Efficacy and safety of Serenoa repens in benign prostatic disorders: a systematic review of recent clinical evidence

Abstract

This systematic review assessed the potential effectiveness and safety of Serenoa repens (saw palmetto) for benign prostatic disorders, mainly benign prostatic hyperplasia and associated lower urinary tract symptoms. Following PRISMA guidance (PROSPERO: CRD420251032255), we searched PubMed, Cochrane and ScienceDirect for human studies from January 2020 to May 2025. Sixteen studies (>3000 participants) met criteria, including randomized trials, observational cohorts, a post hoc analysis, an open-label comparative study and a pharmacovigilance analysis. Overall, S. repens was associated with improvements in symptom severity (International Prostate Symptom Score) in several trials, with variable effects on urinary flow, post-void residual volume, and patient-reported quality of life. Signals of benefit appeared more consistently with hexanic lipidosterolic extracts and β-sitosterol-enriched preparations, and some real-world and head-to-head comparisons suggested outcomes comparable to alpha-blockers with fewer adverse events. Combination therapy, especially with the addition of alpha-blockers, showed larger symptom reductions in select populations, particularly with more pronounced baseline symptoms or prostatic inflammation. However, heterogeneity in extract formulations, dosing, study design, and outcome reporting limited cross-study comparability. Safety findings were generally favourable, with mostly mild gastrointestinal events and fewer sexual adverse effects than reported for conventional pharmacotherapies. Taken together, recent evidence supports S. repens as a potentially useful, well-tolerated option for benign prostatic hyperplasia-related symptoms – especially in certain formulations and as part of combination strategies – whilst underscoring the need for standardized, adequately powered trials to clarify which patients benefit most, optimal dosing, and durability of effects.

PLAIN LANGUAGE SUMMARY

Benign prostatic disorders (BPDs) are non-malignant diseases commonly found in ageing men. They include benign prostatic hyperplasia (BPH; where the prostate is enlarged) and prostatitis (where the prostate is inflamed). These diseases present symptoms that impair the quality of life of the affected men. They include increased urinary frequency and urgency during the day and exacerbated during the night. The total harm that these illnesses cause around the world is high and continues to rise.

Current clinical treatments for BPDs range from lifestyle changes (for example, reducing caffeine and fluid intake, promoting exercise) to various pharmacological treatments and, in more severe cases, surgical procedures. Among the drugs that have beneficial effects on BPDs, there are two different groups: synthetic and natural drugs. Alpha-blockers and 5-alpha-reductase inhibitors are the most used synthetic drugs; however, although these drugs are effective, most men abandon the treatment because they have marked sexual side effects.

Natural drugs include a variety of phytotherapeutic agents, with Serenoa repens being the most widely used. However, a standardized formulation or ideal dosage have not yet been established.

This study determines whether Serenoa repens formulations can benefit men with BPDs in reducing their symptoms. The authors reviewed articles from several studies where Serenoa repens was used in the treatment of BPDs, either alone or in combination with other treatments. The evaluated clinical studies were published within the past 5 years in renowned international journals, and the authors revised these articles in a systematic way (with a scientific and rigorous method to summarize the evidence in the most impartial and complete way). The authors evaluated the efficacy and safety of Serenoa repens formulations, aiming to register the following parameters: symptom relief, objective urinary measures (for example, peak flow, prostate volume), and tolerability.

Overall, treatment of BPDs with Serenoa repens was associated with improvements in symptom severity in most of the studies. Several studies show that Serenoa repens offers similar benefits to synthetic drugs but with a lower risk of adverse events. Combination therapy using Serenoa repens along with alpha-blockers showed several advantages. First, the beneficial effects of alpha-blockers are known to be brief, and the addition of Serenoa repens seems to prolong their duration. Second, combination therapy has shown larger symptom reductions. Finally, as Serenoa repens has been associated with significantly lower sexual side effects, it has been shown that, when administered in combination with an alpha-blocker, it can counteract those side effects — this advantage will make men more predisposed to adhering to treatment.

Taken together, this review supports Serenoa repens as a potentially useful, well-tolerated option for the treatment of BPD-related symptoms, especially in combination with alpha-blockers. This review makes it clear that it is worth the effort to standardize drug formulations and dosages. Doing so would benefit patients and enable greater comparability between studies, which in turn would lead to stronger conclusions.

Introduction

Benign prostatic disorders (BPDs), primarily benign prostatic hyperplasia (BPH) and prostatitis, are prevalent conditions affecting a substantial proportion of ageing men.1 BPH, characterized by the non-malignant enlargement of the prostate gland, commonly results in bothersome lower urinary tract symptoms (LUTS), such as increased frequency, urgency, nocturia and a weakened urinary stream, significantly impairing quality of life (QoL).2

The global burden of BPH is substantial and continues to rise. A meta-analysis involving data from 25 countries found a lifetime prevalence of BPH of approximately 26.2%, with prevalence increasing with age and peaking in men aged 75–79 years.3 Worldwide, the number of prevalent BPH cases was estimated to be 94 million in 2019, compared to approximately 51 million in 2000.3 Histological prevalence is estimated to be ~80% by age 85 years,3 and increases steadily with age, affecting around 50% of men in their fifth decade of life and nearly 90% by their ninth, thereby imposing a considerable healthcare burden.4

Current clinical approaches for managing BPDs range from conservative watchful waiting for mild symptoms to lifestyle interventions (e.g. reducing caffeine and fluid intake, promoting exercise), various pharmacological treatments and, in more severe cases, surgical procedures.5 Pharmacotherapy typically includes alpha-blockers (e.g. tamsulosin), which promote smooth muscle relaxation within the prostate, and 5α-reductase inhibitors (5-ARIs), such as finasteride and dutasteride, which reduce prostate volume by inhibiting the conversion of testosterone to dihydrotestosterone (DHT).6 Beyond these conventional treatments, a variety of phytotherapeutic agents are frequently employed, with Serenoa repens, commonly known as saw palmetto, being amongst the most widely used herbal remedies.7

The proposed mechanism of action for S. repens in BPDs is complex and not yet fully elucidated. Initial hypotheses suggested an inhibitory effect on 5α-reductase, mirroring the action of synthetic 5-ARIs, thereby potentially reducing intraprostatic DHT levels.8 More recent research further explored its anti-proliferative and pro-apoptotic effects on prostatic cells, its inhibition of human prostate and bladder smooth muscle contraction, as well as its anti-inflammatory properties and modulation of androgen receptor signalling.9,10 Whilst foundational clinical trials, like the Complementary and Alternative Medicine for Urological Symptoms (CAMUS) study, provided early insights, the overall evidence regarding the efficacy of S. repens has often been mixed, leading to ongoing debate in clinical practice.11 Some contemporary studies continue to explore its comparative efficacy with established pharmaceuticals, suggesting comparable outcomes for certain preparations in mild-to-moderate BPH.12–18 This influx of recent data requires a comprehensive re-evaluation.

