Noninvasive Indices of MASLD Are Associated With Hypogonadism in Male Patients With Type 2 Diabetes Mellitus.

CONTEXT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, affecting one-fourth of the adult population worldwide. Recent data found an association between MASLD and hypogonadism, but this relation in patients with type 2 diabetes mellitus (T2DM) is still unclear. OBJECTIVE: To evaluate in men with T2DM the association between total testosterone (TT) and noninvasive indices of hepatic steatosis (Fatty Liver Index [FLI], Hepatic Steatosis Index [HSI], Dallas Steatosis Index [DSI]) and fibrosis (AST to Platelet Ratio Index [APRI], Fibrosis-4 Index [FIB-4]), and their predictive cutoff values in identifying hypogonadism. METHODS: Cross-sectional study on 189 men with T2DM, without history of liver diseases and alcoholism, recruited on an outpatient basis. Interventions were andrological evaluation, metabolic parameters, TT, and liver indices. The main outcome measures were comparison of steatosis and fibrosis indices with testosterone levels and presence of hypogonadism. Receiver operating characteristic curves were used to identify cutoff values of liver indices in predicting low testosterone (<12 nmol/L). RESULTS: FLI, HSI, and DSI were negatively related with TT and were higher in the low-testosterone group than in the normal-testosterone group (FLI: 74.1 [61.4-93.5] vs 56.5 [32.1-78.2], P < .001; HSI: 41.5 [39.2-45.9] vs 40.1 [36.6-43.2], P = .005; DSI: 0.45 [-0.08-+1.04] vs -0.07 [-1.02-+0.58], P < .001). FLI and DSI also correlated with clinical symptoms of hypogonadism. No differences between groups were observed for APRI and FIB-4. FLI ≥63 was the best parameter as predictive index of low TT (sensitivity 73%, specificity 64%). CONCLUSION: We found an association between noninvasive indices of steatosis and hypogonadism in patients with T2DM. These indices could be used to direct the patients to andrological evaluation.

Central role of ultrasound in the evaluation of testicular function and genital tract obstruction in infertile males.

BACKGROUND: Scrotal color Doppler ultrasonography and transrectal ultrasonography provide crucial information about the clinical status of testes and male accessory glands. OBJECTIVE: To analyze the impact of ultrasound in the evaluation of infertile males. MATERIALS AND METHODS: A total of 1120 records from infertile men were retrospectively evaluated (from January 2016 up to June 2020). Data on physical examination, semen analysis, sperm culture, scrotal color Doppler ultrasonography and transrectal ultrasonography, as well as sex hormones were analyzed. Among them, 238 reports from oligozoospermic/azoospermic infertile patients (P) fulfilling the inclusion criteria were considered for data analysis. Patients were subdivided into two groups according to follicle-stimulating hormone (FSH) values (Pa with FSH < 8 U/L and Pb with FSH ≥ 8 U/L). Sixty-three fertile volunteers (mean ± SD years) were enrolled as controls (C). RESULTS: A higher prevalence of ultrasound abnormalities was recorded in P compared to C. Pb group had significantly lower bitesticular volume compared to Pa and C. Pa had a higher prevalence of transrectal ultrasonography abnormalities than Pb (69.9% vs. 38.4%), whereas Pb had a higher prevalence of abnormalities at scrotal color Doppler ultrasonography (60.0% vs. 28.3%, both p < 0.01). Bitesticular volume was inversely proportional to the number of altered seminal parameters and able to predict gonadotropin levels. A bitesticular volume <17 cc was associated with a higher risk of azoospermia (odds ratio = 1.799). Intratesticular vascularization was inversely correlated with gonadotropin levels and directly correlated with sperm count. A higher prevalence of prostate and seminal vesicle alterations was detected in patients and in Pa group, when compared with Pb group. DISCUSSION AND CONCLUSION: Ultrasound abnormalities are correlated with seminal parameters and may guide the clinician in the diagnostic workflow of male infertility, suggesting spermatogenesis impairment or genital tract obstructions.

