Wurzel R, Ray P, Major-Walker K, Shannon J, Rittmaster R
Department of Urology, Grove Hill Medical Center, New Britain, CT 06052, USA.
Prostate Cancer Prostatic Dis. 2007;10(2):149-54. doi: 10.1038/sj.pcan.4500931. Epub 2006 Dec 26.
The dual 5alpha-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 (R(2)=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.
双重5α-还原酶抑制剂度他雄胺已被证明可使血清双氢睾酮(DHT)水平降低90%以上。在本研究中,研究了每日0.5毫克度他雄胺对前列腺内DHT水平的影响。在这项多中心、双盲试验中,43例计划接受经尿道前列腺切除术(TURP)的良性前列腺增生(BPH)男性患者被随机分为两组,在手术前3个月分别接受每日0.5毫克度他雄胺或安慰剂治疗。在TURP时测定前列腺内DHT、睾酮和度他雄胺水平。还评估了血清DHT和睾酮相对于基线水平的变化,以及TURP时血清和前列腺内度他雄胺水平。与安慰剂相比,度他雄胺使前列腺内DHT降低了94%(P<0.001);安慰剂组和度他雄胺组经调整后的平均前列腺内DHT浓度分别为3.23和0.209纳克/克。在度他雄胺组,血清DHT在第3个月时较基线水平降低了93%,显著大于安慰剂组观察到的15%的降低幅度(P<0.001)。前列腺内睾酮有相应增加,但度他雄胺组前列腺内睾酮水平往往低于安慰剂组前列腺内DHT水平(P=0.06)。所有接受度他雄胺治疗的受试者,无论前列腺内度他雄胺水平如何,均实现了显著的前列腺内DHT抑制。血清和前列腺内度他雄胺浓度之间存在强正相关(R²=0.73)。经过3个月的治疗,每日0.5毫克度他雄胺几乎完全抑制了BPH男性患者前列腺内和血清中的DHT。