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Background: Phosphodiesterase 5 inhibitors (PDE5is) represent a first-line pharmacological therapy for erectile dysfunction (ED). Men could obtain PDE5is for recreational purposes without any proper medical prescription., Objective: We aimed to analyze clinical characteristics of patients who already used any PDE5i for ED without previous formal medical prescription., Materials and Methods: Data from 2012 heterosexual, sexually active men seeking first medical help for ED at our outpatient clinic between 2005 and 2022 were analyzed. All patients were assessed with a comprehensive sexual and medical history and completed the International Index of Erectile Function (IIEF) at baseline. Comorbidities were scored with the Charlson comorbidity index (CCI). Thereof, according to exposure to any PDE5i before their first visit, patients were subdivided into: PDE5i-naïve and non-PDE5i-naïve patients. Descriptive statistics tested the sociodemographic and clinical characteristics of both groups. A logistic regression model predicted the likelihood of being PDE5i-naïve at the baseline. Linear regression analysis (LRA) estimated the likelihood of being PDE5i-naïve versus non-PDE5i-naïve over the analyzed timeframe. Lastly, local polynomial regression models graphically explored the likelihood of being PDE5i-naïve at the first clinical assessment over the analyzed timeframe, and the sensitivity analyses tested the probability of being PDE5i-naïve at baseline., Results: Overall, 1,491 (70.9%) patients were PDE5i-naïve and 611 (29.1%) were non-PDE5i-naïve at the first assessment. PDE5is-naïve patients were younger, with a lower prevalence of CCI ≥ 1 and of normal erectile function (EF) than non-PDE5i-naïve men (all p < 0.05). Multivariable logistic regression found that patients with lower BMI (OR: 0.99), higher IIEF-EF scores (OR: 1.02), lower rates of severe ED (OR: 0.94), and who had been assessed earlier throughout the study timeframe (OR: 1.27) were less likely to be PDE5i-naïve at baseline. Univariate LRA revealed that younger patients (Coeff: -0.02), with lower CCI (Coeff: -0.29) and higher alcohol intake per week (Coeff: 0.52) were more likely to be PDE5i-naïve over the analyzed timeframe. Moreover, for the same IIEF-EF score, patients with higher CCI had lower probability of being PDE5i-naïve., Conclusions: Self-prescription of PDE5is is an attitude presents in the general population, despite this phenomenon has decreased overtime. Current data outline the importance to keep promoting educational campaigns to promote PDE5is as effective and safe medicinal products, while avoiding their improper use., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background: Orgasmic phase disorders in men worsen the burden of erectile dysfunction on sexual satisfaction., Objectives: To investigate the prevalence of and predictors of unreported orgasmic phase disorder in a cohort of men looking for their first urological assessment for new-onset erectile dysfunction in a real-life setting., Materials and Methods: Data from 1107 heterosexual, sexually active men consecutively assessed for new-onset erectile dysfunction were analysed. Throughout a comprehensive medical and sexual history, all patients were asked to self-report any orgasmic phase disorder and to complete the International Index of Erectile Function and the Beck's Inventory for Depression (depressive symptoms scored as Beck's Inventory for Depression ≥11). Men self-reporting orgasmic phase disorder during the interview were excluded from further analyses. The median value of the International Index of Erectile Function-orgasmic function domain was arbitrarily used to categorise men with (International Index of Erectile Function-orgasmic function ≤5) and without unreported orgasmic phase disorder (International Index of Erectile Function-orgasmic function >5). Circulating hormones were measured in every patient. Descriptive statistics and logistic regression models were used to test the association between clinical variables and unreported orgasmic phase disorder., Results: Of 1098 patients with non-self-reporting orgasmic phase disorder, 314 (28.6%) had International Index of Erectile Function-orgasmic function ≤5. Patients with erectile dysfunction + unreported orgasmic phase disorder were older (median [interquartile range]: 58 [44-66] years vs. 51 [40-60] years), had higher body mass index [25.8 (23.7-28.1) kg/m 2 vs. 25.2 (23.3-27.4) kg/m 2 ], higher prevalence of type 2 diabetes (36 [11.5%] vs. 45 [5.7%]) and lower International Index of Erectile Function-erectile function scores (6 [2-10] vs. 18 [11-24]) than men with erectile dysfunction-only (all p < 0.05). Patients with erectile dysfunction + unreported orgasmic phase disorder depicted higher rates of severe erectile dysfunction (75.5% vs. 25%) and Beck's Inventory for Depression ≥11 (22.6% vs. 17.9%) (all p < 0.05). In the multivariable logistic regression analysis, older age (odds ratio: 1.02) and lower International Index of Erectile