Leonardo Oliveira Reis

Erectile dysfunction and hormonal imbalance in morbidly obese male is reversed after gastric bypass surgery: a prospective randomized controlled trial

The effects of weight loss on erectile function and hormones have not been well studied. The aim of this study was to measure the degree to which sexual function and in particular erectile function and hormonal environment change after substantial weight loss, surgically and non-surgically induced in the morbidly obese male in a prospective randomized long-term controlled trial. Furthermore, how surgery makes a difference when treating morbidly obese men was envisaged in this context. We prospectively studied 20 morbidly obese men for 24 months, divided into two groups: group A included 10 patients who underwent life style modifications (exercise and diet) for 4 months and subsequently gastric bypass, and another 10 patients in group B were kept on weekly follow-up. None of the men were taking phosphodiesterase type-5 inhibitors. All patients underwent International Index of Erectile Function (IIEF)-5 questionnaire, serum oestradiol, prolactin (PRL), luteinizing (LH) and follicle-stimulating (FSH) hormones, free and total testosterone (FT and TT) at baseline (time 0), surgery - 4 months latter baseline (time 1) and final evaluation - 24 months (time 2). From times 0 to 1, group A presented a mean body mass index (BMI) reduction of 12.6 (p < 0.0001), whereas group B, 2.1 (p > 0.05). The BMI reductions between times 0 and 2 were 24.7 (p < 0.0001) and 0.7 (p > 0.05) for groups A and B respectively. BMI average between the two groups was similar at time 0 (p = 0.2142), and different at times 1 (p = 0.0033) and 2 (p < 0.0006). Increase in IIEF-5 score (p = 0.0469), TT (p = 0.0349) and FSH levels (p = 0.0025), and reduction in PRL level (p < 0.0001) were observed in group A from times 0 to 2 and 1 to 2. There were no changes from times 0 to 1. Comparing groups A and B at time 2, IIEF-5, TT and FT increased significantly in group A (p = 0.0224, 0.0043 and 0.0149 respectively). Surgery-induced weight loss increased erectile function quality measured by IIEF-5 questionnaire, increased TT, FT and FSH and reduced PRL levels. The hormonal impact verified could justify the improvement in erectile function. Lifestyle modifications impacted BMI without hormonal or sexual impact in morbidly obese. New studies are warranted in the field to support our data.

Obesity and Male Infertility: A Practical Approach

Obesity in men is associated with infertility in numerous studies, and the temporal trend for a decline in semen parameters parallels the increasing prevalence of obesity in the developed world. In addition to impaired semen quality, fertility among obese men may be affected by decreased libido and erectile dysfunction. This spectrum of expression of hypogonadism among obese men originates from multiple interacting factors including reduced levels of gonadotropins and testosterone, altered androgen-to-estrogen ratios, insulin resistance, and sleep apnea. No evidence-based treatment that increases the likelihood of pregnancy for the infertility associated with male obesity has been demonstrated to date. Interventions associated with improvement of intermediate outcomes that include the endocrine profile, semen parameters, and sexual function may be appropriately selected based on history, physical findings, as well as endocrine and metabolic evaluation. Among these interventions are weight loss through lifestyle change, relief from sleep apnea, use of aromatase inhibitors, gonadotropin administration, phosphodiesterase inhibitors, and insulin-sensitizing agents.

Bariatric Surgery Does not Interfere With Sperm Quality—A Preliminary Long-Term Study

