Investigation of the relationship between reproductive disorders and chromosomal abnormalities in a large-scale, single-center 10-year retrospective study.

OBJECTIVE: Chromosomal changes are an important cause of reproductive disorders. This study investigated the chromosomal changes and prevalence of pathologies in individuals admitted to our Genetic Evaluation Center over a 10-year period due to a reproductive disorder. MATERIALS & METHODS: The chromosomal findings of 4345 individuals with reproductive disorders who applied to our Genetic Evaluation Center at Akdeniz University in Antalya, Turkey between 2011 and 2021 were retrospectively evaluated. RESULTS: In this study, an abnormal karyotype was found in a total of 138 individuals (87 males and 51 females). Although the incidence of this abnormal karyotype varied among the diseases in the reproductive disorder subgroups, it was most frequently seen in azoospermia (17.0%). Of the 138 abnormalities, 75 were numerical and 54 were structural. The remaining 9 abnormalities consisted of 6 sex reversals and 3 patients with both numerical and structural anomalies. Additionally, the X chromosome was the chromosome most frequently involved in these abnormalities, being observed in 40.6% of patients. CONCLUSION: This 10-year, single-center study involved one of the largest case series in the literature to investigate the subtypes of reproductive disorders and their chromosomal relationship. Although the importance of chromosome analysis has been deemphasized, it is still recommended for use by the guidelines and, as the results of this study demonstrate, is still a highly effective method in the investigation of reproductive disorders. Furthermore, chromosome analysis of individuals diagnosed with a reproductive disorder is also very important in the practice of the increasingly utilized preimplantation genetic diagnosis (PGD).

The good, bad, and the ugly of regenerative therapies for erectile dysfunction.

Erectile dysfunction (ED) is a common condition which reduces quality of life of both patients and their partners, and is a significant health care expense every year. Although phosphodiesterase type-5 inhibitors are the current first-line treatment for men with ED, they are limited by their on-demand dosing, intolerance, and variable efficacy in complex patient populations such as men with multiple medical comorbidities or ED after pelvic surgery. Regenerative medicine has been introduced and investigated in andrology as an encouraging strategy to restore diseased erectile tissue structure and function. Novel regenerative therapies for ED are controversial but are perceived to offer a durable and safe tissue restorative approach to act as a long-term solution to this cumbersome disease process. Here, we review platelet-rich plasma, amniotic fluid membranes, low-intensity extracorporeal shockwave therapy, and stem cell therapy as regenerative strategies to treat ED. Most of these approaches have preclinical and occasionally clinical data to support their ongoing investigation; however, none of these treatments are currently supported for use in ED patients outside of clinical trials.

Prevalence of erectile dysfunction in men over 40 years of age in Turkey: Results from the Turkish Society of Andrology Male Sexual Health Study Group.

OBJECTIVE: Previous study conducted by the Turkish Society of Andrology in 1999 reported the prevalence of erectile dysfunction (ED) as 69.2% in men of ≥40 years of age, using a single-item non-validated question. This rate seemed to be higher compared to the studies reported worldwide. So, there was a need to carry out another epidemiological study by using validated questionnaires. Our aim was to investigate ED prevalence, severity, and its correlates in men aged ≥40 years using validated tools. MATERIAL AND METHODS: This cross-sectional, observational, population-based field survey was carried out in randomly selected males of ≥40 years from 19 provinces of Turkey. All participant completed a survey included with socio-demographic and socio-economic characteristics, medical and sexual history, associated physical and medical comorbidities. Erectile function was assessed by the International Index of Erectile Function (IIEF) questionnaire based on a total score of 30. The prevalence of ED, its severity and correlates in men aged ≥40 years were determined for main outcome measures. Data sets were statistically compared and p<0.05 was considered as significant. RESULTS: Median age of 2.760 males was 54.2 years. The median prevalence of ED was calculated as 33% among all males of ≥40 years of age. When subjects were stratified by age; median ED prevalence rates were 17% for 40-49 years, 35.5% for 50-59 years, 68.8% for 60-69 years, and 82.9% for ≥70 years. Among all ED men, 76.9% reported mild, 16.3% moderate, and 5.7% severe ED. At logistic regression analyses; age, diabetes, hypertension, atherosclerosis, dyslipidemia, lower urinary tract symptoms, educational status and monthly income were found to be independent risk factors for having ED. CONCLUSION: This population-based survey in Turkish men of ≥40 years of age reported the prevalence of ED as 33%. Besides, this study reported age as the main predictor for presence and severity of ED.