Association Between Penile Color Doppler Ultrasonography and Cardiorespiratory Fitness in Patients With Vascular Erectile Dysfunction.

INTRODUCTION: Vascular erectile dysfunction (ED) is a burdensome condition, associated with increased cardiovascular risk. Peak systolic velocity (PSV) represents the maximum pulse velocity in the cavernous artery measured by a penile color doppler ultrasonography (PCDU) during a pharmacologically induced erection and is considered a reliable parameter for the diagnosis of vascular ED. However, the cut-off value of standard PSV (30 cm/s) provides high sensitivity only in the diagnosis of advanced arteriogenic disease. Thus, an age-adjusted PSV (6.73 + 0.7 x age cm/s) has been proposed to offer a more accurate diagnosis of vascular ED. AIM: In this study it was aimed to answer the following question: "Is there any positive association between indexes of vascular erectile dysfunction and cardiorespiratory fitness?" MAIN OUTCOME MEASURE AND METHODS: 25 patients with a medical history of ED (median age 55.3 years) underwent PCDU after pharmacological stimulation. Subsequently, a functional evaluation with ECG-monitored, incremental, maximal cardiopulmonary exercise testing was performed. RESULTS: Peak oxygen uptake (VO2 peak), peak oxygen uptake per body weight (VO2 peak/kg) and Watt/kg correlated with standard PSV, even when corrected for age and BMI (p < 0.05). No differences emerged in cardiopulmonary fitness between pathological and healthy patients (4 vs 21) identified using the standard PSV cut-off. Conversely, the age-adjusted PSV cut-off identified a greater number of patients as pathological (18 vs 7), presenting a significantly lower cardiopulmonary fitness, exercise capacity and efficiency when compared to patients with normal age-adjusted PSV (all p < 0.05). CONCLUSION: Data showed an age and BMI independent association between vascular disfunction of cavernous artery and cardiopulmonary fitness, a known solid predictor of all-cause and disease-specific mortality. Moreover, the age-adjusted PSV better identified a subgroup of patients with vascular ED presenting impaired cardiorespiratory fitness and thus increased cardiovascular risk. De Rocco Ponce M, Vecchiato M, Neunhaeuserer D, et al. Association Between Penile Color Doppler Ultrasonography and Cardiorespiratory Fitness in Patients With Vascular Erectile Dysfunction. Sex Med 2021;9:100347.

Efficacy of penile low-intensity shockwave treatment for erectile dysfunction: correlation with the severity of cavernous artery disease.

We analyzed the efficacy of penile low-intensity extracorporeal shockwave treatment for erectile dysfunction (ED) combined with cavernous artery disease (CAD). ED was evaluated by the International Index of Erectile Function, subdividing patients into mild and moderate/severe forms. CAD was assessed using penile color Doppler ultrasonography. Patients (n = 111) with a positive outcome after treatment, based upon the minimal clinically important difference of the International Index of ED, were followed up for 3 months and 6 months. We found a significant mean increase in the index of erectile function, with an overall improvement in hemodynamic parameters of the cavernous artery. In particular, 93.9% of the patients with mild ED without CAD responded to treatment and 72.7% resumed normal erectile function. Only 31.2% of the patients with moderate/severe ED and CAD responded to treatment, and none resumed normal erectile function. All patients with mild ED and no CAD maintained the effects of therapy after 3 months, while no patients with moderate/severe ED and CAD maintained the benefits of treatment after 3 months. Thus, patients with mild ED and no CAD have better and longer lasting responses to such treatment, with a higher probability of resuming normal erectile function than patients with moderate/severe ED and CAD.

Sperm Count and Hypogonadism as Markers of General Male Health.

