High rate of detection of ultrasound signs of prostatitis in patients with HPV-DNA persistence on semen: role of ultrasound in HPV-related male accessory gland infection.

BACKGROUND: Papillomavirus (HPV) often occurs in the semen of patients with male accessory gland infection (MAGI). Ultrasound (US) evaluation has been suggested as a promising diagnostic tool for patients with HPV-related MAGI. No data on the spontaneous clearance of HPV-DNA have been reported so far in HPV-related MAGI. PURPOSE: The primary aim of the study was to assess the percentage of early HPV-DNA spontaneous clearance in patients with prostatitis. The secondary aim was to evaluate the frequency of spontaneous clearance of HPV-DNA among patients with prostatitis associated with the presence or absence of US abnormalities. METHODS: Patients with inflammatory MAGI and at least one suspicious criterion for HPV infection underwent semen HPV-DNA detection and prostate US. The presence of HPV-DNA was further investigated after a 6-month-long follow-up. MAIN RESULTS: Eighty patients satisfied the inclusion criteria and were recruited in the study. 69% of patients (55/80) showed HPV-DNA persistence in the semen. Among them, 82% (45/55) was positive for US signs of prostatitis, while they occurred only in 12% (3/25) of those patients with no sign of HPV-DNA persistence (p < 0.001). All patients with persistent high-risk HPV genotype (n = 30) showed at least two US signs of prostatitis. In 73% of patients (22/30), E6 and E7 mRNAs were detected. CONCLUSION: US signs of prostatitis more frequently occurred in patients with evidence of HPV-DNA persistence on semen, especially in those with high-risk genotypes. This highlights the importance of US in the framework of HPV-related MAGI.

Non-hormonal treatment for male infertility: the potential role of Serenoa repens, selenium and lycopene.

OBJECTIVE: Male infertility is a wide spread disease among couple of childbearing age. Spermatozoa are highly susceptible to oxidative stress. Reactive oxygen species (ROS) are capable of damaging the sperm membrane and DNA, inducing lipid peroxidation and sperm DNA fragmentation (SDF). Antioxidant supplementation is currently suggested after a complete diagnostic work-up, as recognized by the Italian Society of Andrology and Sexual Medicine (SIAMS). Indeed, it has been showed to improve sperm quality, DNA fragmentation and pregnancy rate. The administration of Serenoa repens extracts (SrE), including free fatty acids (FFA), methyl and ethyl esters, glycerides, flavonoids and sterols, has never been investigated for male infertility. However, their antioxidant and anti-inflammatory properties provide the rational for their possible effectiveness. The aim of this review was to collect all the evidence supporting the potential usefulness of SrE, alone or in combination with other molecules with proven antioxidant effects, like selenium and lycopene (along with which they are often commercialized), to improve sperm parameters. MATERIALS AND METHODS: A systematic search was performed using Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar and Scopus databases. The search strategy included the following key words: Serenoa repens, selenium, lycopene, oligozoospermia, oxidative stress, DNA fragmentation, male infertility, pregnancy rate. CONCLUSIONS: By triggering multiple inflammatory and oxidative pathways, the combined administration of SrE, selenium and lycopene might likely improve the sperm quality. Proper studies are needed to test this hypothesis. Finally, since prostatitis can affect the sperm quality and considering the anti-estrogenic properties of SrE, we speculate about a possible specific indication in those patients with male infertility and "metabolic" prostatitis (where obesity and abnormal androgen/estrogen ratio concomitantly occur).

Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.

