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

基本信息

批准号：
7284606
负责人：
WILLIAM J BREMNER
金额：
$ 7.02万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-01 至 2012-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7284606
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 Classification 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 Inflammatory 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 N,N-dimethyl-4-anisidine 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 Rate 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 Treatment Protocols Visceral Weight Weight Gain Woman absorption adiponectin base body system cardiovascular disorder risk cardiovascular risk factor caspase-3 complement C3a, des-Arg-(77)desire hormonal contraception human subject hypothalamic pituitary gonadal axis indexing 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

项目摘要

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，男女都渴望更多男性避孕选择。男性激素避孕方案由雄激素和孕激素是有吸引力的选择，因为它们具有高有效率（超过 95%）并且是完全可逆的。然而，人们对外源激素对男性的性腺外影响知之甚少。我们提出两项随机、安慰剂对照试验，这将进一步加深我们对潜在益处的了解以及雄激素和孕激素对前列腺和心血管系统、高器官系统的风险男性疾病患病率可能受到雄激素和孕激素的调节。我们最近有开发了对前列腺组织样本进行分子分析的技术专业知识激素操作后的正常志愿者。我们在研究 1 中建议确定前列腺内激素接受 3 个月睾酮 (T) 凝胶治疗的男性的水平、细胞更新和细胞特异性基因表达， T + 度他雄胺，一种阻止 T 转化为更有效的雄激素二氢睾酮的药物，可能有助于预防前列腺癌，或 T + 肌内注射去甲羟黄体酮 (IM DMPA)，一种有前景的男性激素避孕方案。这项研究将提供关于其影响的重要见解正常健康男性在分子水平上对前列腺的荷尔蒙控制。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。这些这些变化可能与内脏肥胖增加、全身炎症、胰岛素抵抗和心血管疾病的风险增加。因为目前还没有系统的研究雄激素+孕激素对这些心血管危险因素的影响，我们建议在研究 2 中比较单独使用 T 凝胶、T + IM DMPA 与 T + 口服 MPA 治疗 6 个月对血清 HDL、身体的影响成分、炎症标志物、胰岛素敏感性和精子发生。在研究 2 中，我们将确定单独 T 和 T + IM DMPA 如何影响这些措施，以及是否口服孕激素 MPA 由于首过肝脏效应，对这些心血管危险因素和精子发生的影响不同。这些研究将共同显着提高我们对基于 T 的潜在风险和益处的了解。避孕方案和 T + MPA（一种有前途的男性激素避孕方案）。