Infertility as a Proxy of Men's Health: Still a Long Way to Go.

Male infertility (MI) has been widely associated with the development of certain comorbidities and to a lower overall general health status. Higher risks of developing oncological, autoimmune, and chronic disorders among infertile individuals have led researchers to further investigate this issue. Recent clinical studies have been focusing more onto the concept of general health status and mortality. Overall, it has been postulated and subsequently demonstrated that the coexistence of specific diseases and semen alterations may lead to a decreased lifespan. As in Western countries, fatherhood is increasingly delayed in time, and aging might play an important role as a confounding factor for the after-mentioned statements. Although this holds true, even after adjusting for age, it emerges a worrisome picture regarding MI, lower general health status, and increased mortality. The aim of this nonsystematic narrative review is to provide an overview of the most relevant and recent findings on the topic.

Can We Rely Solely on the International Prostate Symptoms Score to Investigate Storage Symptoms in Men with Lower Urinary Tract Symptoms Associated with Benign Prostatic Enlargement? Findings from a Cross-sectional Study.

BACKGROUND: Discrepancies exist between patient-reported storage phase symptoms severity and International Prostate Symptom Score (IPSS) scores. OBJECTIVE: To investigate whether the Overactive Bladder questionnaire (OABq) can detect further storage phase lower urinary tract symptoms (LUTS) among patients complaining solely of voiding LUTS based on the IPSS questionnaire, and to address the real-life impact of voiding LUTS towards patients' quality of life (QoL). DESIGN, SETTING, AND PARTICIPANTS: Data from 233 consecutive men seeking medical help for LUTS/benign prostate enlargement for the first time were analysed. All patients completed both the OABq and the IPSS questionnaire. In order to investigate patients with predominantly voiding phase symptoms, men with storage phase symptoms at IPSS were eventually excluded from the analysis. Patients with an OABq score of ≥40 were considered as those having moderate-to-severe storage LUTS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics and linear regression models tested the associations between OABq scores, IPSS, and IPSS-QoL. RESULTS AND LIMITATIONS: OABq scores were higher in men with severe voiding symptoms than in men with mild voiding symptoms (p < 0.001). More than half of patients with predominant voiding symptoms, according to the IPSS questionnaire, depicted a pathologic OABq score. A higher rate of pathologic OABq scores was found in men with moderate/severe voiding symptoms than in those with mild scores (67.4% vs 49.6%, p < 0.001). At multivariable analysis, younger age (beta -0.1, p < 0.01), IPSS voiding subscore (beta 0.3, p < 0.001), and OABq score ≥40 (beta 1.1, p < 0.001) emerged as independent predictors of IPSS-QoL after accounting for prostate volume and flow max. CONCLUSIONS: The OABq can detect the presence of further storage phase LUTS in patients presenting solely with voiding LUTS and IPSS suggestive of voiding phase symptoms. In addition, the OABq was associated with worse patient QoL regardless of the severity of voiding symptoms. PATIENT SUMMARY: The Overactive Bladder questionnaire (OABq) is able to detect the presence of additional storage lower urinary tract symptoms (LUTS) in patients presenting solely with voiding LUTS according to the IPSS questionnaire. Moreover, the OABq is associated with worse quality of life in these patients regardless of the severity of voiding symptoms.

Infertile couples still undergo assisted reproductive treatments without initial andrological evaluation in the real-life setting: A failure to adhere to guidelines?

BACKGROUND: The EAU guidelines on male sexual and reproductive health state that both partners of the infertile couple should undergo simultaneous investigation. OBJECTIVES: To assess the prevalence and the characteristics of infertile men who were referred for an andrological evaluation after failed attempts of Assisted Reproductive Technology (ART) with those who were evaluated at the beginning of their infertility pathway at a single academic centre over a 17-year period. MATERIALS AND METHODS: Data of 3213 primary infertile couples assessed between 2003 and 2020 were analysed. Descriptive statistics compared the overall characteristics of male partners of couples with (+ART) or without (-ART) previous ART prior to andrological consultation. Logistic regression models analysed variables associated with +ART. Local polynomial regression models explored the probability of +ART over the analysed time frame. RESULTS: Of all, 493 (15.3%) participants were +ART. Patients and female partners' age was higher in +ART couples (all p ≤ 0.04). Sperm concentration, progressive sperm motility and normal sperm morphology were lower in +ART than in -ART patients (all p < 0.001), along with a greater percentage of non-obstructive azoospermia in +ART compared to -ART men (p < 0.0001). At univariable analysis, patient age and partner age >35 years and a less recent assessment were associated with +ART status (all p ≤ 0.04). Male age and less recent years of assessment were also independent predictors of +ART, after accounting for partner's age >35 years (all p < 0.01). A not significant decrease of this pattern was observed throughout the last 7 years at local polynomial regression models. DISCUSSION: Overall awareness towards the importance of a comprehensive evaluation for the male partner of every infertile couple should therefore be further strengthened. CONCLUSIONS: Approximately 15% of couples still undergo ART without any initial andrological evaluation in the real-life setting. A not significant decrease in this trend was observed over most recent years.

