Serenoa repens and its effects on male sexual function. A systematic review and meta-analysis of clinical trials
https://doi.org/10.4081/aiua.2021.4.475
Accepted: December 3, 2021
Supplementary File: 66
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Background: Serenoa repens (SR) is a plant used to treat benign prostatic hyperplasia and prostatitis. We know that SR act as a 5α-reductase inhibitor, moreover, several studies have proved that SR has anti-inflammatory and antioxidant properties. There is some belief among patients that SR may negatively impact male sexual function. Such belief is circulating in non-medical social networks and is perhaps maintained by patients as a result of incorrect web surfing. However, it is also possible that SR may exert a “nocebo” effect thus negatively impacting on the general well-being of patients.
Objective: The aim of this study is to investigate whether SR is causing negative effects on male sexual function.
Methods: To ascertain the effect of SR on male sexual function, we conducted a systematic review and meta-analysis, by performing an electronic database search in accordance with the PRISMA guidelines.
Results: Out of 20 included papers, 8 papers reported comparisons of SR with placebo, and 7 studies reported comparisons of SR with tamsulosin. The standardized mean difference of changes from baseline scores of sexual function was not significantly different between SR and placebo (SMD: 0.43, 95% CI: 0.18 to 1.05; I^2 = 95%). Similarly, no significant mean differences in the Male Sexual Function-4 (MSF-4) test scores were found between SR and tamsulosin (SMD: -0.31, 95% CI: -0.82 to 0.19; I^2 = 90%).
Conclusions: We found no statistically significant differences between negative effects on sexual function in patients treated with SR compared to patients who received placebo. The results of our meta-analysis are similar to those of other systematic reviews. Studies are warranted to ascertain whether any such effects might occur as a result of a nocebo effect.
Bennet BC, Hicklin JR. Uses of saw palmetto (Serenoa repens, Arecaceae) in Florida. Economic Botany. 1998; 52:381-393. DOI: https://doi.org/10.1007/BF02862068
Duborija-Kovacevic N, Jakovljevic V, Sabo A, et al. Tolerability and toxicity of lipidosterolic extract of American dwarf palm Serenoa repens in Wistar rats: well-known extract, new insight. Eur Rev Med Pharmacol Sci. 2011; 15:1311-1317.
Bayne CW, Donnelly F, Ross M, et al. Serenoa repens (Permixon®): A 5areductase types I and II inhibitor—new evidence in a coculture model of BPH. Prostate. 1999; 40:232-241. DOI: https://doi.org/10.1002/(SICI)1097-0045(19990901)40:4<232::AID-PROS4>3.0.CO;2-0
Habib FK. Serenoa repens: the scientific basis for the treatment of benign prostatic hyperplasia. Eur Urol Suppl. 2009; 8:887-893. DOI: https://doi.org/10.1016/j.eursup.2009.11.005
McNicholas TA, Kirby RS, Lepor H. Evaluation and nonsurgical management of benign prostatic hyperplasia. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, editors. Campbell-Walsh Urology.
Paubert-Braquet M, Mencia Huerta JMM, Cousse H, et al. Effect of the lipidic lipidosterolic extract of Serenoa repens (Permixon®) on the ionophore A23187-stimulated production of leukotriene B4 (LTB4) from human polymorphonuclear neutrophils. Prostaglandins Leukot Essent Fatty Acids. 1997; 57:299-304. DOI: https://doi.org/10.1016/S0952-3278(97)90548-2
Colado-Velázquez J, Mailloux-Salinas P, Medina-Contreras JML, et al. Effect of Serenoa repens on oxidative stress, inflammatory and growth factors in obese wistar rats with benign prostatic hyperplasia. Phytother Res. 2015;29:1525-1531. DOI: https://doi.org/10.1002/ptr.5406
Latil A, Pétrissans MT, Rouquet J, et al. Effects of hexanic extract of Serenoa repens (Permixon® 160 mg) on inflammation biomarkers in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Prostate. 2015; 75:1857-1867.
