Hormonal and molecular consequences of androgen replacement on the prostate

雄激素替代对前列腺的激素和分子影响

基本信息

批准号：
7907609
负责人：
STEPHANIE T PAGE
金额：
$ 12.68万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7907609
关键词：
5 Alpha-Reductase Inhibitor Ablation Affect Aftercare Age Aging American Anatomy Androgen Therapy Androgens Antigens Apoptosis Apoptotic Attenuated Award Benign Prostatic Hypertrophy Biological Preservation Biology Biopsy Blood Body Composition Bone Density Cell Proliferation Cells Chairperson Cholesterol Clinical Research Complex Contraceptive methods Cutaneous Data Diagnosis Disease Doctor of Philosophy Double-Blind Method Dutasteride Epithelial Epithelial Cell Proliferation Epithelial Cells Epithelium Finasteride Gel Gene Expression Genes Gerontology Goals Health Healthcare Systems Hematocrit procedure Hormonal Hormones Human Human Glandular Kallikrein 2 IGFBP3 gene In Situ Incidence International Investigation Label Lipids Long-Term Effects Malignant Neoplasms Malignant neoplasm of prostate Measures Medicine Mentors Molecular Non-Malignant Organ Oxidoreductase Pattern Pharmaceutical Preparations Physiology Placebo Control Placebos Procedures Prostate Prostate Cancer Prevention Trial Prostate-Specific Antigen Prostatic Prostatic Diseases Prostatic Intraepithelial Neoplasias Proteins Randomized Clinical Trials Reproduction Research Research Design Research Personnel Safety Secondary to Sensitivity Training Groups Serum Severities Stanolone Stromal Cells Supplementation Symptoms Testing Testosterone Tissue-Specific Gene Expression Tissues Training Transcript Tumor Markers Universities Washington Work cDNA Arrays cancer risk cardiovascular risk factor career clinical practice design dosage experience high risk human subject in vivo indexing inhibitor/antagonist insulin sensitivity laser capture microdissection lower urinary tract symptoms male medical schools member men novel older men oncology placebo controlled study professor prostate enlargement randomized trial sex sound species difference sulfated glycoprotein 2

项目摘要

DESCRIPTION (provided by applicant): Dr. Page's career goal is to become an independent clinician-investigator proficient in the design and conduct of research evaluating the use of existing and novel selective androgens in aging men. Androgen replacement in older men with low serum testosterone levels is becoming increasingly commonplace, yet the effect this may have on prostate health is unknown. Having gained some experience in designing and conducting clinical research relating to the uses of androgens in men, Dr. Page proposes mentored research and didactic training to evaluate the effects of testosterone replacement on the prostate at the molecular level in older men. In her initial placebo controlled study, older men with low serum testosterone (T) levels will be treated with placebo, T, T plus a potent 5-alpha-reductase inhibitor (dutasteride) which blocks the conversion of T to the more potent androgen dihyrotestosterone (DHT), or DHT gel. Prostate biopsies will be conducted after one month of drug treatment. Careful analyses of intraprostatic tissue concentration and gene expression will allow Dr. Page to determine the effect of these hormone manipulations on prostate hormone levels and to determine the optimal dosage and treatment number for further study. In a subsequent study, testosterone deficient older men will undergo an initial prostate biopsy prior to treatment with either placebo, T, or T and dutasteride for six months followed by a second biopsy procedure. Tissue hormone levels, cell proliferation, and tissue specific gene expression will be analyzed. Long-term androgen-responsive endpoints such as bone mineral density, body composition and serum cholesterol will be followed to ascertain the impact of the addition of a potent 5-alpha-reductase inhibitor to these secondary endpoints. Data from these studies may eventually guide the design of larger, more definitive trials of androgen replacement in older men with low serum T. William J. Bremner MD, PhD, Chairman of the Department of Medicine, and Director of the Center for Research in Reproduction and Contraception, Alvin M. Matsumoto MD, Director, Clinical Research Unit VA Puget Sound Health Care System and Professor of Medicine (Gerontology), University of Washington School of Medicine, and Peter S. Nelson, MD, Associate Professor of Medicine (Oncology), University of Washington School of Medicine will co-mentor this award.

描述（由申请人提供）：佩奇博士的职业目标是成为一名独立的临床医生评估者，精通研究和进行研究，以评估现有和新颖的选择性雄激素在衰老的男性中的使用。血清睾丸激素水平低的老年男性的雄激素替代越来越普遍，但是这种对前列腺健康的影响尚不清楚。佩奇博士在设计和进行与雄激素使用有关雄激素有关的临床研究方面获得了一些经验，佩奇博士建议进行研究并进行教学训练，以评估老年男性在分子水平上睾丸激素替代对前列腺的影响。在她最初的安慰剂对照研究中，患有低血清睾丸激素（T）水平的老年男性将通过安慰剂，T，T和有效的5-α-还原酶抑制剂（Dutasteride）进行治疗，该抑制剂（Dutasteride）阻止T将T转化为更有效的雄激素二睾丸激素（DHT）（DHT）或DHT Gel。在药物治疗一个月后，将进行前列腺活检。仔细分析肉体内组织浓度和基因表达将使Page博士确定这些激素操纵对前列腺激素水平的影响，并确定最佳剂量和治疗数以进行进一步研究。在随后的一项研究中，睾丸激素不足的老年男性将在接受安慰剂，T或T和dutasteride治疗之前进行初始的前列腺活检六个月，然后进行第二次活检手术。将分析组织激素水平，细胞增殖和特异性基因表达。将遵循长期的雄激素响应性终点，例如骨矿物质密度，人体组成和血清胆固醇，以确定添加有效的5-α-还原酶抑制剂对这些次要终点的影响。这些研究的数据最终可能指导了较大，更明确的雄激素替代试验的设计。 S. Nelson，医学博士，华盛顿大学医学院医学副教授（肿瘤学）将获得该奖项。