Figure 1. Flowchart of the study selection process. HESr—hexanic extract of Serenoa repens. LUTS/BPH—lower urinary tract symptoms associated with benign prostate hyperplasia.

Figure 2. Histopathological findings according to Irani’s score at baseline (first prostate biopsy) and after 6 months (second prostate biopsy) [36]. The Irani score classifies prostatic inflammation on a 4-point scale based on the extension of inflammatory cells and their effect on prostate tissue. HESr—hexanic extract of Serenoa repens. Figure 3. Improvement in mean IPSS after ≥12 months of treatment with 8 mg/day of α-blocker silodosin (SIL) alone or in combination with 320 mg/day of HESr (SIL + HESr) in 186 men with LUTS/BPH [40]. HESr—hexanic extract of Serenoa repens; IPSS—International Prostate Symptom Score; SIL—silodosin. Figure 4. Improvement in mean IPSS after 6 months of HESr therapy (320 mg/day) in men without previous treatment (a) and men under treatment with α-blockers (b) [37]. Figure 5. Mechanisms of HESr action in the management of LUTS/BPH. HESr inhibitory effects (green) on different targets and shared intracellular mediators contribute to the LUTS/BPH symptom relief on multiple levels. Modified from [47,48]. TXA2-R—tromboxane A2 receptor; α1A-AR—α1A-adrenoreceptor.

Table 1. Key features of included studies investigating HESr as a combination therapy with α-blockers in the management of LUTS/BPH.

Table 1. Key features of included studies investigating HESr as a combination therapy with α-blockers in the management of LUTS/BPH.

StudyStudy DesignArms (n)Mean Age at Baseline (SD)Follow UpChange in IPSS from Baseline, Mean (SD)Change in QoL Score, Mean (SD)Change in Qmax mL/s, Mean (SD)Hizli and Uygur (2007) [38]Prospective, randomisednHESr (20)56.8 (7.8)6 mo6.1 (2.7)2.6 (0.9)3.2 (2.2)Tam (20)58.9 (5.7)6 mo4.6 (3.3)2.1 (0.8)3.7 (2.6)Tam + nHESr (20)60.2 (6.3)6 mo4.9 (2.3)2.2 (1.0)4.2 (2.5)Ryu et al. (2015) [39]Prospective, randomised, open-labelTam (53)63.4 (1.4)6 mo4.4 (0.4)2.0 (0.3)1.8 (0.2)12 mo5.5 (0.5)2.5 (0.4)2.0 (0.3)Tam + HESr (50)62.5 (1.2)6 mo4.7 (0.3)1.9 (0.2)2.0 (0.3)12 mo5.8 (0.4)2.4 (0.4)2.1 (0.3)Boeri et al. (2017) [40]Retrospective, non-randomised, cross-sectionalSil (93)57.9 (11.3)13.5 mo3.2 (0.6)0.2 (0.2)2.3 (0.4)Sil + HESr (93)55.3 (12.2)13.5 mo6.4 (0.6)1.0 (0.2)4.3 (0.5)Alcaraz et al. (2020) [41]Retrospective, non-randomised, open-labelHESr (262)64.6 (8.9)6 mo5.4 (4.6)1.3 (1.3)3.1 (4.2)Tam (263)65.4 (8.0)6 mo5.7 (4.3)1.3 (1.2)2.9 (3.8)Tam + HESr (184)65.1 (8.0)6 mo7.2 (5.0)1.8 (1.2)2.0 (2.8)Samarinas et al. (2020) [37]Post hoc, randomised, blindedControl (25)68.7 (NR)6 mo1.1 (NR)NR1.5 (NR)HESr (25)71.4 (NR)6 mo3.4 (NR)NR0.3 (NR)α-blocker (23)68.7 (NR)6 mo0.2 (NR)NR0.2 (NR)α-blocker +HESr (24)71.4 (NR)6 mo2.0 (NR)NR0.3 (NR)Alcaraz et al. (2022) [42]Retrospective, paired matchedTam + HESr (68)67.9 (7.9)6 mo6.7 (5.0)1.7 (1.2)1.6 (1.7) *Tam + 5-ARI (68)68.3 (7.3)6 mo7.7 (6.3)1.7 (1.3)2.2 (5.6) *