The Therapeutic Potential of Saw Palmetto Extract in Urological Disorders

Abstract

Saw palmetto extract (SPE) has been widely used as a therapeutic remedy for urinary dysfunction in western countries. Furthermore, as an herb drug, it can be used as an alternative therapy for benign prostatic hyperplasia (BPH) due to its safety and minimum adverse effects. Reportedly, SPE improves the urinary symptoms, which mainly depend on anti-androgenic effects and effects on autonomic receptors in the lower urinary tract. However, the mechanisms of action responsible for the therapeutic roles of SPE have not been fully elucidated. Relevant studies indicate that SPE has some positive effects on the treatment of urological diseases in animals, and clinical trials are ongoing. In this review, we summarize the pharmacological properties and discuss the possible therapeutic mechanisms of SPE in urological diseases, including anti-androgenic effects, effects on autonomic receptors in the lower urinary tract, anti-inflammatory activity, anti-proliferative and pro-apoptotic effects, and highlight a potential therapeutic approach in the clinical treatment of patients with BPH, prostate cancer, chronic prostatitis (CP) and erectile dysfunction (ED).

Introduction

Saw palmetto [Serenoa repens (Bartram) J. K. Small, S. repens; family Arecaceae] is a type of dwarf palm originating from North America. Extract of Saw palmetto berry (SPE) is a most common herbal remedy, which has had several decades of history in countries such as Europe and the USA. SPE has been traditionally used to treat genitourinary problems such as benign prostatic hyperplasia (BPH). SPE has been proven to ameliorate lower urinary tract symptoms (LUTS) by many clinical trials and may be considered a viable first-line agent for managing BPH-associated LUTS.^1–4 This article summarizes the pharmacological properties and clinical efficacy of SPE in urological disorders.

Pharmacological Effects of SPE

Main Chemical Components

As an herbal drug, SPE contains various fatty acids and phytosterols. The National Institute of Standards and Technology of the United States provides two SPE standard products--standard reference materials (SRMs) 3250 and SRM3251. SRM3250 contains 3 phytosterols, 14 fatty acids, and SRM3251 contains 3 phytosterols, 17 fatty acids, β-carotene, and γ-tocopherol. ⁵ Usually, SPE contains 70 to 95% free fatty acids, including caprylic, capric, lauric, myristic, palmitic, steatic, oleic, linoleic, and linolenic acids. Further phytosterols like β-sitosterol and β-sitosterol 3-O-D-glucoside, campesterol, and stigmasterol are found, forming about 0.1% of the total mass of SPE.^6,7 SPE products supplied by different companies have distinct extractive procedures, including hexane, ethanol, and CO₂ extractions. Quality of SPE products is strictly related to the method of preparation and extraction. Potency differs among different brands of SPE products due to differences in the composition of bioactive components in the plant extracts. A hexane extract of saw palmetto (Permixon) with the highest percentage of free fatty acids showed the highest efficacy for the therapeutic effects of SPE. ⁸ Furthermore, recent data demonstrated that phytosterol-enriched SPE exhibited superior efficacy in treating BPH complications compared to the conventional preparations.^9,10 Jiang et al performed a systematic evaluation of the results from previous studies and supported that a high phytosterol intake is inversely related to risk of cancer. ¹¹ An established gas chromatography and ¹H nuclear magnetic resonance spectroscopy method was used to show that it was possible to statistically differentiate between saw palmetto products that had been extracted under different conditions, but not between products that used a similar extraction method. ⁷ This method offers novel opportunities for quality control of the chain of saw palmetto agents and assessment of the complexity of the herbal extract. In addition, SPE also has different dosage forms, including liquids, powders, dried berries, and tinctures. A study in the United States conducted by Penugonda et al compared 20 different SPE supplements on the market and suggested that liquid SPE supplements with the highest concentrations of both phytosterols and fatty acids should be recommended. ⁶ Meanwhile, Tan et al reported that a new substance named NYG (Patent No. WO 2014174703 A1) had been extracted from saw palmetto and demonstrated to target hepatocellular carcinoma as an adjunct drug. ¹²