Correlation among isolated teratozoospermia, sperm DNA fragmentation and markers of systemic inflammation in primary infertile men.

AIM: To assess the prevalence of isolated teratozoospermia (iTZS) in a cohort of infertile and fertile men; explore the relationship between iTZS, inflammatory parameters and sperm DNA fragmentation index (SDF) in the same cohort. MATERIALS AND METHODS: 1824 infertile men and 103 fertile controls. Semen analysis, the neutrophil-to-lymphocyte ratio (NLR) and serum hormones were investigated. DFI was tested in infertile men only. According to 2010 WHO semen analysis, patients were categorized in 3 sub-groups of isolated sperm defects: isolated oligozoospermia (iOZS), isolated asthenozoospermia (iAZS) and iTZS. Descriptive statistics and linear regression models tested the association between clinical variables and inflammatory markers. RESULTS: Among infertile men, iAZS, iTZS, and iOZS were found in 13.9%, 11.9% and 4.1% participants, respectively. iTZS was found in 37 (35.9%) fertile men. Infertile men with iTZS had higher NLR values than those with iOZS, iAZS and men with normal semen parameters (all p<0.001). FSH and LH were higher and inhibin B lower in iOZS infertile men compared to all other groups (p≤0.001). Hormonal characteristics were similar between iTZS infertile and fertile men. Similarly, iTZS infertile men had higher SDF than all other groups (all p<0.001). Infertile men with iTZS had higher NLR values than fertile men with iTZS (p<0.01). Linear regression analysis showed that, in infertile men, iTZS was associated with SDF and NLR (all p≤0.01). CONCLUSIONS: iTZS was found in 11.9% of infertile men but it was even more prevalent in fertile controls. Infertile men with iTZS had higher NLR than fertile controls and increased SDF values than infertile participant with iAZS, iOZS, or normal semen parameters. No differences in hormonal characteristics were found between infertile and fertile men with iTZS.

Substances of abuse consumption among patients seeking medical help for uro-andrological purposes: a sociobehavioral survey in the real-life scenario.

Substances of abuse (SoA), as well as smoking and alcohol consumption, are well known for their impact on male fertility status, erectile function, and ejaculation. We assessed SoA consumption habits in a cohort of men seeking medical attention for uro-andrological purposes. Data from 7447 men seeking medical attention for the first time for uro-andrological purposes were analyzed. A complete medical and sexual history was collected for each patient. Smoking, alcohol, and SoA consumption were investigated. Descriptive statistics was used to describe the whole cohort. The primary motivations for their evaluation were lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and infertility in 1912 (25.7%), 2944 (39.5%), and 2591 (34.8%) men, respectively. Previous use of SoA was reported by 378 (5.1%) men, and 190 (2.6%) individuals were current users. Patients seeking medical attention for infertility were more frequently current SoA users (107; 4.1%) than men with ED (66; 2.2%) and LUTS (17; 0.9%) (both P < 0.001). Current users of SoA were younger than those with past or no SoA history (P < 0.001). Current SoA users were more frequently smokers (P < 0.001) and alcohol consumers (P < 0.001) than those with a previous history or those who had never tried SoA. In conclusion, approximately 3% of men seeking medical attention for uro-andrological purposes were current SoA consumers. Infertile men reported a higher use of SoA than those with ED or LUTS. Current SoA users were younger and more frequently concomitant smokers and alcohol consumers compared to those who did or had never used SoA.

Testicular volume in infertile versus fertile white-European men: a case-control investigation in the real-life setting.

