Mario Mancini

The Association between Varicocele, Premature Ejaculation and Prostatitis Symptoms: Possible Mechanisms

INTRODUCTION No study has ever systematically evaluated the impact of varicocele on sexual function. AIM Two cross-sectional studies were performed in patients attending an andrology unit either for male sexual dysfunction (study 1) or couple infertility (study 2). In study 1, we evaluated the impact of varicocele on sexual function. In study 2, we retrospectively evaluated a possible association between varicocele and prostatitis signs and symptoms. METHODS Study 1 refers to a consecutive series of 2,448 (mean age 52.0 +/- 12.9 years) subjects. Study 2 consists of a consecutive series of 139 male subjects (mean age 37.3 +/- 6.3). MAIN OUTCOME MEASURES In study 1, varicocele was clinically classified into three grades according to Dubin criteria. Different hormonal parameters were also evaluated. All the patients of study 2 underwent simultaneous scrotal and transrectal color-Doppler ultrasonography (CDU) along with seminal characteristics and interleukin-8, a surrogate marker of prostatitis. RESULTS After adjusting for age, subjects with severe varicocele (N = 284, 11.6%; Dubin grade 2 and 3) showed a reduction of testicular volume (P < 0.01), higher luteinizing hormone (LH) (P < 0.05), follicle stimulating hormone (FSH) (P < 0.0001) and prolactin (P < 0.05) levels, and also an enlarged or tender prostate at digito-rectal examination (P < 0.05). Premature ejaculation was the only sexual symptoms significantly associated with varicocele (29.2% vs. 24.9% in subjects with or without varicocele, respectively; P < 0.05). In study 2, subjects with severe echographic-defined varicocele (basal venous reflux increasing or not after Valsalvas maneuver; N = 28, 20.1%) showed CDU features of prostatitis and higher seminal inteleukin-8 levels. The presence of any degree of varicocele (N = 40, 28.8%) was also associated with prostatitis symptoms, as measured by the National Institutes of Health Chronic Prostatitis Symptom Index scoring (P < 0.05), and in particular with the pain domain (P < 0.05). CONCLUSIONS In conclusion, signs and symptoms of prostatitis are more common in varicocele patients, who more often complain of premature ejaculation.

Ultrasonographic and clinical correlates of seminal plasma interleukin-8 levels in patients attending an andrology clinic for infertility

This study was aimed at evaluating the association between seminal plasma interleukin-8 (sIL-8) and colour-Doppler ultrasound (CDU) characteristics of the male genital tract in a series of patients fulfilling the criteria of male accessory gland infections (MAGI). Of 250 subjects seeking medical care for couple infertility, 79 (mean age: 36.4 ± 7.5 years) met the criteria of MAGI and scored higher than the rest of the sample on the National Institutes of Health-Chronic Prostatitis Symptom Index score. All patients underwent simultaneous hormone evaluation and seminal analysis (including sIL-8), along with scrotal and transrectal CDU before and after ejaculation. After adjusting for age, sIL-8 in patients with MAGI was significantly related to several abnormal semen and CDU parameters. In particular, leucocytospermia was closely associated with sIL-8. Ejaculate volume, unlike other semen or hormonal parameters, was negatively associated with sIL-8. When scrotal CDU was performed, sIL-8 was positively related to CDU inhomogeneous, hypo-echoic, hyper-echoic epididymis and to epididymal calcifications. In addition, a positive correlation among sIL-8, hyperaemic epididymis and an increased size of epididymal tail was found. When transrectal CDU was performed, an association among sIL-8 and hyper-echoic seminal vesicles, dilated ejaculatory ducts and duct calcifications was also observed. Finally, sIL-8 was positively related to prostate CDU abnormalities such as calcifications, inhomogeneous/hypo-echoic texture, hyperaemia and high arterial blood flow. No association was found with testis parameters. In conclusion, sIL-8 levels in patients with MAGI are associated with several parameters and CDU abnormalities of epididymis, seminal vesicles, ejaculatory ducts and prostate, but not of the testis. Furthermore, sIL-8 positively correlates with CDU signs of ejaculatory duct inflammatory subobstruction.

