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Clinical Phytoscience

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Open Access 01-12-2022 | Benign Prostatic Hypertrophy | Original contribution

Beneficial effects of pumpkin seed soft extract on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia: a meta-analysis of two randomized, placebo-controlled trials over 12 months

Authors: Winfried Vahlensieck, Stefan Heim, Brigitte Patz, Kurtulus Sahin

Published in: Clinical Phytoscience | Issue 1/2022

Abstract

Background

In clinical practice, plant extracts are an option to treat mild-to-moderate lower urinary tract symptoms suggestive of benign prostate hyperplasia (LUTS/BPH). However, only a few herbal extracts have been investigated in long-term placebo-controlled studies. The safety and efficacy of a well-tolerated proprietary pumpkin seed soft extract (PSE) were investigated in two randomized placebo-controlled 12-month studies (Bach and GRANU study). Both trials studied LUTS/BPH patients with an International Prostate Symptom Score (IPSS) ≥13 points at baseline. The Bach study demonstrated positive effects of PSE compared to placebo, but no difference between treatments was observed in the GRANU study. We aimed to assess the efficacy of PSE in a meta-analysis using the patient-level data of these two studies.

Methods

Pooled analysis was performed in the intention-to-treat set using last-observation-carried-forward (ITT-LOCF). An IPSS improvement of ≥5 points after 12 months of therapy was the predefined response criterion. Logistic regression and ANCOVA models included the covariables treatment group, study, center size, and baseline IPSS. Each analysis was repeated for the per-protocol (PP) set.

Results

The ITT/PP analysis sets consisted of 687/485 and 702/488 patients in the PSE and placebo groups, respectively. At the 12-month follow-up, the response rates in the PSE group were 3% (ITT) and 5% (PP) higher than those in the placebo group. The odds ratio of response obtained by logistic regression analysis for comparing PSE versus placebo was 1.2 (95% CI 0.9, 1.5), favoring PSE (ITT- LOCF). For the IPSS change from baseline to 12 months, the ANCOVA estimated difference between the treatment groups was 0.7 points (95% CI 0.1, 1.2) in favor of PSE. The variables study, baseline IPSS, and center size had a relevant influence on treatment response.

Conclusion

Although the Bach and the GRANU study showed contradictory results, the analysis in a pooled form still pointed towards an advantage of PSE; namely, more patients in the PSE group showed an IPSS improvement of at least 5 points after 12 months. Therefore, the results of this meta-analysis suggest that patients with moderate LUTS/BPH may benefit from PSE treatment in terms of symptomatic relief.

Available only for authorised users

Soft extract from the seeds of Uromedic^® pumpkin is the active ingredient of medicinal products for the treatment of LUTS/BPH. Brand names are GRANU FINK Prosta forte 500 mg (DE), GRANU FINK Prosta kemény (HU), GRANUFINK Prosta forte (AT, CH, NL, UA), and Urostemol Prosta (UK).

Đorđević I, Milutinović M, Kostić M, Đorđević B, Dimitrijević M, Stošić N, et al. Phytotherapeutic approach to benign prostatic hyperplasia treatment by pumpkin seed (Cucurbita Pepo L., Cucurbitaceae). Acta Med Medianae. 2016;55(3):76–84 http://scindeks-clanci.ceon.rs/data/pdf/0365-4478/2016/0365-44781603076D.pdf.CrossRef

Gravas S, Cornu JN, Gacci M, Gratzke C, Herrmann TRW, Mamoulakis C, et al. EAU Guidelines on Management of Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS), incl. Benign Prostatic Obstruction. 2021 https://uroweb.org/wp-content/uploads/EAU-Guidelines-on-Management-of-Non-Neurogenic-Male-LUTS-2021.pdf.

Fourcade RO, Theret N, Taieb C. Profile and management of patients treated for the first time for lower urinary tract symptoms/benign prostatic hyperplasia in four European countries. BJU Int. 2008;101(9):1111–8. https://doi.org/10.1111/j.464-410X.2008.07498.x.CrossRefPubMed

Fornara P, Madersbacher S, Vahlensieck W, Bracher F, Romics I, Kil P. Phytotherapy adds to the therapeutic armamentarium for the treatment of mild-to-moderate lower urinary tract symptoms in men. Urol Int. 2020;104(5-6):333–42. https://doi.org/10.1159/000504611.CrossRefPubMed

