Kaan Aydos

Effect of obesity on prostatic hyperplasia: Its relation to sex steroid levels

In 68 men with benign prostatic hyperplasia, we evaluated the association between obesity and prostatic enlargement, as well as changes in serum levels of oestradiol, testosterone, dihydroepiandrosterone and dihydroepiandrosterone sulphate. Despite the larger adenomas, no increase in the symptom score for BPH was observed with increasing obesity. Average specimen weights increased with increasing obesity and increasing host age from 46 to 80 g. We also found the serum oestradiol level significantly elevated in obese men who were 140% or over recommended weight compared to underweight men younger than 60 years (51.3 pg/ml versus 26.8 pg/ml, p<0.01). This pattern was present in all age groups.These results indicate that obesity is a risk factor for prostatic enlargement but not for obstruction. Also the degree of obesity appears to have a direct effect on oestradiol levels through transformation of androgens in adipose tissue to oestrogens. In conclusion, further studies to evaluate the pathogenesis, pathophysiology, natural history and symptomatology of BPH would be of great interest and should help to define better the associations that we have recognized.

Association of CYP1A1 and glutathione S-transferase polymorphisms with male factor infertility

OBJECTIVE To examine whether a relationship exists between genetic polymorphisms of glutathione S-transferase (GST) M1 and T1, CYP1A1(*)2C, and male factor infertility. DESIGN Genetic polymorphism analysis, case-control study. SETTING University research laboratory and andrology clinic. PATIENT(S) One hundred ten men with infertility and 105 healthy fertile men were recruited for the study. INTERVENTION(S) Physical examination of the genitalia of patients, scrotal colored Doppler ultrasound examination, and blood sampling were performed for DNA extraction and genotyping. MAIN OUTCOME MEASURE(S) CYP1A1(*)2C, GSTM1, and GSTT1 polymorphism genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism methods. Seminal parameters were analyzed. RESULT(S) There were significant differences between infertility and GSTM1, CYP1A1(*)2C genotypes by univariate analyses. A subject carrying CYP1A1 Val/Val or CYP1A1 Ile/Val in association with GSTM null genotype has 6.90 times more risk to be infertile than a subject carrying CYP1A1 Ile/Ile in association with GSTM1 wild-type genotype (odds ratio: 6.90, 95% confidence interval: 2.29-19.3). No correlation was found between the seminal parameters and the genetic variability. CONCLUSION Our results suggest that genetic polymorphisms of xenobiotic-metabolizing enzymes could play an important role in infertility.

The significance of histopathological changes of the normal tunica albuginea in Peyronie's disease

Five patients with Peyronies disease were operated and the tissue specimens from the plaque involving the tunica albuginea and from the tunica of the unaffected contralateral side were obtained. The specimens were then subjected to histopathological examination and the findings were correlated with those of men, proved not to have Peyronies disease but operated for other reasons.In the specimen of plaque, the changes varied from collagen destruction to cartilaginous and osseous metaplasia. However, in the tunica of the contralateral side the changes such as disregularity of collagen bundles extending even to wide-spread focal areas, and apperance of pale, rough, eosinophilic collagen degeneration instead of its characteristic bright birefringence, and focal mucinous degeneration were noted. Interestingly, these alterations were not observed in the specimens of normal tunica, albuginea in the control group. But the existence of minimal alterations, the regularity in the apparently normal contralateral tunica albuginea specimens in Peyronies disease implied that there was an active turnover in collagen production, and the possible factor causing collagen degeneration and so plaque formation was probably the microtraumatization of the tunica albuginea.

Assessment of DNA integrity (COMET assay) in sperm cells of boron-exposed workers

An extension of a male reproductive study conducted in a boric acid/borate production zone at Bandırma, Turkey, is presented. The relation between DNA-strand breaks (COMET assay, neutral and alkaline version) in sperm cells and previously described sperm quality parameters was investigated in boron-exposed males. A correlation between blood boron levels and mean DNA-strand breaks in sperm was weak, and DNA-strand breaks in sperm were statistically not different between control and exposed groups. Therefore, increasing boron exposures had no additional contribution in addition to already pre-existing DNA-strand breaks in the sperm cells. Weak but statistically significant correlations between DNA-strand breaks and motility/morphology parameters of sperm samples were observed in the neutral version of the COMET assay, while correlations between the same variables were statistically not significant in the alkaline version. A likely reason for these negative results, even in highly exposed humans, is that experimental exposures that had led to reproductive toxicity in animals were significantly higher than any boron exposures, which may be reached under realistic human conditions.

Is intracytoplasmic sperm injection essential for the treatment of hypogonadotrophic hypogonadism? A comparison between idiopathic and secondary hypogonadotrophic hypogonadism.

