Fat Mediated Modulation of Reproductive and Endocrine Function in Young Athletes

描述（由申请人提供）：多达25%的青少年和年轻的成年耐力运动员发生闭经，导致闭经的因素在一些，但不是全部，运动员还没有得到很好的表征。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（H-P-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，其他的影响因素还不清楚。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。这项研究将证实这些数据，并确定是否低脂肪质量和改变水平的脂肪因子，如瘦素和脂联素，和激素调节的脂肪质量，如生长激素释放肽和肽YY（PYY），决定改变LH脉动。一个非常令人担忧的影响闭经的运动员是低骨密度（BMD）。初步数据表明，与月经过多的运动员（EA）和非运动对照组相比，闭经的青少年运动员（AA）的BMD较低。AA在青少年中的高患病率尤其令人担忧，因为这一人群的潜在风险更大，因为它正在积极地积累骨骼。重要的是，骨微结构，一个更好的预测骨强度比骨密度，尚未在AA的研究。由于青春期雌激素的增加是优化峰值骨量的组成部分，而AA的特征是雌激素水平低下，这项经皮雌激素与口服雌激素或无雌激素的随机研究也将检查雌激素替代是否增加BMD并改善14-21岁青少年AA的骨微结构。在此期间，将在不进行干预的情况下进行EA和久坐对照。尽管在AA中处方口服避孕药的做法很普遍，但关于这种干预措施在青少年中的益处的数据很少。因为透皮雌激素，不像口服雌激素，不抑制IGF-1，一个重要的骨合成代谢因子，我们预计透皮雌激素的效果超过口服雌激素或没有治疗。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降低运动员的骨增长率，并将在本研究中得到证实。总之，更好地了解生殖功能障碍的病理生理学对于制定使生殖轴和骨增长正常化的治疗策略至关重要，这些是本研究旨在回答的问题。公共卫生相关性：许多高中和大学运动员停止月经，月经的减少对骨骼健康有有害影响。导致月经损失的因素尚未完全了解。这项研究计划将研究低脂肪和相关激素对这些年轻女性月经不调的影响，以及在这个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.