Stesura Seveso Archivio Italiano di Urologia e Andrologia 2024; 96(4):12756 1 ORIGINAL PAPER INTRODUCTION Erectile dysfunction (ED) is an inability to provide ade- quate erection to initiate or maintain any sexual activity (1). ED prevalence in adult males is approximately 20% (2). Previous studies had shown that the neutrophils/lym- phocytes (NLR) and platelets/lymphocytes (PLR) ratios could be used as markers of inflammatory load as well as prognostic factors in several medical conditions (3-4). The common pathophysiological conditions underlying ED, CVD and other vascular diseases included inflamma- tion, atherosclerosis and endothelial dysfunction (5). The NLR and PLR were known to be potential markers of inflammation in vascular diseases and inflammation play a critical role in the initiation and development of vascu- lar endothelial dysfunction and atherosclerosis (6). Neutrophils produce and secrete several inflammatory mediators including myeloperoxidase (MPO) and reactive oxygen species (ROS) which can be responsible of myocar- dial and non-myocardial tissue damages (7). Additionally, platelets release numerous inflammatory mediators that modify leukocyte and endothelial respons- es via different inflammatory stimuli (8). A modern study had revealed that NLR and PLR had been proposed as biomarkers of subclinical inflammation and many studies had investigated these ratios (9). A previous study had demonstrated that onset and severity of ED had been attributed to increased levels of inflammatory bio- markers (10). In the same context, NLR and PLR were used as signs of inflammation together with a significant relationship between development of ED and these inflammatory markers (11). Previous studies reported a chronic effect of sildenafil and tadalafil on endothelial function and pro-inflammatory markers (12). Das (2007) stated that different cohorts of ED patients were associat- Background: Previous studies had shown that the neutrophils/lymphocytes (NLR) and platelets/lymphocytes (PLR) ratios could be used as markers of inflammatory load as well as prognostic factors in several med- ical conditions. The current study aimed to compare between the effect of using daily tadalafil 5 mg/day versus daily sildenafil 25 mg/day in improving erectile function as well as their ability to reduce NLR and PLR. Methods: One hundred and four participants were recruited. Seventy-four randomized patients with erectile dysfunction were equally divided into 2 groups. Patients in group A used daily tadalafil 5 mg for 2 months while patients in group B used daily sildenafil 25 mg for 2 months. Patients were collected from June 2022 to June 2023. Thirty healthy individuals served as con- trols. All patients and controls were evaluated using the validat- ed Arabic version of the international index of erectile function (ArIIEF-5) at baseline and after 2 months of medical treatment. Five cc of venous blood sample was obtained before and after 2 months of medical treatment to compare the effect of phospho- diestrase type 5 inhibitors (PDE-5Is) intake for erectile dysfunc- tion on PLR and NLR before and after treatment. Results: The current study showed that there were no statistical- ly significant differences between the cases and the controls apart from the ArIIEF-5 scores. Moreover, there was no signifi- cant difference between patients in group A and those in group B regarding PLR and NLR post administration of PDE-5Is. Interestingly, patients in group A demonstrated a highly signifi- cant difference between the ArIIEF-5 scores as well as the PLR and the NLR before and 2 months after administration of daily tadalafil 5 mg. On the other hand, patients in group B who were administrated daily sildenafil 25 mg for 2 months demonstrated only a highly significant difference between the ArIIEF-5 scores before and after administration. Meanwhile, patients in group B did not reveal any statistically significant difference in the PLR and the NLR before and 2 months after administration of silde- nafil 25 mg. Further regression analysis after adjustment of dif- ferent variables of the study showed a