Elevated body mass index correlates with higher seminal plasma interleukin 8 levels and ultrasonographic abnormalities of the prostate in men attending an andrology clinic for infertility

Background: Obesity is associated with a systemic, low-grade inflammatory state. Although the relationship between obesity and semen parameters or prostate diseases has been previously investigated, the association between body mass index (BMI), prostate inflammatory diseases and color-Doppler ultrasound (CDU) of the male genital tract (MGT) has been poorly studied. Aim: To evaluate the association between BMI and CDU features of the MGT, signs and symptoms of prostate inflammation, semen parameters. Materials/Subjects and methods: We studied 222 men seeking medical care for couple infertility. According to the World Health Organization classification, subjects were divided into 3 groups: normal weight (no.=131, BMI=18.5–24.9 kg/m2), overweight (no.=71, BMI=25.0–29.9 kg/m2), obese (no.=20, BMI≥30.0 kg/m2). All patients underwent simultaneous testosterone evaluation and seminal analysis, including interleukin 8 (sIL-8), along with scrotal and transrectal CDU, before and after ejaculation. Prostatitis symptoms were evaluated by National Institutes of Health-Chronic Prostatitis Symptom Index questionnaire. Results: After adjusting for age and testosterone levels, higher BMI was significantly related to higher prostate volume and several CDU features of the prostate, including macro-calcifications, inhomogeneity, higher arterial peak systolic velocity (the latter adjusted also for blood pressure), but not with abnormalities of testis, epididymis, seminal vesicles. Furthermore, higher BMI and BMI class were significantly related to higher sIL-8, a reliable surrogate marker of prostate inflammatory diseases, even after adjustment for age. Conversely, no associations among BMI, clinical symptoms of prostatitis or semen parameters were observed. Conclusions: Subjects with higher BMI might develop CDU and biochemical signs suggestive of prostate inflammation, although not clinically overt.

Flaccid penile acceleration as a marker of cardiovascular risk in men without classical risk factors.

INTRODUCTION Conventional cardiovascular (CV) risk factors identify only half of subjects with incident major adverse CV events (MACE). Hence new markers are needed in high CV risk subjects, as those with erectile dysfunction (ED). A role for dynamic peak systolic velocity (D-PSV) at penile color Doppler ultrasound (PCDU) has been suggested, but it is operator dependent and time consuming. Flaccid penile acceleration (FPA) is a PCDU parameter that reflects PSV, the systolic rise time (SRT), and end diastolic velocity (EDV), arithmetically defined as (PSV-EDV)/SRT. AIM The study aims to verify, in a large series of ED patients, whether FPA has a role in predicting MACE. METHODS A selected series of 1,903 patients (aged 54.6 ± 11.7) with a suspected organic component for ED was retrospectively studied from January 2000 until July 2012. A subset of this sample (n = 622) was enrolled in a longitudinal study that ended in December 2007. MAIN OUTCOME MEASURES Several clinical, biochemical, and instrumental (PCDU) parameters were studied. RESULTS Decreased FPA levels were associated with worse metabolic profile and sexual symptoms. In addition, FPA was positively associated with both total and calculated free testosterone. In the longitudinal study, unadjusted incidence of MACE was significantly associated with lower baseline FPA. When FPA was introduced in a multivariate model, along with D-PSV, after adjusting for age and Chronic Disease Score, lower FPA, but not D-PSV, was associated with incident MACE in lower--risk-i.e., younger (HR = 0.48 [0.23-0.99]), nonhypertensive (HR = 0.59 [0.38-0.92]), nonobese (HR = 0.68 [0.49-0.96]), or nondiabetic (HR = 0.67 [0.49-0.96] subjects; all P < 0.05--but not in higher-risk ones. FPA demonstrated a threshold effect in predicting MACE at a value <1.17 m/s(2) which showed a threefold increase in incidence of MACE in apparently lower-risk individuals. CONCLUSIONS FPA is an easily obtained PCDU parameter and capable of identifying adverse metabolic and CV profiles, particularly in apparently lower-risk individuals with ED.

Relationship between plasma insulin and left ventricular mass in normotensive participants of the Gubbio Study

background There is substantial but not conclusive evidence that insulin resistance is related to left ventricular mass (LVM) in hypertensive individuals. To what extent this association is mediated by the relationship between plasma insulin and body size and build is still debated, and is poorly explored in nonhypertensive people.

