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Transrectal ultrasound (TRUS) parameters are not standardized, especially in men of reproductive age. Hence, the European Academy of Andrology (EAA) promoted a multicenter study to assess the TRUS characteristics of healthy-fertile men (HFM) to establish normative parameters.To report and discuss the prostate and seminal vesicles (SV) reference ranges and characteristics in HFM and their associations with clinical, seminal, biochemical parameters.188 men (35.6 ± 6.0 years) from a cohort of 248 HFM were studied, evaluating, on the same day, clinical, biochemical, seminal, TRUS parameters following Standard Operating Procedures.TRUS reference ranges and characteristics of the prostate and SV of HFM are reported herein. The mean PV was ∼25 ml. PV lower and upper limits were 15 and 35 ml, defining prostate hypotrophy and enlargement, respectively. PV was positively associated with age, waistline, current smoking (but not with T levels), seminal volume (and negatively with seminal pH), prostate inhomogeneity, macrocalcifications, calcification size and prostate arterial parameters, SV volume before and after ejaculation, deferential and epididymal size. Prostate calcifications and inhomogeneity were frequent, while midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. Periprostatic venous plexus size was positively associated with prostate calcifications, SV volume and arterial peak systolic velocity. Lower and upper limits of SV anterior-posterior diameter after ejaculation were 6 and 16 mm, defining SV hypotrophy or dilation, respectively. SV total volume before ejaculation and delta SV total volume (DSTV) positively correlated with ejaculate volume, and DSTV correlated positively with sperm progressive motility. SV total volume after ejaculation was associated negatively with SV ejection fraction and positively with distal ampullas size. SV US abnormalities were rare. No association between TRUS and time to pregnancy, number of children or history of miscarriage was observed.The present findings will help in better understanding male infertility pathophysiology and the meaning of specific TRUS findings.

Male accessory gland infection/inflammation (MAGI) is a major cause of male infertility. The importance of ultrasound evaluation in these patients is highly controversial, although evidence of its relevance has increased in recent years. Ultrasound criteria are an important element for confirming the clinical diagnosis. Furthermore, they help to localize the anatomical site or sites of the inflammatory process and in assessing its extension which, in turn, have different consequences on the seminological and symptomatic aspects. This article summarizes the clinical interpretations related to ultrasound aspects in patients with MAGI and the possible effects on the seminological, microbiological, endocrinologic, urological, sexological, and internist aspects.