BACKGROUND: Insulin resistance is a common feature among women with polycystic ovary syndrome (PCOS), especially in those patients with hyperandrogenism and chronic anovulation. PCOS women are at risk for developing metabolic syndrome, impaired glucose tolerance and type II diabetes mellitus (DM II). OBJECTIVE: The aim of this review is to explore the existing knowledge of the interplay between androgen excess, pancreatic ß-cell function, non-alcoholic fatty liver disease (NAFLD), intra-abdominal and subcutaneous (SC) abdominal adipocytes in PCOS, providing a better comprehension of the molecular mechanisms of diabetologic interest. METHODS: A comprehensive MEDLINE® search was performed using relevant key terms for PCOS and DM II. RESULTS: Insulin-induced hyperandrogenism could impair pancreatic ß-cell function, the SC abdominal adipocytes' lipid storage capacity, leading to intra-abdominal adipocyte hypertrophy and lipotoxicity, which in turn promotes insulin resistance, and could enhance NAFLD. Fetal hyperandrogenism exposure prompts to metabolic disorders. Treatment with flutamide showed to partially reverse insulin resistance. CONCLUSIONS: Metabolic impairment seems not to be dependent only on the total fat mass content and body weight in women with PCOS and might be ascribed to the androgen excess.

Dual-release hydrocortisone treatment: glycometabolic profile and health-related quality of life.

OBJECTIVE: Adrenal insufficiency (AI) is a chronic condition associated with increased mortality and morbidity. The treatment of AI in the last years has been object of important changes due to the development of a dual-release preparation of hydrocortisone. It differs from previous therapeutic strategy as it contemplates a once-daily tablet that allows more closely mimicking the physiological circadian cortisol rhythm. The aim of the study was to evaluate the effects of dual-release hydrocortisone treatment on the glycometabolic profile and health-related quality of life of patients with AI. DESIGN AND METHODS: In this clinical open trial, we enrolled ten patients with primary AI (41 ± 2.67 years) and nine patients with AI secondary to hypopituitarism (53.2 ± 17.7 years). We evaluated the glycometabolic profile before and 3, 6, 9 and 12 months after dual-release hydrocortisone administration. We also evaluated health-related quality of life, estimated by the AddiQol questionnaire. The mean dose administered of dual-release hydrocortisone was 28.33 ± 6.68 mg/day. RESULTS: One female hypopituitary patient dropped out from the study. After 12 months of treatment, the mean dosage administered of dual-release hydrocortisone was significantly lower (P < 0.05) and all patients reported improved quality of life and well-being. The glycometabolic profile improved and the glycosylated hemoglobin decreased significantly in patients with primary AI (6.25 ± 0.2 vs 5.35 ± 0.17, P < 0.05). In contrast, hypopituitary patients had worse glycometabolic profile and a trend toward hypertriglyceridemia. CONCLUSIONS: Dual-release hydrocortisone treatment improved the quality of life of patients with AI, and it allowed a decrease of cortisol dosage administered in the absence of side effects. The glycometabolic profile worsened in hypopituitary patients.

Does a male polycystic ovarian syndrome equivalent exist?

The occurrence of a genetic background in the etiology of polycystic ovarian syndrome (PCOS) represents the rational basis to postulate the existence of a male PCOS equivalent. Hormonal and metabolic abnormalities have been described in male relatives of women with PCOS. These males also have a higher prevalence of early onset (<35 years) androgenetic alopecia (AGA). Hence, this feature has been proposed as a clinical sign of the male PCOS equivalent. Clinical evidence has shown that men with early onset AGA have hormonal and metabolic abnormalities. Large cohort studies have clearly shown a higher prevalence of type II diabetes mellitus (DM II) and cardiovascular diseases (CVDs) in elderly men with early onset AGA. In addition, prostate cancer, benign prostate hyperplasia (BPH) and prostatitis have been described. These findings support the existence of the male PCOS equivalent, which may represent an endocrine syndrome with a metabolic background, and might predispose to the development of DM II, CVDs, prostate cancer, BPH and prostatitis later in life. Its acknowledgment would be helpful for the prevention of these long-term complications.

Myo-inositol as a male fertility molecule: speed them up!