Penile traction therapy for Peyronie's disease-what's the evidence?

Penile traction therapy (PTT) is a new therapeutic option for men with Peyronie's disease (PD). However, it has a long history of use in other fields of medicine including bone, skin, skeletal muscle, and Dupuytren's. Mechanotransduction, or gradual expansion of tissue by traction, leads to the formation of new collagen tissue by cellular proliferation. As a molecular result, continuous extension of the fibrous plaque causes significant increases in collagenase and metalloproteinases, and, ultimately, to fibrous plaque softening and extension. This hypothetical knowledge has been supported by recent well designed experimental studies. Furthermore, several clinical papers have provided promising results on the use of PTT in PD patients. It has been shown in some series that the use of PTT significantly increases flaccid and stretched penile lengths and results in significant penile curvature improvement when compared to baseline. Furthermore, the use of PTT concomitantly with either verapamil or interferon α-2b has also been shown to be an effective therapy. Additionally, the beneficial effect of PTT on penile length before or after penile surgery in men with corporal fibrosis has been described. Finally, as a minimally invasive alternative treatment option to penile augmentation surgery in men with dysmorphophobia, PTT use has shown promising results by several experts. Studies have shown that PTT provides an acceptable, minimally invasive method that can produce effective and durable lengthening of the penis in men complaining of a small/short penis. There are, however, several criticisms related to the designs of the reported studies, such as small sample size and selection bias. Well-designed studies with larger numbers of patients and longer follow-up periods are, however, needed to establish the true benefits of PTT.

Exceptional complex chromosomal rearrangement and microdeletions at the 4q22.3q23 and 14q31.1q31.3 regions in a patient with azoospermia.

In this report we describe the first patient ever found to have azoospermia in association with both exceptional complex chromosomal rearrangements and microdeletions at two translocation breakpoints. A 36-year-old male who had been suffering from male factor infertility was admitted to our clinic. The patient also displayed mild dysmorphia. An analysis of the patient's semen revealed azoospermia. GTG banding revealed the presence of an exceptional complex chromosomal rearrangement involving chromosomes 1, 4, 10 and 14. Using subtelomeric FISH analysis, the patient's karyotype was designated as 46,XY,t(1;10)(q43q44;q21q26.1)(CEB108/T7+,D1S3738-;10PTEL006+,D10S2290+, D1S3738+), ins(14;4) (q31.3;q23q33)(D14S1420+; D4S3359+, D4S2930+). Array-CGH analysis revealed two microdeletions at the 4q22.3q23 and 14q31.1q31.3 chromosomal regions. We suggest that microdeletions at the 4q22.3q23 and 14q31.1q31.3 chromosomal regions associated with both an exceptional complex chromosomal rearrangement and the Homo sapiens chromosome 4 open reading frame 37 (C4orf37) gene located at the 4q22.3q23 region might be associated with male factor infertility.

The impact of diabetes mellitus on penile length in men undergoing inflatable penile prosthesis implantation.