Vela Navarrete R, Garcia Cardoso JG, Barat A, et al. BPH and inflammation: pharmacological effects of permixon on histological and molecular inflammatory markers. Results of a double blind pilot clinical assay. Eur Urol. 2003; 44:549-555. DOI: https://doi.org/10.1016/S0302-2838(03)00368-3
Morgia G, Cimino S, Favilla V, et al. Effects of Serenoa repens, selenium and lycopene (Profluss®) on chronic inflammation associated with benign prostatic hyperplasia: results of FLOG (Flogosis and Profluss in Prostatic and Genital Disease), a Multicentre Italian Study. Int Braz J Urol. 2013; 39:214-221. DOI: https://doi.org/10.1590/S1677-5538.IBJU.2013.02.10
Park EJ, Kim SA, Choi YM, et al. Capric acid inhibits NO production and STAT3 activation during LPS-induced osteoclastogenesis. PLoS One. 2011; 6:e27739. DOI: https://doi.org/10.1371/journal.pone.0027739
Kim HJ, Yoon HJ, Kim SY, et al. A medium-chain fatty acid, capric acid, inhibits RANKL-induced osteoclast differentiation via the suppression of NF-kB signaling and blocks cytoskeletal organization and survival in mature osteoclasts. Mol Cells. 2014; 37:598-604. DOI: https://doi.org/10.14348/molcells.2014.0153
Henry GE, Momin RA, Nair MG, et al. Antioxidant and cyclooxygenase activities of fatty acids found in food. J Agric Food Chem. 2002; 50:2231-2234. DOI: https://doi.org/10.1021/jf0114381
Hoshimoto A, Suzuki Y, Katsuno T, et al. Caprylic acid and medium-chain triglycerides inhibit IL-8 gene transcription in Caco-2 cells: comparison with the potent histone deacetylase inhibitor trichostatin A. Br J Pharmacol. 2002; 136:280-286. DOI: https://doi.org/10.1038/sj.bjp.0704719
Srivastava A, Rao LJM, Shivanandappa T. 14-Aminotetradecanoic acid exhibits antioxidant activity and ameliorates xenobiotics-induced cytotoxicity. Mol Cell Biochem. 2012; 364:1-9. DOI: https://doi.org/10.1007/s11010-011-1196-4
Oh YT, Lee JY, Lee J, et al. Oleic acid reduces lipopolysaccharideinduced expression of iNOS and COX-2 in BV2 murine microglial cells: possible involvement of reactive oxygen species, p38 MAPK, and IKK/NF-kappaB signaling pathways. Neurosci Lett. 2009; 464:93-97. DOI: https://doi.org/10.1016/j.neulet.2009.08.040
Ambrozova G, Pekarova M, Lojek A. Effect of polyunsaturated fatty acids on the reactive oxygen and nitrogen species production by raw 264.7 macrophages. Eur J Nutr. 2010; 49:133-139. DOI: https://doi.org/10.1007/s00394-009-0057-3
Ren J, Chung SH. Anti-inflammatory effect of a-linolenic acid and its mode of action through the inhibition of nitric oxide production and inducible nitric oxide synthase gene expression via NF-kB and mitogen-activated protein kinase pathways. J Agric Food Chem. 2007; 55:5073-5080. DOI: https://doi.org/10.1021/jf0702693
Olennikov DN, Zilfikarov IN, Khodakova SE. Phenolic compounds from Serenoa repens fruit. Chem Nat Compd. 2013; 49:526-529. DOI: https://doi.org/10.1007/s10600-013-0659-0
Cristoni A, Di Pierro F, Bombardelli E. Botanical derivatives for the prostate. Fitoterapia. 2000; 71:S21-S28. DOI: https://doi.org/10.1016/S0367-326X(00)00174-X
Nickel JC. Shoskes D, Roehrborn CG, et al. Nutraceuticals in prostate disease: the urologist’s role. Rev Urol. 2008;10:192-206.
Požgain I, Požgain Z, Degmecic D. Placebo and nocebo effect: a mini-review. Psychiatr Danub. 2014; 26:0-107.
