Is marijuana a foe of male sexuality? Data from a large cohort of men with sexual dysfunction.

BACKGROUND: Although it has been assumed that chronic cannabis use may have an unfavorable impact on male sexual function and its metabolic correlates, evidence from clinical studies remains inconclusive. OBJECTIVE: To investigate the relationship between cannabis use and sexual behavior, anthropometrics and metabolic/vascular profiles in a large series of men evaluated for sexual dysfunction. METHODS: A total of 4800 men (mean age 50.8 years) attending an andrology outpatient clinic for sexual dysfunction were studied. Sexual symptoms, hormonal, metabolic, and instrumental (penile color Doppler ultrasound, PCDU) parameters were evaluated according to the reported habitual use of recreational substances (no use, 1-2 joints/week, >2 joints/week, and use of illicit drugs other than cannabis). RESULTS: When compared with non-users, cannabis users were younger and exhibited a lower prevalence of comorbidities as well as better PCDU parameters, despite reporting higher alcohol and tobacco consumption. After adjustment for confounders, cannabis use was associated with a greater instability in the couple's relationship and a higher frequency of masturbation. In addition, the group smoking >2 joints/week showed a significantly lower body mass index than both controls and users of substances other than cannabis. Men who reported using recreational drugs (either cannabis or other) exhibited significantly lower levels of both total and low-density lipoprotein cholesterol than non-users. At the PCDU, smoking 1-2 joints/week was associated with significantly higher dynamic peak systolic velocity than both non-drug use and use of >2 joints/week. Prolactin levels were significantly higher in individuals smoking 1-2 joints/week and in those who used substances other than cannabis when compared with controls, whereas no difference in total testosterone levels was observed. DISCUSSION: In men with sexual dysfunction, mild cannabis consumption may be associated with a more favorable anthropometric and lipid profile and with a better penile arterial vascular response to intracavernous prostaglandin injection.

Does an increase in adipose tissue 'weight' affect male fertility? A systematic review and meta-analysis based on semen analysis performed using the WHO 2010 criteria.

INTRODUCTION: Obesity negatively impact on the metabolism of sex hormones, leading to reduced testosterone serum levels. However, how the obesity could negatively impact on the overall gonadal function, particularly on male fertility, remained unclear so far. OBJECTIVE: To systematically review evidences regarding the influence of body weight excess on the sperm production. METHODS: A meta-analysis was conducted, searching all prospective and retrospective observational studies reporting male subjects older than 18 years old, with body weight excess from overweight to severe obesity were considered. Only studies using the V edition of the World Health Organization (WHO) manual for semen analysis interpretation were considered. No specific interventions were considered. Search was focused on studies comparing overweight/obese to normal weight subjects. RESULTS: Twenty-eight studies were considered. Total sperm count and sperm progressive motility were significantly lower in overweight compared to normal weight subjects. Meta-regression analyses demonstrated that patients' age impacted on sperm parameters. Similarly, obese men showed lower sperm concentration, total sperm number, progressive and total motilities, and normal morphology lower than normal weight subjects. Reduced sperm concentration in obese men was influenced by age, smoking habit, varicocele, and total testosterone serum levels at meta-regression analyses. CONCLUSIONS: The male potential fertility is reduced in subjects with increased body weight, compared to normal weight men. The higher was the increased body weight, the worst was the sperm quantity/quality. This result comprehensively included obesity among non-communicable risk factor for male infertility, shedding new lights on the negative impact of increased body weight on overall gonadal function.

Effect of oestrogen modulation on semen parameters in men with secondary hypogonadism: Systematic review and meta-analysis.

