Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, United States; Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, United States.
J Steroid Biochem Mol Biol. 2013 Nov;138:10-6. doi: 10.1016/j.jsbmb.2013.02.015. Epub 2013 Mar 6.
Studies show that treatment of men with 5α-reductase inhibitors such as finasteride is effective for the primary prevention of prostate cancer. Although it is known that finasteride treatment suppresses serum levels of dihydrotestosterone (DHT) and its distal metabolite, 5α-androstane-3α,17β-diol glucuronide (3α-diol G), and increases serum testosterone (T) levels, little is known about its effect on other precursors and metabolites of DHT, as well as on the relationship of these androgens to prostate specific antigen (PSA), a marker of prostatic intraepithelial neoplasia. The present study provides new data on the effect of finasteride on precursors and metabolites of DHT. Fifty-three men, ages 57-79 years, with elevated PSA levels (>4ng/ml), were randomized to treatment with finasteride (5mg/day) or observation (controls) for 12 months. Blood samples were obtained at baseline, 1, 3, 6 and 12 months for measurement of PSA, androstenedione (A), T, DHT, 3α-diol G, androsterone glucuronide (ADT G) and DHT sulfate (DHT S) in serum by validated, highly specific radioimmunoassays. Statistical analysis was carried out using mixed model ANOVA and t-tests. In the control group, PSA and androgen levels were unchanged throughout the 12 months of treatment. In the finasteride group, PSA, DHT, DHT S, 3α-diol G and ADT G decreased from baseline to 1 month by 23.2%, 78.7%, 71.0%, 75.7% and 43.0%, respectively. The change in PSA decreased further to 46.1% and 55.1% at 3 and 12 months of treatment, respectively, whereas the decrease in androgens observed at 1 month did not change by more than 6.9% for DHT, DHT S and 3α-diol G in the subsequent months of sampling. However, the decline in ADT G was only 22.2% at month 3, and remained essentially at this level after that time. In contrast, T and A increased significantly from baseline, and the increase in A of approximately 34.5% was about 1.9 times the increase in T (approximately 18.3%). The present data suggest that either 3α-diol G or DHT S may serve as a potential diagnostic marker of intraprostatic 5α-reductase activity during treatment of patients with 5α-reductase inhibitors.
研究表明，5α-还原酶抑制剂（如非那雄胺）治疗男性可有效预防前列腺癌。虽然已知非那雄胺治疗可抑制血清中二氢睾酮（DHT）及其远端代谢物 5α-雄烷-3α，17β-二醇葡萄糖醛酸（3α-二醇 G）的水平，并增加血清睾酮（T）水平，但对于 DHT 的其他前体和代谢物以及这些雄激素与前列腺特异性抗原（PSA）的关系，了解甚少，PSA 是前列腺上皮内瘤变的标志物。本研究提供了非那雄胺对 DHT 前体和代谢物影响的新数据。53 名年龄在 57-79 岁之间、PSA 水平升高（>4ng/ml）的男性被随机分为非那雄胺（5mg/天）治疗组或观察组（对照组），治疗 12 个月。在基线、1、3、6 和 12 个月时采集血液样本，通过验证的高特异性放射免疫分析测量血清中的 PSA、雄烯二酮（A）、T、DHT、3α-二醇 G、雄酮葡萄糖醛酸（ADT G）和 DHT 硫酸盐（DHT S）。采用混合模型方差分析和 t 检验进行统计分析。在对照组中，PSA 和雄激素水平在 12 个月的治疗过程中保持不变。在非那雄胺组中，PSA、DHT、DHT S、3α-二醇 G 和 ADT G 从基线到 1 个月分别下降了 23.2%、78.7%、71.0%、75.7%和 43.0%。PSA 的变化在 3 个月和 12 个月的治疗中分别进一步下降至 46.1%和 55.1%，而在随后的几个月中，1 个月时观察到的雄激素变化没有超过 DHT、DHT S 和 3α-二醇 G 的 6.9%。然而，ADT G 在 3 个月时仅下降 22.2%，此后基本保持在这一水平。相比之下，T 和 A 从基线显著增加，A 的增加约 34.5%，约为 T 增加（约 18.3%）的 1.9 倍。本研究数据表明，3α-二醇 G 或 DHT S 可能在 5α-还原酶抑制剂治疗患者时作为前列腺内 5α-还原酶活性的潜在诊断标志物。
