Long-Term Effects of Dihydrotestosterone Treatment on Prostate Growth in Healthy, Middle-Aged Men Without Prostate Disease
Long-Term Effects of Dihydrotestosterone Treatment on Prostate Growth in Healthy, Middle-Aged Men Without Prostate Disease
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双氢睾酮治疗对无前列腺疾病的健康中年男性前列腺生长的长期影响
DOI：
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发表时间：
2010
影响因子：
39.2
通讯作者：
David Handelsman
中科院分区：
文献类型：
--
作者：
A. Idan;K. Griffiths;D. T. Harwood;M. Seibel;L. Turner;A. Conway;David Handelsman
BACKGROUND
Benign prostatic hypertrophy increases with age and can result in substantially decreased quality of life for older men. Surgery is often required to control symptoms. It has been hypothesized that long-term administration of a nonamplifiable pure androgen might decrease prostate growth, thereby decreasing or delaying the need for surgical intervention.
OBJECTIVE
To test the hypothesis that dihydrotestosterone (DHT), a nonamplifiable and nonaromatizable pure androgen, reduces late-life prostate growth in middle-aged men.
DESIGN
Randomized, placebo-controlled, parallel-group trial. (Australian New Zealand Clinical Trials Registry number: ACTRN12605000358640) SETTING: Ambulatory care research center.
PARTICIPANTS
Healthy men (n = 114) older than 50 years without known prostate disease.
INTERVENTION
Transdermal DHT (70 mg) or placebo gel daily for 2 years.
MEASUREMENTS
Prostate volume was measured by ultrasonography; bone mineral density (BMD) and body composition were measured by dual-energy x-ray absorptiometry; and blood samples and questionnaires were collected every 6 months, with data analyzed by mixed-model analysis for repeated measures.
RESULTS
Over 24 months, there was an increase in total (29% [95% CI, 23% to 34%]) and central (75% [CI, 64% to 86%]; P < 0.01) prostate volume and serum prostate-specific antigen level (15% [CI, 6% to 24%]) with time on study, but DHT had no effect (P > 0.2). Dihydrotestosterone treatment decreased spinal BMD (1.4% [CI, 0.6% to 2.3%]; P < 0.001) at 24 months but not hip BMD (P > 0.2) and increased serum aminoterminal propeptide of type I procollagen in the second year of the study compared with placebo. Dihydrotestosterone increased serum DHT levels and its metabolites (5α-androstane-3α,17β-diol and 5α-androstane-3β,17β-diol) and suppressed serum testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels. Dihydrotestosterone increased hemoglobin levels (7% [CI, 5% to 9%]), serum creatinine levels (9% [CI, 5% to 11%]), and lean mass (2.4% [CI, 1.6% to 3.1%) but decreased fat mass (5.2% [CI, 2.6% to 7.7%]) (P <0.001 for all). Protocol-specific discontinuations due to DHT were asymptomatic increased hematocrit (n = 8), which resolved after stopping treatment, and increased prostate-specific antigen levels (n = 3; none with prostate cancer) in the DHT group. No serious adverse effects due to DHT occurred.
LIMITATION
Negative findings on prostate growth cannot exclude adverse effects on the natural history of prostate cancer.
CONCLUSION
Dihydrotestosterone treatment for 24 months has no beneficial or adverse effect on prostate growth but causes a decrease in spinal but not hip BMD. These findings have important implications for the wider use of nonsteroidal pure androgens in older men.
PRIMARY FUNDING SOURCE
BHR Pharma.
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影响因子：
5.8
作者：
Wang, C;Catlin, DH;Swerdloff, RS
通讯作者：
Swerdloff, RS
用于评估性腺功能减退男性性心理功能的简单自我报告日记。
影响因子：
--
作者：
Lee,KaKui;Berman,Nancy;Alexander,GerianneM;Hull,Laura;Swerdloff,RonaldS;Wang,Christina
通讯作者：
Wang,Christina
影响因子：
5
作者：
Guo, Tiedong;Taylor, Robert L.;Soldin, Steven J.
通讯作者：
Soldin, Steven J.
影响因子：
2.8
作者：
Guo, Tiedong;Gu, Jianghong;Soldin, Steven J.
通讯作者：
Soldin, Steven J.
影响因子：
15.9
作者：
Falahati-Nini, A;Riggs, BL;Khosla, S
通讯作者：
Khosla, S