Purpose: Positive impact of weight loss on sexual function and hormones has been demonstrated, and male fertility in this scenario is to be better defined. We evaluated the impact of lifestyle modifications and gastric bypass on sperm quality. Methods: We prospectively studied 20 morbidly obese men during 24 months, randomized for intervention: lifestyle modifications (exercise and diet) for 4 months and subsequently gastric bypass (n = 10); and control: follow-up (n = 10). All patients underwent International Index of Erectile Function (IIEF-5) questionnaire, serum estradiol, prolactin (PRL), luteinizing and follicle-stimulating hormones (LH and FSH), free and total testosterones (FT and TT) and semen analysis at baseline (time 0), surgery 4 months later baseline (time 1) and final evaluation 24 months (time 2). Results: Intervention group presented significant reduction in body mass index (BMI) at times 1 and 2, compared to control. There were no significant differences among sperm parameters between groups at times 0, 1, and 2 and among times 0, 1, and 2 in each group. Increases in IIEF-5 score (P = .0469), TT (P = .0349), and FSH (P = .0025) and reduction in PRL (P < .0001) were observed in the intervention group from times 0 to 2 and 1 to 2. Comparing groups at time 2, IIEF-5, TT, and FT increased significantly in the intervention group (P = .0224, P = .0043, and P = .0149, respectively). Conclusions: Surgery-induced massive weight loss does not interfere with sperm quality, while it increased the quality of sexual function, TT, FT and FSH and reduced PRL. Lifestyle modifications impacted merely the BMI. New studies are warranted, mostly considering birth rate as primary end point and including infertile men.

Prostate Specific Antigen Decrease and Prostate Cancer Diagnosis: Antibiotic Versus Placebo Prospective Randomized Clinical Trial

PURPOSE Prostate inflammation can lead to an increase in serum prostate specific antigen concentration and confound the use of prostate specific antigen kinetics. Repeat prostate specific antigen measurements after a period of observation or a course of empirical antibiotics are controversial in terms of the optimal approach to reduce the confounding impact on prostate cancer screening. This issue was analyzed in patients with a diagnosis of type IV or asymptomatic prostatitis (National Institutes of Health classification) and high prostate specific antigen. MATERIALS AND METHODS We studied 200 men between 50 and 75 years old with a high prostate specific antigen (between 2.5 and 10 ng/dl). Of these patients 98 (49%) had a diagnosis of type IV prostatitis. In a prospective, double-blind trial they were randomized to receive placebo (49 patients, group 1) or 500 mg ciprofloxacin (49 patients, group 2) twice a day for 4 weeks. Prostate specific antigen was determined after treatment and all patients underwent transrectal ultrasound guided biopsy of the prostate. RESULTS In group 1, 29 (59.18%) patients presented with a decrease in prostate specific antigen and 9 (31%) had cancer on biopsy, while in group 2 there were 26 (53.06%) patients with a decrease in prostate specific antigen and 7 (26.9%) with prostate cancer. There was no statistical difference in either group in relation to prostate specific antigen decrease after treatment or the presence of tumor. CONCLUSIONS A considerable number of patients (49%) were diagnosed with type IV prostatitis and high prostate specific antigen in agreement with the current literature. Of the patients 26.9% to 31% presented with a decrease in prostate specific antigen after the use of antibiotic or placebo and harbor cancer as demonstrated on prostate biopsy. Prostate specific antigen decreases do not indicate the absence of prostate cancer.

Intravesical protrusion of the prostate as a predictive method of bladder outlet obstruction

OBJECTIVE Pressure-flow study is the gold standard for diagnosis of bladder outlet obstruction (BOO). A prospective study was carried out to compare urodynamic evaluation and measurement of intravesical protrusion of the prostate for diagnosing BOO. MATERIALS AND METHODS Patients presenting with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia and suspected BOO were prospectively evaluated through conventional urodynamics and classified according to the bladder outlet obstruction index (BOOI). They also underwent abdominal ultrasound measurement of the intravesical prostatic protrusion (IPP) and prostatic volume. The IPP was classified into three stages: grade I under 5 mm; grade II, between 5 and 10 mm; and grade III over 10 mm. RESULTS Forty-two patients, mean age 64.8 +/- 8.5 years were enrolled. Transabdominal ultrasound determined a mean prostatic volume of 45 +/- 3.2 mL. Achieved IPPs values were the following: grade I - 12 (28.5%), grade II - 5 - (12%) and grade III - 25 (59.5%). The results of prostate volume differed significantly between obstructed and non-obstructed men (p = 0.033) and for IPP among obstructed, inconclusive and non-obstructed men (p = 0.016). For IPP, the area under ROC curve was 0.758 (95% confidence interval - 0.601 to 0.876), and the cutoff point to indicate BOO was 5 mm with 95 % sensitivity (75.1 - 99.2) and 50 % specificity (28.2 - 71.8). CONCLUSION IPP and prostatic volume measured through abdominal ultrasound are noninvasive and accessible methods that significantly correlate to urinary BOO, and are useful in the diagnosis of male urinary obstructive problems.

