Transurethral resection of prostate and bleeding: Short term use of Finasteride and Dutasteride on operative blood loss and prostatic micro-vessel density: Beyond the Abstract

Benign prostatic hyperplasia (BPH) is the most frequent urological disorder in men beyond the fifth decade of life. Transurethral resection of the prostate (TURP) remains the standard of care in patients of BPH who fail to respond with medical therapy. Hemorrhage is one of the major complications of TURP. If prolonged it may necessitate blood transfusion and can lead to clot retention in the postoperative period [1]. The aim of this study to evaluate the effects of short-term use of finasteride and dutasteride on the amount of intraoperative blood loss and microvessel density (MVD) of prostatic stromal and suburethral tissues in the patients with benign prostatic hyperplasia (BPH) prior to transurethral resection of prostate (TURP).

The study involved 450 male patients who planned to have TURP and were prospectively randomized into 3 groups (150 patients each). Group 1 received placebo, group 2 received finasteride 5 mg/day and group 3 received dutasteride 0.5 mg/day for 4 weeks before the operation. The HemoCue method was used to calculate the amount of intraoperative hemorrhage [2]. In this method, the hemoglobin (g/dl) value of the irrigant was multiplied by the volume of total irrigation fluid (dl) used. The result was divided by the preoperative value of serum hemoglobin, and thus the total amount of blood loss was obtained. 

Baseline parameters showed no significant differences among the 3 groups in terms of total prostate volume, PVR, total PSA, AUA symptom score, maximum urine flow rate (Q max) and durations of symptoms. Significant differences were observed in total blood loss (265.3 vs 168.7 vs 162.4 ml; p=0.003), total blood loss per gram of resected tissue (10.74 vs 7.3 vs 7.4 ml/gm; p=0.01), and total blood loss per minute of operating time (6.59 vs 4.23 vs 4.3 ml/min; p=0.002). Significant differences were observed in fall of hemoglobin (1.6 vs 0.8 vs 0.7gm; p=0.002), prostatic MVD (27.6 vs 17.2 vs 16.8; p =0.01), and suburethral MVD (21.3 vs 14.2 vs 13.3; p=0.02). In the placebo, finasteride and dutasteride groups, blood transfusion was required in 14 (9.3%), 4 (2.7%) and 3 (2%) patients, respectively, owing to prolonged bleeding in the early postoperative period (p=0.004). Intergroup comparison showed that total blood loss, total blood loss per gram of resected tissue, and total blood loss per minute of operating time in the placebo group were significantly higher as compared with the other 2 groups. Fall in hemoglobin, requirement of blood transfusion, prostatic MVD, and suburethral MVD were also significantly higher.

Puchner and Miller postulated that 5-ARIs act by inhibiting the conversion of testosterone to dihydrotestosterone that leads to reduced level of androgen-derived growth factors (fibroblastic growth factor, epidermal growth factor and vascular endothelial growth factor) required for angiogenesis. This results to decreased blood flow and vascular density of the prostate and reduces the rate of hematuria associated with BPH [3]. Both drugs have been studied in the literature to see their effects on perioperative bleeding and MVDs but to date in the English literature these drugs have never been compared with each other. 

In our study, 5-ARIs were given preoperatively for 4-weeks as we believed that this duration would provide adequate exposure to reduce angiogenesis. Marshall and Narayan postulated that BPH with increased acinar and stromal cell proliferation stimulates increased vascularity (angiogenesis) of vessels [4]. MVD is the histologic indicator of angiogenesis, which may be an important risk factor for perioperative bleeding during TURP in BPH patients. A possible explanation for prostatic bleeding is due to increased vascularity within the prostatic urethra and its close proximity to the mucosal surface. Hemorrhage following ulceration of mucosa would manifest as hematuria more readily [5]. 5-ARI suppresses angiogenesis and MVD by decreasing dihydrotestosterone concentration and thus the activity of androgen-controlled growth factors responsible for angiogenesis is decreased.

The meta-analysis done by Zhu et al [6] showed that treatment with finasteride prior to TURP for BPH reduces the perioperative hemorrhage. However, no significant differences were seen in terms of loss of blood, reduction in hemoglobin, weight of resected prostatic tissue, prostate volume, number of transfusions required, operative time, and reduction in MVD when dutasteride was compared with the control group [7]. This could possibly be due to the fact that dutasteride was a newer drug and the patient group selected for randomized control trials (RCTs) was not similar to those selected for the finasteride RCTs. However, the exact reason for dutasteride being ineffective in decreasing the blood loss and MVD is not clear. Hence, this well designed double blind; placebo-controlled RCT will actually establish its actual role. The results of our present trial are novel and significantly contribute to the knowledge of the role of 5-ARIs in reducing bleeding during TURP. Our study is a step forward than others as it compares the efficacy of dutasteride versus finasteride in preventing blood loss during TURP. Second, we analyzed a large number of patients (450 randomized patients). The administration of 5ARI for 4 weeks is usually well tolerated and may be useful for patients with increased cardiac risk who are susceptible to blood loss. Decreased libido and erectile dysfunction were observed in few patients, which resolved within 3 months of surgery. 

This study provides compelling evidence that Short-term pretreatment with finasteride and dutasteride has similar efficacy and significantly reduces perioperative bleeding during TURP and has minimal negative impact on sexual function. According to our findings, a 4 weeks’ prior administration of 5-ARIs may reduce operative blood loss and prostatic MVD in TURP, thus potentially decreasing blood loss-related complications and the requirement of blood transfusion.

Written by: Ankur Bansal*, Aditi Arora*, Rahul Jena
*Denotes authors of this article

References:
  1. Mebust WK, Holtgrewe HL, Cockett ATK, Peters PC. Transurethral prostatectomy: immediate and postoperative complications. Cooperative study of 13 participating institutions evaluating 3,885 patients. J Urol. 1989;141:243–7 
  2. Ekengren J, Hahn RG. Blood loss during transurethral resection of the prostate as measured by the hemocue photometer. Scand J Urol Nephrol 1993;/27:/501-17 
  3. Puchner PJ, Miller MI. The effects of finasteride on hematuria associated with benign prostatic hyperplasia: a preliminary report. J Urol 1995;154:1779-82 
  4. Marshall S, Narayan P. Treatment of prostatic bleeding: suppression of angiogenesis by androgen deprivation. J Urol 1993;149:1553 
  5. Foley SJ, Bailey DM: Microvessel density in prostatic hyperplasia. BJU Int 2000; 85: 70–73. 
  6. Zhu YP, Dai B, Zhang HL, et al. Impact of preoperative 5alpha-reductase inhibitors on perioperative blood loss in patients with benign prostatic hyperplasia: a meta-analysis of randomized controlled trials. BMC Urol 2015;15:47 
  7. Tuncel A, Ener K, Han O et al. Effects of short-term dutasteride and Serenoa repens on perioperative bleeding and microvessel density in patients undergoing transurethral resection of the prostate. Scand J Urol Nephrol. 2009;43:377-82. 

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