Background Gynecomastia (GM) is a benign proliferation of the glandular tissue of the breast in men. It is a frequent condition with a reported prevalence of 32-65%, depending on the age and the criteria used for definition. GM of infancy and puberty are common, benign conditions resolving spontaneously in the majority of cases. GM of adulthood is more prevalent among the elderly and proper investigation may reveal an underlying pathology in 45-50% of cases. Objectives The aim was to provide clinical practice guidelines for the evaluation and management of GM. Materials and methods A literature search of articles in English for the term 'gynecomastia' was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Results A set of five statements and fifteen clinical recommendations was formulated. Conclusions The purpose of GM assessment should be the detection of underlying pathological conditions, reversible causes (administration/abuse of aggravating substances), and the discrimination from other breast lumps, particularly breast cancer. Assessment should comprise a thorough medical history and physical examination of the breast and genitalia (including testicular ultrasound). A set of laboratory investigations may integrate the evaluation: testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin, human chorionic gonadotropin (hCG), alpha-fetal protein (AFP), liver and renal function tests. Breast imaging may be used whenever the clinical examination is equivocal. In suspicious lesions, core needle biopsy should be sought directly instead. Watchful waiting is recommended after treatment of underlying pathology or discontinuation of substances associated with GM. T treatment should be offered to men with proven T deficiency. The use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and non-aromatizable androgens is not justified in general. Surgical treatment is the therapy of choice for patients with long-lasting GM. Summary of statements (s) and recommendations (r) S1. Gynecomastia (GM) is a benign proliferation of glandular tissue of the breast in males. S2. GM of infancy is a common condition that usually resolves spontaneously, typically within the first year of life. S3. GM of puberty is a common condition, affecting approximately 50% of mid-pubertal boys; in more than 90% of cases, it resolves spontaneously within 24 months. S4. The prevalence of GM in adulthood increases with increasing age; proper investigation may reveal an underlying pathology in approximately 45-50% of the cases. S5. Male breast cancer is rare; GM should not be considered a premalignant condition. The following recommendations are divided into 'strong', denoted by the number 1 and associated with the terminology 'we recommend', and 'weak' denoted by the number 2 and associated with the phrase 'we suggest'. The grading of the quality of evidence is denoted as follows: ⊕○○○ for very low-quality evidence; ⊕⊕○○ for low quality; ⊕⊕⊕○ for moderate quality; and ⊕⊕⊕⊕ for high quality. R1. The presence of an underlying pathology should be considered in GM of adulthood. We recommend that the identification of an apparent reason for GM in adulthood, including the use of medication known to be associated with GM, should not preclude a detailed investigation (1 ⊕⊕⊕○). R2. We suggest that the initial screening to rule out lipomastia, obvious breast cancer, or testicular cancer might be performed by a general practitioner or another non-specialist (2 ⊕○○○). R3. We recommend that in those cases where a thorough diagnostic workup is warranted, it should be performed by a specialist (1 ⊕○○○). R4. We recommend that the medical history should include information on the onset and duration of GM, sexual development and function, and administration or abuse of substances associated with GM (1 ⊕⊕⊕○). R5. We recommend that the physical examination should detect signs of under-virilization or systemic disease (1 ⊕⊕⊕⊕). R6. We recommend that breast examination should confirm the presence of palpable glandular tissue to discriminate GM from lipomastia (pseudo-gynecomastia) and rule out the suspicion of malignant breast tumor (1 ⊕⊕⊕⊕). R7. We recommend that the physical examination should include the examination of the genitalia to rule out the presence of a palpable testicular tumor and to detect testicular atrophy (1 ⊕⊕⊕⊕). R8. We recommend that genitalia examination is aided by a testicular ultrasound, as the detection of a testicular tumor by palpation has low sensitivity (1 ⊕⊕○○). R9. We suggest that a set of evaluations may include T, E2 , SHBG, LH, FSH, TSH, prolactin, hCG, AFP, and liver and renal function tests (2 ⊕⊕○○). R10. We suggest that breast imaging may offer assistance, where the clinical examination is equivocal (2 ⊕⊕○○). R11. We suggest that, if the clinical picture is suspicious for a malignant lesion, core needle biopsy should be performed (2 ⊕⊕○○). R12. We recommend watchful waiting after treatment of underlying pathology or discontinuation of the administration/abuse of substances associated with GM (1 ⊕⊕○○). R13. We recommend that T treatment should be offered only to men with proven testosterone deficiency (1 ⊕⊕⊕○). R14. We do not recommend the use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or non-aromatizable androgens in the treatment of GM in general (1 ⊕⊕○○). R15. We suggest surgical treatment only for patients with long-lasting GM, which does not regress spontaneously or following medical therapy. The extent and type of surgery depend on the size of breast enlargement, and the amount of adipose tissue (2 ⊕⊕○○).

The role of urogenital inflammation in causing infertility and sexual dysfunctions has long been a matter of debate in the international scientific literature. The most recent scientific evidences show that male accessory gland infection/inflammation could alter, with various mechanisms, both conventional and biofunctional sperm parameters, and determine worst reproductive outcome. At the same time, the high prevalence of erectile dysfunction and premature ejaculation in patients with male accessory gland infection/inflammation underlines the close link between these diseases and sexual dysfunctions. The aim of this review was to provide the reader the basis for a correct diagnosis of male accessory gland infection/inflammation and a subsequent appropriate therapeutic approach, particularly in patients with infertility and/or sexual dysfunction.

We carried out a systematic review in order to determine the connection between lower urinary tract symptoms secondary to bladder outlet obstruction and metabolic syndrome with its components. We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the Cochrane Database of Systematic Review and Web of Science from their inception until January 2015 to identify all eligible studies on the effect of metabolic syndrome (or component factors) on the presence or severity of lower urinary tract symptoms/bladder outlet obstruction in men. This analysis was carried out according to the STrengthening the Reporting of OBservational studies in Epidemiology guidelines. In total, 19 studies were identified as eligible for this systematic review. The quality assessment score was ≥50% in more than half of the studies (11/19). The evidence synthesis showed a positive association between metabolic syndrome, number of components and lower urinary tract symptoms/bladder outlet obstruction. In particular, the major endocrine aberrations of this connection are central obesity and hypertriglyceridemia. The links between insulin resistance and lower urinary tract symptoms/bladder outlet obstruction should be better investigated. Ethnic disparities in all examined studies showed a different impact of metabolic syndrome on lower urinary tract symptoms/bladder outlet obstruction severity and such influence still remain unclear. The relationship between metabolic syndrome and lower urinary tract symptoms/bladder outlet obstruction open the way for introducing physical activity and diet as recognized first-line interventions for treating lower urinary tract symptoms. However, this connection should be investigated in two different ethnic cohorts (i.e. Asian vs Caucasian) in order to better understand the impact of ethnic disparities on metabolic syndrome and lower urinary tract symptoms/bladder outlet obstruction severity.

