**Background:** Benign prostatic hyperplasia (BPH) is an age-related disorder characterized by epithelial and stromal proliferation in the prostate gland, affecting over 94 million men worldwide in 2019 (up from 51.1 million in 2000). By age 50, approximately 50% of men are diagnosed with BPH, with a linear increase in cases thereafter. BPH leads to lower urinary tract symptoms (LUTS) including voiding symptoms (hesitancy, intermittency, poor stream, straining, terminal dribble) and storage problems (nocturia, urgency, increased frequency), negatively impacting quality of life. In 2013, Medicare costs in the US exceeded 1.5 billion USD for BPH-related services. Current pharmaceutical treatments—5α-reductase inhibitors and alpha-1 blockers—have serious side effects including impotence, ejaculatory disorders, gynecomastia, depression, anxiety, dizziness, and increased risk of more serious prostate cancer. This dilemma has motivated men to seek treatments from medicinal plants with established safety records.
**Methods:** This narrative overview focused on studies published mainly from January 2018 through January 2023, using databases including PubMed, Science Direct, Scopus, and Google Scholar. Keywords included BPH and hormones, inflammation, growth factors, cell receptor signaling, genetics, diet, physical activity, the prostate microbiome, equol, beta sitosterol, pumpkin seed extract, saw palmetto, lycopene, stinging nettle, green tea, and vitamins A, C, D, and E. The review examined in vitro, in vivo animal studies, and clinical data.
**Key Results:** The review identifies multiple factors influencing BPH: (1) Androgens—testosterone is converted by 5α-reductase enzymes to 5α-dihydrotestosterone (5α-DHT), which has 3–10 times greater androgen action than testosterone. 5α-reductase enzyme expression increases within the prostate with age and disease states. (2) Inflammation—chronic upregulation of pro-inflammatory mediators (IL-1, IL-5, IL-6, IFNγ, TNF-α, IL-8, COX-2, iNOS) via MAPK and NFkβ pathways leads to reactive oxygen species formation and a self-perpetuating cycle of cellular proliferation. (3) Estrogens—17β-estradiol is 100–1000 times more biologically active than parent androgens. ER-α activation leads to aberrant proliferation and inflammation, while ER-β activation mediates anti-proliferative effects. (4) Thyroid hormones—some studies found higher BPH cases with increased plasma T3 levels, though a large clinical study showed hyperthyroidism is not a significant risk after adjustment for comorbidities. (5) IGF-1 and insulin—patients with serum insulin levels >13 mU/L have greater prostate volume and annual BPH growth rates compared to those with insulin levels ≤7 mU/L. (6) Epigenetic factors—Mediterranean and Eastern diets (high in vegetables, fruits, legumes, fish, olive oil) are associated with decreased BPH symptoms, while Western diets (refined carbohydrates, red meat, processed meats) increase risk. (7) Prostate microbiome—emerging evidence suggests dysbiosis may contribute to inflammation, with studies identifying Escherichia coli as a common constituent of BPH-associated microbiota that induces NFkβ signaling and DNA damage.
FOR SPECIFIC NUTRACEUTICALS
Equol (at 6 mg twice daily) improved IPSS scores in men with moderate-to-severe BPH without side effects. Beta-sitosterol (130 mg/day) in a placebo-controlled trial (n=177) showed significant improvements in IPSS, Qmax (4.5 mL/s increase), and post-void residual volume (33.5 mL decrease). Pumpkin seed extract (500 mg daily) in a 24-month study of 83 men showed significant IPSS improvement in over 50% of subjects, with QOL scores rising from 11% (mostly satisfied) at baseline to 62% and 73% at 12 and 24 months. Saw palmetto hexanic extract (320 mg/day or 160 mg twice daily) significantly reduced nocturia and improved Qmax compared to placebo, with efficacy similar to tamsulosin. Lycopene (500 mg twice daily for 16 weeks in 127 patients) significantly improved IPSS, QOL, Qmax, and PVR without affecting prostate volume. Stinging nettle (120 mg root extract) in a study of 558 patients showed 81% of men had significant improvement in LUTS/BPH symptoms. Green tea catechins, particularly EGCG, demonstrated multiple mechanisms including apoptosis induction, cell cycle arrest, anti-inflammatory effects via NFkβ and COX-2 inhibition, and 5α-reductase enzyme inhibition.
**Clinical Implications:** The authors conclude that urologists and medical associations are rethinking the role of plant-derived phytochemicals as treatment options for men with mild-to-moderate LUTS/BPH symptoms as an alternative to watchful waiting. Combination therapies of multiple active ingredients may provide enhanced efficacy compared to monotherapy. The review emphasizes that vitamins A, C, D, and E, along with Mediterranean or Eastern diets and nutraceutical supplementation with equol, β-sitosterol, pumpkin seed extract, saw palmetto, lycopene, stinging nettle, and green tea are associated with decreased BPH symptoms. Further research is warranted on epigenetic factors such as diet, exercise, and nutraceutical supplementation to determine the extent to which these therapies can ameliorate LUTS/BPH symptoms.