The aim of this systematic review is to comprehensively evaluate the efficacy and safety of S. repens (standard extract, β-sitosterol-enriched extracts or standardized hexanic extracts) in the treatment of BPDs, either as monotherapy or in combination with other treatments, focusing on peer-reviewed clinical studies published within the past 5 years. Outcomes of interest include symptom relief, objective urinary measures (e.g. peak flow, prostate volume) and tolerability. The goal is to determine whether S. repens formulations offer clinically meaningful benefits in the management of BPH.

Methods

This study follows recognized standards and is organized in line with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines19 (PRISMA checklist available at: https://www.drugsincontext.com/wp-content/uploads/2026/04/dic.2025-10-2-PRISMA-checklist.pdf).

The protocol for this systematic review was registered in PROSPERO with registration number CRD420251032255.

A summary of the methods is provided in Supplementary Table 1 (available at: https://www.drugsincontext.com/wp-content/uploads/2026/04/dic.2025-10-2-Suppl.pdf).

Literature search

The literature search was conducted on May 4th, 2025. We systematically searched three databases (PubMed, ScienceDirect and Cochrane) to identify relevant studies published from January 1st, 2020, until the search date. The search strategy utilized combinations of specific keywords: “Saw palmetto + Prostatic”, “Saw palmetto + Prostate”, “Serenoa + Prostatic”, “Serenoa + Prostate”, “Phytotherapy + Prostatic”, “Phytotherapy + Prostate”, “Permixon + Prostatic” and “Permixon + Prostate”. We applied filters to ensure that these search terms appeared explicitly within the title and/or abstract of the publications identified.

Study selection

Two reviewers independently screened studies against prespecified inclusion and exclusion criteria, without using any automation tools. Specifically, we considered only studies performed in human participants that provided original research data. Reviews and meta-analyses were excluded from consideration. Eligible studies had to be centred explicitly on populations with prostatic disorders such as BPH or LUTS. Additionally, the studies had to report at least one of the following outcomes: efficacy, QoL or safety data relevant to S. repens treatment. Studies that did not clearly fulfil these criteria or failed to provide adequate data for extraction were excluded from the review.

Outcomes and effect measures

Primary outcomes were lower urinary tract symptom severity (e.g. International Prostate Symptom Score (IPSS) or Overactive Bladder Questionnaire (OAB-q)) and safety (any adverse event (AE) and withdrawals due to AEs). Secondary outcomes included objective uroflowmetry (maximum urinary flow rate; Q_max), disease-specific QoL, and other clinically relevant endpoints reported by the trials. For continuous outcomes, we summarized mean differences and their precision when reported; for binary outcomes, we summarized risk ratios where available. When precision measures were not reported, we present p values or descriptive statistics.

Risk of bias assessment

Risk of bias was assessed at the study–outcome level using RoB 2 for randomized trials and ROBINS-I for non-randomized studies. Two reviewers judged each domain (randomization; deviations from intended interventions; missing outcome data; measurement of the outcome; selection of the reported result), with disagreements resolved by discussion/third reviewer. Overall risk of bias was determined as follows: studies were rated ‘high’ if at least one domain was judged as high risk of bias; ‘some concerns’ if no domains were high risk but at least one domain indicated possible bias (i.e. insufficient information or methodological limitations that could affect the result); and ‘low’ only if all domains were judged as low risk of bias. Full per-study domain judgments and justifications are provided in the Master Risk of Bias Table (Supplementary Table 2).

Synthesis methods

Given clinical and methodological heterogeneity (extract formulations, dosing, designs, and outcome ascertainment), we conducted a narrative synthesis. Results are grouped by comparison (e.g. Serenoa versus placebo/no therapy; versus alpha-blockers; combinations) and outcome, and are tabulated in the main text and tables.

Certainty (confidence) of evidence

We applied a narrative GRADE approach per outcome,20 considering risk of bias, inconsistency, indirectness, imprecision and reporting bias (Supplementary Table 2). Certainty was rated as high, moderate, low or very low with explicit downgrading reasons. Summary judgments and key reasons are presented in the GRADE Summary of Findings (Supplementary Table 3) (e.g. small and inconsistent symptom improvements versus placebo; no consistent Q_max benefit; generally favourable safety), with studies and designs listed for each comparison–outcome.

Results

Figure 1 illustrates the PRISMA flowchart showing the results of the search and selection process for the articles included in this study.

Figure 1.

PRISMA flowchart.

A total of 16 studies investigating the effects of S. repens supplementation on BPH, LUTS and related urological conditions were identified.21–36 These studies explored a range of clinical outcomes, including symptom severity, urinary flow parameters, prostatic inflammation and QoL. Several also compared S. repens to pharmaceutical agents or evaluated its use as adjunctive therapy.

Amongst the 16 included studies, 5 were randomized controlled trials (RCTs),21–25 including 4 double-blind, placebo-controlled designs and 1 randomized open-label comparative trial. Two additional studies were prospective non-randomized interventional trials conducted in a single-arm open-label setting.26,27 Seven studies were prospective observational real-world investigations, primarily comparative cohort analyses evaluating phytotherapy either as monotherapy or in combination with α1-blockers.28–34 The remaining works comprised one post hoc analysis of a randomized biopsy study,35 and one retrospective pharmacovigilance database analysis of adverse drug reactions.36

Combined, these studies reported on over 3000 participants, with sample sizes ranging from 45 in a prospective trial using mobile uroflowmetry27 to 783 in a national registry-based real-world cohort study.29 Most trials enrolled between 50 and 400 individuals. Participants were predominantly men aged 40 to 80 years, with mean ages in the mid-60s in many reports. One Japanese trial enrolled both men and women ≥50 years24 though men represented the majority of the population included.

The primary clinical focus was moderate-to-severe LUTS associated with BPH, including urinary frequency, urgency, nocturia and decreased urinary flow. Nearly all trials assessed changes in IPSS, whilst several also included uroflowmetry endpoints such as Q_max and voided volume. Additional outcomes included prostatic inflammation confirmed by biopsy,35 sexual function26 and longitudinal QoL outcomes.21–24,28–32

With regard to inflammatory conditions, most studies either explicitly excluded prostatitis or indirectly excluded inflammatory aetiologies through criteria such as exclusion of recurrent urinary tract infections, chronic pelvic pain syndrome or other non-BPH urinary disorders.21,24,27,29–34 Only one study specifically required biopsy-confirmed prostatic inflammation for inclusion.35 Therefore, inflammatory prostatitis was not a systematically evaluated population within the reviewed literature.

