Abstract
The dual 5α-reductase inhibitor, dutasteride has been shown to suppress serum dihydrotestosterone (DHT) by >90%. In the present study, the effect of dutasteride 0.5 mg/day on intraprostatic DHT levels was investigated. In this multicenter, double-blind trial, 43 men with benign prostatic hyperplasia (BPH) scheduled to undergo transurethral resection of the prostate (TURP) were randomized to receive dutasteride, 0.5 mg/day or placebo for 3 months before surgery. Intraprostatic DHT, testosterone and dutasteride levels were determined at the time of TURP. Changes in serum DHT and testosterone from baseline, and both serum and intraprostatic dutasteride levels at the time of TURP were also assessed. Dutasteride reduced intraprostatic DHT by 94% relative to placebo (P<0.001); the adjusted mean intraprostatic DHT concentration was 3.23 and 0.209 ng/g in the placebo and dutasteride groups, respectively. In the dutasteride group, serum DHT was reduced from baseline by 93% at month 3, a significantly greater reduction (P<0.001) than the 15% decrease observed in the placebo group. There was a reciprocal increase in intraprostatic testosterone but the level of intraprostatic testosterone in the dutasteride group tended to be lower than the intraprostatic DHT level in the placebo group (P=0.06). Significant intraprostatic DHT suppression was achieved in all subjects who received dutasteride, regardless of the level of intraprostatic dutasteride. There was a strong positive correlation between serum and intraprostatic dutasteride concentrations (R2=0.73). After 3 months of treatment, dutasteride 0.5 mg/day provided near-complete suppression of both intraprostatic and serum DHT in men with BPH.
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References
National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). Prostate Enlargement: Benign Prostatic Hyperplasia. NKUDIC is a service of the National Insititute of Diabetes and Digestive Kidney Diseases (NIDDK), which is part of the National Institutes of Health (NIH). NIH publications no. 04–3012: http://kidney.niddk.nih.gov/kudiseases/pubs/prostateenlargement/, 2004.
American Urological Association. AUA Guideline on Management of Benign Prostatic Hyperplasia (2003). Chapter 1: diagnosis and treatment recommendations. J Urol 2003; 170: 530–547.
Emberton M, Andriole G, de la Rosette JJ, Djavan B, Hoefner K, Vela Navarette R et al. BPH: a progressive disease of aging men. Urology 2003; 61: 267–273.
Iehle C, Radvanyi F, Gil Diez de Medina S, Ouafik LH, Gerard H, Chopin D et al. Differences in steroid 5alpha-reductase iso-enzymes expression between normal, pathological human prostate tissue. J Steroid Biochem Mol Biol 1999; 68: 189–195.
Berthaut I, Mestayer C, Portois MC, Cussenot O, Mowszowicz I . Pharmacological, molecular evidence for the expression of the two steroid 5 alpha-reductase isozymes in normal, hyperplastic human prostatic cells in culture. Prostate 1997; 32: 155–163.
Bruchovsky N, Rennie PS, Batzold FH, Goldenberg SL, Fletcher T, McLoughlin MG . Kinetic parameters of 5 alpha-reductase activity in stroma, epithelium of normal, hyperplastic, carcinomatous human prostates. J Clin Endocrinol Metab 1988; 67: 806–816.
Andriole G, Bruchovsky N, Chung LW, Matsumoto AM, Rittmaster R, Roehrborn C et al. Dihydrotestosterone, the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol 2004; 172: 1399–1403.
Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G . Efficacy, safety of a dual inhibitor of 5-alpha-reductase types 1, 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60: 434–441.
McConnell JD, Bruskewitz R, Walsh PC, Andriole G, Lieber MM, Holtgrewe HL 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: 557–563.
Andriole GL, Humphrey P, Ray P, Gleave ME, Trachtenberg J, Thomas LN et al. Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumour regression in prostate cancer. J Urol 2004; 172: 915–919.
Iczkowski KA, Qiu J, Qian J, Somerville MC, Rittmaster RS, Andriole GL et al. The dual 5-alpha-reductase inhibitor dutasteride induces atrophic changes and decreases relative cancer volume in human prostate. Urology 2005; 65: 76–82.
Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003; 349: 215–224.
Nickel JC . Comparison of clinical trials with finasteride and dutasteride. Rev Urol 2004; 6: S31–S39.
Roehrborn CG, Marks LS, Fenter T, Freedman S, Tuttle J, Gittleman M et al. Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia. Urology 2004; 63: 709–715.
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: 505–508.
Span PN, Voller MC, Smals AG, Sweep FG, Schalken JA, Feneley MR et al. Selectivity of finasteride as an in vivo inhibitor of 5alpha-reductase isozyme enzymatic activity in the human prostate. J Urol 1999; 161: 332–337.
Thomas LN, Wright AS, Lazier CB, Cohen P, Rittmaster RS . Prostatic involution in men taking finasteride is associated with elevated levels of insulin-like growth factor-binding proteins (IGFBPs)-2, -4, and -5. Prostate 2000; 42: 203–210.
Norman RW, Coakes KE, Wright AS, Rittmaster RS . Androgen metabolism in men receiving finasteride before prostatectomy. J Urol 1993; 150: 1736–1739.
Thomas LN, Lazier CB, Gupta R, Norman RW, Troyer DA, O'Brien SP et al. Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer. Prostate 2005; 63: 231–239.
Roehrborn CG, Marks LS, Fenter T, Freedman S, Tuttle J, Gittleman M et al. Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia. Urology 2004; 63: 709–715.
Andriole G, Bostwick D, Brawley O, Gomella LG, Marberger M, Tindall D et al. Chemoprevention of prostate cancer in high risk men: rationale and design of the REDUCE trial. J Urol 2004; 172: 1314–1317.
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Wurzel, R., Ray, P., Major-Walker, K. et al. The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 10, 149–154 (2007). https://doi.org/10.1038/sj.pcan.4500931
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DOI: https://doi.org/10.1038/sj.pcan.4500931
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