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009: 6:e1000097. DOI: https://doi.org/10.1371/journal.pmed.1000097
O'Leary MP, Fowler FJ, Lenderking WR, et al. A brief male sexual function inventory for urology. Urology. 1995; 46:697-706. DOI: https://doi.org/10.1016/S0090-4295(99)80304-5
Rosen RC, Riley A, Wagner G, et al. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997; 49:822-830. DOI: https://doi.org/10.1016/S0090-4295(97)00238-0
Rosen RC, Cappelleri JC, Smith MD, et al. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999; 11:319-326. DOI: https://doi.org/10.1038/sj.ijir.3900472
Marquis P, Marrel, A. Reproducibility and clinical and concurrent validity of the MSF-4: a four-item male sexual function questionnaire for patients with benign prostatic hyperplasia. Value Health. 2001; 4:335-343. DOI: https://doi.org/10.1046/j.1524-4733.2001.44021.x
Avins AL, Bent S, Staccone S, et al. A detailed safety assessment of a saw palmetto extract. Complement Ther Med. 2008; 16:147-154. DOI: https://doi.org/10.1016/j.ctim.2007.10.005
Gerber GS, Kuznetsov D, Johnson BC, et al. Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms. Urology. 2001; 58:960-963. DOI: https://doi.org/10.1016/S0090-4295(01)01442-X
Willetts KE, Clements MS, Champion S, et al. Serenoa repens extract for benign prostate hyperplasia: a randomized controlled trial. BJU Int. 2003; 92:267-70. DOI: https://doi.org/10.1046/j.1464-410X.2003.04316.x
Ye Z, Huang J, Zhou L, et al. Efficacy and safety of Serenoa repens extract among patients with benign prostatic hyperplasia in China: a multicenter, randomized, double-blind, placebo-controlled trial. Urology. 2019; 129:172-179. DOI: https://doi.org/10.1016/j.urology.2019.02.030
Zhang K, Guo RQ, Chen SW, et al. The efficacy and safety of Serenoa repens extract for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome: a multicenter, randomized, double-blind, placebo-controlled trial. World J Urol. 2021; 1-7. DOI: https://doi.org/10.1007/s00345-020-03577-2
Debruyne F, Koch G, Boyle P, et al. Comparison of a phytotherapeutic agent (Permixon) with an a-blocker (tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study. Eur Urol. 2002; 41:497-506. DOI: https://doi.org/10.1016/S0302-2838(02)00066-0
Debruyne F, Boyle P, Calais Da Silva F, et al. Evaluation of the clinical benefit of permixon and tamsulosin in severe BPH patients -PERMAL study subset analysis Eur Urol. 2004; 45:773-780. DOI: https://doi.org/10.1016/j.eururo.2004.01.015
Hizli F, Uygur MC. A prospective study of the efficacy of Serenoa repens, tamsulosin, and Serenoa repens plus tamsulosin treatment for patients with benign prostate hyperplasia. Int Urol Nephrol. 2007; 39:879-886. DOI: https://doi.org/10.1007/s11255-006-9106-5
Latil A, Pétrissans MT, Rouquet J, et al. Effects of hexanic extract of Serenoa repens (Permixon® 160 mg) on inflammation biomarkers in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Prostate. 2015; 75:1857-1867. DOI: https://doi.org/10.1002/pros.23059
Carraro JC, Raynaud JP, Koch G, et al. Comparison of phytotherapy (Permixon®) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Prostate. 1996; 29:231-240. DOI: https://doi.org/10.1002/(SICI)1097-0045(199610)29:4<231::AID-PROS4>3.0.CO;2-E
Marks LS, Partin AW, Epstein JI, et al. Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J Urol. 2000; 163:1451-1456. DOI: https://doi.org/10.1016/S0022-5347(05)67641-0
Pytel YA, Vinarov A, Lopatkin N. et al. Long-term clinical and biologic effects of the lipidosterolic extract of Serenoa repens in patients with symptomatic benign prostatic hyperplasia. Adv Ther. 2002; 19:297-306. DOI: https://doi.org/10.1007/BF02853175
Vela-Navarrete R, Alcaraz A, Rodríguez-Antolín A, et al. Efficacy and safety of a hexanic extract of Serenoa repens
(Permixon®) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta-analysis of randomised controlled trials and observational studies. BJU Int. 2018; 122:1049-1065. DOI: https://doi.org/10.1111/bju.14362
Novara G, Giannarini G, Alcaraz A, et al. Efficacy and safety of hexanic lipidosterolic extract of Serenoa repens (Permixon) in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials. Euro Urol Focus. 2016; 2:553-561. DOI: https://doi.org/10.1016/j.euf.2016.04.002
Cai T, Cui Y, Yu S, et al. Comparison of Serenoa repens With Tamsulosin in the Treatment of Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis. Am J Mens Health. 2020; 14:1557988320905407. DOI: https://doi.org/10.1177/1557988320905407
Colloca L, Barsky AJ. Placebo and nocebo effects. N Engl J Med. 2020; 382:554-561. DOI: https://doi.org/10.1056/NEJMra1907805
Mondaini N, Gontero P, Giubilei G, et al. Finasteride 5 mg and sexual side effects: how many of these are related to a nocebo phenomenon?. J Sex Med, 2007; 4:1708-1712. DOI: https://doi.org/10.1111/j.1743-6109.2007.00563.x
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Downloads
Citations