Clitoral Artery Blood Flow in Healthy Young Women: Preliminary Report on Menstrual Cycle and Hormonal Contraception

The aim of the present study was to measure clitoral artery blood flow throughout the menstrual cycle and in oral contraceptive users. We recruited healthy young women ( n = 19, age range: 21-28 years; body-mass index: 18-23 kg/m 2 ) without sexual dysfunction (Female Sexual Functioning Index criteria; Rosen et al., 2000). Clitoral arterial peak systolic velocity (PSV) in at least two phases of the same ovulatory cycle or during the second week of the pill was measured by doppler ultrasonography. Clitoral arterial PSV measures (cm/s) were superimposable during the follicular and the luteal phase of the menstrual cycle (10.4 - 1.2 versus 10.2 - 1.6), whereas a slight but significant increase (12.2 - 1.2, f = 3.99; p < 0.04) was evident at the time of ovulation. In addition, PSV measures were significantly higher in women taking hormonal contraception compared to women studied throughout the menstrual cycle (14.2 - 2.7 versus 10.8 - 1.5; p < .001). Whether or not these preliminary data may be of any significance to female sexual arousal throughout the menstrual cycle remains to be established.

Sildenafil citrate vs intracavernous alprostadil for patients with arteriogenic erectile dysfunction: a randomised placebo controlled study

We compared the effectiveness of sildenafil citrate and alprostadil in improving arterial penile inflow (peak systolic velocity (PSV)) and penile rigidity in 55 patients with erectile dysfunction caused by atherosclerosis. A total of 35 patients with pure vasculogenic impotency were randomly assigned to alprostadil (Av group; n=11), sildenafil (Sv group; n=12), or placebo (P group; n=12), and 20 patients with nonvasculogenic impotency were randomly assigned to alprostadil (A group; n=10) or Sildenafil (S group; n=10): Av and A used alprostadil injection (capable of giving a full erection) once a week for 1 month, Sv and S took daily oral sildenafil (25 mg) for 1 month, and P took daily oral placebo for one month. The PSV was measured with Duplex sonography and penile rigidity was assessed using the IIEF-15 questionnaire, both of which were administered before and after treatment. Although both treatments improved penile rigidity, they increased PSV only in the Av and Sv groups. Our results suggest that alprostadil and oral therapy should be the starting therapy in men with vasculogenic impotency, whereas alprostadil should be avoided as the first-line approach in men with nonvasculogenic impotency.

Antegrade subinguinal sclerotization with temporary clamping of the spermatic cord: a new surgical technique for varicocele.

OBJECTIVES The purpose of our study was to evaluate the duration, effectiveness, and complications associated with a new operating technique for varicocele, using a subinguinal surgical approach and antegrade sclerotization of the spermatic veins. METHODS A total of 756 varicocele patients who came under our care for infertility underwent surgical treatment with our technique. The diagnosis was based on clinical examination and confirmed by color-Doppler ultrasound of the spermatic cord. Only patients with continuous basal reflux inside the left spermatic vein detected in orthostatism underwent operation. The Colpi technique was used, which consists of a subinguinal incision with suspension of the spermatic cord; cord clamping for 8-10 minutes using two elastic bands; and injection of 1.5-3 mL of sclerosing agent during induced ischemia without any intraoperative radiological control. RESULTS The average operating time was 25 minutes (range: 18-45 minutes). At the 3-month postoperative follow-up, there were 15 cases of persistent reflux (1.9%), 6 cases of hydrocele requiring surgical correction (0.7%), and 50 cases of fibrotic sequelae of penile lymphangiitis (6.6%). CONCLUSIONS The new technique was more effective than the previous ones, with the exception of the microsurgical technique, which, however, takes 2-3 times longer to perform. The only significant complication was superficial single-vessel lymphangiitis of the penis, which resolved within 3 months with no apparent consequences. In conclusion, this new operating technique for varicocele is simpler to perform and may be effective compared with other techniques.

Myoinositol and D-Chiro Inositol in Improving Insulin Resistance in Obese Male Children: Preliminary Data

Myoinositol and D-chiro inositol, which are inositol isomers, have been shown to possess insulin-mimetic properties and to improve insulin resistance, especially in women with polycystic ovary syndrome. However, it has not been determined if this relationship exists also in children. Based on these previous findings, we hypothesized that inositol could be effective in improving insulin sensitivity in children with insulin resistance. To evaluate this hypothesis, we administered both inositol formulations before carrying out an oral glucose tolerance test (OGTT) in a group of obese insulin-resistant male children with high basal insulin levels and compared the values obtained with an OGTT previously conducted without inositol, in the same group, with unchanged BMI. Our results confirm that myoinositol and D-chiro inositol acutely reduce insulin increase after glucose intake mainly in children with high basal insulin level.