Function-erectile function scores (odds ratio: 0.83) were independently associated with unreported orgasmic phase disorder (all p < 0.05)., Conclusions: Almost one in three men seeking first medical help for erectile dysfunction depicted criteria suggestive of unreported orgasmic phase disorder. Men with unreported orgasmic phase disorder were older and had higher rates of severe erectile dysfunction and concomitant depressive symptoms. These real-life findings outline the clinical relevance of a comprehensive investigation of concomitant sexual dysfunction in men only complaining of erectile dysfunction to more effectively tailor patient management., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: Hyperestrogenism is believed to be harmful to male sexuality. We aimed to investigate the prevalence of and the impact of hyperestrogenism on sexual functioning in a cohort of men seeking medical attention for new-onset erectile dysfunction., Materials and Methods: Data from 547 men seeking first medical help for new-onset erectile dysfunction at a single andrology center were analyzed. Patients were assessed with a thorough medical and sexual history. Comorbidities were scored with the Charlson comorbidity index. All patients completed the International index of erectile function; the International index of erectile function-erectile function domain was categorized according to Cappelleri's criteria. Circulating hormones were measured in every patient. Hyperestrogenism was defined as estradiol levels >42.6 pg/mL (Tan et al., 2015). Descriptive statistics and logistic/linear regression models tested the association between hyperestrogenism and International index of erectile function domains score., Results: Overall, 96 (17.6%) participants had serum estrogen levels suggestive of hyperestrogenism. Men with hyperestrogenism were older (median [interquartile range]: 46 [35-59] vs. 44 [31-56] years; p < 0.001), had a higher rate of comorbidities (Charlson comorbidity index ≥1: 26.0% vs. 7.4%; p < 0.001), and higher serum total testosterone values (5.4 [5.2-8.0] vs. 4.3 [4.1-5.7] ng/mL; p = 0.01) than those with normal estradiol values. A higher prevalence of severe erectile dysfunction (135 [29.9%] vs. 47 [48.9%] men; p = 0.01) and of hypogonadism (22 [4.8%] vs. 6 [6.3%] men; p = 0.004) were found in men with hyperestrogenism. Serum estradiol levels were positively correlated with total testosterone levels (β = 0.26, p < 0.001) but negatively correlated with International index of erectile function-orgasmic function (β = -0.24, p = 0.002) and International index of erectile function-erectile function scores (β = -0.03, p < 0.001). When International index of erectile function scores was used to stratify erectile dysfunction patients, hyperestrogenism (odds ratio 2.44, p = 0.02) was associated with severe erectile dysfunction., Conclusions: One out of five men seeking first medical help for erectile dysfunction showed elevated serum estradiol values suggestive of hyperestrogenism. Hyperestrogenism was associated with health-significant comorbidities, orgasmic function impairment, and erectile dysfunction severity., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: Recurrent pregnancy loss and unexplained infertility are the current indications to test sperm DNA fragmentation according to the European Association of Urology Guidelines on sexual and reproductive health., Objective: To identify a novel and better performing model to diagnose primary infertile men presenting with altered sperm DNA fragmentation and to outline its predictive ability in respect to current European Association of Urology Guidelines' recommendations., Materials and Methods: Data from the latest 515 consecutive primary infertile men as for World Health Organization criteria were analyzed. Semen analysis, sperm DNA fragmentation (according to sperm chromatin structure assay), and serum hormones were considered in every patient. Altered sperm DNA fragmentation was defined with levels greater than 30%. Descriptive statistics was applied to compare patients with normal versus SDF > 30%. The new predicting model was identified through logistic regression analysis exploring potential predictors of SDF > 30% at first clinical presentation. Diagnostic accuracy between the two predictive models (European Association of Urology Guidelines vs. new) was assessed, and decision curve analyses tested their clinical benefit., Results: Of 515, 268 (51.9%) patients had SDF > 30% at clinical presentation. Patients with SDF > 30% were older (median [interquartile range] 39 [35-43] vs. 37 [34-41] years), had lower mean testicular volume (Prader 15 [12-20] vs. 17.5 [13.5-20] and lower total motile sperm count (1.80 [0.7-13.2] vs. 11.82 [4.2-44.5] × 10 6 ), all p < 0.001. No other clinical differences were depicted. The two groups showed similar rates of history of recurrent pregnancy loss and unexplained infertility. At multivariable logistic regression analysis, age more than 38 years (odds ratio: 2.43) and baseline total motile sperm