BACKGROUND: Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive. OBJECTIVE: We tested whether semen quality and reproductive function could represent a marker of general male health. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of 5177 individuals from a prospectively collected database of 11516 males of infertile couples who had semen analysis in a tertiary university center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone <10.5nmol/l and/or luteinizing hormone >9.4 IU/l. Individuals with a total sperm count of <10 million had genetic testing (karyotype, Y chromosome microdeletions, and CFTR gene mutations) and those with hypogonadism underwent dual-energy x-ray absorptiometry for bone mineral density. Descriptive statistics and odds ratio (OR) calculation were used. RESULTS AND LIMITATIONS: Men with a low sperm count (<39 million/ejaculate) are at a high risk of hypogonadism (OR 12.2, 95% confidence interval [CI] 10.2-14.6) and have higher body mass index, waist circumference, systolic pressure, low-density lipoprotein cholesterol, triglycerides, and homeostatic model assessment (HOMA) index; lower high-density lipoprotein cholesterol; and a higher prevalence of metabolic syndrome (OR 1.246, 95 CI 1.005-1.545). All data are worse in men with hypogonadism, but a low sperm count per se is associated with a poor metabolic parameter. Men with hypogonadism have lower bone mineral density and 51% prevalence of osteoporosis/osteopenia. Longitudinal studies are necessary to support these data. CONCLUSIONS: This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health. PATIENT SUMMARY: This large study evaluated semen quality, reproductive function, and metabolic risk in men referred for fertility evaluation, and showed that a man's semen count is a marker of his general health. Men with low sperm counts are more likely than those with normal sperm counts to have greater body fat, higher blood pressure, higher "bad" (low-density lipoprotein) cholesterol and triglycerides, and lower "good" (high-density lipoprotein) cholesterol. They also have a higher frequency of metabolic syndrome and insulin resistance, a condition that can lead to diabetes. Men with low sperm counts had a 12-fold increased risk of hypogonadism or low testosterone levels, and half of them had osteoporosis or low bone mass. Fertility evaluation gives men the unique opportunity for health assessment and disease prevention.

Estradiol correlates with erectile dysfunction and its severity in type 2 diabetic patients.

AIMS: Erectile dysfunction (ED) is a frequent microvascular complication of type 2 diabetes mellitus (T2DM). Hormonal derangements such as hypogonadism and hyperestrogenism are common in T2DM. Our aim was to investigate the relationship between estrogens and ED in diabetic patients. METHODS: We performed a retrospective study on 57 patients with T2DM suffering from ED. ED was assessed with the International Index of Erectile Function questionnaire (IIEF-5) and penile color-doppler ultrasound (PCDU). Blood tests included glycated hemoglobin, lipid profile, total testosterone (T), and estradiol (E2). RESULTS: E2 was negatively correlated with IIEF-5 score after correction for age, diabetes duration, BMI, HbA1c, LDL- and HDL-cholesterol, T and PSA (r = -0.457, p < 0.01). Patients in the higher E2 quartile, had statistically higher probability of severe ED (61.5%). In the same patients, the PCDU demonstrated a statistically longer Acceleration Time (120.0 ±â€¯24.5, p = 0.048) indicating an impaired arterial flow. CONCLUSIONS: In diabetic patients, higher E2 is associated with worse erectile function and impaired cavernous arterial flow. Diabetic patients with high E2 are more prone to severe ED. It could be suggested to include estradiol measurement in the hormonal assessment of ED in patients with T2DM.

Hypovitaminosis D is associated with erectile dysfunction in type 2 diabetes.