Safety and Toxicity

Recent systematic reviews concluded that SPE had a favorable safety profile with a very limited impact on sexual function.^13,14 A double blind, placebo-controlled study conducted by Ye et al supported that daily intake of 320 mg SPE for 24 weeks significantly improved the peak urinary flow and International Prostate Symptom Score (IPSS), as well as quality of life, and appeared to be an effective and well-tolerated therapeutic option in the target LUTS/BPH population. ¹⁵ In a subset analysis of data from a 6-month, multicenter, non-interventional study, Alcaraz et al indicated that SPE (320 mg/day) is a valid treatment option for men with moderate/severe LUTS/BPH; improvements in urinary symptoms and quality of life were similar to those observed for tamsulosin, but with considerably fewer adverse effects. ¹⁶ In addition, Cai et al carried out a systematic review and meta-analysis to compare SPE with tamsulosin in the treatment of BPH after at least a 6-month treatment cycle. This study indicated that SPE had the same effect in treating BPH as tamsulosin in terms of IPSS, quality of life, and postvoid residual volume. For adverse events, SPE was well tolerated compared with tamsulosin, especially in ejaculation disorders and libido decrease. ¹⁷ Wyatt et al pointed out that SPE may be a safe herbal supplement, even at a dose of 960 mg daily. ¹⁸ Moreover, a multicenter, randomized, double-blind, placebo-controlled trial performed by Zhang et al showed that SPE was effective and safe for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); only minor side effects such as nausea and stomach discomfort were observed. ¹⁹ Evidence obtained from Asher et al supported that SPE can safely be taken with most medications since there is a low likelihood of drug interactions between SPE and other nutritional supplements. ²⁰

Mechanisms of Action

Anti-Androgenic Effects

As the most active androgen in the human body, 5α-dihydrotestosterone (DHT) is converted from testosterone via the action of 5α-reductase and plays critical roles in the development of male sexual characteristics, prostatic hyperplasia and other physiological and pathological processes through binding to nuclear androgen receptors and activating the transcription of androgen-regulated genes. SPE has been indicated to inhibit 5α-reductase; both sterols and fatty acids of SPE can play a role in the inhibition of the enzyme by competitive interaction with testosterone for the binding site of the enzyme, thereby reducing DHT production and competitive interaction with DHT for binding to the androgen-receptor.^8,21,22 However, of note, many studies indicate that SPE may modulate androgen metabolism and/ or block the effects of androgens because of mitigation of androgen-induced increase in prostatic mass in castrated or non-castrated rodent models.^23,24 Wadsworth et al reported that in the prostate of transgenic adenocarcinoma of the mouse prostate model, treatment with 300 mg/kg/day SPE from 4 to 24 weeks of age significantly reduced the concentration of DHT in the prostate, supporting the view that inhibition of 5α-reductase is a mechanism of action of SPE. ²² Another trial performed by Governa et al validated that both sterols and fatty acids of SPE can play a role in the inhibition of 5α-reductase. ²¹ Sudeep et al indicated that subjects treated with β-sitosterol enriched SPE showed reduced 5α-reductase from baseline to the end of a 12-week treatment as compared to placebo. ¹⁰ The above results confirmed the anti-androgenic effects of SPE through antagonizing 5α-reductase to reduce DHT production and inhibiting DHT binding to androgen receptors contributing to the treatment of urinary-related diseases, such as BPH and prostate cancer. In addition, SPE exhibits anti-estrogenic activity. ¹⁰ SPE appears to display an inhibitory effect both on androgen- and estrogen-receptors, probably because it is composed of several fractions, one with an anti-androgenic action and another with an anti-estrogenic action. ²⁵ However, whether the primary effect is anti-estrogenic and the inactivation of the androgen-receptor and of the 5α-reductase activity is secondary has to be demonstrated.