BACKGROUND: Selective oestrogen receptor modulators and aromatase inhibitors stimulate endogenous gonadotrophins and testosterone in men with hypogonadism. There are no systematic reviews/meta-analyses assessing the effects of selective oestrogen receptor modulators/aromatase inhibitors on semen parameters in men with secondary hypogonadism. OBJECTIVES: To assess the effect of monotherapy or a combination of selective oestrogen receptor modulators/aromatase inhibitors on sperm parameters and/or fertility in men with secondary hypogonadism. MATERIALS AND METHODS: A systematic search was conducted in PubMed, MEDLINE, Cochrane Library and ClinicalTrials.gov. Study selection and data extraction were performed by two reviewers independently. Randomised controlled trials and non-randomised studies of interventions reporting effects of selective oestrogen receptor modulators and/or aromatase inhibitors on semen parameters or fertility in men with low testosterone with low/normal gonadotrophins were selected. The risk of bias was assessed using ROB-2 and ROBINS-I tools. The results of randomised controlled trials were summarised using vote counting while summarising effect estimates where available. Non-randomised studies of intervention meta-analysis were conducted using the random-effect model. The certainty of evidence was assessed using GRADE. RESULTS: Five non-randomised studies of interventions (n = 105) of selective oestrogen receptor modulators showed an increase in sperm concentration (pooled mean difference 6.64 million/mL; 95% confidence interval 1.54, 11.74, I2  = 0%) and three non-randomised studies of interventions (n = 83) of selective oestrogen receptor modulators showed an increase in total motile sperm count (pooled mean difference 10.52; 95% confidence interval 1.46-19.59, I2  = 0%), with very low certainty of evidence. The mean body mass index of participants was >30 kg/m2 . Four randomised controlled trials (n = 591) comparing selective oestrogen receptor modulators to placebo showed a heterogeneous effect on sperm concentration. Three included men with overweight or obesity. The results were of very low certainty of evidence. Limited pregnancy or live birth data were available. No studies comparing aromatase inhibitors with placebo or testosterone were found. DISCUSSION AND CONCLUSION: Current studies are of limited size and quality but suggest that selective oestrogen receptor modulators may improve semen parameters in those patients, particularly when associated with obesity.

The chronic alcohol consumption influences the gonadal axis in men: Results from a meta-analysis.

BACKGROUND: Low testosterone concentrations affect 2-13% of adult males, with a direct association between reduction in testosterone (T) concentrations and cardiovascular events. Lifestyle habits have been linked to visceral fat accumulation and endocrine disorders like secondary hypogonadism. Alcohol intake has also been a topic of debate, with studies showing a detrimental effect on sperm production and underlying mechanisms. This meta-analysis aims to comprehensively evaluate the effect of alcohol consumption on T serum concentrations in adult men. METHODS: The literature search included only controlled clinical trials comparing men who drink alcohol to men who do not, or who assumed placebo or nonalcoholic beverages. The primary outcome was the comparison of total testosterone serum concentrations between the study and control groups. The publications were examined for publication bias using Egger's test. RESULTS: Twenty-one studies were included in the analysis for a total of 30 trials that examined the effects of alcohol consumption on testosterone level in 10,199 subjects. The meta-analysis showed that alcohol consumption overall is related to significant reduction in circulating concentrations of total testosterone (mean difference [MD] = -4.02; 95% CI -6.30, -1.73), free T (MD = -0.17; 95% CI -0.23, -0.12), sex hormone binding globulin (SHBG) (MD = -1.94; 95% CI -3.37, -0.48), an increase in estradiol (E2) (MD = 7.65; 95% CI 1.06, 14.23) and neutral effect on luteinizing hormone (LH) (MD = -0.15; 95% CI -0.36, 0.06), independently by age, body mass index (BMI), E2, and LH serum concentrations and alcohol intake. However, these results are evident only in healthy men exposed to chronic alcohol consumption and not in those with a recognized diagnosis of alcohol use disorder or after acute alcohol intake. CONCLUSION: This study suggests how chronic alcohol consumption may inhibit the gonadal axis in healthy men, although the exact pathophysiological mechanisms connecting alcohol exposure and steroidogenesis are still not completely clarified.

A Systematic Review and Meta-analysis on the Impact of Infertility on Men's General Health.