Male Fertility, Obesity, and Bariatric Surgery

Obesity has become a new worldwide health problem with significant impact not only on cardiovascular diseases but also on many other related disorders, highlighting infertility. Obesity may adversely affect male reproduction by endocrinologic, thermal, genetic, and sexual mechanisms. There is good evidence that obesity can be associated with reduced sperm concentrations, but studies about sperm motility, morphology, and DNA fragmentation have been less numerous and more conflicting. Although weight loss is the cornerstone of the treatment of obesity-related infertility, with promising results in restoring fertility and normal hormonal profiles, bariatric surgery impact on male fertility is still unclear and until now there is not enough data to support the informed consent in this scenario. Physicians are encouraged to highlight possible positive and/or negative impacts concerning male capacity of fertilization when informing patients. A balanced judgment and a personalized case-by-case management with patient involvement in decisions are fundamental in this setting and indication of cryopreservation of semen samples should be considered in selected circumstances. Well-structured trials controlled for confounders including female factors and based on solid outcomes (ie, birth rates) must urgently come up to clarify this emerging scenario.

Experimental animal model and RNA interference: a promising association for bladder cancer research

Animal models are at the centre of laboratory bladder cancer (BC) research and at the same time, the bridge to the clinic. A new and very promising therapeutical approach is to silence abnormally up-regulated genes in cancer, through small interfering RNA (siRNA) molecules. Therapeutic use and success of siRNAs will largely depend on their efficient and safe in vivo delivery and on avoiding accidental off-target effects. Intravesical siRNA is a strategy which may be the best deliver option to surperficial BC like intravesical immunotherapy. Its direct action might allow a continuous intracellular exposure to effective siRNA concentrations. While the procedure of transurethral siRNA administration is promising for BC research allowing detection of new targets in BC therapy, the optimal intravesical carrier and the best target(s) to siRNA are to be determined.

Sex with animals (SWA): behavioral characteristics and possible association with penile cancer. A multicenter study.

INTRODUCTION Zoophilia has been known for a long time but, underreported in the medical literature, is likely a risk factor for human urological diseases. AIM To investigate the behavioral characteristics of sex with animals (SWA) and its associations with penile cancer (PC) in a case-control study. METHODS A questionnaire about personal and sexual habits was completed in interviews of 118 PC patients and 374 controls (healthy men) recruited between 2009 and 2010 from 16 urology and oncology centers. MAIN OUTCOME MEASURES SWA rates, geographic distribution, duration, frequency, animals involved, and behavioral habits were investigated and used to estimate the odds of SWA as a PC risk factor. RESULTS SWA was reported by 171 (34.8%) subjects, 44.9% of PC patients and 31.6% of controls (P < 0.008). The mean ages at first and last SWA episode were 13.5 years (standard deviation [SD] 4.4 years) and 17.1 years (SD 5.3 years), respectively. Subjects who reported SWA also reported more venereal diseases (P < 0.001) and sex with prostitutes (P < 0.001), and were more likely to have had more than 10 lifetime sexual partners (P < 0.001) than those who did not report SWA. SWA with a group of men was reported by 29.8% of subjects and SWA alone was reported by 70.2%. Several animals were used by 62% of subjects, and 38% always used the same animal. The frequency of SWA included single (14%), weekly or more (39.5%), and monthly episodes (15%). Univariate analysis identified phimosis, penile premalignancies, smoking, nonwhite race, sex with prostitutes, and SWA as PC risk factors. Phimosis, premalignant lesions, smoking, and SWA remained as risk factors in multivariate analysis. However, SWA did not impact the clinicopathological outcomes of PC. CONCLUSION SWA is a risk factor for PC and may be associated with venereal diseases. New studies are required in other populations to test other possible nosological links with SWA.

