Erectile dysfunction and central obesity： an Italian perspective

Erectile dysfunction （ED） is a frequent complication of obesity. The aim of this review is to critically analyze the framework of obesity and ED, dissecting the connections between the two pathological entities. Current clinical evidence shows that obesity, and in particular central obesity, is associated with both arteriogenic ED and reduced testosterone （T） levels. It is conceivable that obesity-associated hypogonadism and increased cardiovascular risk might partially justify the higher prevalence of ED in overweight and obese individuals. Conversely, the psychological disturbances related to obesity do not seem to play a major role in the pathogenesis of obesity-related ED. However, both clinical and preclinical data show that the association between ED and visceral fat accumulation is independent from known obesity-associated comorbidities. Therefore, how visceral fat could impair penile microcirculation still remains unknown. This point is particularly relevant since central obesity in ED subjects categorizes individuals at high cardiovascular risk, especially in the youngest ones. The presence of ED in obese subjects might help healthcare professionals in convincing them to initiate a virtuous cycle, where the correction of sexual dysfunction will be the reward for improved lifestyle behavior. Unsatisfying sexual activity represents a meaningful, straightforward motivation for consulting healthcare professionals, who, in turn, should take advantage of the opportunity to encourage obese patients to treat, besides ED, the underlying unfavorable conditions, thus not only restoring erectile function, but also overall health.

Metabolic syndrome and prostate abnormalities in male subjects of infertile couples

No previous study has evaluated systematically the relationship between metabolic syndrome （MetS） and prostate-related symptoms and signs in young infertile men. We studied 171 （36.5 ±8.3-years-old） males of infertile couples. MetS was defined based on the National Cholesterol Education Program Third Adult Treatment Panel. All men underwent hormonal （including total testosterone （TT） and insulin）, seminal （including interleukin-8 （IL-8）, seminal plasma IL-8 （sIL-8））, scrotal and transrectal ultrasound evaluations. Because we have previously assessed correlations between MetS and scrotal parameters in a larger cohort of infertile men, here, we focused on transrectal features. Prostate-related symptoms were assessed using the National Institutes of Health Chronic Prostatitis Symptom Index （NIH-CPSI） and the International Prostate Symptom Score （IPSS）. Twenty-two subjects fulfilled MetS criteria. In an age-adjusted logistic ordinal model, insulin levels increased as a function of MetS components （Wald = 29.5, P〈 0.0001） and showed an inverse correlation with TT （adjusted r = -0.359, P 〈 0.0001）. No association between MetS and NIH-CPSI or IPSS scores was observed. In an age-, TT-, insulin-adjusted logistic ordinal model, an increase in number of MetS components correlated negatively with normal sperm morphology （Wald -- 5.59, P〈 0.02） and positively with slL-8 levels （Wald = 4.32, P〈 0.05）, which is a marker of prostate inflammation, with prostate total and transitional zone volume assessed using ultrasound （Wald = 17.6 and 12.5, both P〈 0.0001）, with arterial peak systolic velocity （Wald = 9.57, P= 0.002）, with texture nonhomogeneity （hazard ratio （HR） = 1.87 （1.05-3.33）, P 〈 0.05）, with calcification size （Wald = 3.11, P 〈 0.05）, but not with parameters of seminal vesicle size or function. In conclusion, in males of infertile couples, MetS is positively associated with prostate enlargement, biochemical （slL8） and ultrasound-derived signs of prostate inflammation but not with prostate-related symptoms, which suggests that MetS is a trigger for a subclinical, early-onset form of benign prostatic hyperplasia.

How to recognize late-onset hypogonadism in men wit sexual dysfunction

Late-onset hypogonadism （LOH） has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone （T） levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T （different thresholds）, sexual parameters, medical history data （delayed puberty, pituitary disease or cryptorchidism） and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.

Clinical correlates of enlarged prostate size in subjects with sexual dysfunction

Digito-rectal examination （DRE） of the prostate provides useful information on the state of prostate growth and on the presence of suspected peripheral nodules. The aim of this study is to describe the clinical and biochemical correlates of finding an enlarged prostate size at DRE in subjects with sexual dysfunction （SD）. A consecutive series of 2379 patients was retrospectively studied. The analysis was focused on a subset of subjects （n = 1823; mean age 54.7± 11.4） selected for being free from overt prostatic diseases. Several parameters were investigated. After adjusting for confounders, the presence of an enlarged prostate size at DRE was associated with a higher risk of metabolic syndrome （HR = 1.346 （1,129-1.759）; P = 0.030）, type 2 diabetes mellitus （HR = 1.489 （1.120-1.980）; P = 0.006）, increased LDL cholesterol （〉100mgdl^-1; HR = 1.354 （1.018-1.801）; P = 0.037） and increased mean blood pressure （BP） values （HR = 1.017 （1.007-1.027） for each mmHg increment; P = 0.001）. Accordingly, enlarged prostate size was also associated with a higher risk of arteriogenic erectile dysfunction （ED）, as well as with other andrological conditions, such as varicocele and premature ejaculation （PE）. PSA levels were significantly higher in subjects with enlarged prostate size when compared to the rest of the sample （HR = 3.318 （2.304; 4.799） for each log unit increment in PSA levels; P 〈 0.0001）. Arteriogenic ED, according to different criteria, was also associated with increased PSA levels. In conclusion, our data support the need to examine prostate size either by clinical （DRE） or biochemical （PSA） inspection in subjects with SD, in order to have insights into the nature of the SD and the metabolic and cardiovascular （CV） background of the patient.