CONTEXT: Male infertility has been associated with increased morbidity and mortality. OBJECTIVE: To perform a systematic review and meta-analysis to provide the most critical evidence on the association between infertility and the risk of incident comorbidities in males. EVIDENCE ACQUISITION: A systematic review and meta-analysis was performed according to the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and registered on PROSPERO. All published studies on infertile versus fertile men regarding overall mortality and risks of cancer, diabetes, and cardiovascular events were selected from a database search on PubMed, EMBASE, Google Scholar, and Cochrane. Forest plot and quasi-individual patient data meta-analysis were used for pooled analyses. A risk of bias was assessed using the ROBINS-E tool. EVIDENCE SYNTHESIS: Overall, an increased risk of death from any cause was found for infertile men (hazard risk [HR] 1.37, [95% confidence interval {CI} 1.04-1.81], p = 0.027), and a 30-yr survival probability of 91.0% (95% CI 89.6-92.4%) was found for infertile versus 95.9% (95% CI 95.3-96.4%) for fertile men (p < 0.001). An increased risk emerged of being diagnosed with testis cancer (relative risk [RR] 1.86 [95% CI 1.41-2.45], p < 0.001), melanoma (RR 1.30 [95% CI 1.08-1.56], p = 0.006), and prostate cancer (RR 1.66 [95% CI 1.06-2.61], p < 0.001). As well, an increased risk of diabetes (HR 1.39 [95% CI 1.09-1.71], p = 0.008), with a 30-yr probability of diabetes of 25.0% (95% CI 21.1-26.9%) for infertile versus 17.1% (95% CI 16.1-18.1%) for fertile men (p < 0.001), and an increased risk of cardiovascular events (HR 1.20 [95% CI 1.00-1.44], p = 0.049), with a probability of major cardiovascular events of 13.9% (95% CI 13.3-14.6%) for fertile versus 15.7% (95% CI 14.3-16.9%) for infertile men (p = 0.008), emerged. CONCLUSIONS: There is statistical evidence that a diagnosis of male infertility is associated with increased risks of death and incident comorbidities. Owing to the overall high risk of bias, results should be interpreted carefully. PATIENT SUMMARY: Male fertility is a proxy of general men's health and as such should be seen as an opportunity to improve preventive strategies for overall men's health beyond the immediate reproductive goals.

Fertility in Acromegaly: A Single-Center Experience of Female Patients During Active Disease and After Disease Remission.

CONTEXT: Fertility represents a major concern in patients with acromegaly. OBJECTIVE: The current retrospective study aimed to investigate gonadal function and fertility rates in acromegalic women. METHODS: In this referral-center study, 50 acromegalic women with disease onset within reproductive age were evaluated for prevalence of gonadal dysfunction and infertility. Anthropometric, metabolic, hormonal parameters, and gynecological ultrasound were evaluated at diagnosis and after disease control. Data about menstrual disturbances, pregnancy, and polycystic ovarian morphology (PCOM) were investigated at disease onset, at diagnosis, and after disease control. RESULTS: At presumed disease onset, menstrual disturbances were reported in 32% of patients. Uterine leiomyoma, ovarian cysts, and PCOM were diagnosed in 18%, 12%, and 8%, respectively; 36.8% of patients were infertile. At diagnosis, menstrual disturbances were found in 58.1% (P = .02), being significantly more prevalent in patients with higher insulin-like growth factor-I quartiles (Q) (P = .03, Q1 vs Q4). Gynecological ultrasound revealed uterine leiomyoma, ovarian cysts, and PCOM in 39.1% (P = .04), 28.2% (P = .09), and 13% (P = .55), respectively. The infertility rate was 100% (P = .02). At disease control, menstrual disturbances were slightly decreased as compared to diagnosis (P = .09). Noteworthy, menstrual disturbances (P = .05) and particularly amenorrhea (P = .03) were significantly more frequent in patients with active disease duration greater than 5 years (median) as compared to those achieving disease control in less than 5 years. Among patients with pregnancy desire, 73.3% conceived at least once, with resulting infertility significantly decreased compared to diagnosis (26.7%; P = .01). At-term deliveries, preterm deliveries, and spontaneous abortions were recorded in 86.7%, 6.6%, and 6.6%, respectively, of the 15 pregnancies reported by the patients. No neonatal malformations and/or abnormalities were recorded. CONCLUSION: Gonadal dysfunction and infertility are common in acromegalic women within reproductive age, being directly influenced by disease status and/or duration.

Selective modulation of estrogen receptor in obese men with androgen deficiency: A systematic review and meta-analysis.