Myo-inositol (MYO) usually represents a therapeutic option for female infertility associated with insulin resistance. Recently, several evidences are accumulating about the potential use of MYO for the treatment of male infertility. This article summarizes the rationale for MYO in the treatment of male infertility. In particular, it illustrates the potential antioxidant and prokinetic role of MYO, and its importance for the modulation of hormonal regulation. In the final part of the manuscript has been added a proposal for a clinical algorithm reserved for patients with asthenozoospermia, where probably MYO could exert specific pharmacological effects.

The -29G/A FSH receptor gene polymorphism is associated with higher FSH and LH levels in normozoospermic men.

PURPOSE: The functional role of the FSHR promoter -29G/A polymorphism (rs1394205) in men is not clear. Some studies failed to find a relationship between the FSHR -29G/A and follicle-stimulating hormone (FSH) levels and did not associate the SNP with male infertility. Only one study showed that the FSHR -29 SNP modulates serum FSH levels in Baltic young male cohort. Because the SNP -29G/A has to be shown to have a strong effect on in vitro transcription activity of the FSHR promoter and the activation of FSHR is necessary for a normal FSH function, this study was undertaken to assess whether the FSHR -29G/A SNP modulates the gonadal endocrine function in men. METHODS: A total of 200 men with alteration of conventional sperm parameters or normozoospermia (according to the parameters WHO 2010), were genotyped by TaqMan Assay. Hormone levels were measured by immunoassay, and sperm analysis was performed according to the World Health Organization criteria. RESULTS: A significant gradient of increasing FSH levels across the FSHR -29G/A genotypes was observed (p < 0.01). Among normozoospermic men (n = 110), those with FSHR -29A-allele carriers (GA + AA and AA) had higher serum FSH (p < 0.01) and LH levels (p < 0.05) and higher body mass index (BMI) (p < 0.01) compared to men with the GG genotype. The carrier status of rs1394205 genotypes did not affect the other endocrine parameters neither in men with altered sperm parameters nor in normozoospermic men. CONCLUSIONS: The FSHR -29G/A polymorphism modulates FSH and, for the first time, LH serum levels and BMI in normozoospermic men. These findings underline the importance to pay close attention to the studies of genetic variations associated with clinical-endocrine parameters.

Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders.

Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS. KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6-3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature. Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4-17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9-17.2) are also more frequent in these subjects. Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT). KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear.

Impact of the FSHB gene -211G/T polymorphism on male gonadal function.

PURPOSE: The FSHB gene -211G/T polymorphism has been reported to modulate gene expression and to cause inter-individual differences in FSH serum levels in men. This study was undertaken to assess the functional relevance of this polymorphism on gonadotropin and total testosterone serum levels and sperm parameters in men from Eastern Sicily (Italy). METHODS: To accomplish this, 200 men with abnormal conventional sperm parameters or normozoospermia (according to the parameters of WHO 2010) were genotyped by TaqMan Assay. RESULTS: The frequency of FSHB -211 T allele was significantly higher (p < 0.005) in patients with altered conventional sperm parameters (18.9% of chromosomes) compared to that observed in men with normozoospermia (10.9% of chromosomes). Decreasing serum levels of FSH and LH were observed across the three FSHB -211 genotype subgroups (p < 0.001 and p < 0.05, respectively). In addition, the FSHB -211G/T polymorphism showed a total testosterone downward trend that became more evident in men with the TT genotype compared to subjects with the GG genotype (p = 0.05). Furthermore, we found a trend towards decreased sperm concentration, total sperm count, sperm forward motility and testicular volume in men with GT and TT genotypes. CONCLUSIONS: These findings showed that the FSHB -211 G/T polymorphism modulates male gonadal function with a clear influence on hormonal levels and sperm parameters. CAPSULE: The present study was undertaken to evaluate the distribution of the FSHB -211 G/T in men with normal or abnormal sperm parameters from Southern Italy to assess its functional relevance on the serum levels of reproductive hormones and on sperm parameters in men.

Hormonal treatment with transdermal testosterone in patients with male accessory gland inflammation (MAGI): Effects on sperm parameters.