count less than 20 × 10 6 (odds ratio: 3.72) were associated with SDF > 30%, after adjusting for Prader < 15, history of miscarriages and unexplained infertility, all p < 0.0001. The newly identified model (unexplained infertility + history of poli-abortions + Prader < 15 + age ≥38 years + total motile sperm count <20 × 10 6 ) showed higher accuracy to identify SDF > 30% at baseline in respect to European Association of Urology Guidelines (area under the curve: 72.1 vs. 52.7), with superior clinical net benefit use., Conclusions: The application of the European Association of Urology sexual and reproductive health guidelines does not ensure proper identification of primary infertile men with pathological sperm DNA fragmentation. We propose a novel and better performing predictive model to identify the infertile men with altered sperm DNA fragmentation at first clinical assessment., Discussion: As altered sperm DNA fragmentation has been widely linked with the inability to conceive, this second-level test could be further implemented over the diagnostic workup of a broader subset of patients presenting for male factor infertility. We propose a better performing model to identify this specific category of patients., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: Infertile men have a worse overall health status than their fertile counterparts., Objective: We aimed to (1) compare kidney function in men presenting for primary couple's infertility with that of fertile men and (2) assess kidney function impairment toward sperm quality in infertile men., Materials and Methods: In this case-control study, 387 consecutive white-European infertile men were matched by age with 134 same-ethnicity fertile men. Complete clinical and laboratory data were available for each patient. The Chronic Kidney Disease Epidemiology Collaboration function was used for estimated glomerular filtration rate calculation. Kidney functional impairment was defined as an estimated glomerular filtration rate <90 mL/min per 1.73 m 2 , according to the Kidney Disease Improving Global Outcomes criteria. Multivariable logistic regression analysis was used to (1) assess the association between kidney function impairment and infertility status and (2) investigate the association between kidney function and semen analysis abnormalities in infertile men., Results: After matching, 34 (8.8%) infertile men depicted at least a mild unknown impairment of kidney function compared to only four (3%) fertile men, with four (3%) of the infertile presenting with an overt kidney function impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m 2 ). There were no differences in terms of age, body mass index and rate of comorbidities between the two groups (all p > 0.05). After adjusting for major confounders, infertility status was associated with a higher risk of reduced estimated glomerular filtration rate (odds ratio 3.20; 95% confidence interval 1.21-5.2; p = 0.002). Conversely, estimated glomerular filtration rate was not associated with sperm abnormalities in infertile men., Conclusions: Mild kidney function impairment was found in 9% of asymptomatic and unaware men presenting for primary couple's infertility investigation. This novel finding corroborates growing data on a significant association of male infertility with a poorer overall male health status and the need for tailored preventive strategies., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: The atherosclerotic cardiovascular disease risk score is a validated algorithm predicting an individual's 10-year risk of developing acute cardiovascular events (cardiovascular disease). Patients who suffer from arteriogenic erectile dysfunction are susceptible to developing cardiovascular disease in the future., Objectives: To apply the atherosclerotic cardiovascular disease score at a homogenous cohort of men with erectile dysfunction undergoing a dynamic penile colour Doppler duplex ultrasound and explore its predictive ability to identify patients with vasculogenic erectile dysfunction at colour Doppler duplex ultrasound., Materials and Methods: Complete data of 219 patients undergoing colour Doppler duplex ultrasound were analysed. All patients completed the International Index of Erectile Function. The atherosclerotic cardiovascular disease score and Charlson comorbidity index were applied to the entire cohort. Patients were divided into those with normal vs. pathological parameters at colour Doppler duplex ultrasound. Descriptive statistics were used to explore differences between the two groups. Logistic regression models tested the potential role of atherosclerotic cardiovascular disease to predict arteriogenic and/or venogenic erectile dysfunction. Local polynomial smoothing models graphically displayed the probability of pathological colour Doppler duplex ultrasound parameters at different atherosclerotic cardiovascular disease scores., Results: Overall, arteriogenic erectile dysfunction and venous leakage were diagnosed in 88 (40.2%) and 28 (12.8%) patients