BACKGROUND: Although selective estrogen receptor modulators have been proposed as a treatment for men with central functional hypogonadism, only a few data have been produced in men with obesity-related functional androgen deficiency. OBJECTIVE: To determine whether and to what extent selective estrogen receptor modulators are an effective and safe therapy in men with obesity-related functional androgen deficiency. MATERIALS AND METHODS: A thorough search of PubMed, Web of Science, Scopus, and Cochrane Library databases was performed to identify studies comparing testosterone levels before and after treatment. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias. RESULTS: Seven studies met the inclusion criteria providing information on 292 men with obesity-related functional androgen deficiency treated with clomiphene citrate (12.5-50 mg daily) or enclomiphene citrate (12.5-25 mg daily) for 1.5-4 months. The pooled estimates indicated a significant increase in testosterone levels both with clomiphene (mean difference: 11.56 nmol/L; 95% coefficient interval: 9.68, 13.43; I2  = 69%, pfor heterogeneity  = 0.01) and enclomiphene citrate (mean difference: 7.50 nmol/L; 95% coefficient interval: 6.52, 8.48; I2  = 4%, pfor heterogeneity  = 0.37). After the exclusion of one study on severely obese men, who exhibited the highest response rate to clomiphene citrate, the heterogeneity disappeared (mean difference: 10.27 nmol/L; 95% coefficient interval: 9.39, 11.16; I2  = 0%, pfor heterogeneity  = 0.66). No publication bias was revealed by Egger's test and trim-and-fill analysis. No treatment-related unexpected findings regarding safety profile were registered. DISCUSSION AND CONCLUSION: Treatment with clomiphene citrate and enclomiphene citrate may be an effective and safe alternative to testosterone replacement therapy in men with obesity-related functional androgen deficiency. Further long-term studies are warranted to define clinical reflections of the selective estrogen receptor modulators-induced increase in testosterone levels and to better clarify the safety profile.

Pharmacotherapy of male hypogonadism.

Hypogonadism is frequent with a prevalence of 2% in the general population. Hypogonadism may derive from any condition able to disrupt the hypothalamic-pituitary-testis (HPT) axis at one or more levels. Hypogonadism may be classified according to the age of onset, its potential reversibility and level of the HPT axis damage. The latter categorization is useful to decide on the treatment. Damages to the hypothalamus-pituitary may benefit from either GnRH, gonadotropin or T therapy with the former carrying the advantage of stimulating spermatogenesis. Conversely, when the testis is damaged, T therapy is the only option and restoration of spermatogenesis is not possible. Therefore, the choice of therapy is primarily based on the diagnosis and patients' needs and both should be carefully considered.

The metabolic role of prolactin: systematic review, meta-analysis and preclinical considerations.

INTRODUCTION: Hyperprolactinemia has been proven to induce hypogonadism and metabolic derangements in both genders, while the consequences of prolactin (PRL) deficiency have been poorly investigated. AREAS COVERED: To systematically review and analyze data from clinical studies focusing on the metabolic consequences of abnormally high prolactin levels (HPRL) and low prolactin levels (LPRL). In addition, data from preclinical studies about underlying pathophysiological mechanisms were summarized and discussed. EXPERT OPINION: PRL contributes to providing the correct amount of energy to support the mother and the fetus/offspring during pregnancy and lactation, but it also has a homeostatic role. Pathological PRL elevation beyond these physiological conditions, but also its reduction, impairs metabolism and body composition in both genders, increasing the risk of diabetes and cardiovascular events. Hence, hypoprolactinemia should be avoided as much as possible during treatment with dopamine agonists for prolactinomas. Patients with hypoprolactinemia, because of endogenous or iatrogenic conditions, deserve, as those with hyperprolactinemia, careful metabolic assessment.

Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis.

BACKGROUND: The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates. OBJECTIVE AND RATIONALE: The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men. SEARCH METHODS: A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated. OUTCOMES: A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias. WIDER IMPLICATIONS: This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.

Consequences of Anabolic-Androgenic Steroid Abuse in Males; Sexual and Reproductive Perspective.

