Archivio Italiano di Urologia e Andrologia 2025; 97(2):13642 1 ORIGINAL PAPER dition continues to increase. According to the recent epi- demiologic studies, the incidence of urolithiasis increased from 77.78 million incident cases in 1990 to 115.55 mil- lion in 2019 (1). Highest incidence rate of kidney stones were reported in Saudi Arabia, Kuwait, South Korea, China, Thailand, Spain, Greece and the United States of America which raise concerns about the cause of kidney stone and whether it is linked to certain foods, faulty habitats and the nature of these countries (2, 3). Medical treatment of kidney stones includes life style modifica- tion, high water intake, weight reduction and exercise (4). Oral or intravenous non-steroidal anti-inflammatory drugs (NSAIDs) may be used to relieve pain. Medical Expulsive Therapy (MET) with alpha blockers has showed promising results on stone expulsion with Tamsulosin being the most commonly used of this family of drugs (5). Silodosin is a selective alpha blocker drug that works by binding to the extracellular domain of the alpha recep- tors, which inhibits activation of G protein and prevents phosphorylation of phospholipase C, giving a net result of smooth muscle relaxation (6). Silodosin is 50 times more potent and selective on alpha 1 receptors than Tamsulosin, which made most urologists and researchers believe that it might be more useful than Tamsulosin con- sidering the specifically high density of alpha 1 receptors in the lower ureter (7). Tadalafil also is a promising drug for MET that acts by inhibiting the phosphodiesterase-5 Enzyme (PDE-5) leading to accumulation of cyclic guano- sine mono phosphate and subsequent smooth muscle relaxation (8). Although the exact mechanism of Tadalafil on lower ureter relaxation is not yet fully understood, it has proven to be a considerable option for MET especial- ly in patients with erectile dysfunction (9). Natural stone passage is enabled with Tadalafil by ureter lumen dilation, whereas alpha-1 adrenergic receptor antagonists induce stone passage by reducing muscle spasms (10, 11). In this study we aimed to compare Tadalafil and Silodosin for MET in lower ureter stones below 10 mm through a comprehensive systematic review and meta-analysis and to assess the incidence of any adverse effects for each drug. Objective: This meta-analysis aims to com- pare the efficacy and safety of Tadalafil and Silodosin as Medical Expulsive Therapy (MET) for lower ureteric stones below 10mm. The study also assesses the incidence of adverse effects associated with each drug. Methods: A comprehensive search of electronic databases was conducted up to October, 2024. The study included randomized controlled trials (RCTs) and cohort studies that compared Tadalafil and Silodosin in patients with lower ureteric stones (5-10 mm). The primary outcomes assessed were stone expulsion time (SET), stone expulsion rate (SER), and adverse effects. Data were analyzed using a random-effects model for heterogeneity and a fixed-effect model for non-heterogeneity. Results: Eight studies involving 797 patients were included. The pooled analysis showed no significant difference in SET between Tadalafil and Silodosin (MD = 0.15, 95% CI [-0.28, 0.57], p = 0.50), with significant heterogeneity. Similarly, the pooled analysis showed no significant difference in SER between the two drugs (RR = 0.92, 95% CI [0.80 to 1.05], p = 0.22), with heterogeneity. However, after excluding one study, Silodosin was favored over Tadalafil for SER (RR 0.88, 95% CI [0.79 to 0.98], p = 0.02). There were no significant differences in headache, backache, or dizziness. Silodosin was associated with a higher incidence of orthostatic hypotension, but this was resolved by excluding one study. A significant difference for abnormal ejacu- lation favored Tadalafil (RR = 0.16, 95% CI [0.09 to 0.29], p = 0.01). Conclusions: While the pooled results initially showed no signifi- cant difference in SET and SER, Silodosin demonstrated a superi- or stone expulsion rate after adjusting for heterogeneity Silodosin showed a trend towards shorter SET. However, Silodosin was associated with a higher risk of orthostatic hypotension and abnormal ejaculation. Further high-quality RCTs with larger sample sizes are needed to confirm these findings. KEY WORDS: Ureter stones; Tadalafil; Silodosin; Alpha blockers; Medical Expulsive Therapy. Submitted 17 January 2025; Accepted 6 February 2025 INTRODUCTION Despite recent advances of endoscopic techniques for management of urinary stones, the prevalence of this con- Is Silodosin better than Tadalafil as a medical expulsive therapy in lower ureter stones? Mohab Alsaid Saad Abdalaziz 1 , Yousif Ahmad Hanafi 1 , Belal Mohamed Hamed 1 , Omar Fayez Abbas 1 , Khaled Omar Mahmoud Khader 2 , Mohammad kh. Alzawahreh 3 , Hesham Ghzayel 4 , Rashed Yousef Al Sharqi 5 , Zaid F. Altawallbeh 6 1 Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 2 Internship at Specialty Hospital, Jordan; 3 Urology, Department of Special Surgery, Ministry of Health, Saudi Arabia; 4 Urology and Andrology, Department of Special Surgery, Ministry of Health, Sultanate of Oman; 5 Urology Department, Al Nadeem Hospital, Ministry of Health, Jordan; 6 Internship at Al Nadeem Hospital, Madaba, Jordan. DOI: 10.4081/aiua.2025.13642 Summary