Efficacy of Combination Dutasteride and Lycopene to Reduce Bleeding in Benign Prostate Hyperplasia (BPH) Post- Transurethral Resection of the Prostate (TURP) Overview of Hypoxia inducible factor-1 alpha (HIF-1 α) Expression and Hematocrit Levels


Eriawan Agung Nugroho(1*), Siti Amarwati(2), Nugroho Akhbar(3)

(1) Division of Urology, Medical Faculty of Diponegoro University – Dr. Kariadi Hospital, Semarang
(2) Division of Pathology Anatomy, Medical Faculty of Diponegoro University – Dr. Kariadi Hospital, Semarang
(3) General Surgery Resident, Medical Faculty of Diponegoro University
(*) Corresponding Author


Trans Urethral Resection of the Prostate (TURP) is one of the gold operating standards for people with Benign Prostate Hyperplasia (BPH), but the complications, like bleedings, often occur both in durante and post-surgery. The risk of bleeding in TURP is caused by angiogenesis. Hypoxia-Induced Factor-1 Alpha (HIF-1 α) is one of the trigger factors for angiogenesis in BPH. Based on the existing literature, it was found that there was a relationship between lycopene and dutasteride which both had a synergistic effect in inhibiting angiogenesis. However, the mechanism is unknown. This study aims to assess the effectiveness of the combination of dutasteride and lycopene on the expression of HIF-1α and hematocrit levels in BPH patients undergoing TURP surgery. This research was an experimental study with "Double-Blind Randomized Controlled Trial Post Test Only Design". The 22 patients were divided into 2 groups, namely T (dutasteride + lycopene), C (lycopene+plasebo), which were given every 24 hours for a minimum of 30 days until the TURP operation was carried out. The observation of HIF-1α expression used immunohistochemical methods. Different tests were conducted between the groups with Independent T-test. The result shows the combination of dutasteride and lycopene was not significant in reducing the HIF-1α expression, indicated by mean rank in the group (C) (= 21.60), group (T) (= 20.00). The results obtained from the Independent   T-test were (p = 0.410), meaning the difference in HIF-1α expression between the 2 groups was not significant: Average Δ Ht group C (= 1.26); group T (= -0,98). The statistical test with the Independent T-test obtained (p = 0.027), where there were significant differences. Giving a combination of dutasteride and lycopene for at least 30 days pre-TURP surgery was not effective in reducing the expression of hypoxia-induced factor - 1 alpha (HIF-1α) but was effective in reducing hematocrit levels compared to a single administration of dutasteride in BPH patients undergoing TURP surgery.


HIF – 1 α; hematocrit; BPH; dutasteride; lycopene

Full Text:



Nugroho EA, Muslim R, Riwanto I, Soetojo. The efficacy of dutasteride and green tea combination towards angiogenesis and bledding on BPH after TURP : study the effect on VEGF, MVD, and Hb. Internat J Sci Eng. Oct 2015; 9(2):80-84. Available from:https://ejournal.undip.ac.id/index.php/ijse

Berry S, Coffey D, Walsh P, Ewing L. The development of human benign prostatic hyperplasia with age. Journal of Urology 1984; 132:474-9.

Fitzpatric JM. The natural history of benign prostatic hyperplasia. BJU Int 2006; 97: 3–6.

Hoffman R, MacDonald R, Wilt T. Laser prostatectomy for benign prostatic obstruction. Cochrane Database of Systematic Reviews; 2000:(1).

McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF et al.,. American Urological Association Guideline: Management of Benign Prostatic Hyperplasia (Revised 2010). Available from URL: http://www.auanet.org/common/pdf/education/clinical-guidance/Benign-Prostatic-Hyperplasia.pdf. [Last Accessed on 2016 April 20].

Pujari NR. Transurethral Resection of Prostate is Still the Gold Standard for Small to Moderate Sized Prostates. J Integr Nephrol Androl 2016;3:68-9.

Walsh PC, Retik AB. Transurethral surgery.In : Campbell’s urology 7th ed. WB saunders. Philadelphia; 1998: 1511-28.

Foley CL, Bott SR, Kirby RS. An update on the 5 alpha reductase inhibitor. Timely Top Med Urol. Jun 2003: vol 4.

Andriole G, Bruchovsky N, Chung LW et al.,. Dihydrotestosterone and the prostate: The scientific rational for 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia. Journal of Urology 2004. 172; 4 Pt 1:1399-403.

Rittmaster RS, Norman RW, Thomas LN et al.,. Evidence for atrophy and apoptosis in the prostates of men given finasteride. J Clin Endocrinol Metab. 1996;81(2):814-19.

Zong HT, Peng XX, Yang CC, Zhang Y. A systematic review of the effects and mechanisms of preoperative 5a-reductase inhibitors on intraoperative haemorrhage during surgery for benign prostatic hyperplasia. Asian Journal of Andrology. 2011; 13: 812–18.

Hahn RG, Fagerström T, Tammela T et al.,. Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride. Journal Complication BJU International. 2007; 99: 587–94.

Shanmugasundaram R, Singh JC, Kekre NS. Does dutasteride reduce perioperative blood loss and postoperative complications after transurethral resection of the prostate?. Uroscan. Vol 23; 3: 334-35.

Martov AG, Ergakov DV. The experience in dutasteride use before transurethral prostatic resection for large adenoma. Urologiia 2008;4:46,48-50,52.

Semenza GL. Hypoxia and cancer. Cancer Metastasis.Rev 2007;26:p.223-24.

Winarsi H. Antioksidan dan Radikal Bebas. Potensi dan Aplikasinya Dalam Kesehatan. Penerbit Kanisius Yogya. 2007.

Febriansah R, Indriyani L, Palupi KD, Ikawati M. Tomat (Solanum lycopersicum L.) Sebagai Agen Kemopreventif Potensial. 2008. URL: https://www.researchgate.net/publication/237534133

Upadhyay J, Kesharwani RK, Misra K. Comparative study of antioxidants as cancer preventives through inhibition of HIF-1 alpha activity. Bio information.2009;4:p.233-36.

Ku JH, Shin JK, Cho MC, Myung JK, Moon KC., Paick JS. Effect of dutasteride on the expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in rat and human prostate tissue. Scand J Urol Nephrol. 2009;43(6): 445 – 53.

Detchokul,S., Frauman A.G. Recent development in prostate cancer biomarker research: therapeutic implications. 2011. Br j Clin Pharmacol / 71:2 / 157 – 174.

Kirollos MM, Campbell N. Factors influencing blood loss in transurethral resection of the prostate (TURP) : auditing TURP. Br J Viol 1997:80: III – IS.

Miyao H, Kotake Y, Kakoi H, Sekiguchi H, Kawazoe T. TURP Syndrome and Changes in Body Fluid Distribution. J Saitama Med School 2001; 28 : 1 – 8.

Boccon – Gibod L, Valton M, Ibrahim H, Comenducci A. Effect of Dutasteride on Reduction of Intraoperative Bleeding Related to Transurethral Resection of Prostate. Prog Urol. 2005 Dec; 15(6): 1085 – 9

DOI: https://doi.org/10.22146/mot.45933

Article Metrics

Abstract views : 2617 | views : 2064


  • There are currently no refbacks.

Copyright (c) 2020 Majalah Obat Tradisional

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

©Majalah Obat Tradisional (Traditional Medicine Journal)
 ISSN 2406-9086
Faculty of Pharmacy
Universitas Gadjah Mada