Special populations included older men with comorbidities such as diabetes, hypertension, metabolic syndrome and obesity.25,28,29,35 Preventive evaluation was also performed in otherwise healthy adults with subclinical urinary symptoms, but no diagnosed BPH or overactive bladder.22 Five studies tested S. repens in combination with alpha-blockers or 5-ARIs,28,30,32,34,35 whilst one pharmacovigilance study described real-world patterns of AE reporting across multiple BPH drug classes.36

The formulation and extraction method of S. repens varied notably. Several trials employed the well-characterized hexanic lipidosterolic extract (HESr),28–31,33,35 whilst others used enriched β-sitosterol extracts,21,22 standardized supercritical CO₂ formulations (USPlus^®),27 or did not specify the exact preparation. This heterogeneity may influence comparisons of efficacy and tolerability.

Geographically, the studies were conducted across Europe (Spain, Italy, France, Greece, Croatia),28–33,35,36 Asia (Japan, Russia, Ukraine),22–24,26,34 North America (USA, Canada),27 and the Caribbean (Cuba).25 Most cohorts were predominantly white or East Asian, though ethnic composition was not consistently reported.

The specific descriptions of the study results were grouped according to the comparisons presented in the publications to facilitate clearer interpretation of the data and enable consistent evaluation across studies.

Efficacy and QoL data

Baseline versus end-of-study follow-up data

A total of five clinical studies evaluated the efficacy of S. repens in men with BPH, each incorporating a statistical comparison of outcomes between baseline and end-of-study follow-up data (Table 1). The participants were men aged 40 years and older, primarily with mild-to-moderate BPH symptoms. Treatment duration ranged from 12 weeks to 12 months. Across the studies, S. repens was administered either as monotherapy or in combination with other active agents. The formulations included conventional lipid extracts, β-sitosterol-enriched oils, HESr and standardized preparations, with daily doses of 320–400 mg.

Table 1.

Summary of studies evaluating Serenoa repens in BPH: baseline versus end of treatment.

Study	Sample size (n)	Population	Treatment	Duration	Main within-group outcomes (end versus baseline)	Statistical significance
Sudeep et al. (2020)21	99 (33/group)	Men 40–65 y with mild-moderate BPH	500 mg BID; β-sitosterol 3%, conventional, placebo	12 weeks	β-sitosterol group: ↓ IPSS (−3.18), ↓ AMS, ↓ ADAM, ↓ PSA, ↓ residual urine, ↑ Qmax (from 11.85 to 14.27 mL/s), ↑ free testosterone	p<0.001 for most outcomes versus baseline
Mederos et al. (2025)25	200 (50/group)	Men ≥40 y with mild-moderate BPH	320 mg/day saw palmetto	6 months	↓ IPSS (from 10.9 to 2.7; −74.6%), ↑ Qmax (+3.6 mL/s), ↓ voiding time, ↓ prostate size	p<0.001 versus baseline
Gurzhenko and Spyrydonenko (2020)26	34	Men with BPH and sexual dysfunction	320 mg/day saw palmetto	12 months	↑ Erectile function (14.28 → 24.86), ↑ orgasm, ↑ intercourse satisfaction, ↑ total satisfaction	p<0.01 (erectile function), p<0.05 (others) versus baseline
Winograd et al. (2024)27	45	Men aged 40–76 y with LUTS	320 mg/day USP-verified extract	12 weeks	↓ IPSS (6.5 → 5), ↓ QoL score (p=0.003), ↑ Qmax in mild BPH (21.5 → 23.9 mL/s)	p=0.03 (IPSS), p=0.01 (Qmax mild group) versus baseline
Samarinas et al. (2020)35	97 (49 HESr, 48 control)	Men with biopsy-confirmed prostatic inflammation	320 mg/day HESr (±α1-blocker)	6 months	↓ IPSS in HESr monotherapy group (19.8 → 16.4, Δ −3.4), ↓ IPSS in HESr + α1-blocker group (13.3 → 11.3)	p=0.001 (monotherapy), p=0.006 (add-on) versus baseline

↑, Increase; ↓, Decrease; α1-blocker, α1 adrenergic receptor blocker (e.g. tamsulosin, silodosin); ADAM, Androgen Deficiency in the Aging Male (questionnaire); AMS, Ageing Males’ Symptoms scale; BID, Bis in die; BPH, benign prostatic hyperplasia; HESr, hexanic extract of S. repens; IPSS, International Prostate Symptom Score; LUTS, lower urinary tract symptoms; PSA, prostate-specific antigen; Q_max, maximum urinary flow rate; QoL, quality of life; USP, United States Pharmacopeia.

In a 12-week double-blind, placebo-controlled trial enrolling 99 patients (33 per group), Sudeep et al. used a β-sitosterol-enriched S. repens oil (3% β-sitosterol, 400 mg/day) and showed significant reductions in IPSS (−3.18±3.14; p<0.001), post-void residual urine volume (−12.76±14.44 mL; p<0.001), prostate-specific antigen (PSA; −0.07±0.32 ng/mL; p=0.233 within group; p=0.008 versus placebo), Androgen Deficiency in Aging Males (ADAM) score (−0.61±1.06; p=0.002), and Ageing Male Symptoms (AMS) total score (−3.64±4.76; p<0.001), as well as an increase in Q_max (+2.42±2.61 mL/s; p<0.001) and serum free testosterone (+0.23±0.77 ng/dL; p=0.093 within group; p=0.015 versus placebo).21

A larger 6-month multicentre, randomized open-label study involving 200 men (50 per group) by Mederos et al. compared S. repens (320 mg/day) to finasteride, tamsulosin and Palmex (Roystonea regia extract).25 S. repens significantly improved IPSS (−74.6%, from 10.9±4.5 to 2.7±2.5; p<0.001), Q_max (from 15.6±7.6 to 19.2±7.7 mL/s; +3.6 mL/s, +23.1%; p<0.01), prostate size (from 41.2±35.3 to 34.5±21.6 cm³; −10.6%; p<0.05), and reduced post-void residual volume (−41.2%). No significant differences were observed between treatment groups.

Gurzhenko and Spyrydonenko administered 320 mg/day of S. repens extract to 34 men with BPH and sexual dysfunction during a 12-month study.26 After treatment, erectile function scores improved significantly from 14.28±0.98 to 24.86±0.23 (p<0.01). Satisfaction with sexual intercourse increased from 7.24±0.31 to 13.52±0.58 (p<0.05), orgasm domain scores from 4.92±0.14 to 9.31±0.38 (p<0.05), and total satisfaction from 4.01±0.29 to 8.13±0.32 (p<0.01), corresponding overall to approximately a twofold increase in integrative International Index of Erectile Function scores. Libido improved by 58.2% during follow-up. The authors reported restoration of erectile function in 83.3% of patients and prolongation of sexual intercourse in 73.5% at study completion.