Testicular volume (TV) is considered a good clinical marker of hormonal and spermatogenic function. Accurate reference values for TV measures in infertile and fertile men are lacking. We aimed to assess references values for TV in white-European infertile men and fertile controls. We analyzed clinical and laboratory data from 1940 (95.0%) infertile men and 102 (5.0%) fertile controls. Groups were matched by age using propensity score weighting. TV was assessed using a Prader orchidometer (PO). Circulating hormones and semen parameters were investigated in every male. Descriptive statistics, Spearman's correlation, and logistic regression models tested potential associations between PO-estimated TV values and clinical variables. Receiver operating characteristic (ROC) curves were used to find TV value cutoffs for oligoasthenoteratozoospermia (OAT) and nonobstructive azoospermia (NOA) status in infertile men. The median testicular volume was smaller in infertile than that of fertile men (15.0 ml vs 22.5 ml; P < 0.001). TV positively correlated with total testosterone, sperm concentration, and progressive sperm motility (all P ≤ 0.001) in infertile men. At multivariable logistic regression analysis, infertile status (P < 0.001) and the presence of left varicocele (P < 0.001) were associated with TV < 15 ml. Testicular volume thresholds of 15 ml and 12 ml had a good predictive ability for detecting OAT and NOA status, respectively. In conclusion, infertile men have smaller testicular volume than fertile controls. TV positively correlated with total testosterone, sperm concentration, and progressive motility in infertile men, which was not the case in the age-matched fertile counterparts.

Severely low testosterone in males with COVID-19: A case-control study.

BACKGROUND: Circulating androgens could have a relevant pathobiological role in clinical outcomes in men with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19). OBJECTIVES: We aimed to assess: (a) circulating sex steroids levels in a cohort of 286 symptomatic men with laboratory-confirmed COVID-19 at hospital admission compared to a cohort of 281 healthy men; and (b) the association between serum testosterone levels (tT), COVID-19, and clinical outcomes. MATERIALS AND METHODS: Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as tT ≤9.2 nmol/l. The Charlson Comorbidity Index (CCI) was used to score health-significant comorbidities. Severe clinical outcomes were defined as patients either transferred to intensive care unit (ICU) or death. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and tT levels. Univariable and multivariable logistic regression models tested the association between tT and severe clinical outcomes. RESULTS: Overall, a significantly lower levels of LH and tT were found in patients with COVID-19 compared to healthy controls (all p < 0.0001); conversely, healthy controls depicted lower values of circulating E2 (p < 0.001). Testosterone levels suggestive for hypogonadism were observed in 257 (89.8%) patients at hospital admission. In as many as 243 (85%) cases, hypogonadism was secondary. SARS-CoV-2 infection status was independently associated with lower tT levels (p < 0.0001) and greater risk of hypogonadism (p < 0.0001), after accounting for age, BMI, CCI, and IL-6 values. Lower tT levels were associated with higher risk of ICU admission and death outcomes (all p ≤ 0.05), after accounting for clinical and laboratory parameters. CONCLUSIONS: We unveil an independent association between SARS-CoV-2 infection status and secondary hypogonadism already at hospital admission, with lower testosterone levels predicting the most severe clinical outcomes.

Patients presenting with lower urinary tract symptoms who most deserve to be investigated for primary bladder neck obstruction.

We aimed to investigate clinical features potentially useful in primary bladder neck obstruction (PBNO) diagnosis in men presenting with lower urinary tract symptoms (LUTS). Data from 1229 men presenting for LUTS as their primary complaint at a single centre were retrospectively analysed. All patients underwent a comprehensive medical and physical assessment, and completed the International Prostate Symptoms Score. All patients were investigated with uroflowmetry, and trans-rectal ultrasound imaging to define prostate volume. Urodynamic evaluation was performed when the diagnosis of benign prostatic enlargement was not confirmed and the patient presented a significant chance of detrusor overactivity or underactivity. As per our internal protocol, patients < 60 years old with bothersome LUTS and > 60 years with a prostate volume (PV) < 40 mL were also investigated with urethrocystoscopy to rule out urethral stricture. Logistic regression analysis tested clinical predictors of possible PBNO. Of 1229 patients, 136 (11%) featured a clinical profile which was consistent with PBNO. Overall, these patients were younger (p < 0.0001), had lower BMI (p < 0.0001), less comorbidities (p = 0.004) and lower PSA values (p < 0.0001), but worse IPSS scores (p = 0.01) and lower PV values (p < 0.0001) compared to patients with other-aetiology LUTS. At multivariable analysis, younger age (OR 0.90; p = 0.003) and higher IPSS scores (OR 1.12; p = 0.01) were more likely to be associated with this subset of patients, after accounting for other clinical variables. One out of ten young/middle-aged men presenting for LUTS may be affected from PBNO. Younger patients with more severe LUTS systematically deserve an extensive assessment to rule out PBNO, thus including urethrocystoscopy and urodynamics with voiding-cysto-urethrogram.