respectively. The median (interquartile range) atherosclerotic cardiovascular disease score was 7.7 (3.9-14). Patients with pathologic colour Doppler duplex ultrasound were older (59 vs. 54 years, p < 0.001), had higher Body Mass Index (26.5 vs. 25.6 kg/m 2 , p = 0.04), more comorbidities (Charlson comorbidity index ≥ 1) (76.5% vs. 54.4%, p = 0.002) and higher median atherosclerotic cardiovascular disease scores (9.95 vs. 7, p = 0.005), respectively. At logistic regression analysis, a higher atherosclerotic cardiovascular disease risk score was independently associated with arteriogenic erectile dysfunction at colour Doppler duplex ultrasound (odds ratio: 1.03, 95% confidence interval: 1.01-1.08, p = 0.02) after adjusting for Body Mass Index, physical activity, alcohol consumption and severe erectile dysfunction., Discussion: As vasculogenic erectile dysfunction may precede by some years the onset of acute cardiovascular diseases, the rigorous identification of patients with deficient cavernosal arterial blood flow, would definitely allow the implementation of earlier and more effective cardiovascular prevention strategies in men with erectile dysfunction., Conclusions: The atherosclerotic cardiovascular disease risk score represents a reliable tool to identify patients with arteriogenic erectile dysfunction in everyday clinical practice., (© 2023 American Society of Andrology and European Academy of Andrology.)

Background: Peyronie's disease (PD) has a huge impact on patients' physical and psychological wellbeing., Objectives: To investigate whether patients' age has an impact on PD symptomatic burden at first presentation., Materials and Methods: Data from 129 consecutive heterosexual patients seeking first medical attention for PD at a single andrological tertiary-referral centre were collected. All patients completed the International Index for Erectile Function (IIEF) and the PD questionnaire (PDQ). Descriptive statistics were used to compare clinical features between younger (≤40years) and older (>40 years) patients. Multivariable linear model assessed the impact of age, the degree of penile curvature and their impact on PDQ (total scores and its domains), after adjusting for PD duration and IIEF-erectile function domain scores., Results: Of 129, 24 (18.6%) patients were ≤40 years old. Young patients presented with a less severe curvature than older patients (median [interquartile ranges] 20° [15-36] vs. 50° [40-80]; p = 0.04). However, younger age was associated with higher psychological and physical symptoms, PDQ-penile pain and PDQ-symptom bother scores (Coeff -0.11, -0.21 and -0.17, respectively) (all p < 0.05). Moreover, the greater the degree of curvature, the higher the PDQ-psychological and physical symptoms and the PDQ-symptom bother scores (Coeff. 0.21 and 0.22, respectively; all p < 0.05)., Conclusion: Around one in five men seeking first medical help for PD is younger than 40 years at presentation in the real-life setting. PD-related distress varies according to patients' age, with younger men presenting with a greater risk of penile pain and symptom bother despite lower curvature., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: Alfa-fetoprotein (AFP) is a serum glycoprotein highly produced during fetal development. While AFP synthesis drops dramatically after birth, AFP production only persists or returns under specific pathological condition., Objective: We sought to investigate the rate of and the potential meaning of high AFP serum levels in men seeking first medical attention for couple's primary infertility., Materials and Methods: Socio-demographic and clinical data from 1803 non-Finnish, White-European primary infertile men were retrospectively analysed. AFP was routinely measured in each patient (high AFP was defined as >7 ng/ml). Men with history of liver diseases, testicular cancer, or other known causes of increased AFP levels were excluded from the final analysis. Semen analyses were based on the 2010 World Health Organization reference criteria. Descriptive statistics and logistic regression models tested the association between serum AFP and clinical variables. Possible nonlinear relationships were graphically explored with locally estimated scatterplot smoothing method., Results: Overall, high serum AFP level was found in 29 (1.7%) patients. Normal versus high AFP levels patients were comparable in terms of body mass index (BMI), Charlson Comorbidity Index, waist circumference, smoking habits, history of cryptorchidism, testicular volume, and serum hormones (i.e., follicle-stimulating hormone, luteinizing hormone, and total testosterone). Conversely, men with higher AFP levels were older (p = 0.02), had lower sperm concentration (p = 0.003), and were more frequently oligozoospermic and azoospermic (all p ≤ 0.03). At multivariate analysis, high AFP levels were independently associated with oligozoospermia (OR 3.79; p = 0.033) and azoospermia (OR 3.29; p = 0.006). Likewise, if AFP levels increase, patients were found to be older, with higher BMI and to have