Brachial artery flow mediated assessment: A tool to predict the response to chronic PDE5 inhibition with tadalafil in patients with erectile dysfunction

Subjects, n 26 11 15 Age, years 60.9±9.6 59.4±10.7 62.0±8.9 BMI 26,5±3,5 26±3,5 26,9±3,5 HB1c 6,8±1,7 5,6±0,3 7,6±1,9 Smoking history 11/26 2/11 9/15 Comorbidities Diabetes, % 6/26 0/11 6/15 Hypertension, % 3/26 0/11 3/15 Diabetes+hypertension 6/26 0/11 6/15 ⁎ Corresponding author. Andrology, San Paolo Hospital, University of Milano, Via A. di Rudini, 8 20142 Milano, Italy. E-mail address: mancinis178@msn.com (M. Mancini). Impairment of cavernosal arteries responsiveness is the most common cause of erectile dysfunction (ED) whose pathogenesis primarily depends on vascular endothelial dysfunction [1]. Atherosclerotic risk factors increase the rate of ED and most male patients with angiographically documented coronary artery disease (CAD) exhibit ED [2]. Endothelial injury is a basic step in the development of artheriosclerosis and its in-vivo evaluation by brachial artery flow mediated dilatation (BAD) technique provides relevant clinical and prognostic information [3]. Phosphodiesterase 5 inhibition (PDE5i) is an effective strategy for ED improvement which improves BAD response in both ED and non-ED patients [4,5]. It is undefined whether different pretreatment endothelial BAD patterns may predict the ED response to chronic PDE5i therapy. 26 impotent patients with no previous cardiovascular events diagnosed by IIEF questionnaire (questions 1, 2, 3, 4, 5, and 15) were enrolled and grouped according to absence (group A; n=11) or coexistence of hypertension and diabetes comorbidities (group B; n=15, n=6 with diabetes n=3 with hypertension, n=6 with diabetes and hypertension). All underwent brachial artery flowmediated evaluation (high resolution ultrasound Philips 11 MHz linear-array transducer) with measures of BAD and hyperemic (HYP) response [6], penile Duplex Ultrasound (DS) cavernosal peak systolic velocity (PSV) measure [7], and IIEF questionnaire evaluation before and after PDE5i treatment with tadalafil 10 mg on alternate days for 30 days. Differenceswithin group A and between group A and Bwere tested by ANOVA analysis and paired and unpaired Student t-test when appropriate. Linear regression analysis with least square method was used to correlate delta PSV with delta BAD and HYP. Populations were similar in terms of age, BMI, HB1c, and smoking history (Table 1). In all patients, a trend but not statistically significant increase in PSV (p=0.08) after tadalafil was observed while IIEF increased significantly (pb0.01) (Table 2). Significant differences in the BAD response were observed between group A and group B before and after treatment, even though tadalafil did not cause significant BAD improvement in both populations. Conversely, group A exhibited a significantly greater HYP response both at preand post-tadalafil treatment (Table 3). Post-tadalafil HYP response was significantly increased just in group A. After disease distribution a significant correlation between delta PSV and delta HYP was found in group A unless group B (Fig. 1A and B, r=0.677; p=0.022 and r=0.24; p=NS). The major finding of our study is that BAD may be a helpful screening technique in the identification of impotent patients that very likely may or may not get a hemodynamic advantage from midterm PDE5i treatment with tadalafil at current doses. Our observation provides a rationale for systematically using PSV evaluation in combination with BAD in the management of ED patients. In populations with variable degrees of cardiovascular risk, brachial ultrasound assessment has emerged as a strong and independent predictor of cardiovascular morbidity and mortality [3]. In this regard, changes in arterial diameter are considered more reliable than changes in flow. This because variations in flow reflect those in forearm microcirculation and brachial artery occlusion may still induce some degree of responsiveness to post-ischemic reperfusion stimuli even when the lumen of brachial conduit artery does not change significantly. In the present study no correlation was observed between changes in BAD and PSV. Conversely, brachial artery HYP response correlated with changes in PSV, at least in ED patients without hypertension and/ or diabetes. Remarkably, this seems to reflect a behavior similar to that observed at penile microcirculatory level and support the idea that in the initial stages of a penile arterial disease, a reduced PSVmay arise from an impaired microcirculation reactivity rather than from a real atherosclerotic process. Major study limitations are the small number of patients investigated, especially when considering the subset with comorbid conditions such as diabetes or hypertension and the lack of a followup period with PDE5i drug withdrawal. In conclusion, a preserved reactivity at brachial artery level in the absence of comorbid conditions predicts a favorable response at penile microcirculatory level to standard doses of PDE5i treatment. This study was supported by funds provided by the Monzino Foundation, Milano-Italy. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [8].