Summary Male infertility is a multifactorial disorder that affects a significant percentage of couples. Its etiology and pathogenesis remain elusive in about one-third of the cases; this is referred to as idiopathic infertility. Inositols mediate the sperm processes involved into oocyte fertilization, such as penetration of the ovum cumulus oophorus, binding with the zona pellucida and the acrosome reaction. The aim of this double-blind, randomized, placebo-controlled trial was to evaluate the efficacy and safety of myoinositol (the most abundant form of inositols present in nature) treatment in men with idiopathic infertility. To accomplish this, we evaluated the effects of myoinositol on sperm parameters and reproductive hormones at baseline and after 3 months of treatment in men with idiopathic infertility. No adverse reaction was observed. Myoinositol significantly increased the percentage of acrosome-reacted spermatozoa, sperm concentration, and total count and progressive motility compared to placebo. In addition, myoinositol rebalanced serum luteinizing hormone, follicle-stimulating hormone, and inhibin B concentrations. The clinical improvement of idiopathic infertile patients should encourage myoinositol use for the treatment of this disorder, even though its detailed mechanisms at the testicular level remain still unclear.

Klinefelter syndrome (KS) results from an extra chromosome X, which is due to the failure of normal chromosomal segregation during meiosis. Patients with KS have gynecomastia, small testes, and azoospermia. Apoptosis is a mechanism responsible for the normal regulation of spermatogenesis. LDOC1 gene is a known regulator of nuclear factor mediated pathway to apoptosis through inhibition of nuclear factor kappa B (NF-kappaB). Furthermore, the transcription factor myeloid zinc finger gene 1 (MZF-1) has been shown to interact with LDOC1 and to enhance LDOC1 activity favoring apoptosis. We investigated the expression of LDOC1 gene mRNA, by quantitative reverse transcription polymerase chain reaction (qRT-PCR), in peripheral blood leukocytes of 13 patients with KS compared to 13 healthy men chosen as controls. LDOC1 expression was higher in 9 of the 13 KS patient compared to normal controls. These finding led us to hypothesize that LDOC1 gene upregulation may play a role in the spermatogenesis derangement observed in patients with KS.

Cryptorchidism represents a risk factor for infertility and germ cell testicular neoplasia. An increased rate of cryptorchidism has been reported in subjects with Down's syndrome. Cyclic nucleotide phosphodiesterases (PDEs) are important messengers that regulate and mediate a number of cellular responses to extracellular signals, such as neurotransmitters and hormones. PDE4B, cAMP-specific (PDE4B) gene which maps to chromosome 1p31.3 appears to be involved in schizophrenia, chronic psychiatric illness, learning, memory, and mood disturbances. Expression of PDE4 enzymes have been studied in testes of cryptorchid rats. Expression of PDE4B protein examination showed marked degenerative changes in the epithelial lining of the seminiferous tubules. These findings led us to evaluate PDE4 mRNA expression in leukocytes of peripheral blood of five men with DS and cryptorchidism and eleven subjects with DS without cryptorchidism compared with healthy men (controls) by quantitative Real Time PCR (qRT-PCR). This study showed that the PDE4B gene was downexpressed in men with DS and cryptorchidism compared to normal controls and DS without cryptorchidism. A lower expression of the PDE4B gene may be involved in the neurological abnormalities in subjects with Down's syndrome. Moreover, PDE4B gene may be involved in the testicular abnormalities of men with DS and cryptorchidism.