significant correlation between ArIIEF-5 and PLR in patients who received daily tadalafil 5 mg (r = 0.430, p = 0.004). Conclusions: Tadalafil and sildenafil have similar clinical effica- cy in treating erectile dysfunction. However, tadalafil is more effective in lowering PLR and NLR compared to sildenafil. Evaluation of the effect of daily tadalafil 5 mg versus daily sildenafil 25 mg on neutrophil-lymphocyte and platelet-lymphocyte ratios in patients with erectile dysfunction: A comparative randomized controlled study Abdel Rahman Bakry 1, Ali Mohamed Mahran 1, Hisham Diab Gaber 1, Mohamed Ismail Sedek 2, Sameh Fayek GamalEl Din 3, Ahmad Tarek Motawi 3, Mohamed Diab Mohamed 1, Ahmed Elshebany 1 1 Department of Andrology & STDs, Faculty of Medicine, Assiut University, Assiut, Egypt; 2 Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt; 3 Department of Andrology & STDs Kasr Alainy Faculty of Medicine, Cairo University, Giza, Egypt. DOI: 10.4081/aiua.2024.12756 Summary KEY WORDS: Erectile dysfunction; neutrophils/lymphocytes (NLR); platelets/lymphocytes (PLR); tadalafil; sildenafil. Submitted 27 June 2024; Accepted 9 July 2024 Archivio Italiano di Urologia e Andrologia 2024; 96(4):12756 A. Rahman Bakry, A. Mohamed Mahran, H. Diab Gaber, et al. 2 ed with increased levels of inflammatory markers as well as the significant ability of oral phosphodiesterase-5 inhibitors (PDE-5Is) to decrease these markers (13). The current study aimed to compare between the effect of using daily tadalafil 5 mg/day versus daily sildenafil 25 mg/day in improving erectile function as well as their ability to reduce NLR and PLR. PATIENTS AND METHODS One hundred and four participants with erectile dysfunc- tion (ED) were recruited. Seventy-four randomized patients were equally divided into 2 groups. Thirty healthy individuals served as controls. Patients in group A used daily tadalafil 5 mg for 2 months while patients in group B used daily sildenafil 25 mg for 2 months. Patients were collected from the andrology outpatient clinic, Assiut University Hospital from June 2022 to June 2023. The institutional review board approved the study (17101846) that conforms to Helsiniki declaration 2013 (14). All Patients signed a written informed consent after explaining the steps and the aim of the study. They were randomized by simple numbering method. Inclusion criteria of the patients Any male patient aged 25 to 60 years in a stable relation- ship and suffering from ED was included. Exclusion criteria of the patients Patients who suffered from severe uncontrolled medical conditions, patients under treatment with sublingual nitrate, patients with blood diseases that affect sexual function and patients using cytotoxic drugs or immuno- suppressive drugs were excluded. Also, patients without partners were excluded. Inclusion criteria of the controls They were age matched potent controls who attended the outpatient clinic for fertility checkup. All participants were subjected to the following steps. Medical as well as sexual and surgical histories were obtained. General and local examinations were done. All patients and controls were evaluated using the validated Arabic version of the international index of erectile function (ArIIEF-5) at baseline and after 2 months of medical treat- ment (15). Five cc of venous blood sample was obtained before and after 2 months of medical treatment by using sterile 5 ml syringe then the sample poured into EDTA vacuum tube. Then gentle mixing was performed to obtain complete blood count using CELL-DYN haematology ana- lyzer device to compare the effect of PDE-5Is intake for ED on PLR and NLR before and after treatment. Patients in group A received daily tadalafil 5 mg while patients in group B received daily sildenafil 25 mg for 2 months. Statistical analysis Data were fed to the computer and analyzed using IBM SPSS software package version 20.0 (Armonk, NY: IBM Corp). Qualitative data were described using number and percent. The Kolmogorov-Smirnov test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, standard deviation, median and inter-quartile range (IQR). Chi-square test was used