Prostate and Cardiovascular Effects of Male Hormonal Contraceptive Regimens

男性激素避孕方案对前列腺和心血管的影响

• 批准号: 8074940
• 负责人: WILLIAM J BREMNER
• 金额: $ 6.59万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8074940
• 关键词: 5a-Reductase Inhibition; Acetates; Adverse effects; Affect; Androgens; Apoptosis; Benefits and Risks; Body Composition; Body Weight decreased; Body fat; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Cell Proliferation; Cells; Cellular biology; Cervical; Cessation of life; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Data; Development; Disease; Dutasteride; Endometrial Carcinoma; Epidemiologic Studies; Epithelial; Epithelial Cells; Epithelium; Estrogens; Fatty acid glycerol esters; Fibrinogen; Gel; Gender; Gene Expression; General Anesthesia; Genes; Hand; Health; Health Care Costs; Hepatic; High Density Lipoproteins; High Prevalence; Hormonal; Hormones; Human; Hypogonadism; Incidence; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Intramuscular; Knowledge; Label; Lead; Leptin; Lipids; Liver; Maintenance; Male Contraceptive Agents; Malignant neoplasm of prostate; Measures; Medroxyprogesterone 17-Acetate; Metabolic; Molecular; Nonesterified Fatty Acids; Obesity; Oral; Oral Administration; Organ; Ovarian; Oxidoreductase; Pharmaceutical Preparations; Phase II Clinical Trials; Physiology; Placebos; Population; Portal vein structure; Prevalence; Progestins; Prostate; Prostatic; Prostatic Diseases; Regimen; Research Design; Risk; Risk Factors; Route; Safety; Serum; Serum amyloid A protein; Severities; Specimen; Spermatogenesis; Stanolone; Stromal Cells; Surveys; System; Technical Expertise; Techniques; Testing; Testosterone; Tissues; Visceral; Weight; Weight Gain; Woman; absorption; adiponectin; base; body system; cardiovascular disorder risk; cardiovascular risk factor; caspase-3; complement C3a, des-Arg-(77); control trial; hormonal contraception; human subject; hypothalamic pituitary gonadal axis; indexing; inflammatory marker; inhibitor/antagonist; insight; insulin sensitivity; male; male health; malignant breast neoplasm; man; men; middle age; older men; prevent; prostate cancer prevention; protein expression; randomized placebo controlled trial; species difference; sperm cell; volunteer

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.

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。男性激素避孕方案，包括雄激素加一个residestin是有吸引力的选择，因为他们有效率高（超过95%），是完全可逆的。然而，很少有人知道外源性激素管理的男性性腺外的影响。我们提出了两个随机，安慰剂对照试验，这将进一步了解雄激素和孕激素对前列腺和心血管系统的潜在益处和风险，这些器官系统在男性中具有高疾病患病率，可能受到雄激素和孕激素的调节。我们最近开发了技术专长，对激素操作后从正常志愿者获得的前列腺组织标本进行分子分析。我们在研究1中提出，在接受睾酮（T）凝胶、T +度他雄胺（一种阻断T转化为更有效的雄激素双氢睾酮并可能有助于预防前列腺癌的药物）或T +肌内去甲羟孕酮（IM DMPA）治疗3个月的男性中，测定前列腺内激素水平、细胞更新和细胞特异性基因表达。 很有前途的男性荷尔蒙避孕法这项研究将提供显着的见解激素操纵前列腺在分子水平上的影响，在正常，健康的男性。外源性睾酮和孕激素抑制血清高密度脂蛋白（HDL）并导致体重增加。这些变化可能与内脏肥胖、全身炎症、胰岛素抵抗和心血管疾病风险增加有关。由于目前还没有关于雄激素+孕激素对这些心血管危险因素影响的系统研究，我们建议在研究2中比较 单独使用T凝胶与T + IM DMPA与T +口服MPA治疗6个月对血清HDL、身体成分、炎症标志物、胰岛素敏感性和精子发生的影响。在研究2中，我们将确定单独的T和T + IM DMPA如何影响这些指标，以及由于首过肝脏效应，口服给予孕酮MPA是否会不同地影响这些心血管风险因素和精子发生。这些研究将大大提高我们对T基避孕方案和T + MPA（一种有前途的男性激素避孕方案）的潜在风险和益处的认识。