Summary Recently, it has been reported that treatment with testosterone (T) could have favourable effects on prostate inflammation; however, the data appear inconsistent. The main evidences concern experimental studies, and there is lower information obtainable from clinical studies. This study was conducted on patients with diagnosis of male accessory gland infection (MAGI) and a concomitant hormonal condition of acquired hypergonadotropic hypogonadism and has evaluated the effects on sperm parameters of the administration of a transdermal formulation of T gel for 3 months. The treated patients showed a significantly increased percentage of spermatozoa with normal form and progressive motility (p

Recently, we reported an increased prevalence of chronic bacterial prostatitis (CBP) in patients with prostatitis syndromes (PS) and irritable bowel syndrome (IBS) compared with patients with PS alone. The aim of this study was to evaluate the frequency of male accessory gland infections (MAGI) in patients with CBP plus IBS and to compare the sperm parameters of patients with or without MAGI. Fifty consecutive patients with the following criteria were enrolled: (i) infertility; (ii) diagnosis of CBP; and (iii) diagnosis of IBS according to the Rome III criteria. The following two aged-matched control groups were also studied: infertile patients with CBP alone (n = 56) and fertile men (n = 30) who fathered a child within the previous 3 months. Patients and controls underwent to an accurate anamnesis, administration of the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) and the Rome III questionnaires for prostatitis and IBS, respectively, physical examination, and semen analysis. A significantly higher frequency of MAGI was found in patients with CBP plus IBS (82.0%) compared with the patients with CBP alone (53.6%) or the fertile men (0%). The presence of MAGI in the patients with CBP plus IBS was associated with a significantly lower sperm concentration, total number, and forward motility, and with a higher seminal leucocyte concentration compared with the patients with CBP alone and MAGI. Sperm normal morphology was similar in the groups of patients. All sperm parameters did not differ significantly in both the groups of patients without MAGI. The patients with CBP plus IBS had a significantly higher frequency of MAGI compared with the patients with CBP alone. This was associated with worse sperm parameters and, hence, poorer reproductive prognosis. We suggest to search for the presence of IBS in the patients with PS and in particular when CBP and/or worse sperm parameters are present.

Summary Male accessory gland infection (MAGI) has been identified among those diagnostic categories which have a negative impact on the reproductive function and fertility in males (Rowe et al., World Health Organization Manual for the Standardised Investigation and Diagnosis of the Infertile Couple, Cambridge University Press, Cambridge, 1993). MAGI is a hypernym which groups the following different clinical categories: prostatitis, prostate-vesiculitis and prostate-vesiculo-epididymitis. Some of the characteristics they share are: common diseases, mainly have a chronic course, rarely cause obstruction of the seminal pathways, can have an unpredictable intracanicular spread to one or more sexual accessory glands of the reproductive tract, as well as to one or both sides. In this review, we show that all components involving the inflammatory response (from the agents which first trigger it to each component of the inflammatory response dynamic) can deteriorate conventional and/or non-conventional sperm parameters arising from one or more of the following mechanisms: altered secretory function of the epididymis, seminal vesicles, and prostate which reduce the antioxidant properties or scavenging role of the seminal plasma; deterioration of spermatogenesis; and (unilateral or bilateral) organic or functional sub-obstruction of the seminal tract.

The prevalence of erectile dysfunction is high in men of all ages and increases greatly in the elderly. In particular, severity and prevalence both increase with aging. Because erectile dysfunction is a symptom, physicians should diagnose underlying pathologies that might lead to it instead of focusing only on finding a viable treatment. Physical inactivity negatively impacts on erectile function; experimental and clinical exercise interventions have been shown to improve sexual responses and overall cardiovascular health. Several studies have confirmed that combining 2 interventions (Mediterranean diet and physical activity) provides additional benefit to erectile function, likely via reduced metabolic disturbances (eg, inflammatory markers, insulin resistance), decreased visceral adipose tissue, and improvement in vascular function (eg, increased endothelial function). This brief review shows the main clinical evidence of benefits induced by physical activity on erectile and endothelial dysfunction. The literature shows that erectile dysfunction in middle-aged men is often an early event in endothelial damage, and physical activity is able to improve both erectile and endothelial dysfunction. There are conflicting data regarding the effects of exercise on androgen status. In clinical practice it would be recommended to add regular physical activity to balanced diet and drugs to achieve better therapeutic results.