Effects on Autonomic Receptors in the Lower Urinary Tract

Symptoms of BPH are mainly caused by mechanical and dynamic obstruction. Dynamic obstruction is mainly caused by enhanced sympathetic nerve function in the prostate and bladder neck. The existing α1-adrenergic receptor antagonist can relax prostatic smooth muscle to improve symptoms. In addition, the muscarinic receptors (M receptors) of the M3 type are mainly distributed in the bladder detrusor, and anticholinergics can treat the overactive bladder by antagonizing M receptors. ²⁶ Oki et al ²⁷ demonstrated that SPE can significantly increase the bladder volume of rats to relieve the symptoms of overactive bladder, thereby prolonging the interval between urinations. Meanwhile, SPE can inhibit the activation of M receptors and α1-adrenergic receptors. It is indicated that SPE inhibits the specific binding of [³H] prazosin (α1-adrenergic receptor), [N-methyl-³H] scopolamine methyl chloride (NMS, muscarinic receptor) and ( + )-[³H]PN200 to 110(1,4-dihydropyridine receptor), but not αβ-methylene adenosine triphosphate [2, 8-⁽³⁾ H] tetrasodium salt (purinergic receptor) in the prostate and bladder.^28,29 Moreover, the binding activity of SPE for muscarinic receptors was four times greater than that for α1-adrenergic and1,4-dihydropyridine receptors. In addition, SPE administered orally specifically affects muscarinic and α1-adrenergic receptors in the lower urinary tract. It may be concluded that SPE exerts significant binding activity on autonomic receptors in the lower urinary tract under in vitro and in vivo conditions. A study carried out by Chevalier et al on rats given orally SPE, supplemented with [14C]-labelled oleic or lauric acid or β-sitosterol, indicated that radioactivity uptake in prostatic tissues showed the highest level in the case of administration of SPE supplemented with [14C]-labelled oleic acid. Ratios of radioactivity in tissues compared to plasma showed an uptake of radioactivity greater in the prostate as compared to other genital organs. The results suggested that oral administration of SPE has a certain organ selectivity and it mainly accumulates in the prostate. ³⁰ Furthermore, an experiment conducted by Chua et al ³¹ evaluated the response of fatty acids to SPE in prostate contractions induced by adrenaline, ATP, choline and potassium chloride. It was found that SPE can exert concentration-related inhibition effects, and further proved that SPE may inhibit prostate smooth muscle contraction through a non-specific mechanism.

