Division of Metabolism, Endocrinology, and Nutrition, University of Washington School of Medicine, Box 357138, 1959 NE Pacific Street, Seattle, Washington 98195, USA.
J Clin Endocrinol Metab. 2011 Feb;96(2):430-7. doi: 10.1210/jc.2010-1865. Epub 2010 Dec 22.
Concern exists that androgen treatment might adversely impact prostate health in older men. Dihydrotestosterone (DHT), derived from local conversion of testosterone to DHT by 5α-reductase enzymes, is the principal androgen within the prostate. Exogenous androgens raise serum DHT concentrations, but their effects on the prostate are not clear.
To determine the impact of large increases in serum DHT concentrations on intraprostatic androgen concentrations and androgen action within the prostate.
Double-blind, randomized, placebo-controlled.
Single academic medical center.
31 healthy men ages 35-55.
Daily transdermal DHT or placebo gel.
Serum and prostate tissue androgen concentrations and prostate epithelial cell gene expression after 4 wk of treatment.
Twenty-seven men completed all study procedures. Serum DHT levels increased nearly sevenfold, while testosterone levels decreased in men treated with daily transdermal DHT gel but were unchanged in the placebo-treated group (P < 0.01 between groups). In contrast, intraprostatic DHT and testosterone concentrations on d 28 were not different between groups (DHT: placebo = 2.8 ± 0.2 vs. DHT gel = 3.1 ± 0.5 ng/g; T: placebo = 0.6 ± 0.2 vs. DHT gel = 0.4 ± 0.1, mean ± se). Similarly, prostate volume, prostate-specific antigen, epithelial cell proliferation, and androgen-regulated gene expression were not different between groups.
Robust supraphysiologic increases in serum DHT, associated with decreased serum T, do not significantly alter intraprostatic levels of DHT, testosterone, or prostate epithelial cell androgen-regulated gene expression in healthy men. Changes in circulating androgen concentrations are not necessarily mimicked within the prostate microenvironment, a finding with implications for understanding the impact of androgen therapies in men.
人们担心雄激素治疗可能会对老年男性的前列腺健康产生不利影响。二氢睾酮（DHT）是前列腺内的主要雄激素，由局部转化而来，由 5α-还原酶将睾酮转化为 DHT。外源性雄激素会提高血清 DHT 浓度，但它们对前列腺的影响尚不清楚。
确定血清 DHT 浓度大幅升高对前列腺内雄激素浓度和前列腺内雄激素作用的影响。
双盲、随机、安慰剂对照。
单一学术医疗中心。
31 名年龄在 35-55 岁的健康男性。
每日透皮 DHT 或安慰剂凝胶。
治疗 4 周后血清和前列腺组织雄激素浓度以及前列腺上皮细胞基因表达。
27 名男性完成了所有研究程序。与安慰剂组相比，接受每日透皮 DHT 凝胶治疗的男性血清 DHT 水平增加了近 7 倍，而睾酮水平下降（组间差异 P < 0.01）。相比之下，两组间第 28 天的前列腺内 DHT 和睾酮浓度没有差异（DHT：安慰剂=2.8±0.2 vs. DHT 凝胶=3.1±0.5 ng/g；T：安慰剂=0.6±0.2 vs. DHT 凝胶=0.4±0.1，均为均值±标准差）。同样，前列腺体积、前列腺特异性抗原、上皮细胞增殖和雄激素调节的基因表达在两组间也无差异。
在健康男性中，血清 DHT 大幅升高至超生理水平，同时血清 T 降低，不会显著改变前列腺内的 DHT、睾酮或前列腺上皮细胞雄激素调节基因的表达。循环雄激素浓度的变化不一定在前列腺微环境中得到模拟，这一发现对理解男性雄激素治疗的影响具有重要意义。