Diabetes is an established risk factor for erectile dysfunction (ED). The pathophysiology of ED in diabetic men is multifactorial, but it mainly involves a vascular disorder related to a reduction of endothelial function. Recently, several studies have correlated ED risk factors with vitamin D deficiency. In this study, we evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] levels, erectile dysfunction, and vascular disease, in type 2 diabetes mellitus men (T2DM). In this observational study, 92 T2DM males (58.83 ± 9.73 years) underwent medical history collection, International Index of Erectile Function (IIEF-5) questionnaire, that allows the identification and grading of DE, physical examination, biochemical/hormonal blood tests, and penile echo-color Doppler ultrasonography. T2DM patients with lower 25(OH)D levels (<25 nmol/l) showed higher penile IMT (p < 0.05), waist circonference (p < 0.05), glucose concentrations (p < 0.05), and lower IIEF-5 score (p < 0.005), testosterone concentrations (p < 0.05), and cavernous peak systolic velocity (PSV) (p < 0.05), compared to patients with 25(OH)D >50 nmol/l. 25(OH)D levels were directly correlated with IIEF-5 (R = 0.39; p = 0.0001), testosterone (R = 0.24; p = 0.02), and PSV (R = 0.24; p = 0.04) and inversely with waist (R = -0.33; p = 0.002), HbA1c (R = -0.22; p = 0.03), triglyceride (R = -0.21; p = 0.06), and penile IMT (R = -0.30; p = 0.009). At multivariate analysis, 25(OH)D deficiency remained an independent predictor of DE. We demonstrate a significant association between 25(OH)D deficiency and erectile dysfunction in T2DM men. This association may be due to the influence of 25(OH)D deficiency on cardiovascular risk factor (glycaemia, HDL cholesterol, and triglycerides), testosterone plasma levels and endothelial dysfunction.

Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients.

OBJECTIVE: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). METHODS: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. RESULTS: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. CONCLUSIONS: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients.

Twenty-four-hour monitoring of scrotal temperature in obese men and men with a varicocele as a mirror of spermatogenic function.

STUDY QUESTION: How do day and night scrotal temperatures, spermatogenesis parameters, sex hormones and intratesticular perfusion in obese men and men with a varicocele compare with healthy controls? SUMMARY ANSWER: Compared with healthy controls, 24-h monitoring of scrotal temperature in men with a varicocele and obese men showed higher temperatures and this condition was related to a significant alteration of spermatogenesis and stasis of testicular perfusion. WHAT IS KNOWN ALREADY: Several studies have shown that increased scrotal temperature has dramatic effects on spermatogenesis. Scrotal hyperthermia by exposure to sauna is able to induce a significant alteration of sperm production. STUDY DESIGN, SIZE AND DURATION: In a case-control study, data were collected over a period of 2 years from 60 subjects with risk factors for testicular heating and 20 healthy subjects who consecutively attended an andrology unit as participants in an infertility prevention program. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Forty subjects with a left varicocele, 20 obese men and 20 healthy subjects who served as controls, were evaluated for testicular volumes, sex hormones, sperm parameters, sperm aneuploidies, mean transit time (MTT) of intratesticular blood and 24-h scrotal temperature monitoring by a cutaneous thermochip. Subjects with a varicocele were further subgrouped on the basis of normo or oligozoospermia (VN and VO). Student's t-test was used for statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: We found a significant increase in 24-h mean scrotal temperature in obese men and men with a varicocele compared with controls (both P < 0.01). This increase in scrotal temperature was associated with impaired sperm parameters and higher FSH plasma levels compared with controls. Dynamic evaluation of scrotal temperatures showed wide fluctuations in controls, but little variation in obese men and men with a varicocele. Men with VO had left and right increase in scrotal temperatures (the right was increased also versus VN, P < 0.01) (both P < 0.001). Men with VN showed a left scrotal temperature higher than controls (P < 0.01) and a right scrotal temperature no different from controls (34.92 ± 0.53 and 34.66 ± 0.65, respectively). Mean MTT values recorded in men with VO were significantly higher than men with VN and obese men (both P < 0.001). LIMITATIONS AND REASONS FOR CAUTION: Different lifestyle, diet, occupation, stress level and environmental temperatures due to seasonal conditions are major limitations of this study. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggested for the first time that dynamic evaluation of scrotal temperatures seems to reflect alterations of testicular function and perfusion in obese men and men with a varicocele. In these clinical conditions, spermatogenic impairment and scrotal heating seem to be related to different mechanisms. The dynamic evaluation of scrotal temperature in subjects with risk factors for testicular heating could allow the identification of subjects needing treatment or a change in lifestyle. STUDY FUNDING/COMPETING INTERESTS: No external funding was sought for this study, and the authors have no conflict of interest to declare.

Low serum testosterone as a new risk factor for chronic rejection in heart transplanted men.

