Introduction: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTSs) in males. Curcumin exhibits anti-inflammatory and anti-tumor properties which may be effective for BPH. This multi-arm observational study evaluated the real-world efficacy of QURMIN® (Gamma-cyclodextrin-curcumin Complex-CAVACURMIN®) as single or combination therapy for BPH. Methods: Men with moderate-severe LUTS/BPH, receiving a 6-month supplementation with QURMIN® alone or in combination with BPH-specific medication were propensity score matched with patients not taking curcumin and then divided into subgroups based on concomitant baseline treatment. Cohorts were compared in the 6-month variation of IPSS, quality of life (IPSS-QoL), Benign Prostatic Hyperplasia Impact Index (BII) and uroflowmetry parameters. Curcumin tolerability was evaluated in terms of discontinuations and adverse effects. Results: The 1:1 propensity score matching resulted in a treatment-naïve (n = 152), an alpha-blocker only (AB) (n = 138) and AB + 5-alpha reductase inhibitors (5-ARIs) (n = 78) subgroup. After 6 months, drug-naïve patients taking curcumin reported significant improvement in IPSS-storage (−3.9, p < 0.001), IPSS-voiding (−2.0, p = 0.011), IPSS-total (−5.9, p < 0.001), IPSS-QoL (−3.9, p < 0.001), BII (−2.0, p < 0.001), Qmax (+3.1 mL/s, p < 0.001), Qmean (+1.9 mL/s, p = 0.005), post-void residual volume (−7.7 mL, p < 0.001), and PSA (−0.3 ng/mL, p = 0.003), compared to controls. Patients taking ABs and curcumin showed improvement in IPSS-storage (−2.7, p < 0.001), IPSS-voiding (−1.3, p = 0.033), IPSS-total (−3.5, p < 0.001), IPSS-QoL (−1.1, p = 0.004), BII (−1.7, p = 0.006), Qmax (+1.0 mL/s, p = 0.006), and PSA (−0.2 ng/mL, p = 0.01). Patients taking curcumin and AB + 5-ARI showed improvement in IPSS-storage (−1.3, p = 0.007), IPSS-total (−1.6, p = 0.034), IPSS-QoL (−1.1, p < 0.001), and BII (−2.0, p < 0.001). No adverse reactions were reported for curcumin supplementation. Conclusion: QURMIN® (CAVACURMIN®) led to significant improvements in symptom burden, uroflow parameters, and QoL, without significant additional side effects, thus proving to be a potential new treatment for BPH, either as a single therapy or in addition to standard treatment.

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