Anti-Inflammatory Activity

In addition to the aforementioned mechanisms of action, SPE also has an anti-inflammatory effect targeting enzymes and chemokines in the inflammatory reaction process. Gravas et al conducted a randomized biopsy study, in which inflammation was assessed by the Irani‘s score and immunohistochemical staining using CD3, CD4 and CD8 (for T-leucocytes), CD20 (for B-leucocytes) and CD163 (for macrophages) antibodies. The mean decrease in all inflammation scores was statistically higher in patients receiving SPE (320 mg/day) compared to controls. Immunohistochemical staining showed a statistically significant change in the expression of the analyzed antibodies for the SPE group compared to the control. Thus, SPE seems to reduce prostatic inflammation in terms of histological and immunohistochemical parameters in this specific patient population. ³² The current evidence from De Nunzio et al showed that SPE significantly reduced persistent prostatic inflammatory status and relieved LUTS to the same extent as α1-adrenergic receptor antagonists and short-term 5α-reductase inhibitors. ³³ Lipopolysaccharide (LPS) carried by bacteria can induce the secretion of chemokines in the prostate during inflammation. Furthermore, SPE has been reported to inhibit epidermal growth factor (EGF) and LPS induced proliferation of prostatic epithelial. Additionally, SPE reduced the LPS-induced secretion of IL-12. Taken together, the data suggest that SPE inhibits EGF-dependent growth and proinflammatory responses of prostate epithelial cells. ³⁴ Chronic prostatitis (CP) is also one of the complications of BPH. A clinical study conducted by Latil et al investigated the amelioration of inflammatory marker levels after SPE was applied to patients with LUTS. The average down-regulation of inflammatory marker protein expression in the SPE group was significantly higher than that in the control group (65.4% vs. 46.2%). Thus, SPE was demonstrated to exert an anti-inflammatory effect in clinical samples. ³⁵ Another experiment performed by Morgia et al examined the number of T cells, B cells, and macrophages in biopsy specimens of patients with LUTS before and after SPE treatment to assess inflammatory levels. The results showed that the mean value of the experimental group was lower than that of the control group, suggesting that the anti-inflammatory effect of SPE has a certain significance for treating CP. ³⁶ Multiple actions derived from different constituents may contribute to SPE efficacy. A recent review by Kwon et al reported that phytosterol(β-sitosterol) in SPE reduced prostatic inflammation. ⁸ SPE is frequently combined with other natural compounds. It is noted that the lycopene-selenium-SPE mixture has greater and enhanced anti-inflammatory activity in the treatment of BPH.^37,38 SPE, in combination with Crocus sativus and Pinus massoniana, has previously been demonstrated to improve sexual function and limit urinary symptoms. The study found that the tested extracts, either alone or in combination, were able to reduce ROS production and NF-κB and PGE2 activity in prostate specimens challenged with LPS. The antioxidant and anti-inflammatory activity of a combined formulation of SPE and Urtica dioica in an in vitro human model of BPH was evaluated in another study performed by Saponaro et al The results showed that SPE and U. dioica reduced ROS production, NF-κB translocation inside the nucleus, and interleukin 6(IL-6) and interleukin 8(IL-8) production, confirming both the antioxidant and anti-inflammatory effects of SPE and U. dioica. ³⁹

Anti-Proliferative and Pro-Apoptotic Effects

Changes in cell proliferation and apoptosis are of great importance in prostate diseases, especially in BPH and prostate tumors. SPE may affect the proliferation of prostate tumors by inhibiting the expression of Cox-2. ⁴⁰ Vacherot et al ⁴¹ analyzed apoptosis and cell proliferation in the stroma and epithelium of normal prostate and in BPH tissue from patients treated with or without SPE. The results showed that SPE significantly inhibited proliferation and induced apoptosis in both epithelium and stroma in the BPH treated group in comparison with the normal group. Roell et al ⁴² found that anthranilate in SPE can antagonize androgens and inhibit prostate tumor proliferation. Recent data collected by Morgia et al have demonstrated that synthetic agents of SPE that added lycopene and selenium can promote apoptosis by reducing the production of survivin and neuronal apoptosis transplant proteins in BPH patients. ⁴³ The lycopene-selenium-SPE association is more effective than SPE alone in augmenting the pro-apoptotic Bax and caspase-9 and blunting the anti-apoptotic Bcl-2 mRNA. The lycopene-selenium-SPE association also markedly decreased the EGF and Vascular Endothelial Growth Factor (VEGF) expression in hyperplastic prostates.^37,38 In addition, treatment with saladette tomato pomace and SPE could enhance prostate function by reducing contractility and hyperplasia and improve smooth muscle fiber structure and decrease cell proliferation in the bladder, suggesting their possible health-beneficial effects in LUTS. Further, Sudeep et al demonstrated that β-sitosterol enriched SPE significantly regulated the expression of apoptotic marker proteins in BPH rats and could be efficacious in treating the BPH complications. ⁹

Clinical Application of SPE in Urinary System Diseases

Benign Prostatic Hyperplasia (BPH)