for categorical variables, to com- pare between different groups. Student t-test was used for normally distributed quantitative variables and to com- pare between two studied groups. Paired t-test was used for normally distributed quantitative variables and to com- pare between two repeated measures. Mann-Whitney test was used for nonparametric quantitative variables and to compare between two studied groups. Wilcoxon test was used for nonparametric quantitative variables and to com- pare between two repeated measures. Significance of the obtained results was judged at the 5% level. RESULTS Table 1 showed that there were no statistically significant differences between the cases and the controls apart from the ArIIEF-5 scores. Furthermore, the current study revealed that there was no statistically significant differ- ence between patients in group A and those in group B regarding the ArIIEF-5 prior to administration of PDE5- Is (Table 2). Also, the current study demonstrated that there were no statistically significant differences between patients in group A and those in group B regarding PLR and NLR prior to administration of PDE5-Is (Table 2). Conversely, there was no statistically significant differ- ence between patients in group A and those in group B regarding the ArIIEF-5 after intake of PDE5-Is (Table 3). Table 2. ArIIEF-5 and NLR and PLR among studied cases before intervention. Group A - Tadalafil Group B - Sildenafil P (n = 37) (n = 37) ArIIEF-5 Range 5-20 5-19 0.507 Median (IQR) 9 (7-15) 8 (6-15) Erectile dysfunction N % N % No 0 0 0 0 0.741 Mild 7 18.9 7 18.9 Moderate 17 45.9 14 37.8 Severe 13 35.1 16 43.2 PLR Range 45.6-185 60-194 0.296 Mean ± SD 126.25 ± 36.04 117.33 ± 36.91 NLR Range 0.48-3.9 0.56-4.3 0.384 Median (IQR) 2.1 (1-3.2) 1.8 (0.8-3.1) ArIIEF5 = the validated Arabic version of the international index of erectile function; PLR = platelets/lymphocyte ratio; NLR = neutrophils/lymphocyte ratio. Table 1. Socio-demographic data of the participants. Tadalafil Sildenafil Controls P-value Mean SD Mean SD Mean SD Age 44.2 ± 6.9 45.7 ± 6.1 45.1 6.5 0.602 ArIIEF5 before 10.8 ± 4.7 10.2 ± 4.8 23.9 ± 0.9 0.000 PLR before 126.3 ± 36 117.3 ± 36.9 110 ± 46.9 0.206 NLR before 2.2 ± 1.17 2 ± 1.19 1.9 ± 1.4 0.686 ArIIEF5 = the validated Arabic version of the international index of erectile function; PLR = platelets/lymphocyte ratio; NLR = neutrophils/lymphocyte ratio. Archivio Italiano di Urologia e Andrologia 2024; 96(4):12756 3 Evaluation of the effect of daily tadalafil 5 mg versus daily sildenafil 25 mg on neutrophil-lymphocyte and platelet-lymphocyte ratios... Moreover, there was no significant difference between patients in group A and those in group B regarding PLR and NLR post administration of PDE5-Is (Table 3). Interestingly, patients in group A demonstrated a highly significant difference between the ArIIEF-5 scores as well as the PLR and the NLR before and 2 months after admin- istration of daily tadalafil 5 mg (Table 4). On the other hand, patients in group B who were admin- istrated daily sildenafil 25 mg for 2 months demonstrat- ed only a highly significant difference between the ArIIEF-5 scores before and after administration (Table 5). Meanwhile, patients in group B did not reveal any statis- tically significant difference in the PLR and the NLR before and 2 months after administration of sildenafil 25 mg (Table 5). Further regression analysis after adjustment of different variables of the study showed a significant correlation between ArIIEF-5 and PLR in patients in group A who received daily tadalafil 5 mg (r = 0.430, p = 0.004) (Table 6). It should be mentioned that no other correlation was observed (Table 6). DISCUSSION The current study demonstrated that baseline PLR and NLR were higher in the patients compared to the con- trols. However, they did not show any significant differ- ence. Consistently, Demirci and Ozgur (2019) found that the median NLR level and PLR level were higher when compared to controls in mild-moderate ED and severe ED groups (16). Similarly, Aslan et al. (2019) found that NLR was higher in the patients compared to the controls (17) and that it also predicted ED and it might be helpful in diagnosing ED (17). Zhang et al. (2022) reported that NLR and PLR were significantly higher in ED patients compared with healthy controls (18) and Ventimiglia et al. (2018) determined that NLR was 3 times higher in severe ED patients and that they were independent predictors (19). A modern retrospective study conducted by Akbaş et al. (2016) showed that the PLR value increased pro- portionately with the severity of ED (20). Our study did not show any statistically significant differ- ence between the studied groups regarding PLR and NLR post-intervention. Kilic et al. (2023) reported that there was no significant difference in NLR or PLR between ED patients who did not respond to PDE5I treatment and controls who responded to treatment (21) and that there was a highly significant difference between ArIIEF-5 scores before and after intervention in the studied groups who received daily tadalafil 5 mg and daily sildenafil 25 mg. Similarly, Gong et al. (2017) revealed that sildenafil and tadalafil had equivalent abilities to improve IIEF Table 3. ArIIEF-5 and NLR and PLR among studied cases post intervention. Group A - Tadalafil Group B - Sildenafil P (n = 37) (n = 37) ArIIEF-5 Range 5-24 5-24 0.102 Median (IQR) 20 (17-22) 18 (10-22) Erectile dysfunction N % N % No 17 45.9 11 29.7 0.323 Mild 12 32.4 11 29.7 Moderate 4 10.8 7 18.9 Severe 4 10.8 8 21.6 PLR Range 31.6-148 43.8-182.5 0.197 Mean ± SD 99.73 ± 24 108.58 ± 33.69 NLR Range 0.38-3.52 0.56-4.5 0.523 Median (IQR) 1.1 (1-1.4) 1.1 (0.7-1.9) ArIIEF5 = the validated Arabic version of the international index of erectile function; PLR = platelets/lymphocyte ratio; NLR = neutrophils/lymphocyte ratio; IQR: Interquartile range. Table 4. ArIIEF-5 and NLR and PLR pre and post-intervention in group A. Group A who received Pre-intervention Post-intervention P tadalafil 5 mg (n = 37) (n = 37) ArIIEF-5 Range 5-20 5-24 < 0.001* Median (IQR) 9 (7-15) 20 (17-22) Erectile dysfunction N % N % No 0 0 17 45.9 < 0.001* Mild 7 18.9 12 32.4 Moderate 17 45.9 4 10.8 Severe 13 35.1 4 10.8 PLR Range 45.6-185 31.6-148 < 0.001* Mean ± SD 126.25 ± 36.04 99.73 ± 24 NLR Range 0.48-3.9 0.38-3.52 < 0.001* Median (IQR) 2.1 (1-3.2) 1.1 (1-1.4) ArIIEF5 = the validated Arabic version of the international index of erectile function; PLR = platelets/lymphocyte ratio; NLR = neutrophils/lymphocyte ratio; IQR: Interquartile range. Table 5. ArIIEF-5 and PLR and NLR pre and post-intervention in group B. Group B who received Pre-intervention Post-intervention P tadalafil 25 mg (n = 37) (n = 37) ArIIEF-5 Range 5-19 5-24 < 0.001* Median (IQR) 8 (6-15) 18 (10-22) Erectile dysfunction N % N % No 0 0 11 29.7 < 0.001* Mild 7 18.9 11 29.7 Moderate 14 37.8 7 18.9 Severe 16 43.2 8 21.6 PLR Range 60-194 43.8-182.5 0.229 Mean ± SD 117.33 ± 36.91 108.58 ± 33.69 NLR Range 0.56-4.3 0.56-4.5 0.368 Median (IQR) 1.8 (0.8-3.1) 1.1 (0.7-1.9) ArIIEF5 = the validated Arabic version of the international index of erectile function; PLR = platelets/lymphocyte ratio; NLR = neutrophils/lymphocyte ratio; IQR: Interquartile range. Table 6. PLR and NLR and smoking in both groups and tadalafil and sildenafil post intervention. ArIIEF-5 PLR NLR Smoking Tadalafil Pearson correlation 0.430 0.029 0.072 P value 0.004 0.433 0.336 Sildenafil Pearson correlation 0.168 -0.066 - 0.061 P value 0.161 0.349 0.360 ArIIEF5 = the validated Arabic version of the international index of erectile function; PLR = platelets/lymphocyte ratio. Archivio Italiano di Urologia e Andrologia 2024; 96(4):12756 A. Rahman Bakry, A. Mohamed Mahran, H. Diab Gaber, et al. 4 scores (22). However, Rubio-Aurioles et al. (2012) revealed that the time concerns domain score of the Psychological and Interpersonal Relationship Scales (PAIRS) was signifi- cantly lower for daily tadalafil 5 mg compared with silde- nafil on demand treatment (23) showing that tadalafil improves sexual confidence more efficiently than silde- nafil (23). Interestingly, our patients in group A who received daily tadalafil 5 mg for 2 months showed a high statistically sig- nificant difference between pre and post-intervention