In a post hoc analysis, Samarinas et al. included 97 patients with confirmed prostatic inflammation and evaluated a 6-month treatment with HESr at 320 mg/day.35 Amongst 25 treatment-naive patients, IPSS significantly improved from 19.8 to 16.4 (p=0.001), whilst the control group showed no significant change. In patients already on α1-blockers, the addition of HESr led to further significant IPSS improvement (13.3 to 11.3; p=0.006). Q_max remained stable overall, though some improvement trends were observed in patients with metabolic syndrome and higher body mass index.

Finally, in a 12-week prospective trial, Winograd et al. evaluated a United States Pharmacopeia-verified S. repens extract (USPlus^®, 320 mg/day).27 Using mobile uroflowmetry, they observed a significant reduction in IPSS from 6.5 to 5 (p=0.03) and QoL improvement (p=0.003). In patients with moderate baseline symptoms, the IPSS dropped from 10 to 7 and the voiding subscore from 6 to 2 (both p<0.02). Finally, authors reported that Q_max increased significantly in patients with mild symptoms from baseline (from 21.5 to 23.9 mL/s; p=0.01).

S. repens treatment versus placebo data

A total of four randomized, double-blind, placebo-controlled studies assessed the efficacy of S. repens extract in improving urinary symptoms in adult men, with all studies performing statistical comparisons between treatment and placebo groups (Table 2). These studies evaluated different populations, ranging from healthy individuals with mild urinary symptoms to patients with clinically diagnosed BPH, using various formulations and dosages of S. repens oil.

Table 2.

Summary of studies evaluating Serenoa repens in BPH: S. repens treatment versus placebo.

Study	Sample size (n)	Population	Treatment	Duration	IPSS (treatment versus placebo)	OABSS or symptom score	QoL (treatment versus placebo)
Ishii et al. (2020)23	40 (20/group)	Japanese men, 40–69 years, nocturia ≥2, mild–moderate LUTS	320 mg/day S. repens extract (Yawata)	12 weeks	↓ IPSS at 8 weeks (p=0.028); group × time interaction (p=0.047)	NS	KHQ incontinence impact improved (p=0.013)
Hisajima et al. (2024)22	54 (27/group)	Healthy Japanese men, 40–65 yrs, mild LUTS (IPSS ≤7)	200 mg× 2/day 3% β-sitosterol, 85% FA	12 weeks	↓ IPSS over time (p<0.01)	↓ OABSS (p<0.05)	WHOQOL-26: NS
Sudeep et al. (2020)21	99 (33/group)	Men 40–65 years, symptomatic BPH (IPSS >7)	500 mg × 2/day 3% β-sitosterol	12 weeks	↓ IPSS at 12 weeks (p<0.001)	Not assessed	↑ SF-12 total, PCS-12, MCS-12 versus placebo (p<0.001)
Kimura et al. (2024)24	66 (33/group)	Healthy adults ≥50 years with urinary frequency, not diagnosed BPH or OAB	320 mg/day S. repens extract (Yawata)	12 weeks	Not assessed via IPSS	↓ OAB-q symptom bother score (p=0.018); ↓ daytime urination frequency (p=0.032)	HRQL (OAB-q): NS, but trend in social interaction

3% β-Sitosterol, a preparation enriched with 3% β-sitosterol; BPH, benign prostatic hyperplasia; FA, fatty acids; HRQL, health-related quality of life; IPSS, International Prostate Symptom Score; KHQ, King’s Health Questionnaire; LUTS, lower urinary tract symptoms; MCS-12, Mental Component Summary of the SF-12 health survey; NS, not significant; OAB, overactive bladder; OAB-q, Overactive Bladder Questionnaire; OABSS, Overactive Bladder Symptom Score; PCS-12, Physical Component Summary of the SF-12 health survey; QoL, quality of life; SF-12, 12-Item Short Form Survey; WHOQOL-26, World Health Organization Quality of Life – abbreviated 26-item version.

Participants in these trials included healthy middle-aged and older Japanese men with mild LUTS, individuals with urinary frequency-related QoL complaints but no formal diagnosis of BPH or overactive bladder and men with clinically defined symptomatic BPH. Across studies, S. repens was administered orally for 12 weeks, with daily dosages ranging from 320 mg to 1000 mg.21–24 In two studies, the extract was enriched with 3% β-sitosterol and 85% total fatty acids,21,22 whilst others used standard extracts derived via supercritical fluid extraction.22,23 Treatments were well tolerated in all studies, with no AEs attributed to S. repens.

The study conducted by Sudeep et al., previously described in the baseline versus end-of-treatment subsection, also reported significant advantages of β-sitosterol-enriched S. repens over placebo.21 Compared to placebo, significant improvements were observed in IPSS (−3.18±3.14 versus +0.73±5.01; p<0.001), Q_max (+2.42±2.61 versus −0.64±2.28 mL/s; p<0.001), and post-void residual urine volume (−12.76±14.44 versus +1.11±13.89 mL; p<0.001). Hormonal parameters also favoured the active treatment, with significant reductions in ADAM score (−0.61±1.06 versus +0.15±0.94; p=0.003), total AMS score (−3.64±4.76 versus +1.70±3.37; p<0.001), and PSA levels (−0.07±0.32 versus +0.18±0.40 ng/mL; p=0.008). Free testosterone increased in the active group (+0.23±0.77 ng/dL) compared to a decrease with placebo (−0.19±0.43 ng/dL; p=0.015 between groups). These findings confirm the superiority of the extract to placebo in both symptom relief and physiological parameters.

Ishii et al. enrolled 44 Japanese men aged 40–69 years with mild-to-moderate LUTS (IPSS ≤19) and nocturia.23 Participants received either 320 mg/day of a supercritical fluid extract (Yawata SP) or placebo for 12 weeks. IPSS was significantly lower in the S. repens group at 8 weeks (p=0.028), with a significant group–time interaction (p=0.047). However, QoL improvements were limited, with the King’s Health Questionnaire showing significant benefit only in the incontinence impact domain (p=0.013 interaction; p=0.078 at 12 weeks). Uroflowmetry and salivary hormone measurements showed no significant differences.

In the third trial, Hisajima et al. investigated the efficacy of a 3% β-sitosterol-enriched S. repens oil (200 mg twice daily) in 54 healthy Japanese men aged 40–65 years with mild LUTS (IPSS ≤7).22 Over 12 weeks, the S. repens group showed a significantly greater reduction in IPSS across time points (p<0.01). Overactive Bladder Symptom Score also improved significantly (p<0.05), whilst the Core LUTS Symptom Score showed a non-significant time effect. No group differences were observed in WHOQOL-26 domains or objective uroflowmetry measures.