BPH is a nonmalignant enlargement of the prostate, which can cause obstructive and irritative LUTS. As there is controversy about the use of phytotherapy in men with LUTS suggestive of BPH, all available clinical trial data were analyzed in two large-scale systematic reviews to determine the efficacy of SPE against placebo. Data from 27 studies (15 RCTs and 12 observational studies) by Vela-Navarrete et al suggested that compared with men receiving placebo, men treated with SPE was associated with 0.64 (95% confidence interval [CI] −0.98 to −0.31) fewer voids/night (P ＜ .001) and an additional mean increase in Q _max of 2.75 mL/s (95% CI 0.57 to 4.93; P = .01) along with a mean improvement in IPSS from a baseline of −5.73 points (95% CI −6.91 to −4.54; P ＜ .001). ¹³ SPE did not negatively affect sexual function and no clinically relevant effect was observed on prostate-specific antigen. Prostate volume decreased slightly. Similar efficacy results were seen in patients treated for ≥ 1 year (n = 447). ¹³ Another study conducted by Ye et al showed a statistically significant improvement in peak urinary flow, IPSS, scores of storage symptoms and voiding symptoms, quality of life score, four-item male sexual function questionnaire score, and International Index of Erectile Function score of subjects treated with SPE compared with those treated with placebo (P ＜ .05). ¹⁵ Additionally, subjects treated with β-sitosterol enriched SPE showed significant efficacy as compared to conventional preparations, thus extending the scope of effective BPH treatment with improved quality of life through the intake of functional ingredients.^9,10 However, the latest network meta-analysis by Russo et al, which assessed 22 RCTs, demonstrated that SPE did not show clinically meaningful improvement in relieving LUTS/BPH and may not justify its clinical use before a higher level of evidence is available, due to a high level of heterogeneity in the quality of SPE products and methodological limitations of the published trials and meta-analyses. ⁴⁴ The use of SPE also remains controversial in the US. Contributing to such an opposing view are the wide variability in quality, composition, and dosage of SPE products, the commercial prevalence of dried berry powder supplements, and the lack of awareness of a standardized SPE phytotherapy lipidosterolic profile. ⁴⁵ Ooi et al indicated that a strong placebo effect, potentially influenced by positive patients’ expectation of SPE, shapes both the clinical practice outcomes and the findings of clinical trials. ³ However, the totality of evidence, including favorable patients’ response from clinical experience, impact of placebo effect, early positive studies, subjective nature of symptom reporting, pharmacological properties of SPE, and potential synergistic effects when combined with other therapies, continues to suggest that SPE is a prudent therapeutic option as part of the naturopathic treatment for LUTS/BPH and is safe in its application. ³ Clinical results obtained by Ooi et al also show that SPE can ameliorate urinary symptoms and improve the quality of patients’ lives, and its safety has been recognized. So there is no need to prohibit its use in clinical application. ³ In addition to the therapeutic effect on males with BPH/LUTS, the recent publication by Yamada et al demonstrated that SPE also showed a significant improvement of LUTS in female rats (no prostate), possibly by targeting bladder pharmacological receptors. ⁴⁶ Among all SPE supplements, Permixon has the highest activity and the most accurate standards of drug preparation and extraction. A systematic review of the literature by Novara et al pointed out that Permixon reduced nocturia and improved urinary flow and Qmax compared with placebo and had a similar efficacy to tamsulosin and short-term finasteride. ¹⁴ Moreover, Permixon appears to be an efficacious and well-tolerated therapeutic option with a very limited impact on sexual function, which is significantly affected by all other drugs used to treat LUTS/BPH. ¹⁴ SPE also has a number of combined regimens to treat BPH clinically. A literature review by Russo et al investigated the effects of SPE + Selenium + Lycopene on the management of LUTS secondary to BPH. ⁴⁷ SPE + Selenium + Lycopene in combination with tamsulosin is more efficacious than single therapies in improving IPSS and increasing maximal urinary flow-rate in patients affected by LUTS/BPH. Other combination therapies, such as with tamsulosin,^48–50 Urtica dioica, ³⁹ Pinus pinaster ³⁶ and Peucedanum japonicum, ⁵¹ have also shown positive results in co-prescriptions for treating BPH and BPH-linked disorders.

