Dutasteride, who is it more effective for? Second to fourth digit ratio and the relationship with prostate volume reduction by dutasteride treatment, "Beyond the Abstract," by Tae Beom Kim, MD, et al

BERKELEY, CA (UroToday.com) - Five α-reductase inhibitor (5ARI) is approved for the treatment of benign prostatic hyperplasia (BPH) and provides long-term symptom relief, increased urinary flow, and reduces the risk of long-term complications such as acute urinary retention and BPH-related surgery,[1,2] Most importantly, 5ARI reduces the prostate volume of patients with BPH. In general, both dutasteride and finasteride were effective in reducing prostate volume, reaching ~25% reduction at 2 years.,[1,2,3,4]

However, in large-scale placebo-controlled studies,[1,3,5,6] wide values of standard deviation (SD) were observed in prostate volume reduction after 5ARI treatment (the mean decrease in prostate volume was -14.6 ± 13.5 cc,,[1] -24.4 ± 19.47%,,[3] -12 ± 30%,,[5] and -5.8 ± 18.4 cc[6]). In particular, the value of SD was two-times higher than mean value in the MTOPS study.[5] These values indicate that patients with BPH do not always respond well to 5ARI treatment. Namely, if the data of the placebo-controlled study with 5ARI followed a normal distribution, more than 15% of all patients treated with 5ARI had more than 40% reduction in prostate volume, whereas more than 15% of all patients with 5ARI treatment had less than 5% reduction in prostate volume. This means that some patients had a large reduction of prostate volume and others did not.

To date, despite the diversity of responses to 5ARI treatment, few studies have revealed the reasons why one patient’s response to 5ARI is different from another’s. To solve this problem, we performed the study on the assumption that digit ratio is reflective of androgen receptor (AR) activity among individuals, and that under conditions of relative androgen depletion due to treatment with 5ARI, relative AR activity among individuals may predict response to 5ARI treatment. Actually, despite 5ARI treatment, unsuppressed DHT of over 5% remains in prostatic cells.,[7,8,9] We think that if the AR activity is very high, unsuppressed DHT (over 5%) might bind to the AR, which might still exert some functions in the prostate.

Thus, we investigated the relationship between the response to dutasteride treatment (prostate volume reduction) and digit ratio. Our study demonstrated that patients with a higher digit ratio responded well to dutasteride treatment. We believe that our study shows one reason for the individual variation in the response to 5ARI treatment.

References:

  1. Roehrborn CG, Boyle P, Nickel JC et al. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60: 434-41
  2. McConnell JD, Bruskewitz R, Walsh P et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. N Engl J Med 1998; 338: 557-63
  3. Roehrborn CG, Marks LS, Fenter T et al. Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia. Urology 2004; 63: 709-15
  4. Debruyne F, Barkin J, van Erps P et al. Efficacy and safety of long-term treatment with the dual 5 alpha-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia. Eur Urol 2004; 46: 488-94
  5. McConnell JD, Roehrborn CG, Bautista OM et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349: 2387-98
  6. Kaplan SA, Lee JY, Meehan AG, Kusek JW. Long-term treatment with finasteride improves clinical progression of benign prostatic hyperplasia in men with an enlarged versus a smaller prostate: data from the MTOPS trial. J Urol 2011; 185: 1369-73
  7. Rittmaster R, Hahn RG, Ray P, Shannon JB, Wurzel R. Effect of dutasteride on intraprostatic androgen levels in men with benign prostatic hyperplasia or prostate cancer. Urology 2008; 72: 808-12
  8. McConnell JD, Wilson JD, George FW, Geller J, Pappas F, Stoner E. Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab 1992; 74: 505-8
  9. Andriole GL, Humphrey P, Ray P et al. Effect of the dual 5alphareductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol 2004; 172: 915-9

 

Written by:
Tae Beom Kim,a Jin Kyu Oh,a Khae Hawn Kim,a Han Jung,a Sang Jin Yoon,a Min Sung Lee,b and Soo Woong Kimc as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

aDepartment of Urology, Gachon University Gil Hospital, Incheon, Republic of Korea
bHealth Insurance Review & Assessment Service, Seoul, Republic of Korea
cDepartment of Urology, Seoul National University Hospital, Seoul, Republic of Korea

Dutasteride, who is it more effective for? Second to fourth digit ratio and the relationship with prostate volume reduction by dutasteride treatment - Abstract

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