A more recent trial by Kimura et al. included 66 Japanese adults aged 50 years and older who experienced bothersome daytime urinary frequency but were not diagnosed with BPH or overactive bladder.24 Participants received 320 mg/day of S. repens extract or placebo for 12 weeks. The primary outcome, derived from the OAB-q, was the change in the score of ‘symptom bother’ from frequent daytime urination. This score significantly improved in the treatment group compared to placebo (p=0.018). The average daytime frequency of urination, assessed via daily diaries, also significantly decreased in the S. repens group (p=0.032). No significant AEs were attributed to treatment, and the findings suggest meaningful improvements in urinary-related QoL in otherwise healthy older adults.

Studies comparing S. repens versus other treatments

A total of five studies evaluated the comparative effectiveness of S. repens-based treatments against other interventions for BPH (Table 3). Treatments involving S. repens included β-sitosterol-enriched extracts, standardized HESr and standard 320 mg S. repens. The comparators included conventional pharmaceutical agents such as tamsulosin, finasteride, and alpha-blockers as well as a watchful waiting approach.

Table 3.

Summary of studies evaluating Serenoa repens in BPH: S. repens treatment versus other treatments.

Study (Author, Year)	Sample size (n)	Population	Treatment	Duration	IPSS change	Qmax change	PSA/prostate volume	QoL/AMS/ADAM
Sudeep et al. (2020)21	99 randomized (33/group); 91 completed	Men 40–65 years; symptomatic BPH (IPSS >7; AMS ≥27; ADAM positive)	β-Sitosterol enriched saw palmetto oil (3%) versus conventional saw palmetto oil (0.2%) versus placebo	12 weeks	Significant ↓ IPSS in enriched group versus placebo	Significant ↑ Qmax (p<0.001)	↓ PSA (p<0.01); 5α-reductase ↓; prostate volume not primary	↓ AMS and ADAM scores (p<0.001)
Alcaraz et al. (2021)31	737 (353 TAM; 384 HESr; iterative matched)	≥40 yrs; moderate–severe LUTS/BPH (IPSS >7)	HESr 320 mg/day versus tamsulosin 0.4 mg/day	6 months	TAM: −5.0; HESr: −4.5 (NS between groups)	Baseline-matched; not primary endpoint; similar changes	PSA and prostate volume matched at baseline; no major differential change reported	QoL (IPSS item 8 and BII): similar improvement both groups
Alcaraz et al. (2022)29	783 (102 WW; 681 HESr; iterative matched)	Moderate–severe LUTS/BPH (IPSS ≥8)	HESr 320 mg/day versus watchful waiting	6 months	HESr −3.8 versus WW −2.2	Not primary; Qmax included in matching; no large differential change reported	PSA and prostate volume matched at baseline	BII: −1.8 versus −1.0
Mederos et al. (2025)25	200 (50/group)	≥40 yrs; mild–moderate BPH (IPSS 1–18)	Palmex® 320 mg versus saw palmetto 320 mg versus finasteride 5 mg versus tamsulosin 0.4 mg	6 months	IPSS ↓ 74.2% (Palmex), 74.6% (SP), 60.3% (Fin), 74.2% (TAM)	↑ Qmax: +3.8 (Palmex), +3.6 (SP), +4.2 (Fin), +4.1 mL/s	↓ Prostate size and residual volume; PSA not primary	QoL improved (via IPSS reduction)
de la Taille et al. (2023)33	759 total; 644 without treatment change (309 AB; 324 HESr)	Moderate–severe LUTS/BPH (IPSS ≥12)	HESr versus alpha-blockers	6 months	Mean −10.1 points (overall); severe pts −13.6 (HESr)/−14.8 (AB)	Not primary endpoint; not detailed	Not primary focus	≥95% reported global improvement; QoL improved

3% β-Sitosterol, Preparation enriched with 3% β-sitosterol; 0.2% β-Sitosterol, preparation containing 0.2% beta-sitosterol; ADAM, Androgen Deficiency in the Aging Male (questionnaire); AMS, Aging Males’ Symptoms scale; BII, Benign Prostatic Hyperplasia Impact Index; HESr, hexanic extract of S. repens; IPSS, International Prostate Symptom Score; NS, not significant; PSA, prostate-specific antigen; QoL, quality of life; Q_max, maximum urinary flow rate; SRO, S. repens oil.

As mentioned in the versus baseline and versus placebo subsections, Sudeep et al. conducted a 12-week double-blind, placebo-controlled trial comparing 3% β-sitosterol-enriched S. repens oil (βSEO) with conventional S. repens oil (SRO; 0.2% β-sitosterol) and placebo.21 Compared to SRO, βSEO demonstrated superior efficacy across multiple clinically relevant endpoints, including significant reductions in LUTS measured by the IPSS (−3.18±3.14 versus −0.91±3.34; p<0.001), androgen deficiency assessed by the ADAM questionnaire (−0.61±1.06 versus +0.06±0.90; p=0.003), and total AMS score (−3.64±4.76 versus −1.12±4.14; p<0.001). Improvements in urodynamic parameters were also more pronounced in the βSEO group, including increases in Q_max (+2.42±2.61 mL/s versus +0.48±1.56 mL/s; p<0.001) and reductions in post-void residual volume (−12.76±14.44 mL versus −1.88±10.93 mL; p<0.001). Additionally, free testosterone levels increased in the βSEO group (+0.23±0.77 ng/dL versus −0.11±0.60 ng/dL; p=0.015), whilst 5α-reductase activity was slightly reduced in βSEO but increased in the SRO group.

Alcaraz et al. conducted a large real-world prospective study comparing HESr to tamsulosin in men with moderate-to-severe LUTS/BPH.31 After 6 months, both groups showed similar improvements: IPSS decreased by 5.0±4.3 in the tamsulosin group and by 4.5±4.7 in the HESr group (p=0.117), and BPH Impact Index score improved by 2.3±2.4 versus 2.2±2.5, respectively (p=0.417). AEs were significantly lower in the HESr group (2.1%) than in the tamsulosin group (14.7%).

In another QUALIPROST analysis, Alcaraz et al. compared HESr to watchful waiting.29 After 6 months, IPSS improvement was significantly greater in the HESr group (−3.8±4.4 versus −2.2±4.5; p=0.002), and QoL improved by 1.8±2.4 versus 1.0±2.2 (p<0.001). The responder rate for IPSS (≥3 point reduction) was higher in the HESr group (71.6%) versus in the watchful waiting group (65.6%).