Although infertility of hypogonadotrophic aetiology is uncommon (0.5–1%), it is important as a potentially treatable cause of male infertility. Broadly, hypogonadotrophic hypogonadism (HH) is divided into two categories, idiopathic and secondary postpubertal. In order to determine whether gonadotrophin replacement is sufficient to treat hypo gonadotrophic infertile men or there is a substantial need for intracytoplasmic sperm injection to increase chances of pregnancy, we performed a retrospective clinical analysis of seventeen hypogonadotrophic adult men (aged 25–38). Five patients had orchiopexy for cryptorchidism; three prepubertal and two postpubertal. All had non-obstructive azoospermia and received a combination of human chorionic gonadotrophin (hCG) and follicle stimulating hormone (FSH) for 4–24 months. Viable sperms started to appear in the ejaculate 3 months after treatment. Natural conception was achieved in six men with secondary HH (developed after head trauma, infection and surgery). By contrast, intracytoplasmic sperm injection (ICSI) was needed to produce successful fertilisation in the eleven men with idiopathic HH after failed gonadotrophin treatment. In conclusion, we recommend that ICSI should be considered, in addition to gonadotrophins to enhance the fertility of men with IHH, once oligospermic.

Analysis of the relationship between histologic alterations and the generation of reactive oxygen species in vasectomized rat testes

OBJECTIVES To evaluate the effects of vasal obstruction on testicular structure, to determine if tissue and/or cell damage can cause significant reactive oxygen species (ROS) generation, and to correlate the histologic alterations to the measured levels of ROS products. METHODS To evaluate the effects of ROS generation in vasectomized testes, unilateral vasectomy was performed on 17 rats and tissue samples were examined by light microscopy. The histologic alterations were correlated to the measured tissue malondialdehyde levels by thiobarbituric acid analysis as an indicator of the ROS-induced tissue damage. RESULTS Unilateral vasectomy significantly affected the weights of the ipsilateral testes, but not the contralateral testes. No significant changes were noted in plasma estradiol, follicle-stimulating hormone, luteinizing hormone, and testosterone levels. The mean values of malondialdehyde were found to be significantly higher in vasectomized rats than in control rats (0.025 +/- 0.008 versus 0.018 +/- 0.007 nmol/mg protein) (P < 0.01). The malondialdehyde level was a mean of 28% lower in the contralateral testes tissue as compared to that found in ipsilateral testes (P < 0.01). Malondialdehyde output from vasectomized rats had a parallel correlation to tissue destruction. CONCLUSIONS Our results indicate that overproduction of ROS may be involved in vasectomy-induced testicular damage.

The effect of pure FSH administration in non-obstructive azoospermic men on testicular sperm retrieval

BACKGROUND In cases of azoospermia due to impaired spermatogenesis, spermatozoa can be retrieved by sperm extraction (TESE) from testicular biopsy. OBJECTIVE To evaluate the efficacy of pure follicle-stimulating hormone (pFSH) on sperm recovery, and measure the predictive value of testicular histology. STUDY DESIGN In all, 108 patients were studied. These included those with Sertoli cell-only (n=16), focal spermatogenesis (n=36), maturation arrest (n=19) and hypospermatogenesis (n=37) in previous explorative biopsies. All had normal serum FSH, LH and testosterone levels. In 63 cases, 75IU pFSH were administered, either i.m. or s.c., three times a week, for 3 months and the control group (n=45) no treatment was given. RESULTS The sperm retrieval rate was 64% (40/63 pts.) in pFSH treated men versus 33% (15/45 pts.) in controls (P<0.01). In Sertoli cell-only patients, the rate was 2/7 (28%) versus 4/9 (44%) in controls and treated men, respectively (P>0.05); and 3/8 (37%) versus 5/11 (45%) in maturation arrest (P>0.05); 6/14 (42%) versus 18/23 (78%) in hypospermatogenesis (P<0.05); and 4/16 (25%) versus 13/20 (65%) in focal spermatogenesis (P<0.01). Treatment with pFSH also improved the quantity of retrieved spermatozoa compared to control values (P<0.05). CONCLUSION pFSH treatment improves the success of TESE for non-obstructive azoospermic men with normal FSH levels.