Ullah R, Wazir J, Hossain MA, Diallo MT, Khan FU, Ihsan AU, et al. A glimpse into the efficacy of alternative therapies in the management of benign prostatic hyperplasia. Wien Klin Wochenschr. 2021;133(3):153–62. https://doi.org/10.1007/s00508-020-1692-z.CrossRefPubMed

Deutsche Gesellschaft für Urologie. DGU, Deutsche Gesellschaft für Urologie. S2e Leitlinie Therapie des Benignen Prostatasyndroms (BPS). Akademie der Deutschen Urologen. AWMF-Reg.Nr.: 043-035. 2014. https://www.awmf.org/leitlinien/detail/ll/043-035.html. Accessed 11 Jan 2021.

Gravas S, Cornu JN, Gacci M, Gratzke C, Herrmann TRW, Mamoulakis C, et al. EAU Guidelines on Management of Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS), incl. Benign Prostatic Obstruction (BPO). 2019. https://uroweb.org/wp-content/uploads/EAU-Guidelines-on-the-Management-of-Non-Neurogenic-Male-LUTS-2019.pdf. Assessed 11 Jan 2021.

Fourcade R-O, Lacoin F, Rouprêt M, Slama A, Le Fur C, Michel E, et al. Outcomes and general health-related quality of life among patients medically treated in general daily practice for lower urinary tract symptoms due to benign prostatic hyperplasia. World J Urol. 2012;30(3):419–26. https://doi.org/10.1007/s00345-011-0756-2.CrossRefPubMed

Pinggera GM, Frauscher F. Do we really need herbal medicine in LUTS/BPH treatment in the 21(st) century? Exp Opin Drug Saf. 2016;15(12):1573–5. https://doi.org/10.1080/14740338.2016.1214267.CrossRef

10.

Eredics K, Madersbacher S, Schauer I. A relevant midterm (12 months) placebo effect on lower urinary tract symptoms and maximum flow rate in male lower urinary tract symptom and benign prostatic hyperplasia-a Meta-analysis. Urology. 2017;106:160–6. https://doi.org/10.1016/j.urology.2017.05.011.CrossRefPubMed

11.

Sech SM, Montoya JD, Bernier PA, Barnboym E, Brown S, Gregory A, et al. The so-called "placebo effect" in benign prostatic hyperplasia treatment trials represents partially a conditional regression to the mean induced by censoring. Urology. 1998;51(2):242–50. https://doi.org/10.1016/S0090-4295(97)00609-2.CrossRefPubMed

12.

van Leeuwen JH, Castro R, Busse M, Bemelmans BL. The placebo effect in the pharmacologic treatment of patients with lower urinary tract symptoms. Eur Urol. 2006;50(3):440–53. https://doi.org/10.1016/j.eururo.2006.05.014.CrossRefPubMed

13.

Aso Y, Baccon-Gibob L, Calais da Silva F, Cockett ATK, Moriyama N, Okajima E, et al. Clinical Research Criteria. In: Cockett ATK, Chatelain C, Aso Y, editors. Proceedings of the 2nd International Consultation on Benign Prostatic Hyperplasia (BPH), Paris, 1993. Jersey: Scientific Communication International Ltd; 1993. p. 345–58.

14.

Madersbacher S, Berger I, Ponholzer A, Marszalek M. Plant extracts: sense or nonsense? Curr Opin Urol. 2008;18(1):16–20. https://doi.org/10.1097/MOU.0b013e3282f0d5c8.CrossRefPubMed

15.

Vela-Navarrete R, Alcaraz A, Rodríguez-Antolín A, Miñana López B, Fernández-Gómez JM, Angulo JC, 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(6):1049–65. https://doi.org/10.1111/bju.14362.CrossRefPubMed

16.

Bach D. Placebokontrollierte Langzeittherapiestudie mit Kürbissamenextrakt bei BPH-bedingten Miktionsbeschwerden. Der Urologe B. 2000;40(5):437–43. https://doi.org/10.1007/s001310050432.CrossRef

17.

Vahlensieck W, Theurer C, Pfitzer E, Patz B, Banik N, Engelmann U. Effects of pumpkin seed in men with lower urinary tract symptoms due to benign prostatic hyperplasia in the one-year, randomized, Placebo-Controlled GRANU Study. Urol Int. 2015;94(3):286–95. https://doi.org/10.1159/000362903.CrossRefPubMed

18.