Chronic Prostatitis (CP) and Chronic Pelvic Pain Syndrome (CPPS)

A recent placebo-controlled trial performed by Zhang et al concluded that SPE was effective, safe and clinically superior to placebo for the treatment of CP and CPPS. ¹⁹ Compared to the placebo, SPE led to statistically significant improvements in the Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total score and sub-scores after 2 weeks from the first dose, and continued to the end of the treatment. Furthermore, a significantly higher rate of patients achieved a clinical response in the SPE group compared with that in the placebo group (73.0% vs. 32.9%, P ＜ .0001), with only minor adverse events being observed across the entire study population. It is reported by Iglesias-Gato et al that SPE has unique significance in the treatment and control of CP and CPPS due to its androgen-independent effects on inflammation. ³⁴ Colado-Velázquez et al ⁵² investigated the effects of SPE in markers of oxidative stress, inflammation, and growth factors in obese rats with testosterone-induced prostatic hyperplasia. The results showed that SPE significantly decreased prostate weight, total nitrite, and malondialdehyde; improved total glutathione, SOD, and catalase activity; and significantly reduced inflammatory markers (TNF-α, IL-1β and IL-6) and growth factors (VEGF and FGFb). Therefore, SPE demonstrated high antioxidant and anti-inflammatory activity in obese rats, suggesting that it could be beneficial in the treatment of CP and CPPS. An international, randomized, double-blind study by Latil et al has also shown that SPE can attenuate inflammation biomarkers, control LUTS, and can be considered to prevent progression of CP. ³⁵ Gallo et al found that a pure anti-inflammatory scheme including nimesulide, SPE, bromelain, and quercetin, can effectively reduce PSA levels in patients diagnosed with a histologic prostatitis and showing a persisting level of PSA greater than 4 ng/dL. ⁵³ Bifiprost® is a combination of Vaccinium macracarpon, Lycium barbarum and probiotics (Lactobacillus plantarum LP01 and L. paracasei LPC09). A double-blind randomized study by Chiancone et al, involving 120 patients with chronic bacterial prostatitis, found that the association of Bifiprost® and SPE 320 mg improved the prevention of the episodes of chronic bacterial prostatitis due to Enterobacteriaceae and ameliorated prostatitis-related symptoms after 6 months of therapy. ⁵⁴ The long-term impact on the entero-urinary route was also seen 3 months after the end of the treatment.

Prostate Cancer

SPE also has a certain clinical application value in terms of tumor treatment due to its anti-inflammatory and anti-proliferative effects. Cox-2 is considered to be an enzyme produced by prostate tumor cells and can promote tumor cell proliferation. Goldmann et al found that SPE can inhibit cell growth and Cox-2 expression in a set of prostatic cancer cell lines; 267B-1, BRFF-41 T and LNCaP. Reduced cellular growth after SPE treatment of these cell lines may relate to decreased expression of Cox-2 and may be due to changes observed in the expression of Bcl-2. ⁴⁰ In a transgenic adenocarcinoma mouse prostate model, treatment with 300 mg/kg/day SPE from 4 to 24 weeks of age significantly reduced the concentration of DHT in the prostate and resulted in a significant increase in apoptosis and a significant decrease in pathological tumor grade and frank tumor incidence. This study by Wadsworth et al indicated that SPE could prevent the progression of prostate cancer. ²² In addition, Habib et al suggested that SPE can up-regulate the expression of p53 in the LNCaP cell line and down-regulate IL-6-induced phosphorylation of STAT3. In vivo experiments have shown that SPE can inhibit the volume of LNCaP tumor xenografts in nude mice. ⁵⁵ The PSA routine test is crucial in predicting prostate tumors. Habib et al indicated that SPE inhibits 5α-reductase activity of human prostate cancer cell lines without interfering with PSA expression. Therefore, the therapeutic advantage of SPE over other 5α-reductase inhibitors as treatment will permit the continuous use of PSA measurements as a useful biomarker for prostate cancer screening and for evaluating tumor progression. ⁵⁵ However, the research results in this respect were not consistent. Roell et al reported that SPE exhibited anti-androgenic potential and inhibited the androgen receptor-induced expression of endogenous PSA. ⁴² Recently, SPE has been used in symptom management during radiation therapy for prostate cancer. LUTS affects 75%-80% of men undergoing radiation therapy for prostate cancer. The results suggested that the use of SPE supplements is not associated with outcomes or toxicities, but its efficacy in managing LUTS during radiation therapy needs further investigation.^18,56

