-like syndrome. Finally, available data do not support the presence of SARS-CoV-2 in plasma seminal fluid of infected subjects. CONCLUSION: Data derived from other SARS-CoV infections suggest that in patients recovered from COVID-19, especially for those in reproductive age, andrological consultation and evaluation of gonadal function including semen analysis should be suggested. Studies in larger cohorts of currently infected subjects are warranted to confirm (or exclude) the presence of risks for male gametes that are destined either for cryopreservation in liquid nitrogen or for assisted reproduction techniques.

People smoke for nicotine, but lose sexual and reproductive health for tar: a narrative review on the effect of cigarette smoking on male sexuality and reproduction.

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.

MANAGEMENT OF ENDOCRINE DISEASE: Female sexual dysfunction for the endocrinologist.

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.

Regulation of PDE5 expression in normal prostate, benign prostatic hyperplasia, and adenocarcinoma.

BACKGROUND: Type 5 phosphodiesterase (PDE5) expression in the normal and pathological prostate is controversial. OBJECTIVES: This study aimed at identifying the cell type/s, if any, expressing PDE5 in human healthy or pathological prostate sections in order to further validate the rationale of PDE5 inhibitor (PDE5i) treatment of benign prostatic hyperplasia (BPH) and their safety in the treatment of erectile dysfunction following prostate cancer (PCa) surgery. MATERIALS AND METHODS: By immunohistochemical analysis, we studied PDE5 expression in tissue microarrays containing sections obtained from healthy, BPH, and PCa samples. RESULTS: Our results showed that PDE5 is barely expressed in the epithelial or stromal compartment of normal human prostates, but it is highly expressed in the stromal compartment of BPH sections. We also found that a low but significant number of PCa samples (22%) expressed PDE5 in the epithelial cancer cells but not in stromal cells and that such expression was not correlated with the tumor aggressiveness, according to their Gleason score. DISCUSSION AND CONCLUSION: PDE5 overexpression in the stromal compartment of BPH samples supports the rationale of PDE5 as a target in lower urinary tract symptoms of BPH. PDE5 expression in a significant percentage of PCa samples but the lack of correlation with the Gleason score suggests that this enzyme is not correlated with tumor aggressiveness; however, a role of PDE5 in the minimal residual disease of PCa cannot be excluded.

Erectile function recovery in men treated with phosphodiesterase type 5 inhibitor administration after bilateral nerve-sparing radical prostatectomy: a systematic review of placebo-controlled randomized trials with trial sequential analysis.

The impact of phosphodiesterase type 5 inhibitor (PDE5I) treatment modality (on-demand vs. daily), PDE5I half-life and time from surgery to PDE5I prescription on the achievement of drug-assisted erectile function (EF) recovery is uncertain. We systematically reviewed published randomized clinical trials (RCTs). We performed meta-analyses of data on 2317 men treated with PDE5Is after nerve-sparing radical prostatectomy (NSRP). A PubMed and SCOPUS search was performed for trials published from 1 January 1969 to 30 June 2016. PDE5Is are effective in achieving drug-assisted recovery of erectile function (EF). From a statistical standpoint, these studies were subjected to Trial Sequential Analysis to determine whether the pooled data were adequately powered to verify the study outcomes. On-demand treatment with PDE5Is was significantly better than daily treatment in recovering drug-assisted EF. This effect was maintained even when the drugs were stratified according with half-life. Although not based on head-to-head trials, Avanafil used on-demand was the most effective PDE5I in recovering drug-assisted EF. Whereas tadalafil was equally effective when used both on-demand and daily, vardenafil significantly improved drug-assisted EF recovery only when used on-demand. The start of PDE5I treatment six months or more after surgery compared to treatment started earlier did not negatively affect the rate of drug-assisted EF recovery or the possibility to have successful intercourse based on the Sexual Encounter Profile question-3 (SEP-3). Current trials do not support the hypothesis that PDE5I use recovers drug-unassisted EF, although chronic low-dose tadalafil administration may help to preserve erectile tissue integrity. Potential shortcomings in the trials design may partially explain these disappointing results and several questions concerning the recovery of drug-unassisted EF remain unanswered. Thus, there is a need for well-designed new RCTs requiring changes in the timing of PDE5I administration as well as in the dose and the treatment duration.