PLR and NLR. Meanwhile, patients in group B who received daily sildenafil 25 mg for 2 months did not show any statistically significant difference between pre and post-intervention PLR and NLR. Consistently, La Vignera et al. (2014) showed that tadalafil has a preventive effect on both endothelial apoptosis and excessive platelet adhesion in ED patients (24). Furthermore, a recent Egyptian study demonstrated that daily tadalafil 5 mg supplementation lowers these markers with significant improvement in the erectile function (25). The superior- ity of tadalafil versus sildenafil in lowering PLR and NLR in the current study might be explained by the shorter half-life of sildenafil but no available data support this hypothesis that needs further investigations. Although tadalafil and sildenafil showed significant improvement in improving the ArIIEF-5 scores, yet, tadalafil was superior to sildenafil in lowering the studied inflammatory markers. A previous systematic review con- ducted by Mirone et al. (2008) stated that tadalafil was pre- ferred by the patients compared to sildenafil for several reasons (26). Firstly, patients preferred tadalafil owing to its flexibility (27). Secondly, tadalafil was also preferred owing to its better tolerance (28). Finally, tadalafil was preferred by the patients for its higher efficacy (28-29). To the best of our knowledge, the current study is one of the first to demonstrate higher efficacy of tadalafil compared to sildenafil in lowering NLR and PLR. However, there were several limitations of the current study that should be acknowledged. The sample size was relatively small and the patients were followed up for short duration. CONCLUSIONS Tadalafil and sildenafil have similar clinical efficacy in treating ED. However, tadalafil is more effective in lower- ing PLR and NLR compared to sildenafil. Future studies are required to replicate this finding as it may add supe- riority to tadalafil compared to sildenafil. REFERENCES 1. Impotence NIH Consensus Development Panel on Impotence. JAMA1993; 270:83-90. 2. Burnett AL. Evaluation and management of erectile dysfunction. In Kavoussi LR, Novick AC, Partin AW, & Peters Içinde CA (Eds.), Campell-Walsh Urology. Philadelphia, PA: Elsevier. 2012; pp. 721- 748. 3. Bhat T, Teli S, Rijal J, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther. 2013; 11:55-9. 4. Feng JR, Qiu X, Wang F, et al. Diagnostic Value of Neutrophil-to- Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Crohn's Disease. Gastroenterol Res Pract. 2017; 2017:3526460. 5. Zhang Y, Feng X, Wu X, et al. A systematic review and meta- analysis of the relationship between erectile dysfunction and the neu- trophil-to-lymphocyte and platelet-to-lymphocyte ratios. Andrologia. 2022; 54:e14337. 6. Liao Z, Tang Y, Li X, Li D. The relationship between hematologic parameters and erectile dysfunction. Sex Med. 2021; 9:100401. 7. Winterbourn CC, Kettle AJ, Hampton MB. Reactive Oxygen Species and Neutrophil Function. Annu Rev Biochem. 2016; 85:765-92. 8. Thomas MR, Storey RF. The role of platelets in inflammation. Thromb Haemost. 2015; 114:449-58. 9. Karabakan M, Bozkurt A. Relationship Between Erectile Dysfunction, the Neutrophil-to-Lymphocyte Ratio, and the Platelet- to-Lymphocyte Ratio. J Acad Res Med. 2019; 9:27-31. 10. Furuncuoğlu Y, Tulgar S, Dogan AN, et al. How obesity affects the neutrophil/lymphocyte and platelet/lymphocyte ratio, systemic immune-inflammatory index and platelet indices: a retrospective study. Eur Rev Med Pharmacol Sci. 2016; 20:1300-6. 11. Diniz LR, de Lima SG, de Amorim Garcia JM and de Oliveira Diniz KL. Neutrophil to Lymphocyte Ratio as a Prognostic Predictor in Older People With Acute Coronary Syndrome. Angiology. 2019; 70:264-71. 12. Santi D, Giannetta E, Isidori AM, et al. Therapy of endocrine dis- ease: effects of chronic use of phosphodiesterase inhibitors on endothelial markers in type 2 diabetes mellitus: a meta-analysis. Eur J Endocrinol. 2015; 172:R103-14. 13. Das UN. Is erectile dysfunction a low-grade systemic inflamma- tory condition? Eur Heart J. 2007; 28:642-3. 