BACKGROUND: Among the various complications of heart transplantation (HTx), the vasculopathy of the allograft (CAV), a phenomenon of chronic rejection, is still a serious problem. Recently, the literature has shown that low testosterone levels in men are associated with cardiovascular disease. In this study, we evaluated the influence of testosterone plasma levels on CAV development. METHODS: We studied, with a prospective observational study, all consecutive male HTx patients evaluated from May 2010 to June 2011 at our center. All subjects underwent accurate medical history collection, physical examination, biochemical blood tests, hormone levels, transthoracic Doppler echocardiography, coronary flow velocity reserve assessment, and coronary angiogram. RESULTS: HTx subjects with CAV had significant lower total testosterone plasma levels (12.9±3.9 vs. 15.8±5.8 nmol/L), free testosterone (0.26±0.07 vs. 0.31±0.08 nmol/L), and coronary flow velocity reserve (2.35±0.60 vs. 2.81±0.78 s) with respect to No-CAV patients. Considering the patients as a whole group, a significant negative relation was found between free and total testosterone plasma levels and some cardiovascular risk factors (cholesterol and fasting blood glucose). A significant linear inverse relation was found between total and free testosterone plasma levels and CAV grading. Only free testosterone plasma levels were independent predictors for CAV. CONCLUSIONS: We showed for the first time the influence of testosterone plasma levels on CAV development: indirectly increasing traditional risk factors and directly with a probable influence on alloimmune response.

Erectile dysfunction, penile atherosclerosis, and coronary artery vasculopathy in heart transplant recipients.

INTRODUCTION: Vascular erectile dysfunction (ED) is the expression of a systemic vascular disease and in particular of endothelial dysfunction. Dysfunctional endothelium plays also a significant role in the onset and progression of coronary artery vasculopathy (CAV). AIM: This pilot study was designed to evaluate the prevalence and pathogenesis of ED and its correlation with CAV in heart transplanted male. METHODS: A total of 77 male heart transplanted patients (HTx) evaluated in our center (mean age 61.6 + 10.6 years) were enrolled in the study. MAIN OUTCOME MEASURES: All subjects underwent accurate medical history collection, including lifestyle (cigarette smoking, dietary and sedentary habits, drug intake, and erectile function before cardiac transplantation), physical examination (body mass index and arterial pressure), biochemical blood tests (fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and triglycerides), and hormones (prolactin, luteinizing hormone and total testosterone). Furthermore, they were studied with penile, carotid, femoral echo-color Doppler ultrasonography and coronary angiogram. RESULTS: Incidence of ED was 24% before HTx and increased up to 65% after. Postischemic cardiomiopathy was an indication to HTx in ED group more frequently than in patients without ED (No-ED group) (45.1% vs. 20%). ED patients showed a lower peak systolic velocity, a higher cavernosal intima-media thickness (IMT), a higher prevalence of cavernosal plaques (26.7% vs. 5.2%, P < 0.05), peripheral vascular disease (60.87% vs. 26.1%, P < 0.05) and CAV (45.8% vs. 25.8%, P < 0.05) with respect to No-ED patients. Coronary flow reserve was significantly reduced in ED vs. No-ED patients (2.43 + 0.7 vs. 2.9 + 0.8, P < 0.04). Finally, cavernous plaque and testosterone plasma levels were statistically associated with CAV. CONCLUSIONS: We showed that ED is a frequent disease in HTx patients, more common when the original pathology is postischemic cardiomiopathy and associated with higher prevalence of cavernous plaques and CAV. Its evaluation should be integral to an HTx rehab program.

Metabolic syndrome and erectile dysfunction: the ultrasound evaluation of cavernosal atherosclerosis.

