Effects of weight and insulin sensitivity on reproductive function in PCOS

项目摘要 该K99/R 00奖项的目的是完成女性生殖内分泌学的进一步培训， 特别是在多囊卵巢综合征妇女的原代细胞肌肉培养中的转化研究 （多囊卵巢综合征），分析，出版和介绍在2个试点研究中收集的数据，并完成课程 在杜兰大学临床研究计划理学硕士所需。在R 00期间 （独立阶段）PI将在肥胖PCOS女性中进行一项随机对照试验， 确定以下因素的影响：a）运动训练，B）25%饮食限制，c）二甲双胍和d）无干预 （对照组）对神经内分泌功能（脉冲式LH分泌）、生殖功能（排卵率）、 卵巢形态/功能和胰岛素敏感性。PCOS是一种内分泌疾病， 雄激素的产生和生殖功能障碍是女性最常见的生殖障碍， 生育年龄PCOS的病因尚不清楚。然而，神经内分泌功能异常， 高胰岛素血症被认为是参与PCOS发展的主要候选者。减肥是 被视为治疗超重妇女不孕症的首选。但它不是 已知生殖功能是否由于改善胰岛素敏感性和/或降低体重而改善 重量. PI进行的初步研究表明，运动，独立于体重减轻， PCOS妇女的月经周期。由于运动不会导致体重减轻，我们现在假设， 观察到的胰岛素敏感性的增加可能介导生殖功能的改善，而不是 减肥.为了支持这一假设，我们的16周有氧运动研究减少了空腹胰岛素， 在高胰岛素血正葡萄糖钳夹过程中增加胰岛素刺激的葡萄糖处置。此外，委员会认为， 胰岛素增敏剂治疗PCOS患者可改善雄激素过多和排卵功能 没有重量变化。拟议的随机对照试验将提供数据，表明可能 生活方式改变可以影响PCOS女性生殖功能的机制。是 希望进一步的研究将导致循证治疗方案的发展， 超重PCOS女性不孕症

Project Summary The objective of this K99/R00 award is to complete further training in female reproductive endocrinology, particularly translational studies in primary cell muscle cultures from women with polycystic ovary syndrome (PCOS), analyze, publish and present data collected during 2 pilot studies and complete the coursework required for the Masters of Science in Clinical Research program at Tulane University. During the R00 (independent phase) the PI will conduct a randomized controlled trial in obese women with PCOS to determine the effect of: a) exercise training, b) 25% dietary restriction c) metformin and d) no intervention (control group) on neuroendocrine function (pulsatile LH secretion), reproductive function (ovulation rate), ovarian morphology/function and insulin sensitivity. PCOS, an endocrinopathy characterized by excessive androgen production and reproductive dysfunction is the most common reproductive disorder in women of reproductive age. The etiology of PCOS is unclear. However abnormal neuroendocrine function and hyperinsulinemia are considered primary candidates involved in the development in PCOS. Weight loss is regarded as the choice treatment of infertility in overweight women with the condition. However it is not known if reproductive function is improved as a result of improving insulin sensitivity and/or reducing body weight. Preliminary studies conducted by the PI indicate that exercise, independent of weight loss, induces menstrual cyclicity in women with PCOS. Since exercise did not cause weight loss, we now hypothesize that the observed increase in insulin sensitivity may mediate the improvement in reproductive function rather than weight loss. In support of this hypothesis, our 16-week aerobic exercise study reduced fasting insulin and increased insulin-stimulated glucose disposal during a hyperinsulinemic euglycemic clamp. Furthermore, treatment of PCOS patients with insulin sensitizers improves both androgen excess and ovulatory function without weight change. The proposed randomized controlled trial will provide data to indicate possible mechanisms by which lifestyle modification can influence reproductive function in women with PCOS. It is hoped that further studies will then lead to the development of evidence based treatment programs for infertility in overweight women with PCOS.