OBJECTIVE: To evaluate the changing cavernosal length of patients with diabetes mellitus (DM) and organic erectile dysfunction (ED) who were treated with inflatable, three-piece penile prostheses, a current surgical treatment option in our clinic, over the course of 12 years. MATERIALS AND METHODS: Between April 2000 and December 2012, we retrospectively investigated data from patients who were diagnosed with organic ED and undergone penile prosthesis implantation (PPI). Of the 239 patients, 235 of them were included in the study. Four patients who were operated on for trans-sexuality were excluded from the study. All patients were divided into two groups as those with (Group 1) or without DM (Group 2). Data, including age, body mass index (BMI) in kg/m(2), surgical history, comorbidities, International Index of Erectile Function (IIEF) questionnaire scores, combined intracavernous injection and stimulation (CIS) test results, length of corpus cavernosum while implanting the penile prosthesis, complications, operative times, mean hospital stay, and satisfaction of the patient and partner, were recorded. Kruskal-Wallis and Mann-Whitney U tests were used for statistical analysis. A p-value of <0.05 was considered to be statistically signifcant. RESULTS: The mean age was 57.9±10.5 years. Study population consisted of patients with DM (n=65), hypertension (n=21), DM, and hypertension (n=28), hyperlipidemia (n=5), a history of previous radical pelvic surgery with (n=4) or without DM (n=51) or cases without any comorbidity (n=62). Mean length of the corpus cavernosum was 17.277±0.1509 cm in Group 1 and 17289±0.1598 cm in Group 2 (p<0.05). Additionally, the other parameters, including age, operative time, and the satisfaction of the patient and partner, were not different between these groups (p>0.05). CONCLUSION: The length of the corpus cavernosum and the destruction of cavernosal tissues do not depend only on DM. We conclude that these features may have multifactorial causes.

Evaluation of reproductive functions in male adolescents following renal transplantation.

The aim of this study was to analyze the semen variables and hormone profiles in kidney transplanted male adolescents. Eight post-pubertal male patients who underwent successful renal tx during the peripubertal period and who had ESRD during childhood were enrolled in the study. Patients who underwent tx before 14 yr old (group I) and patients who underwent tx after 14 yr old (group II) were evaluated separately. Semen was collected and analyzed. Serum levels of LH, FSH, and testosterone were measured and found to be normal in all patients except one. The mean age at the diagnosis of CKD was six yr and 13 yr in groups I and II, respectively. The mean age at the time of tx was 12 yr in the first and 17.8 yr in the second group. The patients in group I had received prednisone, cyclosporine A and azathioprine with a longer duration of time compared with patients in group II. Sperm counts (15.5 +/- 15.7 vs. 82.3 +/- 64.2 millions/mL) and sperm motilities (37.8 +/- 30.9 vs. 57.8 +/- 22.1%) were lower in group I than group II. Only one patient in group II had normal sperm parameters and azospermia was observed in one patient from group I. We conclude that the earlier onset and the longer duration of uremia, the more impairment of reproductive function. Also, it seems that duration of exposure to corticosteroids or cyclosporine combined with azathioprine contribute to sperm dysfunction in peripubertal transplanted boys.

Hypogonadism and erectile dysfunction: an overview.

In humans androgen decline is presented as a clinical picture which includes decreased sexual interest, diminished erectile capacity, delayed or absent orgasms and reduced sexual pleasure. Additionally, changes in mood, diminished well being, fatigue, depression and irritability are also associated with androgen insufficiency. The critical role of androgens on the development, growth, and maintenance of the penis has been widely accepted. Although, the exact effect of androgens on erectile physiology still remains undetermined, recent experimental studies have broaden our understanding about the relationship between androgens and erectile function. Preclinical studies showed that androgen deprivation leads to penile tissue atrophy and alterations in the nerve structures of the penis. Furthermore, androgen deprivation caused to accumulation of fat containing cells and decreased protein expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS), and phosphodiesterase type-5 (PDE-5), which play crucial role in normal erectile physiology. On the light of the recent literature, we aimed to present the direct effect of androgens on the structures, development and maintenance of penile tissue and erectile physiology as well. Furthermore, according to the clinical studies we conclude the aetiology, pathophysiology, prevalence, diagnosis and treatment options of hypogonadism in aging men.

