The review was prepared in accordance with the PRISMA 2020 reporting framework [13]. No prospective registration in PROSPERO or another systematic-review registry was undertaken. This absence of prospective registration is reported explicitly as a methodological limitation.

Information sources and search strategy

The literature search covered PubMed/MEDLINE, Embase, Scopus, and CENTRAL from database inception through May 15, 2026, without language or geographic restriction. The search combined concepts for tadalafil/PDE5 inhibition, tamsulosin/alpha-blockade, and ureteral stents/stent-related symptoms. Database-specific reproducible search syntax is provided in reference list. Reference lists of eligible articles and relevant reviews were also examined for additional randomized comparisons.

Population(P):Adult patients (Age ≥ 18 years) undergoing unilateral indwelling double-J ureteral stenting following primary endourological interventions (URS, RIRS, or PCNL).Intervention (I):Tadalafil monotherapy (5 mg or 10 mg daily) OR structured combination protocols (Tadalafil + Tamsulosin).Comparator (C):Tamsulosin monotherapy (0.4 mg daily).

Outcomes (O): The prespecified efficacy outcomes were the USSQ urinary-symptoms, body-pain, and sexual-matters domains. USSQ symptom-domain scores are interpreted such that lower scores indicate fewer or less severe stent-related problems. Because assessment schedules differed among trials, the intended principal endpoint was the latest prespecified assessment obtained while the stent remained in situ and before stent removal, provided that the corresponding arm-level summary statistics were reported. Aggarwal et al. assessed the USSQ at weeks 1 and 3, with treatment administered from week 1 until stent removal at week 3 [8]. Chauhan et al. assessed patients on days 7 and 21 [9]. Balaji et al. assessed outcomes during the stenting period [10]. Ilyas et al. administered the USSQ on days 7, 14, 21, and 28 [11]. Komisarenko et al. reported the treatment endpoint at day 14 [12].

The sexual-matters domain is not applicable to every participant. Therefore, analyses of this domain require the number of participants in each treatment arm who provided an applicable and analyzable response. Missing or inapplicable responses must remain missing and must not be coded as zero. When a primary report did not provide a domain-specific analyzable denominator, that study was not assigned an assumed denominator for quantitative pooling.

Study Design (S):Parallel-group prospective randomized controlled trials (RCTs) only.

Exclusion Criteria: Trials evaluating medical expulsive therapy without an indwelling-stent symptom outcome, non-randomized studies, single-arm studies, case series, and placebo-only comparisons without an active tamsulosin comparator were excluded from the principal comparative synthesis. Other active-drug and placebo arms in multi-arm trials were not incorporated into the direct tadalafil-versus-tamsulosin effect.

Two reviewers independently assessed eligibility and extracted study characteristics, randomized and analyzed arm sizes, intervention dose, stent duration, USSQ assessment schedule, endpoint definition, domain-level summary statistics, and adverse events.

For a multi-arm trial contributing both a tadalafil-versus-tamsulosin comparison and a tadalafil-plus-tamsulosin-versus-tamsulosin comparison, the two questions were treated as separate analyses. The tamsulosin arm was therefore not split merely because it appeared in two different analyses. Splitting or otherwise adjusting a shared comparator is required when correlated comparisons from the same control group are entered simultaneously into the same pooled effect; that circumstance did not arise in the present stratified framework [14].

For continuous outcomes, the planned effect measure was the mean difference (MD) with 95% confidence interval when studies reported the same USSQ domain scale. Endpoint scores and change-from-baseline scores were not combined indiscriminately. If a study reported a change score without its standard deviation, derivation from baseline and follow-up standard deviations would require a prespecified baseline-to-follow-up correlation according to the Cochrane Handbook [14]. Sensitivity analyses across plausible correlations (0.25, 0.50, and 0.75) were prespecified if such imputation became necessary. No correlation was retrospectively invented for a study lacking the information needed to reconstruct variance.

A pooled estimate was reported only when at least two clinically comparable trials supplied traceable arm-level means, dispersion measures, and analyzable denominators for the same outcome definition and time-point framework. Where these requirements were not met, narrative synthesis was used. This decision was made to prevent conversion of ranges or other non-equivalent summary statistics into unverified standard deviations and to avoid reproducing pooled estimates that could not be independently reconstructed.