OBJECTIVE: To study the relation between metabolic syndrome (MS), cavernosal morphological vasculopathy, and peripheral vascular alterations (carotid and femoral wall) in patients with erectile dysfunction. RESEARCH DESIGN AND METHODS: A total of 207 patients and 50 control subjects were evaluated for cardiovascular risk factors, physical examination, reproductive hormones, ultrasound analysis of cavernosal, carotid and femoral arteries (intima-media thickness), and cavernosal flow measurement (peak systolic velocity). RESULTS: A total of 28% of patients had MS, and they presented with a high prevalence of cavernosal alterations (70.3%) and systemic vascular impairment (59.3%), whereas patients with cavernosal alterations (44%) showed the higher prevalence of MS (48.9%). The number of MS components was related to the prevalence of penile vasculopathy. However, multivariate analysis showed that MS is not an independent predictor for cavernosal vasculopathy. CONCLUSIONS: Patients with cavernosal vasculopathy have an increased cardiometabolic risk, and screening for MS components might identify individuals with a higher risk for cavernosal and systemic atherosclerosis.

Heat shock protein and heat shock factor expression in sperm: relation to oligozoospermia and varicocele.

PURPOSE: Varicocele may be associated with normozoospermia or oligozoospermia. Much controversy still exists regarding the diagnosis, management and pathophysiology of spermatogenesis alterations associated with varicocele. The increased temperature induced by varicocele and stress in general may activate heat shock proteins and heat shock factors with a protective function in cells. We analyzed the expression of 5 heat shock proteins and heat shock factors in the sperm of men with normozoospermia and oligozoospermia with or without varicocele. MATERIALS AND METHODS: We performed a prospective study between June 2008 and February 2009 at an academic clinic in 117 consecutive patients with varicocele and 68 controls without varicocele. Four groups were based on the presence/absence of varicocele and normozoospermia/oligozoospermia. Subjects were studied by history, physical examination, scrotal Doppler ultrasound, semen analysis, reproductive hormone plasma levels and quantitative real-time polymerase chain reaction in RNA extracted from ejaculated sperm to analyze HSP90, HSPA4, HSF1, HSF2 and HSFY expression. RESULTS: Increased HSPA4, HSF1 and HSF2 were observed in the sperm of men with varicocele and in those with oligozoospermia. Levels were maximum when the 2 conditions were present. Increased HSP90 was observed in oligozoospermia cases independent of varicocele. HSFY was up-regulated only in patients with varicocele, especially those with normozoospermia. CONCLUSIONS: To our knowledge we describe for the first time the expression of different heat shock proteins and heat shock factors in ejaculated sperm. While some of these proteins are up-regulated in men with oligozoospermia and varicocele, HSFY is up-regulated only in the presence of varicocele and especially in men with normozoospermia. This suggests that it may be a molecular marker of an adequate or inadequate response to the damaging effect of varicocele on spermatogenesis.

Increased levels of osteocalcin-positive endothelial progenitor cells in patients affected by erectile dysfunction and cavernous atherosclerosis.

INTRODUCTION: Erectile dysfunction (ED) was shown to be the expression of a systemic vascular disease that can precede coronary artery disease of some years. Endothelial progenitor cells (EPCs) are a population of circulating cells with endothelial-regenerative potential that may be reduced in ED and coronary patients. Recently, increased levels of osteocalcin (OCN)-positive EPC have been reported in coronary patients. AIM: Investigate the correlation between OCN-positive EPC and cavernous atherosclerotic lesion in ED patients. METHODS: A total of 35 subjects (20 ED patients and 15 controls) were evaluated in our andrological center and enrolled in the study. MAIN OUTCOME MEASURE: All subjects underwent routine clinical examination. Patients were also evaluated with high resolution echo color doppler of penile districts (intima media thickness [IMT] before and after intracavernous alprostadil injection) and circulating levels of progenitor cells (PC), EPC, and OCN-positive fraction of EPC. RESULTS: A progressive reduction of circulating EPC with the severity of cavernous artery atherosclerosis was found. Conversely circulating OCN-positive EPC levels undergo to a significant increase with cavernous atherogenesis progression. CONCLUSIONS: OCN-positive EPC levels in association with penile-color Doppler ultrasound evaluation of cavernous IMT could be predictive markers of subsequent coronary artery disease in ED patients.