Testicular Effects of Vasectomy in Rats: An Ultrastructural and Immunohistochemical Study

OBJECTIVES The correlation between infertility and morphofunctional alterations following vasal occlusion is not clearly understood. Although a correlation has been found between the expression of a high titer of antisperm antibodies and the status of infertility, the relationship between the immunoglobulin (Ig) depositions in the testis and ultrastructural alterations of the peritubular structures has not been clearly established. The objective of this study is to explain the etiopathogenesis of diffuse and focal testicular lesions caused by vasal obstruction. METHODS Unilateral vasectomy was performed on adult male rats. Ultrastructural changes of testicular tissues and immunostaining affinity of peritubular structures with anti-actin, anti-vimentin, anti-laminin, and anti-immunoglobulin G (anti-IgG) antibodies were analyzed. RESULTS In an ultrastructural study, vasectomized animals presented abundant collagen fibril accumulation in the peritubular area. In testis with intense IgG antibodies, staining revealed weak immunostaining of peritubular myoid cells with anti-actin antibodies, but intense immunostaining with anti-vimentin antibodies. The tubules of rats with no IgG deposition on peritubular structures revealed intense immunostaining with anti-actin antibodies but scant immunostaining with anti-vimentin antibodies. Anti-laminin deposits decreased severely in most of the tubules demonstrating intense IgG deposition. CONCLUSIONS Our findings suggest that spermatogenesis deteriorates more severely in testes with dense IgG deposition. The sclerosis of the lamina propria in cases with vasal occlusion is secondary to alterations in the peritubular myoid cells. With the progressive changes that occur in the peritubular myoid cells or differentiation of the peritubular myoid cells that acquire active cell characteristics, collagen accumulation adjacent to these cells increases markedly. The alterations of the peritubular myoid cells reported here may be caused by alterations in basement membrane structures.

Near Infrared Spectroscopy to Diagnose Experimental Testicular Torsion: Comparison With Doppler Ultrasound and Immunohistochemical Correlation of Tissue Oxygenation and Viability

PURPOSE Near infrared spectroscopy measures tissue oxygenation even when there is complete cessation of blood flow. We evaluated near infrared spectroscopy to diagnose testicular torsion and blindly compared its accuracy with that of Doppler ultrasound. We also compared it by immunohistochemical evaluation of hypoxia and cell viability. MATERIAL AND METHODS Rats were randomized to 4 groups, including group 1-720-degree unilateral torsion, group 2-360-degree unilateral torsion, group 4-sham operation and group 4-720-degree unilateral torsion followed by surgical torsion reduction at minute 180. Near infrared spectroscopy and Doppler ultrasound were done blindly at minutes 0, 5, 30, 60, 180 and 400. All torsed and contralateral testicles were excised for pathological examination using hypoxia inducible factor-α for hypoxia and the TUNEL test for apoptosis. We compared all groups with the contralateral testis and the sham operated group. RESULTS All blinded, near infrared spectroscopy measurements correctly identified the torsed testis after minute 5. Median oxygen saturation in groups 1 and 2 was significantly different compared to that in the sham operated group after minute 5. In group 4 near infrared spectroscopy detected detorsion with the loss of a significant oxygen saturation difference between the affected and the contralateral testicle after detorsion. At minute 400 median oxygen saturation in group 4 was not statistically different compared to that in the sham operated group (p = 0.09) but it was significantly different compared to that in groups 1 and 2 (p <0.001). In each torsed testis oxygen saturation was at least 18.75% lower than in the contralateral testis. In groups 1 and 2 hypoxia inducible factor-α staining in torsed testicles was significantly greater than that in the contralateral organ and the sham operated group. In group 4 hypoxia inducible factor-α staining after detorsion was significantly decreased compared to that in groups 1 and 2. There was no significant difference in the apoptotic index between the experimental and the contralateral testis or the sham operated group. CONCLUSIONS Near infrared spectroscopy is as effective but quicker than Doppler ultrasound for detecting testicular torsion without a radiologist. Near infrared spectroscopy accurately reveals oxygen saturation, which is more vital than blood flow, on which Doppler ultrasound focuses.

Clinical experience with inflatable and malleable penile implants in 104 patients

Penile prosthesis was implanted for erectile impotence of mainly organic origin in 104 patients. The AMS Dynaflex penile prosthesis was inserted in 39 cases, the AMS Malleable 600 prosthesis in 61 and the AMS Ultrex Plus prosthesis in 4. In 1 patient receiving a malleable prosthesis both rods had to be removed owing to erosion into the urethra and reimplantation was performed at the same operation. Only 1 patient who underwent implantation of the Dynaflex device had mechanical failure that necessitated surgical revision. After implantation of the new prosthesis both patients had satisfactory intercourse. One Dynaflex penile prosthesis, implanted into a juvenile-onset diabetic, became infected and required removal. Another complication was secondary to spontaneous erosion (noninfected) in 1 patient with malleable prosthesis who suffered loss of only one rod and who is still satisfied with the result. The overall complication rate in our series has been approximately 4%. The rest of the patients report satisfaction with the ability to move the penis voluntarily permitting normal sexual activities as well as normal appearance in the flaccid position. According to our experience, careful preoperative assessment from the views of both patient and device selection along with patient education, and strictly obeying the rules of sterility during implantation and applying systemic and local antimicrobial prophylaxis are essential in obtaining a successful result in prosthesis implantation for the individual patient.