Adverse events were extracted as reported by each trial, including treatment-arm denominator, event count, event definition, and ascertainment method when available. Relative effects were to be calculated only when sufficiently consistent event definitions and denominators were available. Double-zero studies were not assigned an automatic continuity correction because they contain no information about a relative risk. Because adverse-event definitions and ascertainment were not sufficiently standardized across the verified reports, the principal safety synthesis is descriptive rather than a pooled risk-ratio analysis.

Risk of bias was evaluated conceptually using the Cochrane RoB 2 domains: randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result [15]. Particular attention was paid to participant blinding because the USSQ is self-reported; knowledge of treatment allocation can influence reported pain, urinary symptoms, and sexual outcomes even if a separate outcome assessor is blinded. Certainty of evidence was judged by outcome using GRADE domains—risk of bias, inconsistency, indirectness, imprecision, and publication bias—and clinical importance was not inferred from statistical significance alone.

Five verifiable randomized studies directly compared tadalafil with tamsulosin for ureteral stent-related symptoms [8]-[12]. The study identification, screening, eligibility, and inclusion process is summarized in Figure 1.

Figure 1. PRISMA 2020 flow diagram of study selection.

Participant accounting

Participant accounting was performed at the relevant arm level rather than by summing total enrollment across all arms of multi-arm studies. Aggarwal et al. randomized 161 symptomatic patients to tadalafil (n = 54), tamsulosin (n = 53), or placebo (n = 54), with 52, 51, and 50 patients, respectively, represented in the reported analysis [8]. Chauhan et al. randomized 144 participants equally to tadalafil 5 mg or tamsulosin 0.4 mg [9]. Ilyas et al. randomized 50 participants equally to tadalafil 10 mg or tamsulosin 0.4 mg [11]. Komisarenko et al. randomized 279 participants to tadalafil plus tamsulosin (n = 67), tamsulosin (n = 71), tadalafil (n = 69), or placebo (n = 72) [12]. The characteristics of the included randomized studies are summarized in Table 1. Balaji et al. randomized 146 participants among placebo, solifenacin, tamsulosin, and tadalafil; only the tadalafil and tamsulosin arms were relevant to the present comparison [10].

Table 1. Characteristics of included randomized studies.

Pain/body-pain outcomes showed the most consistent direction of benefit for tadalafil. Aggarwal et al. reported greater improvement in body pain with tadalafil than with tamsulosin, while Chauhan et al. reported a significantly greater reduction in body pain with tadalafil at the later assessment [8][9]. Balaji et al. likewise concluded that tadalafil was more effective than tamsulosin for body pain [10]. Ilyas et al. reported lower pain-domain scores with tadalafil across the serial assessment framework [11]. Komisarenko et al. found improvement with both monotherapies, while the combination arm produced the greatest overall symptom relief [12]. The direction of evidence therefore favors tadalafil for pain, but a single pooled MD was not considered defensible because the reports used heterogeneous time points and did not consistently provide compatible arm-level SDs.

Urinary-symptom results were less uniform. Aggarwal et al. found tadalafil and tamsulosin comparable for urinary symptoms [8]. Chauhan et al. reported a lower later urinary index with tamsulosin [9]. Ilyas et al. reported time-dependent differences across serial assessments [11]. Komisarenko et al. reported day-14 urinary-symptom means of 20.6 ± 2.8 with tadalafil and 21.8 ± 3.6 with tamsulosin, indicating a small numerical difference between monotherapies, while the combination group had a lower score of 15.2 ± 4.3 [12]. Taken together, the evidence does not establish tadalafil as clinically superior to tamsulosin for urinary symptoms.

Sexual-matters outcomes generally favored tadalafil in the direct comparisons [8]-[11]. However, the USSQ sexual domain is not applicable to all participants, and the primary reports did not consistently provide treatment-arm denominators restricted to participants with valid, applicable responses. The direction of effect is therefore clinically suggestive, but the magnitude and precision of a pooled sexual-domain effect cannot be verified without domain-specific denominators.

Komisarenko et al. directly compared tadalafil 5 mg plus tamsulosin 0.4 mg with tamsulosin 0.4 mg alone. At day 14, the combination group had a lower urinary-symptom score than the tamsulosin group (15.2 ± 4.3 vs 21.8 ± 3.6; p = 0.0003), and body pain and analgesic requirements were also lower with combination therapy [12]. This trial supports an additive symptomatic effect. However, the second combination trial cited in the earlier manuscript was misattributed. The 2026 Zhou et al. study used tamsulosin 0.2 mg in both the combination and comparator groups [16] and therefore did not satisfy the prespecified 0.4-mg comparator criterion. Consequently, a two-study pooled combination estimate is not presented.

