PROS-1-Male Hormonal Contraceptive Regimens on Prostate Tissue
Condition: Healthy
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Detailed description: 
      The purpose of this research study is to understand the effects of testosterone on the
      prostate. This knowledge will be used to help in the development of a safe male hormonal
      contraception.

      We will be administering three drugs in this study: Testim (testosterone (T) gel),
      dutasteride (which affects testosterone break down) and Depomedoxyprogesterone (DMPA, a
      progestin). We want to see their effects on levels of hormones in the blood and prostate. In
      addition, we will be examining the effects of these drugs on the expression of genes within
      the prostate. DMPA suppresses LH and FSH, which are hormones made by the pituitary gland,
      thus blocking the signal from the brain that causes the testes to make testosterone.
      Prolonged (> 1 month) low levels of LH and FSH cause decreased sperm production in normal
      men. However, men may experience some side effects from the low levels of testosterone caused
      by DMPA; adding testosterone to DMPA eliminates these side effects while more effectively
      blocking LH and FSH release and sperm production. This combination of drugs is a promising
      male contraceptive regimen. However, the effect of these drugs on the prostate is not known.
      Some studies suggest that testosterone administration may promote prostate growth.
      Dutasteride blocks the conversion of testosterone to dihydrotestosterone and is used to treat
      men with enlarged prostates. Dutasteride shrinks the prostate. It is possible that combining
      testosterone and dutasteride may be an effective part of a male hormonal contraceptive
      regime. Therefore, further studies examining the effect of testosterone, DMPA and dutasteride
      on the prostate are needed.
    

Intervention name(s): Testosterone gel; Dutasteride; Depo-Medroxyprogesterone (DMPA); Placebo Testosterone gel; Placebo dutasteride; Placebo DMPA
Intervention type(s): Drug; Drug; Drug; Other; Other; Other
Intervention description(s): Testosterone gel 10 g; dutasteride 0.5 mg orally; 300 mg DMPA injection on Day 0 IM (into the muscle); Place gel applied daily for 12 weeks; placebo pill for 12 weeks; placebo DMPA injection Once
Other intervention name(s): Testim; Avodart; Depo-Provera
Intervention MeSH terms: Methyltestosterone; Medroxyprogesterone Acetate; Medroxyprogesterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate; Dutasteride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Male Contraception; Testosterone; Testis; Contraception; Prostate