Prostate and Cardiovascular Effects of Male Hormonal Contraceptive Regimens

世界人口继续以惊人的速度增长，调查表明，男女都希望有更多的男性避孕选择。由雄激素加黄体酮组成的男性激素避孕方案是有吸引力的选择，因为它们的有效率高（95%以上）并且完全可逆。然而，外源性激素对男性的性腺外影响知之甚少。我们提出了两项随机、安慰剂对照试验，以进一步了解雄激素和黄体酮对前列腺和心血管系统的潜在益处和风险，以及可能由雄激素和黄体酮调节的男性高患病率器官系统。我们最近发展了技术专长，对正常志愿者在激素操作后获得的前列腺组织标本进行分子分析。在研究1中，我们建议在接受睾酮(T)凝胶治疗3个月的男性中，确定前列腺内激素水平、细胞周转率和细胞特异性基因表达，T +度他雄胺（一种阻断T向更有效的雄激素二氢睾酮转化的药物，可能有助于预防前列腺癌）或T +肌内depomdroxyprogesterone （IM DMPA）

World population continues to grow at an astonishing rate and surveys suggest that both genders desire more male contraceptive options. Male hormonal contraceptive regimens that consist of androgens plus a progestin 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. We propose two randomized, placebo-controlled trials that will further our understanding of the potential benefits and risks of androgens and progestins on the prostate and cardiovascular system, organ systems with high disease prevalence in men that might be modulated by androgens and progestins. We have recently developed technical expertise performing molecular analyses on prostate tissue specimens obtained from normal volunteers after hormone manipulation. We propose in Study 1 to determine intraprostatic hormone levels, 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 and may contribute to prostate cancer prevention, or T + intramuscular depomedroxyprogesterone (IM DMPA), a promising male hormonal contraceptive regimen. This study will provide significant insights into the impact of hormonal manipulation on the prostate at the molecular level in normal, healthy men. Exogenous testosterone and progestins suppress serum high density lipoprotein (HDL) and cause weight gain. These changes may be associated with increased visceral adiposity, systemic inflammation, insulin resistance and increased risk of cardiovascular disease. Because there have been no systematic studies done on the effects of androgens + progestins on these cardiovascular risk factors, we propose in Study 2 to compare the effects of 6 months of treatment with T gel alone vs. T + IM DMPA vs. T + oral MPA on serum HDL, body composition, inflammatory markers, insulin sensitivity, and spermatogenesis. In Study 2, we will determine how T alone and T + IM DMPA affect these measures, and whether oral administration of the progestin MPA impacts 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-based contraceptive regimens and T + MPA, a promising male hormonal contraceptive regimen.