Effect of Dihydrotestosterone (DHT) on Prostate Tissue [Short Title: DHT-3]
Condition: Healthy
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this research study is to understand the effects of a male hormone normally
      made in the body called Dihydrotestosterone (DHT) on the prostate gland that is located under
      the bladder. The knowledge gained from this study may be used to help in the future to
      develop a safe male hormonal contraceptive to prevent pregnancy, in the safe treatment of low
      male hormone levels in men, and in the treatment and prevention of diseases of the prostate.

      The investigators will be giving DHT in a gel form, to be applied to the skin, or a placebo
      gel (with no active drug in it). The investigators want to see the effects of DHT on levels
      of hormones in the blood and in the prostate gland itself. In addition, the investigators
      will be studying the effects of DHT on the cells and genes expressed within the prostate.

      The effect of DHT on the prostate is not known. Some studies suggest blocking production of
      DHT in the prostate helps growth of the gland with aging (a condition known as benign
      prostatic hyperplasia, or BPH for short) and may prevent prostate cancer. On the other hand,
      DHT administration may shrink the prostate, suggesting it may be beneficial for some men.
      Therefore, further studies looking at the effect of DHT on the prostate are needed.
    

Detailed description: 
      In this study, we will examine the in vivo effects of DHT supplementation on the prostate and
      serum inflammatory markers at the molecular level. We hypothesize that increases in serum DHT
      will not increase intraprostatic DHT or prostate epithelial proliferation, and will be
      associated with decreases in markers of systemic inflammation. Normal, healthy, male study
      volunteers will be treated with either placebo gel (Group 1) or DHT gel (Group 2) for one
      month. Serum hormonal and inflammatory measurements will be assessed before, during, and
      after treatment, and the relationship between hormones and inflammatory markers associated
      with cardiovascular risk will be determined. Prostate biopsies will be taken after one month
      of treatment. Prostate tissue will be analyzed for changes in intraprostatic hormone levels
      as well as gene expression following treatment.

      SPECIFIC AIMS:

        1. To determine the effect of increases in serum DHT, without concomitant increases in
           serum T or estrogen, on intraprostatic androgen levels.

        2. To determine the effect of increases in serum DHT, without concomitant increases in
           serum T or estrogen, on prostate epithelial gene expression.

        3. To determine the effect of increases in serum DHT, without concomitant increases in
           serum T or estrogen, on serum lipids and inflammatory markers including C-Reactive
           Protein [CRP], Tumor necrosis factor-alpha [TNFα], Interleukin-6 [IL-6], adiponectin,
           plasminogen activator inhibitor [PAI-I], and leptin.

      We will test the hypothesis in normal men (rather than hypogonadal men) as a "proof of
      principle" investigation. A normal hypothalamic-pituitary-testicular axis and regulation,
      circulating T and DHT levels and intraprostatic androgen concentrations in healthy, normal
      men will permit optimal testing of the hypothesis. Exogenous DHT administration in normal men
      is expected to suppress endogenous gonadotropin and testosterone secretion, compared to more
      variable effects in hypogonadal men that depend on the degree of hypogonadism in these men
      and whether they have primary (testicular) or secondary (hypothalamic-pituitary)
      hypogonadism. Furthermore, intraprostatic T and DHT concentrations and 5 alpha-reductase
      activity (that is androgen-dependent) is expected to be more variable in hypogonadal men,
      depending on the degree of androgen deficiency and circulating T and DHT levels. If results
      in normal men support the hypothesis, subsequent studies could be performed in hypogonadal
      men. Because of the larger variability in circulating and probably intraprostatic androgen
      concentrations in hypogonadal men, these studies will require much larger numbers of
      subjects.
    

Intervention name(s): Dihydrotestosterone (DHT) gel (0.7%); Placebo gel
Intervention type(s): Drug; Drug
Intervention description(s): DHT gel, 70 mg/day for one month; Placebo gel for one month
Other intervention name(s): 17β-Hydroxy-5α-androstane-3-one
Intervention MeSH terms: Dihydrotestosterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Dihydrotestosterone; Androgen; Prostate