Safety reporting was heterogeneous. Aggarwal et al. described side effects of tadalafil and tamsulosin as minimal and reported no withdrawal because of drug adverse effects [8]. Chauhan et al. reported adverse effects in 9 tadalafil-treated and 10 tamsulosin-treated participants, including headache, dizziness, weakness, flushing, and abnormal ejaculation, with no discontinuations attributed to these events [9]. Komisarenko et al. reported that side effects were rare and did not differ statistically among treatment groups [12]. Across the evidence base, the available reports did not provide sufficiently uniform event definitions, active-versus-passive ascertainment procedures, and event-specific arm denominators to justify pooled risk ratios for retrograde ejaculation, headache, or myalgia. The defensible conclusion is therefore that no clear serious safety signal was identified in these small trials; absence of a statistically detected difference should not be interpreted as proof of no additive toxicity. Risk-of-bias considerations for the included randomized trials are summarized in Table 2.

Table 2. Risk-of-bias considerations for included randomized studies.

Urinary symptoms—Low-to-moderate certainty. Findings vary by trial and assessment time, and there is no robust evidence of tadalafil superiority.Body pain—Moderate certainty for direction of effect, but lower certainty for the exact magnitude. Multiple direct trials favor tadalafil, while heterogeneous reporting and incomplete variance data preclude a reliable pooled MD.Sexual matters—Low-to-moderate certainty. The direction generally favors tadalafil, but applicability and missing-response denominators are incompletely reported.Combination therapy—Low certainty for a pooled comparative effect under the prespecified tamsulosin 0.4-mg comparator because only one verified eligible trial contributed the direct combination comparison.Adverse events—Low certainty for comparative event rates because event definitions and ascertainment were inconsistent and events were sparse.

The pathophysiology of stent-induced body pain involves two primary mechanical drivers: localized smooth muscle hyperperistalsis/spasms along the ureter and hydrostatic urine reflux toward the kidney during micturition [1][5]. Alpha-1 adrenergic receptors are concentrated in the human distal ureter, bladder neck, and trigone [10]. Consequently, tamsulosin effectively attenuates trigonal tone and distal contraction pressure, explaining its equivalence to tadalafil in lowering USSQ storage LUTS scores [11][16]. However, because alpha-1 receptor density decreases in the proximal and mid ureter, tamsulosin fails to suppress proximal ureteral spasms or adequately dampen intra-renal hydrostatic backpressure [10].

Conversely, PDE5 enzymes are expressed across the entire length of the human ureter—encompassing proximal, mid, and distal smooth muscle layers—as well as the bladder dome and trigone [13]. By inhibiting PDE5, tadalafil prevents cGMP degradation [12]. The resulting accumulation of cGMP activates PKG, opening calcium-activated potassium channels and hyperpolarizing the smooth muscle cell membrane [12]. This continuous, pan-ureteral relaxation reduces smooth muscle spasms and enhances luminal compliance around the indwelling double-J stent [12]. Furthermore, increased ureteral compliance minimizes peak intra-renal pressure surges during voiding by facilitating low-resistance fluid flow around the stent, providing a biologically plausible explanation for the directionally favorable pain-related outcomes observed with tadalafil in several randomized comparisons. However, the available clinical data do not permit a sufficiently robust pooled estimate of the magnitude of this effect [8]-[12].

The divergence in sexual health outcomes between the two drugs is similarly governed by their pharmacodynamics [11][12]. Tamsulosin causes alpha-1 blockade at the bladder neck, inducing loss of internal urethral sphincter tone during ejaculation and resulting in retrograde ejaculation [11][12]. Tadalafil completely avoids this mechanism [12]. Instead, through upregulation of NO-cGMP signaling, tadalafil promotes arterial vasodilation and enhances pelvic, cavernosal, and prostatic tissue perfusion [12]. This preserves erectile capacity and overall sexual satisfaction during the stenting period, which is biologically consistent with the generally favorable sexual-matters outcomes observed with tadalafil in the direct randomized comparisons [8]-[11], although a reliable pooled effect size could not be calculated.

Furthermore, factorial trial models and combined comparative analyses confirm that co-administering PDE5 inhibitors with alpha-1 adrenergic antagonists provides a complementary mechanism of action [1]. By simultaneously targeting trigonal tone via alpha-blockade and pan-ureteral spasm/vascular perfusion via PDE5 inhibition, combination regimens represent an effective clinical strategy for severe or refractory stent symptoms.