14. World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 2013; 310: 2191-2194. 15. Shamloul R, Ghanem H, Abou-Zeid A. Validity of the Arabic ver- sion of the sexual health inventory for men among Egyptians. Int J Impot Res. 2004; 16:452-5. 16. Demirci A, Ozgur BC. The effect of using tadalafil 5 mg/day on neutrophil-lymphocyte and platelet-lymphocyte ratios in mild-medi- um and severe erectile dysfunction patients; and comparison of clin- ical response. Andrologia. 2019; 51:e13347. 17. Aslan A, Kaya Y, Cirakoglu A, et al. Neutrophil-Lymphocyte Ratio Could Be a Marker for Erectile Dysfunction. Urol J. 2019; 16:216-20. 18. Zhang Y, Feng X, Wu X, et al. A systematic review and meta- analysis of the relationship between erectile dysfunction and the neu- trophil-to-lymphocyte and platelet-to-lymphocyte ratios. Andrologia. 2022; 54:e14337. 19. Ventimiglia E, Cazzaniga W, Pederzoli F, et al. The role of neu- trophil-to-lymphocyte ratio in men with erectile dysfunction—pre- liminary findings of a real-life cross-sectional study. Andrology. 2018; 6:559-63. 20. Akbas A, Gulpınar MT, Sancak EB, et al. The relationship between platelet-lymphocyte ratio and severity of erectile dysfunc- tion. Kaohsiung J Med Sci. 2016; 32:91-5. 21. Kilic M, Erkan A, Zengin S, et al. Inflammatory biomarkers may predict response to phosphodiesterase type 5 inhibitor treatment in patients with erectile dysfunction. Investig Clin Urol. 2023; 64:404-411. 22. Gong B, Ma M, Xie W, et al. Direct comparison of tadalafil with Archivio Italiano di Urologia e Andrologia 2024; 96(4):12756 5 Evaluation of the effect of daily tadalafil 5 mg versus daily sildenafil 25 mg on neutrophil-lymphocyte and platelet-lymphocyte ratios... sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis. Int Urol Nephrol. 2017; 49:1731-40. 23. Rubio-Aurioles E, Porst H, Kim ED, et al. A randomized open- label trial with a crossover comparison of sexual self-confidence and other treatment outcomes following tadalafil once a day vs. tadalafil or sildenafil on-demand in men with erectile dysfunction. J Sex Med. 2012; 9:1418-29. 24. La Vignera S, Condorelli RA, Burgio G, et al. Functional charac- terization of platelets in patients with arterial erectile dysfunction. Andrology. 2014; 2:709-15. 25. GamalEl Din SF, Nabil Ismail N, Moawad HH, et al. Evaluation of tadalafil supplementation on the neutrophil/lymphocyte and the platelet/lymphocyte ratios in patients with erectile dysfunction: A prospective study. Urologia. 2024; 91:598-603. 26. Mirone V, Fusco F, Rossi A, et al. Tadalafil and vardenafil vs sildenafil: a review of patient-preference studies. BJU Int. 2009; 103:1212-7. 27. Von Keitz A, Rajfer J, Segal S, et al. A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil. Eur Urol 2004; 45:499-509 28. Eardley I, Montorsi F, Jackson G, et al. Factors associated with preference for sildenafil citrate and tadalafil for treating erectile dys- function in men naive to phosphodiesterase 5 inhibitor therapy: post hoc analysis of data from a multicentre, randomized, open-label, crossover study. BJU Int 2007; 100:122-9. 29. Eardley I, Mirone V, Montorsi F, et al. An open-label, multicen- tre, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in men naïve to phosphodi- esterase 5 inhibitor therapy. Sex Med 2005; 96:1323-32. 30. Rodriguez Tolra JR, Cuadrado Campaña JM, Fumadó Ciutat L, Franco Miranda E. Prospective, randomized, open-label, fixed dose, crossover study to establish preference of patients with erectile dysfunc- tion after taking the three PDE-5 inhibitors. J Sex Med 2006; 3:901-9. Correspondence Abdel Rahman Bakry, MD Ali Mohamed Mahran, MD Hisham Diab Gaber, MD Mohamed Diab Mohamed, MSc Ahmed Elshebany, MD Department of Andrology & STDs, Faculty of Medicine, Assiut University, Assiut, Egypt Mohamed Ismail Sedek, MD Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt Ahmad Tarek Motawi, MD Sameh Fayek GamalEl Din, MD (Corresponding Author) samehfayek@kasralainy.edu.eg Department of Andrology & STDs Kasr Al-Ainy, Faculty of Medicine Cairo University, Al-Saray Street, El Manial, Cairo, 11956, Egypt Conflict of interest: The authors declare no potential conflict of interest.