Extensive Assessment of Underlying Etiological Factors in Primary Infertile Men Reduces the Proportion of Men With Idiopathic Infertility.

Objective: Up to 40% of infertile men remain without a recognized cause (i.e., idiopathic infertility). We aimed to identify, categorize, and report the supposed causes of male infertility in a cohort of white-European men presenting for primary couple's infertility, by using a thorough and extensive baseline diagnostic work-up. Material and Methods: Cross-sectional study of 1,174 primary infertile men who underwent a thorough diagnostic work-up including: detailed medical history, physical examination, hormonal assessment, genetic testing, semen analyses; semen and urine cultures; testis color Duplex US. Men without any identified causal factor were considered as idiopathic. Six different etiological categories were established, and their prevalence was estimated. Logistic regression models estimated the risk of missing causal identification. Results: A possible causal factor was identified in 928 (81%) men. Hypogonadism was the most frequent identified cause (37%), followed by varicocele (27%). Genetic abnormalities were found in 5% of patients. A causal factor was more easily identifiable for the more severe infertility cases, and azoospermic men were those less likely to be defined as idiopathic (OR and 95% CIs: 0.09; 0.04-0.20). Relative proportion of identified causes remained constant during the 10-year study period (p>0.43). Conclusions: Due to a more comprehensive and extensive diagnostic work-up, at least one underlying cause of male infertility factor in 4 out of 5 infertile men can be identified. Men with a less severe phenotype remain a clinical challenge in terms of establishing a possible etiologic factor. Further studies are needed to assess which subset of infertile men deserves a more extensive work-up.

Infertile Men Have Higher Prostate-specific Antigen Values than Fertile Individuals of Comparable Age.

BACKGROUND: Infertile men are at greater risk for oncological and nononcological chronic disease than fertile individuals. OBJECTIVE: To investigate prostate-specific antigen (PSA) values in men presenting for primary couple's infertility compared with a cohort of fertile individuals, according to the recommendation of the European Association of Urology guidelines that a first PSA assessment should be done at 40-45 yr of age. DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional study. Data from 956 (90%) infertile men and 102 (9.6%) fertile participants were analysed. Circulating hormones, total PSA, and semen parameters were investigated in every man. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics, local polynomial smoothing, and linear regression models were used to test potential associations with PSA levels. RESULTS AND LIMITATIONS: Overall, PSA >1 ng/ml was found in 318 (30%) men. Serum PSA was higher (p = 0.02), while serum testosterone (p < 0.01) was lower in infertile than in fertile men. In participants younger than 40 yr, 176 (27%) men had PSA >1 ng/ml; of them, a greater proportion were infertile (28% infertile vs 17% fertile, p = 0.03). At multivariable linear regression analysis, infertile status (coefficient 0.21; 95% confidence interval 0.02-0.39) was associated with higher PSA values, after adjusting for age and serum testosterone level. This was a single-centre study, raising the possibility of selection biases. CONCLUSIONS: Infertile men have higher PSA values than fertile individuals. Of all, almost one out of three primary infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. PATIENT SUMMARY: In this study, we observed that (1) infertile men have higher prostate-specific antigen (PSA) values than fertile individuals and (2) a greater proportion of infertile men younger than 40 yr had total PSA >1 ng/ml at the first assessment. These data might be relevant to study the potential clinical impact of more rigorous screening in primary infertile men.

Trends in reported male sexual dysfunction over the past decade: an evolving landscape.