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 < .05 vs baseline), a significant reduction of CD45pos leucocytes in the semen (p < .05 vs baseline) and finally a significant increase of the seminal concentrations of zinc, fructose and alpha-glucosidase (p < .05 vs baseline) identified as key parameters associated to secretory function of the male accessory glands. The results of this study suggest the use of transdermal T in hypogonadal patients with MAGI for favourable effects on sperm parameters.

The role of carnitine in male infertility.

This review explores the role of carnitine in male infertility. The structure of this review is organized into short paragraphs that address the following aspects: antiapoptotic effect of l-carnitine on germ cells, effects of l-carnitine on conventional sperm parameters, in vitro effects of l-carnitine on sperm function, and the role of l-carnitine on erectile function.

Varicocele and concomitant dilation of the periprostatic venous plexus: effects on semen viscosity sperm parameters.

INTRODUCTION: Since varicocele is often associated with other venous abnormalities, this study was undertaken to evaluate the frequency of dilation of the periprostatic venous plexus (DPVP) in these patients and the effects of this association on sperm parameters before and after varicocelectomy. MATERIALS AND METHODS: Sperm parameters were evaluated using the conventional WHO criteria, and seminal fluid viscosity was further evaluated by quantitative viscometry, in 50 patients (aged 20-38 years) who underwent surgical treatment for grade III bilateral varicocele. RESULTS: Thirty patients with varicocele had also DPVP (DPVP+) (60 %). Sperm concentration and the percentage of spermatozoa with normal morphology did not differ significantly in patients with DPVP- or DPVP+ before or after surgical repair. On the other hand, sperm progressive motility was low in all patients and increased significantly after varicocele repair, but only in DPVP- patients. Before varicocele treatment, a significantly higher number of DPVP+ patients (25/30 = 83.3 %) had seminal fluid hyperviscosity compared to DPVP- patient (2/20 = 10.0 %). Viscosity quantitative measurement was significantly higher in DPVP+ patients both before and after varicocele repair compared to DPVP- patients. These latter showed a statistically significant reduction of sperm viscosity after varicocele surgical repair compared to pretreatment values. Finally, periprostatic venous plexus diameter and seminal fluid viscosity correlated directly in DPVP+ patients. CONCLUSIONS: In conclusion, these results showed that a large number of patients with varicocele had a concomitant DPVP. This subset of patients did not take advantage from varicocele surgical repair since only DPVP- varicocele patients showed a significant improvement of sperm progressive motility and seminal fluid viscosity. These findings suggest the evaluation of the periprostatic venous plexus and seminal fluid viscosity before patients with varicocele undergo surgical repair for asthenozoospemia.

Reproductive function in male patients with type 1 diabetes mellitus.

This study was undertaken to evaluate conventional and some of the main bio-functional spermatozoa parameters, serum gonadal hormones and didymo-epididymal ultrasound features in patients with type 1 diabetes mellitus (DM1). DM1 affects an increasing number of men of reproductive age. Diabetes may affect male reproduction by acting on the hypothalamic-pituitary-testicular axis, causing sexual dysfunction or disrupting male accessory gland function. However, data on spermatozoa parameters and other aspects of the reproductive function in these patients are scanty. Thirty-two patients with DM1 [27.0 (25.0-30.0 years)] and 20 age-matched fertile healthy men [28.0 (27.25-30.75 years)] were enrolled. Patients with diabetic neuropathy, other endocrine disorders or conditions known to alter spermatozoa parameters were excluded. Each subject underwent semen analysis, blood withdrawal for fasting and post-prandial glycaemia, hormonal analysis and didymo-epididymal ultrasound evaluation before and after ejaculation. Patients with DM1 had a lower percentage of spermatozoa with progressive motility [10.0 (7.0-12.75) vs. 45.0 (42.0-47.75) %; p < 0.01] and a higher percentage of spermatozoa with abnormal mitochondrial function than controls [47.0 (43.0-55.0) vs. 2.0 (1.0-5.0) %; p < 0.01]. Patients also had greater post-ejaculatory diameters of cephalic [11.5 (10.2-13.6) vs. 6.0 (4.0-7.0) mm; p < 0.01] and caudal epididymis [5.5 (4.00-7.55) vs. 3.0 (2.0-4.0) mm; p < 0.01] compared to controls, suggesting a lack of the physiological post-ejaculation epididymal shrinkage. Correlation analysis suggested that progressive motility was associated with fasting glucose (r = -0.68; p < 0.01). The other parameters did not show any significant difference. Patients with DM1 had a lower percentage of spermatozoa with progressive motility, impaired mitochondrial function and epididymal post-ejaculatory dysfunction. These findings may explain why patients with DM1 experience fertility disturbance. Larger multi-centric studies are necessary to confirm these results.