As described in the versus baseline subsection, Mederos et al. performed a study where patients received 6-month treatments of S. repens, finasteride, tamsulosin or Palmex^® (Roystonea regia).25 All groups demonstrated statistically significant improvements in Q_max (e.g. +3.6 mL/s with S. repens; p<0.01) and IPSS (−74.6% with S. repens). S. repens was not significantly different in efficacy from finasteride or tamsulosin.

Finally, the PERSAT study compared HESr to alpha-blockers over 6 months in a French general practice setting.33 Although a statistical test was not performed between groups, IPSS decreased by 9.9±5.1 with HESr and 10.4±6.1 with alpha-blockers. Amongst patients with severe symptoms (IPSS >19), reductions reached 13.6 and 14.8 points, respectively. QoL scores also improved similarly in both groups.

Studies comparing S. repens in combination with other components

A total of five studies evaluated the clinical outcomes of combination therapies containing the HESr or mixed phytotherapies versus simplified or monotherapy versions in the treatment of BPH-related LUTS (Table 4). These studies consistently explored whether the inclusion of HESr or similar plant-based extracts provides clinical advantages when used in combination regimens, particularly with alpha-blockers like tamsulosin or silodosin.

Table 4.

Summary of studies evaluating Serenoa repens in BPH: combinations with Serenoa repens.

Study	Sample size (n)	Comparison	Duration	IPSS Change	QoL/other outcomes	Key findings
Samarinas et al. (2020)35	97	HESr + α1-blocker versus α1-blocker or none	6 months	−3.4 (HESr monotherapy), −2.0 (HERs add-on)	QoL not reported	HESr improves IPSS alone or as add-on
Di Maida et al. (2020)32	148	TAM + HESr + BC versus TAM	12 months	−5.5 versus −5.1	IPSS-QoL: −2.9 versus −2.1 (p=0.04)	Significant benefit in storage and QoL symptoms
Alcaraz et al. (2020)30	709	TAM + HESr versus TAM or HESr	6 months	−7.2 versus −5.7 / −5.4	BII: −3.4 versus −2.7 (p=0.02)	Greater efficacy in combination
Alcaraz et al. (2022)28	136	TAM + HESr versus TAM + 5-ARI	6 months	−6.7 versus −7.7	BII: −2.9 versus −3.1 (NS); AE: 10.3% versus 26.5%	Similar efficacy, better tolerability with HESr
Krakhotkin et al. (2022)34	389	Silodosin + Rotaprost (containing 80 mg of S. repens) versus each alone	6 months	−12.4 versus −9.3 / −3.0	Qmax: +6.9 mL/s; PSA ↓25.7%; PVR ↓46 mL	Best IPSS, Qmax and volume reduction in combo

5-ARIs, 5α-reductase inhibitor; AE, adverse events; BC, bovine colostrum; BII, Benign Prostatic Hyperplasia Impact Index; HESr, hexanic extract of S. repens; IPSS, International Prostate Symptom Score; NS, not significant; PSA, prostate-specific antigen; PVR, post-void residual urine volume; QoL, quality of life; Q_max, maximum urinary flow rate; TAM, tamsulosin.

All studies involved men with moderate-to-severe LUTS (IPSS ≥10–12). Inclusion criteria typically restricted PSA levels to <4 ng/mL and Q_max to 5–15 mL/s. Treatment durations ranged from 6 to 12 months.

Samarinas et al. showed that HESr alone significantly improved IPSS after 6 months in previously untreated patients (p=0.001).35 In patients already on alpha-blockers, the addition of HESr further reduced IPSS (p=0.006) compared to stable scores with alpha-blockers alone (p=0.346). These improvements occurred without significant changes in Q_max.

Di Maida et al. explored a triple combination of tamsulosin, HESr and bovine colostrum, showing that it led to greater reductions in IPSS storage subscore (−1.8 versus −0.8; p=0.02) and IPSS-QoL score (−2.9 versus −2.1; p=0.04) compared with tamsulosin alone.32

Alcaraz et al. compared monotherapies and combination therapy of tamsulosin and HESr.30 The combination group had the greatest improvements in IPSS (−7.2 versus −5.7 or −5.4) and BPH Impact Index (−3.4 versus −2.7) (p<0.001 and p=0.02, respectively). Amongst patients with severe symptoms (IPSS >19), the benefit was even more pronounced. AEs remained acceptable, with no significant increase over monotherapy.

In a paired comparison study, also by Alcaraz et al., the combination of tamsulosin and HESr achieved symptom relief and QoL outcomes comparable to tamsulosin plus 5-ARI but with significantly fewer sexual side-effects (10.3% versus 26.5%; p=0.027).28

The study by Krakhotkin et al. added a broader phytotherapy formulation – Rotaprost, which includes S. repens, Urtica dioica, Cucurbita pepo, selenium, and zinc − to the evidence base.34 In their 6-month trial, the combination of silodosin 8 mg + Rotaprost 530 mg significantly improved IPSS (−12.4), Q_max (+6.9 mL/s) and prostate volume (−6.9 cm³), outperforming both silodosin alone (IPSS −9.3) and Rotaprost alone (IPSS −3.0) (p<0.001). PSA reductions were also observed (25.7% in the combination group), and AEs remained manageable, though higher in the silodosin-only arm. These results align with prior studies showing that combinations involving S. repens result in more robust symptomatic and structural benefits.

Safety data

A total of 12 scientific studies were reviewed to assess the safety of S. repens in the treatment of BPH and LUTS (Table 5).21,22,24,25,27–31,34–36 All studies included in this review provided explicit data related to the AEs, tolerability or laboratory safety markers, which allowed for a comprehensive summary of the safety profile of this herbal extract.

Table 5.

Summary of safety data.

Study	Sample size	Population type	Serenoa repens treatment	Adverse effects	Safety conclusion
Sudeep et al. (2020)21	72	Men with BPH	500 mg × 2/day 3% β-sitosterol	None reported	Well tolerated and safe
Hisajima et al. (2024)22	30	Healthy men with mild LUTS	200 mg× 2/day 3% β-sitosterol, 85% FA	None reported	Well tolerated in healthy adults
Krakhotkin et al. (2022)34	87	Men with BPH (clinical comparison)	80 mg/day S. repens + herbs	6.9% (versus 37.9% silodosin)	Fewer AEs than silodosin
Kimura et al. (2024)24	66	Healthy Japanese adults	320 mg/day S. repens extract (Yawata)	2 mild AEs (unrelated)	Safe, no therapy-related side-effects
Kuliš et al. (2023)36	438	Men in national pharmacovigilance system	Various (national database)	Mostly GI (mild), no serious AEs	Safe with known mild GI AEs
Mederos et al. (2025)25	200	Men with mild-moderate BPH	320 mg/day S. repens	6% (mild, incl. ejaculation disorders)	Safe
Samarinas et al. (2020)35	97	Men with LUTS and prostatic inflammation	320 mg/day HESr	Not reported	No safety issues noted
Winograd et al. (2024)27	45	Men with mild-moderate LUTS	320 mg/day USP-verified extract (with ≥80% fatty acids)	None reported	Well tolerated, no AEs
Alcaraz et al. (2022)28	136	Men with moderate-severe LUTS/BPH	320 mg/day HESr	10.3% (HESr) versus 26.5% (TAM+5-ARI)	HESr better tolerated than TAM+5-ARI
Alcaraz et al. (2022)29	783	Men with moderate-severe LUTS/BPH	320 mg/day HESr	0.9% (HESr only)	Very low AE rate for HESr
Alcaraz et al. (2020)30	709	Men with moderate-severe LUTS/BPH	320 mg/day HESr	1.9% (HESr), 13.3% (TAM), 12% (HESr+TAM)	HESr safest, combo therapy tolerable
Alcaraz et al. (2021)31	737	Men with moderate-severe LUTS/BPH	320 mg/day HESr	2.1% (HESr) versus 14.7% (TAM)	HESr significantly safer than TAM