We investigated changes in patterns of reported male SDs at a single academic centre over a 10-year time frame. Comprehensive data of 2013 patients consecutively assessed for the first time by a single Sexual Medicine expert between 2006 and 2019 has been analysed. All patients were assessed with a thorough sexual and medical history. Primary reason for seeking medical help at first assessment was recorded for all patients and categorized as: erectile dysfunction (ED), premature ejaculation (PE), low/reduced sexual desire/interest (LSD/I), Peyronie's disease (PD), and other SDs. Linear and logistic regression models tested the association between different reasons for seeking medical help and the time at first evaluation. Local polynomial regression model explored the probability of reporting different SDs over the analysed time frame. Median (IQR) age at first clinical assessment was 50 (38-61) years. Overall, most patients were assessed for ED (824; 41%), followed by PD (369; 18%), PE (322; 16%), LSD/I (204; 10%) and other SDs (294; 15%). Significant changes in terms of reported SD over the analysed time frame were observed. The likelihood of assessing patients for ED significantly increased up to 2013, with a decrease in the past 5 years (p < 0.001). PE assessment at presentation linearly decreased over time (OR: 0.94; 95% CI: 0.91-0.96; p < 0.001). Patients assessed during the past few years were more likely to report PD (OR: 1.20; 95% CI: 1.15-1.25; p < 0.001) and LSD/I (OR: 1.21; 95% CI: 1.16-1.26; p < 0.001), with a linear increase over the evaluated time frame. Likewise, patients were also more likely to report other SDs (Coeff: 1.06; 95% CI: 1.02-1.10; p = 0.004), with a linear increase over time. These results may reflect real changes in SD incidence, increased public awareness towards different SDs and the possible impact of novel treatments available on the market throughout the same time frame.

Normal sperm parameters per se do not reliably account for fertility: A case-control study in the real-life setting.

A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting.

Is It Compulsory to Investigate for Erectile Dysfunction in Patients Presenting for Low Urinary Tract Symptoms?

BACKGROUND: Current European Association of Urology guidelines suggest investigation of erectile dysfunction (ED) among patients with lower urinary tract symptoms (LUTS) whenever there is a clinical suspicion. OBJECTIVE: To assess factors predictive of ED, which may drive the need for a clinical assessment in men only presenting for LUTS. DESIGN, SETTING, AND PARTICIPANTS: Data from 914 men presenting for LUTS at a single-center outpatient clinic and without a previous diagnosis of ED were analyzed. INTERVENTION: All patients completed the International Prostatic Symptom Score (IPSS) and the International Index of Erectile Function-erectile function (IIEF-EF) questionnaires. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression analyses tested potential predictors of ED and severe ED. The accuracy of the predictive models was assessed, and decision curve analyses (DCAs) tested their clinical benefit. RESULTS AND LIMITATIONS: The median baseline IPSS score was 12 (7-19). IIEF-EF scores suggestive of unreported ED were observed in 503 (55%) patients; of all, 251 (27%) men showed severe ED. At logistic regression analysis, age (odds ratio [OR]: 1.04; p<0.001), IPSS score (OR: 1.04; p<0.001), diabetes mellitus (OR: 2.37; p=0.02), and smoking history (OR 1.36; p=0.03) were associated with unreported ED, after accounting for body mass index, hypertension, other cardiovascular diseases, and dyslipidemia. The same factors were associated with severe ED (all p≤0.03). The predictive model including these variables showed good accuracy for predicting ED (areas under the curve 0.69 and 0.72, respectively). However, DCAs showed no greater clinical benefit regarding identifying which patients should actually be screened for ED using these variables versus screening all patients with LUTS. Conversely, the net clinical benefit of the tested model was higher when predicting severe ED. As a limitation, we could not check prospectively the clinical impact of detecting ED in LUTS patients. CONCLUSIONS: Given the importance of ED in terms of overall men's health, segregating patients to be investigated or not for ED according to the traditional risk factors did not emerge more clinically useful than screening all patients presenting for LUTS. PATIENT SUMMARY: Lower urinary tract symptoms (LUTS) are frequently associated with erectile dysfunction (ED). Patients presenting for LUTS only in the everyday clinical practice should always be screened for ED and managed accordingly.

Male factor infertility trends throughout the last 10 years: Report from a tertiary-referral academic andrology centre.

