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. ? ? ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23AG027238-01A1
Application #
7147500
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Nayfield, Susan G
Project Start
2006-09-01
Project End
2011-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
1
Fiscal Year
2006
Total Cost
$126,792
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Mostaghel, Elahe A; Lin, Daniel W; Amory, John K et al. (2012) Impact of male hormonal contraception on prostate androgens and androgen action in healthy men: a randomized, controlled trial. J Clin Endocrinol Metab 97:2809-17
Rubinow, Katya B; Tang, Chongren; Hoofnagle, Andrew N et al. (2012) Acute sex steroid withdrawal increases cholesterol efflux capacity and HDL-associated clusterin in men. Steroids 77:454-60
Rubinow, K B; Snyder, C N; Amory, J K et al. (2012) Acute testosterone deprivation reduces insulin sensitivity in men. Clin Endocrinol (Oxf) 76:281-8
Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet et al. (2011) Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy. J Urol 186:191-7
Roth, Mara Y; Page, Stephanie T (2011) A role for dihydrotestosterone treatment in older men? Asian J Androl 13:199-200
Roth, M Y; Page, S T; Lin, K et al. (2011) The effect of gonadotropin withdrawal and stimulation with human chorionic gonadotropin on intratesticular androstenedione and DHEA in normal men. J Clin Endocrinol Metab 96:1175-81
Page, Stephanie T (2011) Physiologic role and regulation of intratesticular sex steroids. Curr Opin Endocrinol Diabetes Obes 18:217-23
Page, Stephanie T; Lin, Daniel W; Mostaghel, Elahe A et al. (2011) Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial. J Clin Endocrinol Metab 96:430-7
Attardi, Barbara J; Page, Stephanie T; Hild, Sheri A et al. (2010) Mechanism of action of bolandiol (19-nortestosterone-3beta,17beta-diol), a unique anabolic steroid with androgenic, estrogenic, and progestational activities. J Steroid Biochem Mol Biol 118:151-61
Roth, Mara Y; Lin, K; Amory, J K et al. (2010) Serum LH correlates highly with intratesticular steroid levels in normal men. J Androl 31:138-45

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