PROS-1-Male Hormonal Contraceptive Regimens on Prostate Tissue
Status:
Completed
Trial end date:
2012-03-01
Target enrollment:
Participant gender:
Summary
The investigators propose to examine the in vivo responses to hormonal manipulation at the
molecular level directly in the tissue of interest (prostate). As in the investigators'
previous, pilot study, the investigators will use the novel approach of procuring tissue
specimens from normal, healthy men who might be chose to use a male hormonal contraceptive
regimen were it available. The investigators will employ state of the art techniques such as
laser capture microdissection (LCM) and cDNA microarrays to determine the tissue-specific
consequences of male hormonal contraceptive regimens on the prostate. The results will help
guide the design, safety monitoring, and selection of male hormonal contraceptive agents and
provide valuable insights into prostate human prostate biology.
The investigators will test the hypothesis that exogenous T administration that results in
increased circulating T and dihydrotestosterone (DHT) levels will increase intraprostatic
concentrations of T and its metabolite DHT.
The investigators will test the hypothesis that the addition of a potent 5α-reductase
inhibitor, dutasteride, or the progestin, Depomedoxyprogesterone (IM DMPA), to T
administration in young and middle aged men will decrease intraprostatic DHT and increase
intraprostatic T concentrations compared to T alone.
The investigators will test the hypothesis that the addition of a 5α-reductase inhibitor
dutasteride or the progestin IM DMPA to exogenous T, by reducing intraprostatic DHT, will
decrease prostate epithelial proliferation, assessed by Ki-67 labeling index (Ki-67LI), and
increase apoptosis, assessed by caspase-3 expression, and decrease androgen-regulated protein
expression such as prostate specific antigen (PSA).
The investigators will test the hypothesis that the addition of a 5α-reductase inhibitor or
the progestin IM DMPA to exogenous T, by modifying the intraprostatic hormonal milieu, will
alter prostate epithelial gene expression. Specifically, the investigators expect that the
addition of the 5α-reductase inhibitor dutasteride or the progestin IM DMPA to exogenous T,
will result in decreased expression of androgen-regulated genes such as PSA.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
University of Washington
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)