World population continues to grow at an astonishing rate and surveys suggest that both genders desiremore male contraceptive options. Male hormonal contraceptive regimens that consist of androgens plus aprogestin are attractive options as they have high efficacy rates (over 95%) and are fully reversible.However, little is known about the extra-gonadal effects of exogenous hormone administration in men. Wepropose two randomized, placebo-controlled trials that will further our understanding of the potential benefitsand risks of androgens and progestins on the prostate and cardiovascular system, organ systems with highdisease prevalence in men that might be modulated by androgens and progestins. We have recentlydeveloped technical expertise performing molecular analyses on prostate tissue specimens obtained fromnormal volunteers after hormone manipulation. We propose in Study 1 to determine intraprostatic hormonelevels, cell turnover, and cell-specific gene expression in men treated with 3 months of testosterone (T) gel,T + dutasteride, a drug that blocks the conversion of T to the more potent androgen dihydrotestosterone andmay contribute to prostate cancer prevention, or T + intramuscular depomedroxyprogesterone (IM DMPA), apromising male hormonal contraceptive regimen. This study will provide significant insights into the impactof hormonal manipulation on the prostate at the molecular level in normal, healthy men. Exogenoustestosterone and progestins suppress serum high density lipoprotein (HDL) and cause weight gain. Thesechanges may be associated with increased visceral adiposity, systemic inflammation, insulin resistance andincreased risk of cardiovascular disease. Because there have been no systematic studies done on theeffects of androgens + progestins on these cardiovascular risk factors, we propose in Study 2 to compare theeffects of 6 months of treatment with T gel alone vs. T + IM DMPA vs. T + oral MPA on serum HDL, bodycomposition, inflammatory markers, insulin sensitivity, and spermatogenesis. In Study 2, we will determinehow T alone and T + IM DMPA affect these measures, and whether oral administration of the progestin MPAimpacts these cardiovascular risk factors, and spermatogenesis, differently, due to first-pass hepatic effects.Together these studies will significantly advance our knowledge of the potential risks and benefits of T-basedcontraceptive regimens and T + MPA, a promising male hormonal contraceptive regimen.
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