Tindall Donald J, Rittmaster Roger S
Mayo Clinic, Rochester, Minnesota 55905, USA.
J Urol. 2008 Apr;179(4):1235-42. doi: 10.1016/j.juro.2007.11.033. Epub 2008 Feb 20.
Androgens are essential for prostatic growth and development but they also have a significant role in prostate disease pathogenesis. Dihydrotestosterone, the primary prostatic androgen, is transformed from testosterone by types 1 and 2 5alpha-reductase and, thus, a potential therapeutic benefit could be achieved through the inhibition of 5alpha-reductase.
A literature review was performed using PubMed/MEDLINE and congress abstracts to examine evidence supporting the potential of 5alpha-reductase inhibitors in the primary prevention of prostate cancer and in limiting the progression of diagnosed disease.
Prostate disease development is associated with increased expression of each 5alpha-reductase isoenzyme with over expression of type 1 of particular importance in prostate cancer development and progression. The 2 5alpha-reductase inhibitors currently clinically available are finasteride, a type 2 5alpha-reductase inhibitor, and dutasteride, a dual 5alpha-reductase inhibitor. Dual inhibition by dutasteride has been shown to translate into a greater degree and consistency of dihydrotestosterone suppression compared with finasteride. The Prostate Cancer Prevention Trial showed that finasteride significantly decreased the 7-year risk of prostate cancer in men with prostate specific antigen 3.0 ng/ml or less, while the ongoing Reduction by Dutasteride of Prostate Cancer Events study is assessing whether dutasteride decreases the risk of biopsy detectable prostate cancer in men with prostate specific antigen 2.5 to 10 ng/ml and a previous negative biopsy. Small-scale studies have demonstrated potential effects of 5alpha-reductase inhibition in prostate cancer treatment that warrant further investigation, while dutasteride use in men undergoing expectant treatment is also being examined.
The inhibition of 5alpha-reductase represents a valid target for prostate cancer risk reduction and treatment strategies. The greater suppression of dihydrotestosterone observed with agents that inhibit each 5alpha-reductase isoenzyme may translate into enhanced outcomes and studies are under way to test this hypothesis.
雄激素对前列腺的生长和发育至关重要，但它们在前列腺疾病发病机制中也起着重要作用。双氢睾酮是前列腺主要的雄激素，由1型和2型5α-还原酶将睾酮转化而来，因此，通过抑制5α-还原酶可能会带来治疗益处。
使用PubMed/MEDLINE和会议摘要进行文献综述，以检验支持5α-还原酶抑制剂在前列腺癌一级预防和限制已确诊疾病进展方面潜力的证据。
前列腺疾病的发展与每种5α-还原酶同工酶的表达增加有关，其中1型的过度表达在前列腺癌的发生和发展中尤为重要。目前临床上可用的两种5α-还原酶抑制剂是非那雄胺（一种2型5α-还原酶抑制剂）和度他雄胺（一种双重5α-还原酶抑制剂）。与非那雄胺相比，度他雄胺的双重抑制作用已被证明能在更大程度上和更持续地抑制双氢睾酮。前列腺癌预防试验表明，非那雄胺显著降低了前列腺特异性抗原为3.0 ng/ml或更低的男性患前列腺癌的7年风险，而正在进行的度他雄胺降低前列腺癌事件研究正在评估度他雄胺是否能降低前列腺特异性抗原为2.5至10 ng/ml且既往活检为阴性的男性经活检可检测到前列腺癌的风险。小规模研究已证明5α-还原酶抑制在前列腺癌治疗中具有潜在作用，值得进一步研究，同时也在研究度他雄胺在接受观察等待治疗的男性中的应用情况。
抑制5α-还原酶是降低前列腺癌风险和治疗策略的一个有效靶点。观察到抑制每种5α-还原酶同工酶的药物对双氢睾酮有更强的抑制作用，这可能会带来更好的治疗效果，目前正在进行相关研究以验证这一假设。