5-ARI, 5α-reductase inhibitor; AE, adverse event; BPH, benign prostatic hyperplasia; GI, gastrointestinal; HESr, hexanic extract of S. repens; LUTS, lower urinary tract symptoms; TAM, tamsulosin; USP, United States Pharmacopeia (refers to standardized, verified supplement quality).

The studies covered a wide variety of patient populations.21,22,24,25,27,29–31,34–36 Most studies included men diagnosed with BPH or LUTS, though some studies also evaluated healthy men with mild urinary symptoms. Collectively, the studies evaluated a total of 3400 patients. The populations studied included healthy adults with mild symptoms, men with moderate to severe LUTS secondary to confirmed BPH, patients under real-world long-term phytotherapy management, and data reported in national pharmacovigilance databases. The size of the populations studied ranged from 30 patients to 783 patients, and the duration of follow-up varied from 12 weeks to 10 years.

Across all studies, S. repens was consistently shown to be safe and well tolerated.21,22,24,25,27,29–31,34–36 AEs related to the use of S. repens were rare and were generally mild, most frequently involving mild gastrointestinal symptoms such as nausea, constipation or abdominal discomfort. In studies comparing S. repens with standard pharmaceutical treatments, such as tamsulosin or finasteride, S. repens demonstrated fewer AEs overall.25,33 Specifically, reports of sexual side-effects were absent or less frequent compared with pharmaceutical medications. Laboratory safety parameters, including liver enzyme levels, PSA levels and haematological parameters, remained stable throughout the duration of treatment. Importantly, none of the studies reported serious AEs directly related to the use of S. repens.

The safety data provided by the study by Kuliš et al. deserves special attention due to the extent of the data collected from real-world clinical practice.36 This study analysed 438 reports of adverse drug reactions related to treatments used for BPH submitted to the Croatian national agency (HALMED) between 2008 and 2021. Of these reports, 32 involved S. repens. The majority of these reactions were mild and involved primarily gastrointestinal symptoms, such as dyspepsia, constipation and abdominal discomfort. No serious AEs were reported in association with S. repens. In contrast, pharmaceuticals like tamsulosin and finasteride were associated with higher frequencies of sexual and serious AEs. The findings from the study of Kuliš et al. align closely with data from clinical trials and confirm the overall favourable safety and tolerability profile of S. repens in routine clinical use (Table 5).

Discussion

This systematic review presents updated evidence supporting the efficacy and safety of S. repens as a therapeutic option for BPDs, particularly BPH. RCTs and observational studies demonstrate the potential benefits of Serenoa repens, both as monotherapy and in combination with pharmaceutical treatments.

Summary of main findings

The findings from these studies collectively reinforce previous evidence suggesting modest yet clinically meaningful benefits of S. repens.12–18,37 For example, the RCT conducted by Sudeep et al. reported significant improvements in urinary symptoms, flow parameters and QoL in patients treated with a phytosterol-enriched S. repens formulation compared to placebo.21 Specifically, the group treated with phytosterol-enriched S. repens experienced significant reductions in IPSS, post-void residual volume, PSA, and improved QoL scores (p<0.001).21 These improvements were consistent with general trends noted in other trials, even those lacking statistical tests, where patient-reported outcomes consistently favoured the intervention group in mild-to-moderate LUTS.

The findings of this review offer a compelling contrast to earlier large-scale studies, such as the CAMUS trial, which concluded that S. repens had no significant benefit over placebo in reducing LUTS in men with BPH.11 The CAMUS study, whilst methodologically robust, was limited by the use of a single extract formulation and did not account for the variability in preparation types that have since been shown to influence clinical outcomes.11 In contrast, more recent trials included in this review demonstrate that certain formulations – particularly HESr and β-sitosterol-enriched preparations – are associated with statistically and clinically significant improvements in symptom scores, urinary flow rates, and QoL measures. These findings suggest that the previous scepticism surrounding the efficacy of S. repens may be attributable to inconsistencies in extract standardization rather than to an inherent lack of therapeutic activity. Despite this growing body of supportive evidence, most current clinical guidelines continue to marginalize or omit phytotherapy from recommended treatment pathways. This disconnect between guideline conservatism and real-world clinical practice – where S. repens is frequently used, especially in Europe and parts of Asia – highlights the urgent need for updated recommendations that reflect emerging data on efficacy, safety and patient preference.

Combination of S. repens with alpha-blockers

The combination of S. repens with alpha-blockers appears to offer enhanced clinical benefits beyond those achieved with monotherapy, particularly in patients presenting with moderate-to-severe LUTS or comorbid prostatic inflammation.28,30,32,34,35 Alpha-blockers, such as tamsulosin and silodosin, are widely recognized as first-line agents due to their rapid onset of action, which results from the relaxation of smooth muscle fibres in the prostate and bladder neck.38 This leads to short-term improvements in urinary flow and symptom scores. However, alpha-blockers do not exert any influence on the underlying pathophysiology of BPH, particularly in patients whose symptoms are driven by chronic inflammation, hormonal imbalance or epithelial-stromal proliferation.39 As a result, symptom control may plateau over time, and some patients continue to experience bothersome LUTS despite treatment.40 In this context, the addition of S. repens, particularly in its HESr form, which was used in three of the five studies,28,30,32,34,35 may offer a complementary therapeutic mechanism. Experimental and clinical data suggest that S. repens exerts anti-inflammatory, antiandrogenic and antiproliferative effects on prostatic tissue, potentially targeting pathways that are unaddressed by alpha-blockers alone. This multifaceted action makes it a compelling candidate for combination therapy, especially in patients with more complex or refractory symptomatology. Several studies included in this review provide evidence supporting this approach. For instance, in the study by Samarinas et al.,35 the addition of HESr to alpha-blocker therapy in men with biopsy-confirmed prostatic inflammation resulted in significantly greater IPSS reductions compared to alpha-blocker monotherapy, highlighting the potential of S. repens to improve outcomes in inflammation-driven BPH. Similarly, in the multicentre study by Alcaraz et al.,30 combination therapy with HESr and tamsulosin yielded more substantial symptom relief and QoL improvements than either agent alone, with particular benefit observed in patients with severe LUTS (IPSS >19). Di Maida et al. also reported enhanced storage symptom improvement and QoL gains when HESr was added to tamsulosin and bovine colostrum.32 These results suggest additive effects of combining HESr with other agents targeting prostatic inflammation.