more comorbidities (all p < 0.05)., Discussion: Unexplained high AFP levels account for almost 2% of cases in primary infertile patients without a previous history of associated disorders. Higher serum AFP levels are linked with aberrant sperm counts, older age, obesity, and a greater amount of comorbid conditions., Conclusion: Despite the need for additional validation, these data suggest that serum AFP measurement might have a multifaceted role over the diagnostic work-up of males presenting for couple's infertility., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: Erectile dysfunction aetiology has been historically identified as organic, psychogenic and mixed., Objectives: To stratify and compare a cohort of patients seeking medical help for erectile dysfunction for the first time according to the newly proposed binary classification of the European Association of Urology guidelines: 'primary organic' versus 'primary psychogenic'., Materials and Methods: Complete data from 2009 consecutive patients presenting for erectile dysfunction were analysed. All patients completed the International Index of Erectile Function at baseline. According to the presence of erectile dysfunction-related risk factors indexed by the European Association of Urology Guidelines on Sexual and Reproductive Health, patients were categorised as having primary organic (≥1 risk factor) or primary psychogenic (0 risk factor) erectile dysfunction. Descriptive statistics compared the two groups. Linear regression analysis tested the association between the number of risk factors and erectile dysfunction severity. Locally estimated scatterplot smoothing method graphically explored the relationship between the number of risk factors for erectile dysfunction and the International Index of Erectile Function domain scores., Results: Median (interquartile range) age at first presentation was 50 (39-61) years. Of all, 1632 (86.2%) and 377 (13.8%) were identified as having primary organic and primary psychogenic erectile dysfunction, respectively. Overall, 1488 (74.1%) patients were >40 years of age; in this subgroup, the most frequent risk factors were age, hypertension (29%), active smoking (42%) and alcohol intake (25.1%). Median (interquartile range) International Index of Erectile Function-erectile function score was 15 (7-22). Primary organic erectile dysfunction patients depicted lower International Index of Erectile Function-sexual desire and International Index of Erectile Function-orgasmic function scores (all p ≤ 0.02), whilst groups did not differ in terms of International Index of Erectile Function-erectile function, International Index of Erectile Function-intercourse satisfaction and International Index of Erectile Function-overall satisfaction scores., Discussion: One out of nine patients complaining of erectile dysfunction depict criteria for primary psychogenic erectile dysfunction. Erectile function severity could be as severe as patients with organic erectile dysfunction. The single-centre-based cross-sectional nature of the study, raising the possibility of selection biases, is our main limitation., Conclusions: One out of nine patients presenting for erectile dysfunction depict criteria suggestive for primary psychogenic erectile dysfunction in the real-life setting. Patients with primary psychogenic and primary organic erectile dysfunction have comparable erectile dysfunction severity, thus outlining the importance of a comprehensive and tailored management work-up in every patient seeking medical help for the first time., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: In 2021, the World Health Organization (WHO) has provided the latest update on processing and evaluating semen analysis., Objectives: To assess (i) the rate of discordance in semen parameters categorization across three different WHO reference values (namely WHO21, 2010 and 1999) and (ii) the clinical differences among discordant semen analyses from a cohort of primary infertile men., Materials and Methods: Data from 788 infertile men were analyzed. Semen parameters were interpreted based on WHO21, WHO10, and WHO99 reference criteria. Pregnancy outcomes with assisted reproductive techniques (ART) were available for 110 (14%) patients. Descriptive statistics was applied to describe potential differences among the three consecutive WHO references criteria., Results: Semen parameters categorizations were highly different across the three groups (p < 0.001). Of all, 271 (42.2%) patients had normal semen parameters according to WHO10 but were pathologic when considered with WHO21 reference criteria (namely, men with increased semen abnormalities). Infertile men with increased semen abnormalities had lower testicular volume (p < 0.001) but higher FSH (p < 0.01) and LH (p < 0.001) values than those who had no change in terms of semen parameters categorization. Negative ART outcomes were more frequently reported in men with worsening semen parameters compared with those with confirmed semen parameters at WHO21 versus WHO10 (26.8% vs. 