Relevance of genetic investigation in male infertility.

Genetic causes can be directly responsible for various clinical conditions of male infertility and spermatogenic impairment. With the increased use of assisted reproduction technologies our understanding of genetic basis of male infertility has large implications not only for understanding the causes of infertility but also in determining the prognosis and management of such couples. For these reasons, the genetic investigations represent today an essential and useful tool in the treatment of male infertility. Several evidences are available for the clinical practice regarding the diagnosis; however, there are less information relative to the treatment of the genetic causes of male infertility. Focus of this review is to discuss the main and more common genetic causes of male infertility to better direct the genetics investigation in the treatment of spermatogenic impairment.

In vitro effects of nicotine on sperm motility and bio-functional flow cytometry sperm parameters.

The aim of this experimental study was to evaluate the effects of nicotine on sperm motility and on non-conventional sperm parameters in vitro. Capacitated spermatozoa isolated from 10 normozoospermic, healthy, non-smoker men were evaluated. Spermatozoa were exposed to increasing concentrations of nicotine (0, 1, 10, and 100 ng/ml) for 3 and 24 hours. Progressive motility and the following non-conventional sperm parameters, evaluated by flow cytometry, were assessed: mitochondrial membrane potential, viability, phosphatidylserine externalization, late apoptosis, degree of chromatin compactness, and DNA fragmentation. Nicotine suppressed, in a concentration-dependent manner, sperm progressive motility starting from the lowest concentration used (1 ng/ml). Similarly, it reduced the percentage of viable spermatozoa and increased the number of spermatozoa in late apoptosis, with altered chromatin compactness, or DNA fragmentation already after 3 hours of incubation. These effects were observed at a concentration similar (100 ng/ml) to that found in the seminal plasma of smokers (70 ng/ml), with the exception of the effects on sperm DNA fragmentation whose significant effect was detected also at a lower concentration (10 ng/ml). Nicotine may be regarded as a noxious component of cigarette smoke on the male reproductive function.

Risk factors of sexual dysfunction after transurethral resection of the prostate (TURP): a 12 months follow-up.

The aim of this study was to evaluate the impact of risk factors of erectile dysfunction (ED) after transurethral resection of the prostate (TURP) in men with lower urinary tract symptoms caused by bladder outlet obstruction secondary to benign prostatic hyperplasia. The study was conducted prospectively on 178 consecutive patients (normal IIEF-5 before surgery, ≥ 22) who underwent TURP. Patients were assessed before surgery and at 12 months. At 12 months, the IIEF-5 score significantly decreased from24 to 18 (p<0.0001). No statistical associations were found between hypertension, diabetes, dyslipidemia and capsular perforation and the development of ED after TURP. Operating time, duration of catheterization, and BMI did not determine a significant decrease of the IIEF-5 score after TURP. On univariable and multivariable linear regression analysis, age was the only risk factor associated with newly-reported ED 12 months after TURP (p<0.0001). On univariable andmultivariable logistic regression analysis, patients older than 65 yr had an higher risk of developing ED after TURP (p<0.0001) and they developed a lower IIEF-5 score (p<0.0001) at followup when compared with those ≤ 65 yr. These results suggest that age of patients represents an independent risk factor of ED at 12 months follow-up after TURP.