Effects of weight and insulin sensitivity on reproductive function in PCOS

项目摘要 这个K99/R00奖项的目的是完成女性生殖内分泌学的进一步培训， 尤其是多囊卵巢综合征患者原代细胞肌肉培养中的翻译研究 (PCOS)，分析、发布和展示在2个试点研究期间收集的数据，并完成课程工作 杜兰大学临床研究理学硕士课程所要求的。在R00期间 (独立阶段)PI将在患有多囊卵巢综合征的肥胖女性中进行随机对照试验 确定：a)运动训练，b)25%饮食限制，c)二甲双胍和d)不干预的效果 (对照组)神经内分泌功能(搏动性黄体生成素分泌)、生殖功能(排卵率)、 卵巢形态/功能和胰岛素敏感性。多囊卵巢综合征，一种内分泌疾病，以过度 雄激素产生和生殖功能障碍是女性最常见的生殖障碍 生育年龄。多囊卵巢综合征的病因尚不清楚。然而，神经内分泌功能异常和 高胰岛素血症被认为是多囊卵巢综合征发生的主要因素。减肥就是 被认为是治疗超重不孕症妇女的首选方法。然而，它并不是 是否知道通过改善胰岛素敏感性和/或减少体型可以改善生殖功能 重量。PI进行的初步研究表明，锻炼与减肥无关，可以诱导 多囊卵巢综合征患者的月经周期。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是生殖功能改善的中介，而不是 减肥。为了支持这一假设，我们为期16周的有氧运动研究降低了空腹胰岛素和 在高胰岛素正血糖钳夹期间增加胰岛素刺激的葡萄糖处置。此外， 胰岛素增敏剂治疗多囊卵巢综合征可改善雄激素过剩和排卵功能 没有重量变化。拟议的随机对照试验将提供数据，以表明 生活方式改变影响多囊卵巢综合征患者生殖功能的机制。它是 希望进一步的研究将导致开发基于证据的治疗方案 患有多囊卵巢综合征的超重妇女的不孕症。

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.