49%, p = 0.03). Conversely, infertile men with worsening semen parameters at WHO21 versus WHO99 were similar in terms of clinical and hormonal characteristics compared with those with the same rate of semen abnormalities., Conclusions: One out of three infertile men showed worsened semen categorization according to WHO21 versus WHO10. Infertile men with worsening of semen parameters had worse clinical and hormonal characteristics than those with confirmed numbers of semen abnormalities. Moreover, live birth rates were lower in men with worsening semen abnormalities as for WHO21., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: Male factor contributes to up to 50% of cases of couples experiencing infertility. Cannabis is one of the most commonly used recreational drugs, and its effects on the reproductive system have been largely debated in the literature., Objectives: The aim of this study is to evaluate the effect of recreational cannabis use on total T (tT) levels, gonadal status, and sperm parameters in a cohort of primary infertile non-Finnish, white-European men., Materials and Methods: Data of 2074 white-European men visited for primary couple's infertility were analyzed. Lifestyle factors and cannabis use were investigated in all participants. Semen analyses were based on the 2010 World Health Organization reference criteria. Serum hormones were evaluated, and patients were subdivided based on their gonadal status. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Descriptive statistics and linear regression analyses were used to test the association between cannabis use, sperm parameters, and hormonal levels. Logistic regression analyses tested potential predictors for abnormal sperm parameters and gonadal status., Results: Of 2074, 225 (10.9%) patients reported cannabis use in their lifetime. Total Testosterone levels were lower in cannabis users compared to nonusers (p = 0.03). In a multivariable linear regression analysis, cannabis use was inversely associated with tT levels (ß = -0.372 ng/ml; p = 0.005) but not with follicle-stimulating hormone nor with luteinizing hormone levels. Conversely, at multivariable logistic regression model cannabis use was not associated with the type of hypogonadism. At multivariable linear regression analysis, cannabis use was inversely associated with sperm morphology (p = 0.007), while not with both sperm concentration and sperm motility. Similarly, at adjusted logistic regression analysis cannabis use resulted associated with teratozoospermia (p = 0.039) but not with oligo-, astheno-, and azoospermia., Conclusions: Infertile men using cannabis are at higher risk of having lower testosterone levels and altered sperm morphology as compared with nonusers., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: A severe male infertility factor has been associated with both lower health status and increased mortality in infertile men., Objectives: To investigate reproductive factors associated with health status impairment in infertile men over a 10-year time frame since the first clinical evaluation., Materials and Methods: Data from 899 infertile men were analysed at baseline between 2003 and 2010. Health-significant comorbidities were scored with the Charlson Comorbidity Index. Patients were followed up yearly recording any worsening in their health status until 2019. Cox regression models were used to estimate hazard ratios and 95% confidence intervals of Charlson Comorbidity Index score increase., Results: At a median follow-up of 136 months (Interquartile range: 121, 156), 85 men (9.5%) depicted an increase of their baseline Charlson Comorbidity Index score of at least one point. The most frequent reason for Charlson Comorbidity Index upgrade was cancer (34%), cardiovascular diseases (29%) and diabetes mellitus (22%). Compared to patients without a Charlson Comorbidity Index increase, patients with a Charlson Comorbidity Index increase presented with higher body mass index and follicle-stimulating hormone values, a higher rate of baseline Charlson Comorbidity Index ≥ 1 (all p < 0.01) and a greater proportion of non-obstructive azoospermia (p < 0.001). In the Cox regression model, the patient's BMI (p < 0.001), baseline Charlson Comorbidity Index ≥ 1 (p < 0.01) and azoospermia status (p = 0.001) were found to be independently associated with Charlson Comorbidity Index increases., Conclusions: Almost 10% of men presenting for primary infertility had a decrease of the overall health status already in the relatively short 10-year time frame after the first presentation. Non-obstructive azoospermic men showed the worst health status impairment and should be strictly followed-up regardless of their fertility status., (© 2021 American Society of Andrology and European Academy of Andrology.)

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., (© 2021 American Society of Andrology and European Academy of Andrology.)

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., (© 2020 American Society of Andrology and European Academy of Andrology.)