Testicular contrast harmonic imaging to evaluate intratesticular perfusion alterations in patients with varicocele.

PURPOSE: To determine whether changes in intratesticular microcirculation perfusion affect spermatogenesis in patients with left varicocele we performed testicular contrast harmonic imaging. MATERIALS AND METHODS: A total of 90 patients with left varicocele (oligospermia in 50 and normozoospermia in 40) and 36 controls without varicocele (oligospermia in 16 and normozoospermia in 20) were enrolled in the study. Before contrast harmonic imaging all participants were evaluated by clinical examination, hormonal analysis, semen sample and scrotal ultrasound. We calculated contrast material arrival time in the arteriolar circulation (wash-in), time to peak in arterial circulation, arrival time in the venular circulation (washout) and mean transit time in each testis on contrast harmonic imaging. RESULTS: We found no difference in the distribution rate of varicocele grade in patients with vs without oligospermia. All contrast harmonic imaging parameters were significantly higher in patients with varicocele plus normozoospermia or oligospermia and controls. We found no significant differences in contrast harmonic imaging parameters in patients with lower varicocele grading with respect to the higher grades. In patients with varicocele we found a negative linear correlation between total sperm count and left mean transit time (r = -0.29). In a multivariate model left mean transit time was the only independent predicting parameter of oligospermia (p <0.05). Mean transit time greater than 36 seconds predicted oligospermia in patients with left varicocele with 78% sensitivity and 58% specificity. CONCLUSIONS: To our knowledge we report for the first time that testicular contrast harmonic imaging may be a new diagnostic tool able to improve our knowledge about the influence of varicocele on intratesticular microcirculation.

Cavernous artery intima-media thickness: a new parameter in the diagnosis of vascular erectile dysfunction.

INTRODUCTION: A precise characterization of erectile dysfunction (ED) of vascular origin has not yet been achieved. Although cavernous peak systolic velocity (PSV) is generally considered a major parameter, it has many false positives and negatives because of anatomic variations of the cavernous artery course, challenging site of sampling, insufficient caracterization of an early phase of vascular disease, and significant influence of adrenergic tone. AIM: We performed a high magnification ultrasonographic study in order to compare functional and morphological parameters of the cavernous artery to PSV and their relation with penile and systemic atherosclerosis. METHODS: A total of 109 subjects (84 ED patients and 25 controls) evaluated in our andrological center from March 2007 to January 2008 were enrolled in the study. MAIN OUTCOME MEASURES: All subjects underwent medical history, erectile function domain of the International Index of Erectile Function, physical examination, routine and sex hormone blood tests, and high resolution echo color doppler evaluation of carotid, femoral and penile districts (acceleration time, intima media thickness [IMT], intima adventitia thickness, caliper before and after intracavernous alprostadil injection [Delta-cavernous calliper]). RESULTS: Cavernous parameters were significantly different between ED and controls. Multivariate model showed that IMT was the only predicting parameter for ED of vascular origin. Cavernous IMT showed a strong direct correlation with carotid and femoral IMT. ED patients with two or more cardiovascular risk factors had a significantly higher cavernous IMT. CONCLUSIONS: An increased cavernous IMT (>or=0.3 mm) might predict ED of vascular origin with more accuracy than PSV and could be a sensitive predictor also for systemic atherosclerosis at an earlier phase.

Effect of vardenafil on endothelial progenitor cells in hypogonadotrophic hypogonadal patients: role of testosterone treatment.

