Fat Mediated Modulation of Reproductive and Endocrine Function in Young Athletes

描述（由申请人提供）：多达25%的青少年和青年耐力运动员发生闭经，导致闭经的因素发生在一些运动员身上，但不是全部，没有很好的特征。最近的数据表明，负能量平衡状态和瘦素在调节下丘脑-垂体-性腺（hp -g）轴中至关重要。然而，这些因素并不能完全解释这个轴的变化，其他因素也不清楚。我们的初步数据表明，低脂肪量和脂肪相关激素在介导年轻运动员性腺功能减退中的重要性。本研究将证实这些数据，并确定低脂肪量和脂肪因子水平的改变，如瘦素和脂联素，以及由脂肪量调节的激素，如胃饥饿素和肽YY (PYY)，是否决定了LH脉搏的改变。闭经对运动员的影响是低骨密度（BMD）。初步数据表明，闭经（AA）青少年运动员的骨密度低于痛经运动员（EA）和非运动对照组。青少年中AA的高患病率尤其令人担忧，因为这一人群正在积极积累骨骼，潜在的风险更大。重要的是，骨微结构，一个比骨密度更好的预测骨强度的指标，还没有在AA中得到研究。由于青春期雌激素的增加是优化骨量峰值的必要条件，而AA具有雌激素水平低下的特征，因此，这项随机研究将透皮雌激素与口服雌激素或不服用雌激素进行比较，也将研究雌激素替代是否会增加14-21岁AA青少年的骨密度并改善骨微结构。在此期间，EA和久坐对照组将在没有干预的情况下进行。尽管在互戒协会中开口服避孕药的做法很普遍，但关于这种干预对青少年的益处的数据却很缺乏。由于透皮雌激素与口服雌激素不同，不抑制重要的骨合成代谢因子IGF-1，我们预计透皮雌激素的作用将超过口服雌激素或不治疗。此外，初步数据表明，低脂肪量和脂肪相关激素的改变可能有助于运动员的骨累积率降低，这将在本研究中得到证实。总之，更好地理解生殖功能障碍的病理生理学对于制定治疗策略至关重要，这些策略将使生殖轴和骨积累正常化，这是本研究旨在回答的问题。公共健康相关性：许多高中和大学运动员停止了月经，月经的减少对骨骼健康有有害的影响。导致月经减少的因素尚不完全清楚。这项研究计划将研究低脂肪量和相关激素对这些年轻女性月经不来的影响，以及在这一关键时期增加骨密度的策略。

DESCRIPTION (provided by applicant): As many as 25% of adolescent and young adult endurance athletes develop amenorrhea, and factors that cause amenorrhea to occur in some, but not all, athletes have not been well characterized. Recent data indicate the critical importance of a negative energy balance state and leptin in regulating the hypothalamo- pituitary-gonadal (H-P-G) axis. However, these factors do not completely account for alterations in this axis, and other contributing factors are unclear. Our preliminary data indicate the importance of low fat mass and fat related hormones in mediating hypogonadism in young athletes. This study will confirm these data and determine whether low fat mass and altered levels of adipokines, such as leptin and adiponectin, and hormones regulated by fat mass, such as ghrelin and peptide YY (PYY), determine alterations in LH pulsatility. A very concerning impact of amenorrhea in athletes is low bone mineral density (BMD). Preliminary data indicate lower BMD in adolescent athletes with amenorrhea (AA) compared with eumenorrheic athletes (EA) and non-athletic controls. The high prevalence of AA in adolescents is particularly concerning, because this population is potentially at greater risk as it is actively accruing bone. Of importance, bone microarchitecture, a better predictor of bone strength than BMD, has not been studied in AA. Because pubertal increases in estrogen are integral to optimizing peak bone mass, and AA is characterized by hypoestrogenism, this randomized study of transdermal estrogen versus oral estrogen or no estrogen will also examine whether estrogen replacement increases BMD and improves bone microarchitecture in adolescent AA 14-21 years old. EA and sedentary controls will be followed without intervention for this period. Despite the prevalent practice of prescribing oral contraceptives in AA, there is a paucity of data regarding benefits of this intervention in teenagers. Because transdermal estrogen, unlike oral estrogen, does not suppress IGF-1, an important bone anabolic factor, we expect effects of transdermal estrogen to exceed those of oral estrogen or no therapy. In addition, preliminary data indicate that low fat mass and alterations in fat related hormones may contribute to decreased bone accrual rates in athletes, and will be confirmed in this study. To summarize, a better understanding of the pathophysiology of reproductive dysfunction is critical to develop therapeutic strategies that will normalize the reproductive axis and bone accrual, and these are the questions that this study aims to answer. PUBLIC HEALTH RELEVANCE: Many high school and college athletes stop having their periods, and loss of periods has deleterious effects on bone health. Factors that lead to loss of periods are not completely understood. This research proposal will examine the impact of low fat mass and related hormones on absence of periods in these young women, and strategies to increase bone density at this critical time.