Anti-Angiogenic Effects of the Superantigen Staphylococcal Enterotoxin B and Bacillus Calmette-Guérin Immunotherapy for Nonmuscle Invasive Bladder Cancer

PURPOSE We compared and characterized the effects of intravesical bacillus Calmette-Guérin and/or staphylococcal enterotoxin B for nonmuscle invasive bladder cancer. MATERIALS AND METHODS A total of 75 female Fisher 344 rats were anesthetized. Of the rats 15 received 0.3 ml saline (control) and 60 received 1.5 mg/kg MNU (N-methyl-n-nitrosourea) intravesically every other week for 6 weeks. The rats were divided into 5 groups. The MNU and control groups received 0.3 ml saline. The bacillus Calmette-Guérin group received 10(6) cfu bacillus Calmette-Guérin. The staphylococcal enterotoxin B group received 10 μg/ml staphylococcal enterotoxin B. The bacillus Calmette-Guérin plus staphylococcal enterotoxin B group received the 2 treatments simultaneously. Each group was treated intravesically for 6 weeks. At 15 weeks all bladders were collected for histopathological and immunological evaluation, and Western blot. RESULTS Papillary carcinoma (pTa) and high grade intraepithelial neoplasia (carcinoma in situ) were more common in the MNU group. Papillary hyperplasia was more common in the bacillus Calmette-Guérin and enterotoxin groups. Flat hyperplasia was more common in the bacillus Calmette-Guérin plus enterotoxin group. No significant toxicity was observed. The apoptosis and cellular proliferation indexes decreased in the bacillus Calmette-Guérin, enterotoxin and bacillus Calmette-Guérin plus enterotoxin groups compared to the MNU group. Intensified vascular endothelial growth factor, matrix metalloproteinase-9, Ki-67 and insulin-like growth factor receptor-1 immunoreactivity was verified in the MNU group, moderate in the bacillus Calmette-Guérin and enterotoxin groups, and weak in the bacillus Calmette-Guérin plus enterotoxin and control groups. In contrast, intense endostatin immunoreactivity was verified in the control and bacillus Calmette-Guérin plus enterotoxin groups. CONCLUSIONS Bacillus Calmette-Guérin and staphylococcal enterotoxin B showed similar anti-angiogenic effects. Bacillus Calmette-Guérin plus enterotoxin treatment had additional activity compared to that of monotherapy. It was more effective in restoring apoptosis and balancing cellular proliferation, and it correlated with increased endostatin, and decreased vascular endothelial growth factor, matrix metalloproteinase-9, Ki-67 and insulin-like growth factor receptor-1 reactivity.

Female urethral carcinoma: Evidences to origin from Skene's glands

PURPOSE Urethral carcinoma is among the rarest neoplasias of the genitourinary tract and its origin is unclear. Prostate-specific antigen (PSA) is considered an evidence of origin from Skenes glands. We considered the origin from these glands in PSA negative cases. MATERIAL AND METHODS We studied 3 patients with urethral carcinoma surgically treated. The surgical specimens were examined including cytochemical and immunohistochemical stains. The possible origin of the tumors was based on a comparative study of normal Skenes glands from autopsies and noninvolved glands in periurethral tumors. RESULTS The gross findings and the microscopic examination of 2 adenocarcinomas, including the cytochemical and immunohistochemical studies, favor an origin from Skenes glands. CONCLUSIONS The origin from Skenes glands may be established in PSA negative cases. The establishment of this origin in a higher number of urethral carcinomas may have an impact on diagnostic and treatment strategies in the future.