BACKGROUND: Trends of male factor causes of couples' infertility over time have been poorly investigated. OBJECTIVE: We investigated trends in the causes of pure male factor infertility (MFI) throughout the last 10 years in a tertiary-referral academic andrology center. MATERIAL AND METHODS: Baseline characteristics at first presentation from a cohort of 1647 consecutive male factor infertility patients belonging to primary infertile couples between 2008 and 2018 have been comprehensively collected over time. Seven major causes of male factor infertility were identified: varicocoele; history of cryptorchidism; hypogonadism (primary and secondary); obstructive azoospermia; genetic abnormalities; other causes (large group including the remnant conditions of known causes); and idiopathic infertility. Rates of different male factor infertility causes over the study period were analyzed. Multivariable logistic regression models tested the likelihood of male factor infertility causes over time. Estimated trends were explored graphically. RESULTS: Of all, varicocoele was found in 615 (37.3%), cryptorchidism in 124 (7.5%), genetic abnormalities in 61 (3.7%), hypogonadism in 165 (10%), obstructive conditions in 55 (3.3%), other causes in 129 (7.8%) patients, and idiopathic infertility in 498 (30.3%) patients, respectively. Over time, a reduction in the proportions of cryptorchidism and varicocoele (all P < 0.001) cases was observed, along with an increase in the proportions of hypogonadism, other causes of MFI and idiopathic cases (all P ≤ 0.01). Rates of genetic and obstructive cases remained stable. The observed trends were confirmed at logistic regression models. DISCUSSION AND CONCLUSIONS: A decreasing trend in the proportions of varicocoele and cryptorchidism at first presentation was observed over the last 10 years; conversely, the proportions of idiopathic cases, hypogonadal patients, and infertile men presenting with other male factor infertility causes significantly increased over the same time frame at a single tertiary-referral academic andrology center.

Leukocytospermia is not an informative predictor of positive semen culture in infertile men: results from a validation study of available guidelines.

STUDY QUESTION: Are the European Association of Urology (EAU) guidelines for performing semen culture accurate enough for detecting a positive semen culture in Caucasian-European infertile men? SUMMARY ANSWER: The majority (80%) of asymptomatic infertile men with a positive sperm culture may miss a proper diagnostic assessment when relying on EAU guidelines; no single parameter can assist in medical decision-making. WHAT IS KNOWN ALREADY: The EAU guidelines suggest performing semen culture in case of increased leukocytes in semen (>106 peroxidase positive white blood cells/ml, i.e. leukocytospermia). STUDY DESIGN SIZE DURATION: A cross-sectional validation study including 523 infertile men was carried out during 2010-2018. PARTICIPANTS/MATERIALS SETTING METHODS: Infertile men who were asymptomatic for genital infections were enrolled at a single academic center, and a semen culture was obtained in every case. A concentration of >103 cfu/ml urinary tract pathogens in the ejaculate was considered indicative of significant bacteriospermia. Semen analysis values were assessed on the basis of 2010 World Health Organization reference criteria. EAU guidelines for semen culture were used to predict positive semen culture in our cohort and thus validated. Moreover, we tested the predictive performance and accuracy of several clinical parameters and compared them to EAU guidelines. MAIN RESULTS AND THE ROLE OF CHANCE: A positive semen culture was found in 54 men (10%). The application of EAU guidelines would have missed 43 out of 54 (80%) positive semen cultures with 120/131 (92%) useless examinations. EAU guidelines specificity, sensitivity and discrimination were 74%, 20% and 47%, respectively. When trying to improve positive semen culture prediction, we were unable to find any informative baseline parameter except for serum neutrophil-to-lymphocyte ratio (odds ratio 1.70 (95% CI 1.04-2.77)), although without any improvement in terms of discrimination (P = 0.10). LIMITATIONS REASONS FOR CAUTION: The study was limited by the lack of a control group of fertile men its retrospective nature. Moreover, monoclonal antibodies were not used for leukocyte assessment. WIDER IMPLICATIONS OF THE FINDINGS: Since it is not possible to identify infertile men at risk of semen infection, further studies are needed to tailor the execution of semen culture. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. There are no competing interests.

Serum testosterone levels are not associated with the severity of penile curvature in men with Peyronie's disease-findings from a cross-sectional study.

We aimed to evaluate the relationship between serum testosterone (T) levels and penile curvature in a cohort of men presenting for chronic phase Peyronie's disease (PD). Clinical data from 149 patients assessed for chronic phase PD between 2016 and 2019 at a single academic center were analyzed. Deformity assessment was conducted during an intracavernosal injection-induced rigid erection. Both total T (tT) and calculated free T (cFT) were assessed in every patient and considered as continuous variables or according to quartiles of the normal range. Hypogonadism was defined for tT < 10.4 nmol/L. Descriptive statistics and linear regression models tested the association between T values and the severity of penile curvature. Overall, median tT value was 15.9 (11.4-20.8) nmol/L in the whole cohort; median curvature magnitude and plaque size were 45 (30-60) degrees and 1.5 (0.8-2.0) cm, respectively. Penile curvature (40.0 vs. 45.0 degree; p = 0.7) and plaque size (1.5 vs. 1.3 cm; p = 0.4) were similar between eugonadal and hypogonadal patients. The magnitude of penile curvature did not differ across tT quartiles (p = 0.31). Both at univariable (ß 1.32; p < 0.01) and multivariable (ß 1.34; p < 0.01) linear regression model, only duration of PD was associated with the severity of penile curvature magnitude. The results of this cross-sectional study confirmed that there is no association between serum T values and the severity of penile curvature in patients with chronic phase PD. Only PD duration is associated with penile deformity severity.