Differential PTEN protein expression profiles in superficial versus invasive bladder cancers.

INTRODUCTION: The prognostic significance of PTEN protein loss in bladder cancer is not well established. The objective of this study was to investigate the PTEN expression profile in superficial noninvasive papillary transitional cell carcinoma (TCC) versus invasive TCC and compared the results with pathological and clinical parameters. MATERIALS AND METHODS: Bladder tumor samples were obtained from 29 patients who underwent surgery for superficial (n=11) and invasive (n=18) bladder cancers at the Akdeniz University Hospital. The patient profile including sex, age, histological grade and the stage, presence of carcinoma in situ, cystoscopy findings (tumor size, location, multiplicity) were obtained by examining the patients' medical records. No patient received anticancer agents prior to the operation. Western blotting was performed using bladder carcinoma samples in order to determine the level of PTEN protein expression for each patient. RESULTS: Only 4 (13.7%) patients with bladder carcinoma manifested a decrease in the level of PTEN expression. Regarding the correlation between tumor stage and the PTEN expression, with the exception of patient 23 all patients who displayed a reduction in PTEN expression had muscle-invasive TCC. CONCLUSION: Future studies with a clinical follow-up will be needed to determine if those superficial tumors with decreased PTEN expression are going to progress to a later stage. Based on our results PTEN by itself does not seem to be a good candidate as an independent marker to predict the behavior of bladder cancers.

The potential role of advanced glycation end product and iNOS in chronic renal failure-related testicular dysfunction. An experimental study.

OBJECTIVES: To investigate the impact of advanced glycation end products (AGEs) and inducible nitric oxide synthase (iNOS) in chronic renal failure (CRF)-associated testicular dysfunction in an experimental model. In additionally, we examined whether different peritoneal dialysis (PD) fluids could contribute to the elevation in AGE level and iNOS expression in the testes. METHODS: Adult male Wistar rats, 10 and 12 weeks of age and weighing 200-330 g, were divided into 5 groups. Group 1 served as the control group. In group 2, CRF was induced and a peritoneal catheter was implanted, but the dialysis procedure was not performed until the end of the study. In group 3, CRF was induced and PD was performed with dialysis fluids containing 1.36% glucose and icodextrin. In group 4, CRF rats received dialysis fluids containing 3.86% glucose and icodextrin. Finally, an indwelling catheter was implanted and the dialysis procedure was performed using dialysis fluids containing 3.86% glucose and icodextrin (group 5). Chronic PD began 4 weeks after insertion of the catheter. Each morning, this fluid was drained and 20 ml dialysis fluid, containing either 1.36 or 3.86% glucose, was given intraperitoneally for 4 h in unanesthetized animals. Each evening, 20 ml icodextrin was given for 10 h. The dialysis procedure was performed for 8 weeks. The AGE level was determined from the 5-hydroxymethyl-2-furaldehyde (5-HMF) content of penis samples and iNOS expression was assessed by immunohistochemistry. RESULTS: The elevation of 5-HMF was significant in the testes from groups 2, 3, 4, and 5 when compared with group 1. Furthermore, the differences between groups 2 and 4, 3 and 4, and 4 and 5 were also significant (p < 0.05). Immunohistochemical analysis revealed the presence of iNOS predominantly in the Leydig cells. While iNOS staining was significantly lower in group 1 than in other groups, there were also significant differences between groups 2 and 3, 2 and 4, 2 and 5, 3 and 5, and 4 and 5 (p < 0.05). Finally, a significant statistical correlation was found between the 5-HMF and iNOS levels (r = 0.698, p = 0.001). CONCLUSIONS: The present study identifies, for the first time, a potential role of AGE and iNOS in experimental CRF-associated testicular dysfunction. In addition, we found that PD fluids containing glucose contribute to this effect. These results may lead to a better understanding of the pathophysiological pathway in CRF-related testicular dysfunction.