The real epidemiology and the possible consequences of anabolic-androgenic steroids (AAS) use still represent a very tricky task due to the difficulties in the quantification and detection of these drugs. Chronic use of AAS, frequently combined with other illicit substances, can induce tremendous negative effects on the reproductive system, but it is also associated with an increased overall and cardiovascular mortality risk. In the present review we summarize and discuss the available evidence regarding the negative impact of AAS on the male reproductive system, providing practical suggestions to manage these problems. For this purpose a meta-analysis evaluating the effects of AAS abusers vs. controls on several hormonal, reproductive and metabolic parameters was performed. In addition, in order to overcome possible limitations related to the combined use of different AAS preparations, we also retrospectively re-analyzed data on animal models treated with supraphysiological dosage of testosterone (T), performed in our laboratory. Available data clearly indicated that AAS negatively affect endogenous T production. In addition, increased T and estradiol circulating levels were also observed according to the type of preparations used. The latter leads to an impairment of sperm production and to the development of side effects such as acne, hair loss and gynecomastia. Furthermore, a worse metabolic profile, characterized by reduced high density lipoprotein and increased low density lipoprotein cholesterol levels along with an increased risk of hypertension has been also detected. Finally sexual dysfunctions, often observed upon doping, represent one the most probable unfavorable effects of AAS abuse.

Harm Reduction in Sexual Medicine.

INTRODUCTION: Strategies of harm reduction (HR) include policies and community-based measures aimed to reduce the risk of self-harm while continuing potentially hazardous behaviors, such as illegal drug, alcohol, and tobacco use. OBJECTIVES: To assess whether and to which extent strategies of HR could have beneficial, or harmful, effects on sexual and reproductive health, for general and at-risk populations. METHODS: A literature research was performed between July 2020 and January 2021, investigating the association between harm reduction strategies and sexual and reproductive health. RESULTS: HR strategies are mostly aimed at providing support to at-risk population, such as injection drug users or sex workers. Alcohol and drug use, smoking and high-risk sexual behaviors are among the main targets for HR strategies. Barriers to access, such as stigma, marginalization or lacking awareness, are often present as negative risk factors and require attention from professionals. Preventing sexually transmitted infections (STIs), early/unwanted pregnancies and violence are the most important results HR programs could provide for sexual and reproductive health. However, evidence is limited and often qualitative, rather than quantitative. CONCLUSION: HR strategies are important measures to improve sexual and reproductive health in at-risk populations. Increasing personal and social awareness is a key factor for the success of HR programs. A Sansone, E. Limoncin, E Colonnello, et al. Harm Reduction in Sexual Medicine. Sex Med Rev 2022;10:3-22.

ESSM Position Statement on Surgical Treatment of Peyronie's Disease.

INTRODUCTION: Patients with Peyronie's disease may experience significat distress. The choice of treatment depends on a variety of factors, including the stage of the disease, the presence of pain, severity and direction of the curvature, penile length and the quality of erectile function. AIM: To review the evidence associated with surgical treatment of Peyronie`s Disease and provide clinical recommendations on behalf of the European Society for Sexual Medicine. 131 peer-reviewed studies and systematic reviews, which were published from 2009 to 2019 in the English language, were included. METHODS: MEDLINE, Google Scholar and EMBASE were searched for randomized clinical trials, meta-analyses, open-label prospective and retrospective studies. MAIN OUTCOME MEASURE: The panel provided statements on clinically relevant questions including patient involvement in the decision process, indications for surgery, choice of the approach, and the management of patient expectations. A comparison of the different grafts used in patients who have undergone plaque incision/excision and grafting in order to identify an ideal graft, has been carried out. The prevalence of postoperative complications has been summarized. Levels of evidence were provided according to the Oxford 2011 criteria and Oxford Centre for Evidence-Based Medicine recommendations. RESULTS: In order to allow shared decision making, a patient preoperative counselling regarding the pros and cons of each intervention is recommended. In particular, adverse effects of surgical treatments should be discussed to set realistic understanding and expectations of surgical outcomes and ultimately improve postoperative satisfaction rates. Surgical treatment should be only offered in the chronic phase of the condition, when the deformity and/or degree of erectile dysfunction, prevent patients from engaging in satisfying sexual interaction, or if the deformity is the cause of severe bother. CONCLUSIONS: Current European Society for Sexual Medicine recommendations cover several aspects of Peyronie's disease treatment. These recommendations aim both to ensure patients and partners have accurate and realistic expectations of their treatment options, as well as to formulate algorithms to guide clinician management pathways. Osmonov D, Ragheb A, Ward S et al, ESSM Position Statement on Surgical Treatment of Peyronie's Disease. Sex Med 2022;10:100459.

