Hormonal and molecular consequences of androgen replacement on the prostate

Page博士的职业目标是成为一名独立的临床研究员，精通设计和开展研究，评估现有和新型选择性雄激素在老年男性中的使用。雄激素替代治疗在血清睾酮水平低的老年男性中越来越普遍，但这可能对前列腺健康的影响尚不清楚。佩奇博士在设计和进行男性使用雄激素相关的临床研究方面获得了一些经验， 和教学培训，以评估睾酮替代对老年男性前列腺在分子水平上的影响。在她最初的安慰剂对照研究中，血清睾酮（T）水平较低的老年男性将接受安慰剂、T、T加强效5-α-还原酶抑制剂（度他雄胺）治疗，该抑制剂可阻断T转化为更强效的雄激素二氢睾酮（DHT）或DHT凝胶。药物治疗一个月后将进行前列腺活检。对前列腺内组织浓度和基因表达的仔细分析将使Page博士能够确定这些激素操作对前列腺激素水平的影响，并确定进一步研究的最佳剂量和治疗次数。在随后的研究中，睾酮缺乏的老年男性将在接受安慰剂、T或T和度他雄胺治疗6个月之前进行首次前列腺活检，然后进行第二次活检。将分析组织激素水平、细胞增殖和组织特异性基因表达。将随访长期雄激素应答终点，如骨矿物质密度、身体组成和血清胆固醇，以确定添加强效5-α-还原酶抑制剂对这些次要终点的影响。来自这些研究的数据可能最终指导设计更大、更明确的雄激素替代治疗老年低血清睾酮男性的试验。威廉J布雷姆纳医学博士，博士，医学系主任，生殖和避孕研究中心主任，阿尔文M。松本医学博士，主任，临床研究单位弗吉尼亚州普吉特健全的医疗保健系统和医学教授（老年学），华盛顿大学医学院，和彼得S。华盛顿大学医学院医学（肿瘤学）副教授纳尔逊博士将共同指导该奖项。

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.