PROS-1-Male Hormonal Contraceptive Regimens on Prostate Tissue

• Status: Completed
• Trial end date: 2012-03-01
• Target enrollment: 0
• Participant gender: Male

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
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Washington
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Contraceptive Agents; Dutasteride; Medroxyprogesterone; Medroxyprogesterone Acetate; Methyltestosterone; Testosterone; Testosterone 17 beta-cypionate; Testosterone enanthate; Testosterone undecanoate

Criteria

Inclusion Criteria:

• Men in good health, and without a history of chronic androgen therapy or known history of gonadal or prostate abnormalities.

• PSA ≤ 2.

• Age 25-55 years

• Ability to understand the study,study procedures and provide consent

• Normal serum total T, LH, FSH, urine analyses, and sperm count > or equal to 15million/ml

• International Prostate Symptom Score (IPSS) < 10

• Normal seminal fluid analysis (>20 million sperm/ml)

• Agree not to donate blood during the treatment and recovery periods

Exclusion Criteria:

• A history or evidence of prostate or breast cancer

• History of invasive therapy for BPH

• History of acute urinary retention

• Current or past treatment with a 5α-reductase inhibitor

• History of anti/androgenic drugs or drugs that interfere with steroid metabolism within past 3 months

• Severe systemic illness (renal, liver, cardiac, lung disease, cancer, poorly controlled diabetes)

• Known untreated obstructive sleep apnea

• Hematocrit > 52%

• Skin disease that might interfere with T gel absorption

• Hypersensitivity to any of the drugs used in the study

• History of a bleeding disorder or anticoagulation

• History of drug or alcohol abuse within 12 months

• History of infertility or desire for fertility within 12 months, or current pregnant partner

• A first-degree relative (i.e. father, brother) with a history of prostate cancer

• Abnormal digital rectal examination or prostate ultrasound