Effect of Dihydrotestosterone (DHT) on Prostate Tissue [Short Title: DHT-3]

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Dihydrotestosterone (DHT) gel (0.7%); Drug: Placebo gel

• Registration Number: NCT00490022
• Lead Sponsor: University of Washington

Brief 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.

Study Timeline

• Study Start: 2007-06
• Study First Submitted: 2007-06-20
• Study First Submitted QC: 2007-06-21
• Study First Posted: 2007-06-22
• Primary Completion: 2009-01
• Study Completion: 2009-01
• Results First Submitted: 2011-01-10
• Results First Submitted QC: 2011-05-10
• Status Verified: 2011-06
• Results First Posted: 2011-06-09
• Last Update Submitted: 2011-06-20
• Last Update Posted: 2011-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 31

Inclusion Criteria

• Males 35-55 years old
• Normal serum total testosterone (300 ng/dl-1000 ng/dl)
• Normal Luteinizing Hormone [LH] and Follicle Stimulating Hormone [FSH] levels
• Informed consent
• Taking no regular medications
• Normal baseline prostate ultrasound, hematology, and liver function tests

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Exclusion Criteria

• History of prostate cancer
• Prostate Specific Antigen [PSA] > 2.0
• American Urological Association [AUA] prostate symptom score > 10
• History of testosterone or anabolic steroid use in the past
• Chronic medical illness or prostate disease
• History of a bleeding disorder or need for anticoagulation
• A first-degree relative (i.e. father, brother) with a history of prostate cancer
• Abnormal digital rectal examination
• Skin condition that might interfere with or be exacerbated by DHT gel use
• History of untreated sleep apnea and/or psychiatric problems
• Participation in another study in the past 2 months
• Participating in a regular physical relationship with a pregnant woman

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Dihydrotestosterone (DHT) gel (0.7%)	DHT gel (70 mg/day) for one month
2	Placebo gel	Placebo gel for one month

Primary Outcome Measures

Name	Time	Method
Prostate Tissue DHT and Testosterone Levels After 28 Days of Treatment With Dihydrotestosterone [DHT] Gel Versus Placebo Gel.	28-days	After 4 weeks of either daily dihydrotestosterone transdermal gel or placebo gel, subjects underwent a prostate biopsy. Intraprostatic hormone concentrations, specifically DHT and Testosterone, were measured. Unit of measure is ng/g.

Secondary Outcome Measures

Name	Time	Method
Prostate Epithelial Cell Proliferation	28-days	Prostate epithelial cell proliferation in the prostate biopsy tissue was measured using Ki-67 immunohistochemical staining of prostate epithelium as a marker of cell proliferation (values are number of Ki-67 positive stained cells per 100 prostate epithelial cells). The placebo and treatment groups were compared.

Trial Locations

Locations (1)

University of Washington; 🇺🇸 Seattle, Washington, United States