Erectile Dysfunction (ED)

Sexual function is one of the aspects in the treatment of LUTS associated with BPH that has gained increasing attention. Zlotta et al compared the influence on men‘s sexuality of Permixon, a lipido-sterolic extract of Saw palmetto, with Tamsulosin and Finasteride using a specific validated questionnaire exploring the patient‘s sexual function. The study demonstrated that Permixon therapy had no negative impact on male sexual function. Both Finasteride and Tamsulosin had a slight impact on sexual function, although these effects were rare and in line with previous reports about these two drugs. ⁵⁷ A recent experiment conducted by Yang et al found that the relaxant response to electrical stimulation of nerves in the corpus cavernosum was significantly and dose-dependently augmented in SPE-treated animals, whereas phosphodiesterase 5(PDE5) activity was significantly and dose-dependently inhibited. The experiment also measured the mRNA level of inducible nitric oxide synthase (iNOS) associated with erection. The results indicated that SPE may have potential application value for the prevention or treatment of ED through an increase in iNOS mRNA expression and inhibition of PDE5 activity in corpus cavernosum smooth muscles. ⁵⁸ An open multicentric clinical pilot trial implemented by Suter et al examined the role of SPE preparation in improving BPH symptoms and sexual dysfunction. The brief Sexual Function Inventory was found to improve from 22.4 ± 7.2 to 31.4 ± 9.2 (P < .0001), showing that SPE plays a certain role in improving BPH symptoms and sexual dysfunction as well. ⁵⁹ Additionally, Quarto et al demonstrated that treatment once daily with IDIProst® Gold (SPE combined with Crocus sativus and Pinus massoniana bark extract) for three months significantly improved sexual function, urinary symptoms and quality of life in patients with concomitant LUTS and ED, especially in the 40 to 60 age group. ⁶⁰ No adverse events were reported.

Summary and Outlook

There are currently more than 20 kinds of SPE supplements on the drug markets in western countries, the main components of which are various fatty acids and sterols. Drugs made from liquid solvent are described as the most effective at present. The current safety of SPE has been widely recognized, and the mechanisms of action for treating urinary diseases--anti-androgenic effects, effects on autonomic receptors in the lower urinary tract, anti-inflammatory activity, anti-proliferative and pro-apoptotic effects, have been studied intensively. Although many previous studies have demonstrated that SPE is effective in treating BPH, large-scale RCT results recently showed no significant difference between SPE and placebo. However, the strong placebo effect is potentially influenced by the positive patients’ expectation of SPE, which shapes both the clinical practice outcomes and the findings of the clinical trial. Furthermore, the improvement in symptoms and life quality after SPE treatment is confirmed in clinical practice. So SPE can be considered to have no safety problem and still has its value in improving the prognosis of patients. Since SPE has anti-inflammatory effects independent of anti-androgenic effects, it is worthy of application in treating BPH combined with CP and CPPS. SPE is currently used as a supplementary drug in the control of tumors. However, its role in radiotherapy is not remarkable and still needs further research and understanding. SPE has no negative effects on male sexual function and erectile function. Meanwhile, studies have shown that the drug can improve erectile function by increasing iNOS and lowering PDE5. In addition, as an herb drug, there are multiple options for combination with other drugs. As a consequence, SPE is safe, but its clinical application still needs further research in order to better serve patients with urological disorders.