Beyond symptom efficacy, combination therapy offers an important safety advantage. Whilst dual therapy with alpha-blockers and 5-ARIs is commonly used, it is often limited by AEs, particularly sexual dysfunction, reduced libido and ejaculatory disorders. Notably, S. repens, even in combination with alpha-blockers, has been associated with a significantly lower incidence of sexual side-effects. Alcaraz et al. demonstrated that patients treated with HESr plus tamsulosin reported fewer sexual AEs (10.3%) compared to those receiving tamsulosin combined with 5-ARIs (26.5%), without compromising clinical efficacy.28 This safety profile has important implications for adherence, as sexual side-effects are a well-documented cause of treatment discontinuation in BPH management. Preserving sexual function whilst achieving symptom control is particularly valuable in sexually active men, and S. repens may enable a better balance between efficacy and tolerability.

Furthermore, the benefits of combination therapy are not limited to controlled trial settings. In real-world practice – where patients are older, more heterogeneous and more likely to have comorbidities – combination regimens involving S. repens continue to show promise. The large QUALIPROST study30 and the trial by Krakhotkin et al.,34 which combined S. repens with silodosin and other phytocomponents, both demonstrated robust improvements in IPSS, Q_max and prostate volume across broad patient populations. These findings suggest that phytotherapeutic combination strategies may be especially relevant in primary care or urology clinics where individualization of treatment is key.

Taken together, the evidence suggests that combining S. repens with alpha-blockers represents a rational, effective and safe approach for managing BPH-related LUTS, particularly in patients with more severe or inflammation-associated symptom profiles. The dual mechanistic action – rapid functional relief from alpha-blockade, paired with the longer-term anti-inflammatory and anti-proliferative effects of S. repens – may provide both immediate and sustained benefits. This combination may also serve as an alternative to alpha-blocker/5-ARI therapy in patients at risk for AEs or those unwilling to use synthetic drugs in the long term. Despite these promising findings, further randomized, placebo-controlled and head-to-head trials are warranted to confirm these benefits and to formally integrate phytotherapeutic combination regimens into evidence-based clinical guidelines.

Safety

The safety profile of S. repens was consistently favourable across the reviewed studies, with a notably low incidence of AEs, most of which were mild and transient.21,22,24,25,27,29–31,34–36 Most studies did not statistically analyse safety outcomes. However, when compared with conventional pharmacotherapies, HESr consistently showed significantly lower overall AE rates, with differences mainly driven by drug-class effects (particularly sexual and vascular AEs). In a matched QUALIPROST analysis, AEs occurred in 2.1% of patients taking HESr versus 14.7% of patients taking tamsulosin (p<0.001), with tamsulosin-associated events including ejaculatory dysfunction and orthostatic hypotension.31 In another QUALIPROST subset, AE rates were 1.9% (HESr) versus 13.3% (tamsulosin) versus 12.0% (tamsulosin + HESr) (p<0.001).30 Finally, in a matched comparison of tamsulosin + HESr versus tamsulosin + 5-ARI, AEs were reported in 10.3% versus 26.5%, respectively (p<0.027), with events mostly affecting sexual function.28 This improved tolerability was further supported by national pharmacovigilance data, which confirmed a minimal number of adverse drug reaction reports related to S. repens over more than a decade of clinical use. Collectively, these findings reinforce its suitability as a well-tolerated therapeutic option, particularly for patients who prioritize safety, seek alternatives to synthetic drugs, or are at higher risk for medication-related complications.

Exclusion of studies

To ensure transparency, we acknowledge the exclusion of certain studies from this review that, though they fulfilled the inclusion criteria, were not included due to, in our assessment, significant methodological flaws or reporting inadequacies. Specifically, a study by Yaseen et al. reported positive outcomes but failed to provide adequate quantitative data or clear statistical analyses, thereby precluding meaningful inclusion in the present analysis.41 Similarly, Ali et al. employed, in our opinion, inappropriate statistical methods, comparing only endpoint values rather than analysing changes from baseline, which limits the validity of their reported conclusions.42 The trial conducted by Luciani et al. omitted critical baseline data for key subpopulations, rendering bias assessment impossible and compromising internal validity.43 Furthermore, Cai et al. raised concerns regarding the integrity of the randomization process, as evidenced by near-significant differences in baseline characteristics between groups – the S. repens treatment group had almost statistically worse prostate volume, Charlson Comorbidity Index, and urinary symptoms than the Prostaflog group – as well as unexplained discrepancies in group sample sizes.44 In our opinion, these methodological shortcomings necessitated the exclusion of these studies from the primary analysis in order to preserve the rigour and credibility of our conclusions.

Limitations

When interpreting the conclusions of this review, it remains important to recognize the limitations inherent to this study. Despite using comprehensive search strategies in major bibliographic databases (PubMed, Cochrane, Embase), there is the possibility of overlooked studies, particularly those published in non-English languages or within smaller, regional journals. Additionally, variability in S. repens formulations, dosage schedules, study durations and outcome-reporting standards complicated direct comparisons and may have contributed to observed heterogeneity in the results. Such limitations underline the need for standardized reporting criteria in future trials investigating S. repens and related herbal supplements. Furthermore, inflammatory prostatitis was not systematically evaluated in the included studies. Most trials either explicitly excluded prostatitis or indirectly excluded inflammatory urinary conditions, and only one study required biopsy-confirmed prostatic inflammation as an inclusion criterion.35 Therefore, the conclusions of this review primarily apply to obstructive/growth-related BPH populations rather than to inflammatory prostatitis.

Conclusion

In conclusion, the present systematic review substantiates the efficacy of S. repens for reducing urinary symptoms and improving QoL in men with BPDs, particularly BPH. Its favourable safety and tolerability profiles further strengthen its clinical value as a viable therapeutic alternative or adjunct to standard pharmacotherapy. The potential advantages observed with combination therapies warrant additional, carefully designed clinical trials to determine optimal patient selection criteria, dosing strategies and long-term outcomes.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.