The impact of metabolically healthy obesity in primary infertile men: Results from a cross-sectional study.

BACKGROUND: A number of studies showed that obesity may negatively impact on sperm quality and consequently couple's fertility. Recently, specific attention was given to a clinical condition known as metabolically healthy obesity (MHO). OBJECTIVES: To evaluate the effects of MHO on semen and hormonal parameters of men presenting for primary couple's infertility associated with pure male factor infertility (MFI). MATERIALS AND METHODS: Data from a homogenous cohort of 512 white-European primary infertile men belonging to couples with pure MFI have been cross-sectionally analyzed. Semen analysis was based on 2010 WHO reference criteria. Patients were segregated into eugonadal, secondary hypogonadal, primary hypogonadal, and compensated hypogonadal. The Harmonized International Diabetes Federation criteria were used to define metabolic syndrome (MetS). Based on BMI and MetS, patients were further segregated into the following: (a) metabolically healthy non-obese (MHNO); (b) metabolically unhealthy non-obese (MUNO) (c) metabolically healthy obesity (MHO); and, (d) metabolically unhealthy obesity (MUHO). Main outcome measures were the prevalence of MHO and the impact of MHO on semen and hormonal parameters in this cohort of MFI primary infertile men. RESULTS: Overall, MHNO, MUNO, MHO, and MUHO were found in 462 (90%), 13 (2.5%), 27 (5.2%), and 10 (1.9%) men, respectively. MHO patients had lower total testosterone and SHBG levels (all P < .05) but higher E2 values (P < .005) compared with MHNO men. Groups did not differ in terms of semen parameters. At multivariable logistic regression, analysis MHO was associated with an increased risk of primary and secondary hypogonadism (all P ≤ .02) compared with MHNO, after accounting for age and comorbid conditions. DISCUSSION AND CONCLUSIONS: Metabolically healthy obesity is threefold more prevalent than unhealthy obesity in primary infertile men. Despite semen parameters are comparable among groups, MHO patients show worse endocrine parameters and a higher risk of primary and secondary hypogonadism compared with metabolically healthy normal infertile men.

SHBG levels in primary infertile men: a critical interpretation in clinical practice.

OBJECTIVE: We aimed to test the association between age, BMI and sex-hormone-binding globulin (SHBG) in a homogenous cohort of white-European men presenting for primary couple's infertility. DESIGN: Retrospective study. METHODS: Data from 1547 infertile men were analysed. Health-significant comorbidities were scored with the Charlson comorbidity index (CCI). Fasting serum hormones were measured in every patient. Age was considered according to quartile groups (<33, 33-41, >41 years) and BMI as normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) and obesity (>30 kg/m2). Descriptive statistics and linear regression analysis tested the associations between age, BMI and SHBG. RESULTS: Median SHBG levels increased across quartiles of age and decreased along with BMI increases (all P < 0.001). For each year increase in age, SHBG increased 0.32 nmol/L; conversely, for each unit increase in BMI, SHBG decreased by 1.1 nmol/L (all P < 0.001). SHBG levels decline with increasing BMI was greater than SHBG progressive increase with age. Overall, BMI explained 3.0 times more of the variability in SHBG than did ageing. At multivariate linear model, age and BMI were the most significant factors influencing SHBG concentration (all P < 0.001), after accounting for CCI, albumin levels and smoking status. CONCLUSIONS: We found a wide distribution of SHBG concentrations across age and BMI values in primary infertile men. The association between BMI and lowered SHBG levels seems to be greater than the association of ageing with increased SHBG.

Longitudinal Risk of Developing Cardiovascular Diseases in Patients With Erectile Dysfunction-Which Patients Deserve More Attention?

