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Decreasing Blood Loss in TURP Surgery: The Role of 5-Alpha Reductase Inhibitors: Enough To Make A Difference?

A recent online publication1 in the British Journal of Urology International highlighted a systemic review of randomized controlled trials evaluating bleeding related outcomes in patients undergoing transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) who were treated preoperatively with 5-alpha reductase (f5 ARI) inhibitors, either finasteride or dutasteride, compared to placebo or nothing. The efficacy of these agents was evaluated by blood loss, rate of transfusion, and operative time. The underlying physiological mechanism through which these agents exert their effects was also systematically evaluated through an examination of micro vessel density (MVD) and vascular endothelial growth factor (VEGF) expression in resected tissue.

This was a methodologically rigorous analysis conducted in accordance with PRISMA guidelines, which ultimately included 30 randomized controlled trials with a total sample size of 2974 patients undergoing TURP. Efficacy measures were expressed in terms of mean difference (MD) for continuous outcomes, an odds ratio (OR) for dichotomous outcomes, and a subgroup analysis included looking at whether duration of therapy, two weeks or less, or more than two weeks, made a difference.

The article included 66 well-chosen references dating back to 2001, including two articles first authored by John Donohue (Chair at Indiana U, best known as the leading expert of his time in testicular cancer and surgery) from 2002 and 2005.2,3

Note that not all factors were reported in all studies, but the relevant data analyzed revealed:

  1. Intraoperative blood loss was statistically significantly less in 5ARI treated patients, MD -82.58 ml (95% CI -107.98 to 57.18ml). There were no significant differences between patients treated with the two drugs.
  2. Intraoperative blood loss was normalized relative to the mass of prostate tissue resected. MD −2.60 mL/g in treated patients. For those treated with drug, the values were – 2.60 ml/g, CL -3.79 to -1.41 ml/g. For a 10g resection, this would amount to only 26 ML, but for a 50-gram resection, 130ml. There was no difference between drugs.
  3. Drug-treated patients demonstrated a significantly lower decrease in hemoglobin from preoperative to postoperative day one, -0.90g/dl, CL -1.16 to -0.64. This finding may be partially influenced by perioperative fluid, which warrants consideration.
  4. Drug treated patients required transfusion significantly less frequently (OR 0.33, CL 0.17-0.66. The odds of requiring blood transfusion for drug treated patients ranged from 0.27 to 0.37. There was no difference between drugs.
  5. Operative resection time was significantly shorter in drug treated patients, MD 3.47 min, CL -6.29 to -0.65). Correlation with resected tissue weight would further strengthen the interpretation of this finding.
  6. A significantly lower volume of irrigation agent was required in drug treated patients, MD-2.07L. CL -3.06 to -1.08). It would have been interesting to correlate this with resected weights.
  7. MVD was significantly reduced in the resected specimens of drug treated patients, MD – 6.27 vessels/cubic mm, CL -8.28 to -4.26. There was no difference between the drug cohorts.
  8. In the four studies evaluating VEGF expression, drug treated patients showed a significant decrease in expression within the resected specimen, MD -4.24, CL -7.14 to -1.35, with no differences between drugs.
  9. With respect to duration of drug therapy, intraoperative blood loss was significantly reduced in those patients treated with two weeks or less of therapy, although the magnitude of change was greater among patients who received over 2 weeks of therapy; there was no statistically significant difference between the groups. The MVD of the resected specimen was also significantly reduced in patients treated with two weeks or less therapy and greater than two weeks. Short term therapy was associated with a significantly greater reduction than therapy for greater than two weeks.
  10. Psychosexual adverse effects were evaluated in only four studies, limiting interpretability. Erectile dysfunction was more commonly reported among drug treated patients (2.6%) compared to control (0%). Meta analysis demonstrated a non-significant increase in OR of erectile dysfunction among drug treated patients, 4.58, CL 0.76—27.60. Decreased libido was reported with increased frequency among drug treated patients (4.1% versus 0% in controls). Drug treated patients were significantly more likely to experience decreased libido, OR 6.99, CL 1.22-40.04. All reported cases of de novo psychosocial dysfunction resolved by three month follow up.
From a clinical perspective, these findings support a biologically plausible mechanism whereby 5-AR therapy reduces VEGF expression and microvascular density, resulting in decreased perioperative bleeding during TURP. Benefit was achieved with short term therapy, and adverse sexual effects disappeared by three months. There appears to be no difference between finasteride and dutasteride in achieving these effects. These findings suggest that 5-ARI therapy may be of limited utility in smaller glands, while offering greater benefit in larger prostates. Consideration may be given to preoperative 5-ARI therapy in patients:

  • baseline anemia
  • increased bleeding risk
  • anticipated large-volume resection
Whether these findings translate to other procedures, such as deobstruction, such as Holmium Laser Enucleation of the Prostate (HoLEP) and Aquablation, remains to be determined.

Is there an alternative approach to reducing perioperative bleeding? The evidence base for tranexamic acid (TXA) in this setting remains comparatively limited. TXA is an antifibrinolytic agent that inhibits the conversion of plasminogen to plasmin, thereby preventing fibrin clot degradation. Given the elevated urinary fibrinolytic activity in prostatic tissue, driven by urokinase release, there is a strong mechanistic rationale for its use in reducing blood loss during TURP. Pranata et al4 published a recently updated systematic review and meta-analysis, utilizing PRISMA guidelines, of randomized controlled trials utilizing preoperative administration of this compound in TURP patients. From an initial search identifying 94 articles, a total of 6 randomized controlled trials including 582 patients were included. Only four of these were randomized double-blind trials. Prostate sizes were not individually characterized as a parameter but ranged from 36.6 g to 108.32 g. One of the trials used finasteride before the surgery. The reported dosage of TXA ranged from 10 milligrams to 30 milligrams per kilogram body weight.

The main Findings were reported as:

  1. The rate of blood transfusion was similar between drug patients and controls.
  2. Three trials evaluated the amount of blood loss during surgery. The drug group had a significantly lower blood loss compared to controls, -127.03 ml, CL -233.1 to -20.95.
  3. There was a significantly lower change in hemoglobin levels in drug treated patients compared to controls, MD -0.53. CL -0.84 to – 0.22)
  4. There was no significant difference in the mean operative time of drug treated patients compared to the control group
  5. There was no significant drug effect on the length of hospitalization
  6. The authors reported no complications from drug administration in the included studies
The authors acknowledge several limitations of the review, including the heterogeneity of the included randomized controlled trials, the varying dosages of drug cover different routes of administration of the drug, and the fact that blood loss calculations might not be accurate because of the limited or incomplete data provided in the studies. They concluded, “Therefore, thorough research, preferably with homogeneous data, is required to better understand the effects of tranexamic acid on bleeding related outcomes during TURP”. At present, TXA shows potential but lacks sufficient high-quality, consistent evidence to support routine use in TURP.

In summary, preoperative 5-ARI therapy demonstrates consistent and clinically meaningful reductions in bleeding-related outcomes during TURP, supported by both mechanistic and clinical data. While TXA represents a promising adjunct, further high-quality studies are required before integration into standard practice. Future work should focus on procedure-specific applicability and patient selection to optimize perioperative outcomes.

Written by: Alan Wein, MD, PhD, FACS, Professor of Clinical Urology, Department of Urology, Desai Sethi Urology Institute (DSUI), University of Miami Miller School of Medicine, University of Miami Health Systems, Miami, FL

References:

  1. Hehir, CM et al, The role of 5-alpha reductase inhibitors in transurethral resection of the prostate: a meta-analysis of randomized controlled trials. BJU Int 2026; doi:10.1111/bju.70117
  2. Donohue, JF et al, Transurethral prostate resection and bleeding: a randomized placebo-controlled trial of finasteride for decreasing operative blood loss J Urol 2002; 168: 2024-2026
  3. Donohue, JF, Randomized placebo control trial showing that finasteride reduces prostatic vascularity rapidly within two weeks. BJU Int 2005; 96: 319-322
  4. Pranata, FH et al, The role of tranexamic Acid in reducing bleeding during transurethral resection of the prostate: an updated systematic review and meta-analysis of randomized controlled trials. Indian J Urology 2022; 38: 258-267