Damiano R, Cai T, Fornara P, Franzese CA, Leonardi R, Mirone V. The role of Cucurbita pepo in the management of patients affected by lower urinary tract symptoms due to benign prostatic hyperplasia: a narrative review. Arch Ital Urol Androl. 2016;88(2):136–43. https://doi.org/10.4081/aiua.2016.2.136.CrossRefPubMed

19.

EMA/HMPC. Assessment report on Cucurbita pepo L., semen. European Medines Agency/Committee on Herbal Medicinal Products EMA/HMPC/136022/2010. 2012. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-cucurbita-pepo-l-semen_en.pdf. Assessed 11 Jan 2021.

20.

Müller C, Bracher F. Determination by GC-IT/MS of Phytosterols in herbal medicinal products for the treatment of lower urinary tract symptoms and food products marketed in Europe. Planta Med. 2015;81(7):613–20. https://doi.org/10.1055/s-0035-1545906.CrossRefPubMed

21.

Barkin J. Benign prostatic hyperplasia and lower urinary tract symptoms: evidence and approaches for best case management. Can J Urol. 2011;18(Suppl):14–9 PMID: 21501546.PubMed

22.

Braeckman J, Denis L. Management of BPH then 2000 and now 2016 - from BPH to BPO. Asian J Urol. 2017;4(3):138–47. https://doi.org/10.1016/j.ajur.2017.02.002.CrossRefPubMedPubMedCentral

23.

Roehrborn CG, Casabe A, Glina S, Sorsaburu S, Henneges C, Viktrup L. Treatment satisfaction and clinically meaningful symptom improvement in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: secondary results from a 6-month, randomized, double-blind study comparing finasteride plus tadalafil with finasteride plus placebo. Int J Urol. 2015;22(6):582–7. https://doi.org/10.1111/iju.12741.CrossRefPubMed

24.

Barry MJ, Girman CJ, O'Leary MP, Walker-Corkery ES, Binkowitz BS, Cockett AT, et al. Using repeated measures of symptom score, uroflowmetry and prostate specific antigen in the clinical management of prostate disease. Benign prostatic hyperplasia treatment outcomes study group. J Urol. 1995;153(1):99–103. https://doi.org/10.1097/00005392-199501000-00036.CrossRefPubMed

25.

Debruyne F, Koch G, Boyle P, Da Silva FC, Gillenwater JG, Hamdy FC, et al. Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study. Eur Urol. 2002;41(5):497–506. https://doi.org/10.1016/S0302-2838(02)00066-0.CrossRefPubMed

26.

EMA/HMPC. Assessment report on Serenoa repens (W. Bartram) Small, fructus. EMA/HMPC/137250/2013. 2015.

27.

Russo GI, Scandura C, Di Mauro M, Cacciamani G, Albersen M, Hatzichristodoulou G, et al. Clinical efficacy of Serenoa repens Versus placebo versus alpha-blockers for the treatment of lower urinary tract symptoms/benign prostatic enlargement: a systematic review and network Meta-analysis of randomized placebo-controlled clinical trials. Eur Urol Focus. 2021;7(2):420–31. https://doi.org/10.1016/j.euf.2020.01.002.CrossRefPubMed

28.

Ebrahim S, Sohani ZN, Montoya L, Agarwal A, Thorlund K, Mills EJ, et al. Reanalyses of randomized clinical trial data. JAMA. 2014;312(10):1024–32. https://doi.org/10.1001/jama.2014.9646.CrossRefPubMed

29.

Oelke M. Leitlinien der Deutschen Urologen zur Therapie des benignen Prostatasyndroms (BPS). Der Urologe A. 2003;42(5):722–38. https://doi.org/10.1007/s00120-003-0318-3.CrossRefPubMed

Title: Beneficial effects of pumpkin seed soft extract on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia: a meta-analysis of two randomized, placebo-controlled trials over 12 months
Authors: Winfried Vahlensieck
Stefan Heim
Brigitte Patz
Kurtulus Sahin
Publication date: 01-12-2022
Publisher: Springer Berlin Heidelberg
Keywords: Benign Prostatic Hypertrophy
Benign Prostatic Hypertrophy
Published in: Clinical Phytoscience / Issue 1/2022
Electronic ISSN: 2199-1197
DOI: https://doi.org/10.1186/s40816-022-00345-0

At a glance: The STEP trials

Springer Medicine

Beneficial effects of pumpkin seed soft extract on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia: a meta-analysis of two randomized, placebo-controlled trials over 12 months

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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