BACKGROUND: Erectile dysfunction (ED) is widely considered as an early manifestation of cardiovascular diseases (CVDs), sharing similar risk factors. AIM: Assess rates and predictors of developing CVD and/or hypertension (HTN) over a long-term follow-up period using user-friendly and clinically reliable tools in men presenting with ED but without CVD/HTN or known vascular risk factors at baseline. METHODS: Data from 108 patients presenting between 2005 and 2011 with ED were analyzed. All patients were free from CVD and/or HTN (CVD/HTN) at baseline. Patients completed the International Index of Erectile Function (IIEF) at baseline and were followed up every 6 months with clinical assessment or phone interview. Kaplan-Meier analyses estimated the probability of developing CVD/HTN over time. Cox-regression models tested the association between patient baseline characteristics (for example, age, Charlson Comorbidity Index, baseline IIEF-EF, ED severity, alcohol intake, smoking), response to phosphodiesterase type-5 inhibitors (PDE5is), and the risk of developing CVD/HTN. RESULTS: Of all, 43 (40%) patients showed IIEF-EF scores suggestive of severe ED; 37 (39%) and 59 (61%) were nonresponders and responders to PDE5i, respectively. Median (interquartile range) age was 51 (41, 61) years. Median (interquartile range) follow-up was 95 (86-106) months. Overall, the estimated risk of developing CVD/HTN was 15% (95% confidence interval [CI]: 9-27) at 10-year assessment. Men with baseline severe ED had a higher risk of developing CVD/HTN (34%; 95% CI: 17-59, P = .03) at 10 years than patients with mild to moderate ED (5% [95% CI: 2-14]). At the Cox regression analysis, severe ED (Hazard ratio [HR], 4.62; 95% CI: 1.43, 8.89; P = .01) and baseline IIEF-EF score (HR, 0.92; 95% CI: 0.86, 0.99; P = .02) were associated to the risk of CVD/HTN overtime. Conversely, age and nonresponders to PDE5is (HR, 0.92; 95% CI: 0.32, 2.68; P = .9) were not associated to a risk of CVD/HTN over time. CLINICAL IMPLICATIONS: The use of an easy and user-friendly tool, as the IIEF-EF domain score, would allow to reliably assess which men with ED at first presentation may deserve a different, more specific and detailed cardiologic investigation to prevent inauspicious CV events. STRENGTHS & LIMITATIONS: A single-center-based, observational longitudinal study, raising the possibility of selection biases are the main limits. CONCLUSIONS: Patients with severe ED and lower baseline IIEF-EF but no vascular risk factors at first presentation have more than 30% risk of developing CVD/HTN in 10-year time. Those patients may benefit from medical preventive strategies to lowering the risk of CV events and HTN. Pozzi E, Capogrosso P, Boeri L, et al. Longitudinal Risk of Developing Cardiovascular Diseases in Patients With Erectile Dysfunction-Which Patients Deserve More Attention?. J Sex Med 2020;17:1489-1494.

Semen infections in men with primary infertility in the real-life setting.

OBJECTIVE: To study the impact of asymptomatic semen infections on seminal parameters in men presenting for primary couple's infertility. DESIGN: Cross-sectional study. SETTING: Academic center. PATIENTS: Socio-demographic, clinical, and laboratory data from 1689 infertile men were analyzed. INTERVENTION(S): Semen analysis was based on 2010 World Health Organization reference criteria. Each patient underwent semen culture test to identify common urogenital pathogens. Infections by Mycoplasma, Ureaplasma, and Chlamydia spp. were evaluated through a real time polymerase chain reaction platform. Descriptive statistics and linear and logistic regression models were used to test the association between semen infections and clinical, seminal, and hormonal parameters. MAIN OUTCOME MEASURE(S): Prevalence of asymptomatic semen infection and impact of semen infection on sperm parameters. RESULTS: Of 1689 men, 354 (21.0%) had an asymptomatic positive semen culture. Ureaplasma urealyticum (37.6%) was the most frequent single pathogen, followed by Enterobacteriaceae (any type; 24.8%), other pathogens (20.3%), Chlamydia trachomatis (3.4%) and Mycoplasma spp (3.4%). Positive semen cultures were associated with lower sperm concentrations (P<0.001) and progressive motility (P<.001). These latter findings were mostly particular to men with infections caused by Ureaplasma urealyticum compared with negative semen cultures. A positive semen culture was both univariably (P<.001) and multivariably (P=.04) associated with a lower sperm concentration. CONCLUSION: One out of five men presenting for a couple's primary infertility had asymptomatic semen infections, which were significantly associated with impaired sperm concentration. These observations point out the importance of an accurate investigation of semen infection in the everyday clinical practice diagnostic workup of infertile men.