Both comorbidity burden and low testosterone can explain symptoms and signs of testosterone deficiency in men consulting for sexual dysfunction

Low testosterone(T)is frequent in men with chronic illnesses.The clinical features of T deficiency(TD)overlap with those of chronic diseases.The aim of this study is to evaluate the relative contribution of chronic disease score(CDS)and low T to the presenee of TD symptoms.A consecutive series of 3862 men(aged 52.1±13.1 years)consulting for sexual dysfunction were studied.Several clinical and biochemical parameters were collected,in eluding the structured interview,ANDROTEST,for the assessme nt of TD symptoms.Penile color Doppler ultrasound(PCDU)was also performed.Based on the medications taken,the CDS was calculated.For a subset of 1687 men,information on mortality was collected(follow-up of 4.3±2.6 years).Higher CDS was associated with lower free and total T(TT)as well as with higher ANDROTEST score.When introducing CDS and TT in multivariable models adjusted for age,severe erectile dysfunctio n and impaired morning erectio ns were associated with both CDS(odds ratio and 95%confide nee interaval,OR[95%Cl]=1.25[1.13;1.37]and 1.38[1.29;1.48],respectively)and low TT(OR[95%Cl]=1.11[1.00;1.23]and 1.13[1.06;1.21],respectively).Similar results were obtained for PCDU parameters.Hypoactive sexual desire was associated with low TT(OR[95%Cl]=1.21[1.13;1.30]),whereas it was inversely related with CDS(OR[95%Cl]=0.91[0.84;0.97]).When considering mortality for major cardiovascular events,TT<8 nmol I1,but not CDS,was a significant predictor(hazard ratio[95%Cl]=5.57[1.51;20.63]).Chronic illnesses are associated with an overt TD.Both chronic diseases and low T can be invoIved in determining symptoms present in subjects complaining for sexual dysfunction.This should be considered in the diagnostic workup for TD.

DNA fragmentation in two cytometric sperm populations： relationship with clinical and ultrasound characteristics of the male genital tract

We investigated whether DNA fragmentation in two cytometric sperm populations （PIddimmer and PIbriehter） with different biological characteristics and clinical relevance is related to clinical and color-Doppler ultrasound （CDUS） parameters of the male genital tract. One hundred and sixty males of infertile couples without genetic abnormalities were evaluated for clinical, scrotal, and transrectal CDUS characteristics, presence of prostatitis-like symptoms （with the National Institutes of Health-Chronic Prostatitis Symptom Index） and sperm DNA fragmentation （sDF） in PIdimmer and PIbrighter populations （using TUNEIJPI method coupled with flow cytometry）. Data were adjusted for age （Model 1） along with waistline, testosterone levels, smoking habit, and sexual abstinence （Model 2）. According to the statistical Model 2, PIdi sDF was associated with testicular abnormalities, including lower clinical and ultrasound volume （r = -0.21 and r = -0.20, respectively; P 〈 0.05）, higher FSH levels （r = 0.34, P 〈 0.0001） and occurrence of testicular inhomogeneity （P 〈 0.05） and hypoechogenicity （P 〈 0.05）. PIbrighter sDF was associated with prostate-related symptoms and abnormal signs, including higher NIH-CPSI total and subdomain scores, a higher prevalence of prostatitis-like symptoms and of CDUS alterations such as macro-calcifications, severe echo-texture inhomogeneity, hyperemia （all P 〈 0.05）, and higher arterial peak systolic velocity （r = 0.25, P 〈 0.05）. Our results suggest that DNA fragmentation in PIdimmer sperm, which is related to poor semen quality, mainly originates in the testicles, likely due to apoptosis. Conversely, DNA fragmentation in PIbrighter sperm appears to mainly originate during or after transit through the prostate, increasing with the presence of an inflammatory status of the organ. These results could lead to new perspectives for the identification of therapeutic targets to reduce sDF.

Testosterone therapy: a friend or a foe for the aging men with benign prostatic hyperplasia?

One of the major concerns for the prescription of medications containing testosterone(T)in the aging men with T deficiency(TD)is prostate disorders(such as benign prostatic hyperplasia,BPH)and their related symptoms(lower urinary tract symptoms,LUTS).This is because prostate is an androgen-responsive gland;however,the androgen dependence of prostate growth,well demonstrated in earlier phases of life,has no clear evidence in late adulthood and senescence.In fact,after the age of 40 years,BPH becomes increasingly more prevalent.On the other hand,in men older than 40 year,a progressive decline in T is observed.These epidemiological data are a starting point for questioning a putative detrimental role of T on the prostate health in the ageing man.