This study evaluated the effects of a chronic treatment with tadalafil, a specific phosphodiesterase V inhibitor, on endothelial apoptosis through changes in the serum concentration of endothelial microparticles (EMP). EMPs were arbitrarily chosen as a marker of endothelial apoptosis, and the changes in their concentration were monitored before and after treatment. Additionally, administration of endothelial antioxidant compound (EAC) during the follow-up, after discontinuation of tadalafil, was evaluated to determine whether this treatment improved the potential effects of tadalafil on the endothelium. Seventy-five patients with arterial erectile dysfunction were evaluated at baseline and after administration of tadalafil (5 mg once daily for 90 days). The International Index of Erectile Function questionnaire was administered, and penile dynamic Doppler and flow-cytometric (serum concentrations of EMPs) analyses were performed before (T0) and after treatment. Time points after tadalafil discontinuation: T1, after 1 week; T2, after 3 months; and T3, after 6 months. Three different schemes of follow-up were evaluated: group A, follow-up with EAC administration, after tadalafil discontinuation, for 6 months; group B, follow-up without other treatment; and group C, follow-up with placebo during the follow-up, after tadalafil cessation. The events CD45(neg)/CD144(pos)/annexinV(pos) were defined EMPs. Patients treated with tadalafil showed a significant decrease in serum EMPs 1 week after discontinuing tadalafil (16.4% ± 3.6% vs 7.1% ± 3.3%). This effect was maintained for up to 3 months in the group without other treatment during follow-up and was maintained for up to 6 months in the group treated with EAC during follow-up. Chronic treatment with tadalafil reduces endothelial apoptosis in patients with arterial erectile dysfunction. Further, EAC treatment prolongs and stabilizes the duration of antiapoptotic effects on the endothelium that are initially promoted by tadalafil treatment.

Blood endothelial progenitor cells (EPC) and microparticles (EMP) have been proposed as markers of endothelial dysfunction. The aim of this study was to evaluate both EPCs and EMPs in patients with arterial erectile dysfunction (ED) and metabolic syndrome (MetS). To accomplish this, 100 patients (ages 45-60 years) with ED and MetS (Adult Treatment Panel III [ATP III] 1999 criteria) and 17 healthy men (ages 44-57 years) were selected. EPC (CD45(neg)/CD34(pos)/CD144(pos)) and EMP (CD45(neg)/CD144(pos)/Annexin V(pos)) blood concentrations were evaluated by flow cytometry, before and after administration of tadalafil (20 mg) on demand for 3 months. Before treatment, EPCs and EMPs were significantly higher in patients compared with healthy men. EPCs increased significantly after tadalafil administration, whereas EMPs did not differ significantly. EPCs correlated positively or negatively with body mass index and with some cavernous artery indices, both before and after tadalafil administration. EMPs showed only positive correlations with body mass index and some cavernous artery indices, both before and after tadalafil administration. Patients with arterial ED and MetS have higher EPCs and EMPs compared with healthy men; hence, these cells may be regarded as markers of cavernous artery dysfunction. Tadalafil administration increased EPCs but not EMPs, suggesting that this compound may play a role in the endothelial repair response.

Haematopoietic stem cell transplantation is an important therapy for certain haematological and malignant disorders. Umbilical cord blood contains a high proportion of potentially transplantable haematopoietic progenitor cells. However, the use of cord blood stem cell transplantation is limited by the low number of stem cells obtainable from a single cord blood donor. The aim of our study was to investigate the possibility that procedures during delivery might influence the number of umbilical cord blood haematopoietic progenitor cells available for transplantation. We assessed the effects of upper and lower positions of the newborn infant on the yield of cord blood stem cells in 51 vaginal deliveries. Neonates in the upper position group were placed by the midwife on the maternal abdomen immediately after birth, while those in the lower position group were placed on the delivery table, below the maternal introitus. The total volume of cord blood and the total number of CD34+ cells collected from babies in the upper position group were significantly higher than those from babies in the lower position group. There were no significant differences in cord blood haemoglobin levels and white blood cell counts between the two groups, nor were there any adverse effects in the newborn infants. The simple manoeuvre of placing the newborn on the maternal abdomen after delivery may thus increase the yield of transplantable haematopoietic progenitor cells in cord blood.

Normal subjects show a wide range of growth hormone (GH) responses to growth hormone-releasing hormone (GHRH) stimulation, but it is uncertain whether this variability reflects differences among individuals or whether it would also be observed on repeated tests of the same subject. To clarify this, we tested nine normal men repeatedly with iv bolus doses of 1 mug/kg GHRH(1-44)NH(2). Most subjects showed wide variations in their GH responses on repeated testing, and the intra-individual variability was nearly as great as the inter-individual variability in responses, accounting for about two-thirds of the overall variance. A minority of subjects had lower and less variable responses. Ultradian fluctuations in hypothalamic somatostatin secretion may account for this marked intra-individual variability.