European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility.

CONTEXT: The European Association of Urology (EAU) has updated its guidelines on sexual and reproductive health for 2021. OBJECTIVE: To present a summary of the 2021 version of the EAU guidelines on sexual and reproductive health, including advances and areas of controversy in male infertility. EVIDENCE ACQUISITION: The panel performed a comprehensive literature review of novel data up to January 2021. The guidelines were updated and a strength rating for each recommendation was included that was based either on a systematic review of the literature or consensus opinion from the expert panel, where applicable. EVIDENCE SYNTHESIS: The male partner in infertile couples should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors causing fertility impairment. Infertile men are at a higher risk of harbouring and developing other diseases including malignancy and cardiovascular disease and should be screened for potential modifiable risk factors, such as hypogonadism. Sperm DNA fragmentation testing has emerged as a novel biomarker that can identify infertile men and provide information on the outcomes from assisted reproductive techniques. The role of hormone stimulation therapy in hypergonadotropic hypogonadal or eugonadal patients is controversial and is not recommended outside of clinical trials. Furthermore, there is insufficient evidence to support the widespread use of other empirical treatments and surgical interventions in clinical practice (such as antioxidants and surgical sperm retrieval in men without azoospermia). There is low-quality evidence to support the routine use of testicular fine-needle mapping as an alternative diagnostic and predictive tool before testicular sperm extraction (TESE) in men with nonobstructive azoospermia (NOA), and either conventional or microdissection TESE remains the surgical modality of choice for men with NOA. CONCLUSIONS: All infertile men should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors. Increasing data indicate that infertile men are at higher risk of cardiovascular mortality and of developing cancers and should be screened and counselled accordingly. There is low-quality evidence supporting the use of empirical treatments and interventions currently used in clinical practice; the efficacy of these therapies needs to be validated in large-scale randomised controlled trials. PATIENT SUMMARY: Approximately 50% of infertility will be due to problems with the male partner. Therefore, all infertile men should be assessed by a specialist with the expertise to not only help optimise their fertility but also because they are at higher risk of developing cardiovascular disease and cancer long term and therefore require appropriate counselling and management. There are many treatments and interventions for male infertility that have not been validated in high-quality studies and caution should be applied to their use in routine clinical practice.

European Association of Urology Guidelines on Sexual and Reproductive Health-2021 Update: Male Sexual Dysfunction.

CONTEXT: The present summary of the European Association of Urology (EAU) guidelines is based on the latest guidelines on male sexual health published in March 2021, with a last comprehensive update in January 2021. OBJECTIVE: To present a summary of the 2021 version of the EAU guidelines on sexual and reproductive health. EVIDENCE ACQUISITION: A literature review was performed up to January 2021. The guidelines were updated, and a strength rating for each recommendation was included based on either a systematic review of the evidence or a consensus opinion from the expert panel. EVIDENCE SYNTHESIS: Late-onset hypogonadism is a clinical condition in the ageing male combining low levels of circulating testosterone and specific symptoms associated with impaired hormone production and/or action. A comprehensive diagnostic and therapeutic work-up, along with screening recommendations and contraindications, is provided. Erectile dysfunction (ED) is the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. Along with a detailed basic and advanced diagnostic approach, a novel decision-making algorithm for treating ED in order to better tailor therapy to individual patients is provided. The EAU guidelines have adopted the definition of premature ejaculation (PE), which has been developed by the International Society for Sexual Medicine. After the subtype of PE has been defined, patient's expectations should be discussed thoroughly and pharmacotherapy must be considered as the first-line treatment for patients with lifelong PE, whereas treating the underlying cause must be the initial goal for patients with acquired PE. Haemospermia is defined as the appearance of blood in the ejaculate. Several reasons of haemospermia have been acknowledged; the primary goal over the management work-up is to exclude malignant conditions and treat any other underlying cause. CONCLUSIONS: The 2021 guidelines on sexual and reproductive health summarise the most recent findings, and advise in terms of diagnosis and treatment of male hypogonadism and sexual dysfunction for their use in clinical practice. These guidelines reflect the multidisciplinary nature of their management. PATIENT SUMMARY: Updated European Association of Urology guidelines on sexual and reproductive health are presented, addressing the diagnosis and treatment of the most prevalent conditions in men. Patients must be fully informed of all relevant diagnostic and therapeutic options and, together with their treating physicians, decide on optimal personalised management strategies.