CONTEXT: Endothelial progenitor cells (EPCs) are bone marrow-derived cells required for endothelial repair. Circulating EPC concentration is low in conditions characterized by endothelial dysfunction but their number can be increased by treatment with phosphodiesterase-5 (PDE5) inhibitors. EPCs are also reduced in hypogonadal men and testosterone (T) treatment restores their concentration. OBJECTIVE: To evaluate the relationship between the effect of PDE5 inhibitors and T on EPCs, we analysed the acute effect of vardenafil on the number of EPCs in hypogonadotrophic hypogonadal (HH) patients, before and after T treatment. DESIGN AND SETTING: A case-control study at a university andrology centre. PATIENTS: Fifteen HH subjects and 25 aged-matched controls. MAIN OUTCOME MEASURES: The number of circulating EPCs and progenitor cells (PCs) in HH patients was evaluated after acute vardenafil administration at baseline and after 6 months of T supplementation. RESULTS: At baseline, HH men had significantly lower numbers of PCs and EPCs with respect to controls and vardenafil administration had no effect on the number of these cells. After 6 months of T treatment, all HH patients were eugonadal. With respect to baseline, PCs and EPCs were significantly higher and reached the levels observed in controls. Vardenafil administration in HH men at the end of T treatment induced a significant increase in PCs and EPCs in a manner similar to that in controls. CONCLUSIONS: This study showed that normal T levels are necessary to restore the responsiveness of EPCs to PDE5 inhibitors, suggesting that T positively modulates PDE5 in bone marrow.

Asymmetric development of peripheral atherosclerosis in patients with erectile dysfunction: an ultrasonographic study.

Recent literature focused on erectile dysfunction (ED) as a reliable predictive parameter of cardiovascular diseases. ED patients have a higher prevalence of atherosclerotic lesions (increased intima-media thickness and plaques) at carotid site, but data on femoral site are still lacking. Nevertheless, there is accumulating evidence concerning a significant involvement of femoral atherosclerosis in other clinical conditions associated to ED, such as diabetes mellitus and coronary disease. Therefore, we investigated the prevalence of carotid and femoral atherosclerotic lesions and penile peak systolic velocity (PSV) in 238 ED patients by Eco-Colour Doppler ultrasonography (US). We found - irrespective of the presence of cardiovascular risk factors - a significant increase of atherosclerotic lesions in ED group with respect to 52 controls (66.4% versus 36.5%) and a higher prevalence of atherosclerosis at the femoral site (23.1% versus 5.7%), also with respect to the carotid site (8%). Moreover, PSV was significantly lower in ED patients with atherosclerosis compared to those without atherosclerotic lesions (41.9+/-15.3 cm/s versus 55.2+/-17.7 cm/s), and it was particularly low in those with combined carotid and femoral atherosclerosis (34.8+/-13.3 cm/s) and those with isolated carotid atherosclerosis (37.9+/-13.0 cm/s). These data confirm the strong relation between atherosclerosis and ED, an asymmetric development of atherosclerotic lesions in ED patients and suggest to perform an US study of both femoral and carotid district in these subjects.

Androgens stimulate endothelial progenitor cells through an androgen receptor-mediated pathway.

BACKGROUND AND OBJECTIVE: Testosterone (T) treatment has recently been shown to induce an increase in the number of endothelial progenitor cells (EPCs) through a possible effect on bone marrow. Hypogonadotrophic hypogonadal (HH) men have low circulating EPCs that increase significantly after T treatment. Moreover, expression of the androgen receptor (AR) has been demonstrated by immunohistochemistry in these cells, suggesting that T might also have a direct effect on EPC function. In the present study we investigated the expression and function of the AR in human EPCs and the in vitro effect of androgens on EPC function. Design and patients EPCs obtained from healthy male anonymous blood donors were analysed after androgen stimulation with and without AR antagonist administration (flutamide). RESULTS: Reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence analyses demonstrated the expression of AR mRNA and protein in human EPCs. Stimulation of these cells with the synthetic androgen methyltrienolone (R1881) caused AR translocation in the nucleus, suggesting its activation. Colony forming unit (CFU), proliferation and migration assays under different doses of R1881 demonstrated a dose-dependent increase in EPC proliferation, migration and colony formation. All these effects are abolished by flutamide pretreatment. CONCLUSIONS: This study showed that the increase in the proliferation, migration and colony formation activity of EPCs induced by androgens is an AR-mediated pathway. Androgen exerts these effects at concentrations that are physiologically present in men and therefore further studies are needed to clarify the clinical significance of these effects in normal and pathological conditions.