Serum sodium alterations in SARS CoV-2 (COVID-19) infection: impact on patient outcome.

OBJECTIVE: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. DESIGN AND METHODS: In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. RESULTS: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. CONCLUSIONS: These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.

Diabetes is most important cause for mortality in COVID-19 hospitalized patients: Systematic review and meta-analysis.

The presence of SARS-CoV-2 was officially documented in Europe at the end of February 2020. Despite many observations, the real impact of COVID-19 in the European Union (EU), its underlying factors and their contribution to mortality and morbidity outcomes were never systematically investigated. The aim of the present work is to provide an overview and a meta-analysis of main predictors and of country differences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated mortality rate (MR) in hospitalized patients. Out of 3714 retrieved articles, 87 studies were considered, including 35,486 patients (mean age 60.9 ± 8.2 years) and 5867 deaths. After adjustment for confounders, diabetes mellitus was the best predictors of MR in an age- and sex-dependent manner, followed by chronic pulmonary obstructive diseases and malignancies. In both the US and Europe, MR was higher than that reported in Asia (25[20;29] % and 20[17;23] % vs. 13[10;17]%; both p < 0.02). Among clinical parameters, dyspnea, fatigue and myalgia, along with respiratory rate, emerged as the best predictors of MR. Finally, reduced lymphocyte and platelet count, along with increased D-dimer levels, all significantly contributed to increased mortality. The optimization of glucose profile along with an adequate thrombotic complications preventive strategy must become routine practice in diseased SARS-CoV-2 infected patients.

Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer.

Androgen deprivation therapy (ADT) is the gold standard treatment in patients with locally advanced or metastatic prostate cancer (PC). Emerging evidence has documented a tight association between ADT and body composition, along with metabolic profile impairment. These alterations might underpin the observed ADT-related increase in cardiovascular (CV) and thromboembolic (venous thromboembolism, VTE) mortality and morbidity. However, the specific mechanisms underlying these associations have not yet been completely elucidated. In the present review we summarize and discussed the available evidence linking ADT to increased cardio-metabolic risk, using both preclinical and clinical data. When possible, meta-analytic studies were preferred. Preclinical evidence, using a rabbit model of gonadotrophin-releasing hormone analogue-induced hypogonadism, indicates that the induced condition is associated with a dramatic increase in visceral adiposity and with an impairment of acetylcholine induced vascular relaxation, along with an increased propensity towards fatty liver. This suggests a direct role of ADT in inducing a worsened metabolic profile. In contrast, available clinical data are not sufficient to clarify a direct pathogeniclink between reduced testosterone (T) and altered metabolism. In fact, although T deprivation is associated with an altered metabolism, it is possible that the association between ADT and CV or VTE risk could simply be the result of a selection bias, related to the poor health status of patients with advanced PC. Despite the aforementioned considerations, all patients who are candidatesfor ADT should be screened for CV risk factors at baseline and monitored during the therapy. Life-style modifications and physical exercise are strongly encouraged.

The Role of Hormone Stimulation in Men With Nonobstructive Azoospermia Undergoing Surgical Sperm Retrieval.

Nonobstructive azoospermia, (NOA) is the most common cause of azoospermia. NOA is characterized by hypergonadotropic hypogonadism, testicular failure, and impaired spermatogenesis. The recent development of surgical sperm retrieval techniques such as microsurgical testicular sperm extraction (mTESE) has, for the first time, allowed some men with NOA to father biological children. It is common practice for endocrine stimulation therapies such as gonadotropins, selective estrogen receptor modulators (SERMs), and aromatase inhibitors to be used prior to mTESE to increase intratesticular testosterone synthesis with the aim of improving sperm retrieval rates; however, there is currently a paucity of data underpinning their safety and efficacy. We present 2 cases of men with NOA undergoing endocrine stimulation therapy and mTESE. We also discuss the current evidence and controversies associated with the use of hormonal stimulation therapy in couples affected by this severe form of male infertility.