Fat Mediated Modulation of Reproductive and Endocrine Function in Young Athletes

脂肪介导的年轻运动员生殖和内分泌功能的调节

• 批准号: 8319605
• 负责人: Madhusmita Misra
• 金额: $ 50.01万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-10 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8319605
• 关键词: 21 year old; Accounting; Adolescence; Adolescent; Adult; Affect; Amenorrhea; Athletic; Bone Density; Cross-Sectional Studies; Data; Deterioration; Dose; Dual-Energy X-Ray Absorptiometry; Endocrine; Estradiol; Estrogen Replacements; Estrogens; Fatty acid glycerol esters; Fracture; Functional disorder; Future; Gonadotropins; Health; High Prevalence; Hormones; Hypogonadism; Insulin-Like Growth Factor I; Intervention; Klinefelter' s Syndrome; Lead; Leptin; Mediating; Modeling; Observational Study; Oral; Oral Contraceptives; Pattern; Peptide YY; Physical activity; Population; Prospective Studies; Radial; Randomized; Randomized Controlled Trials; Research Proposals; Risk; Structure; Teenagers; Testing; Therapeutic; Thick; Time; Vertebral column; Weight-Bearing state; adipokines; adiponectin; arm; bone; bone health; bone mass; bone strength; college; cone-beam computed tomography; digital; energy balance; ghrelin; high risk; high school; improved; pituitary gonadal axis; prevent; prospective; reproductive; reproductive axis; sedentary; substantia spongiosa; transdermal estrogen; ultra high resolution; young adult; young woman

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.

描述（由申请人提供）：多达 25% 的青少年和青年耐力运动员出现闭经，而导致某些（但不是全部）运动员发生闭经的因素尚未得到很好的描述。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该轴的变化，并且其他影响因素尚不清楚。我们的初步数据表明低脂肪量和脂肪相关激素在调节年轻运动员性腺功能减退症中的重要性。这项研究将证实这些数据，并确定低脂肪量和脂肪因子（如瘦素和脂联素）水平的改变以及受脂肪量调节的激素（如生长素释放肽和肽 YY (PYY)）是否决定 LH 搏动的变化。闭经对运动员的一个非常令人担忧的影响是骨矿物质密度（BMD）低。初步数据表明，与正常月经运动员 (EA) 和非运动对照相比，闭经 (AA) 青少年运动员的 BMD 较低。青少年中 AA 的高患病率尤其令人担忧，因为这一人群由于骨质增生活跃，因此面临更大的风险。重要的是，骨微结构是比 BMD 更好的骨强度预测指标，但尚未在 AA 中进行研究。由于青春期雌激素的增加对于优化峰值骨量是不可或缺的，而 AA 的特点是雌激素水平低下，因此这项透皮雌激素与口服雌激素或无雌激素的随机研究还将检查雌激素替代是否会增加青少年 AA 的 BMD 并改善骨微结构 14-21岁了。在此期间，将遵循 EA 和久坐控制，无需干预。尽管在 AA 中开口服避孕药的做法很普遍，但有关这种干预措施对青少年的益处的数据却很少。由于透皮雌激素与口服雌激素不同，不会抑制 IGF-1（一种重要的骨合成代谢因子），因此我们预计透皮雌激素的效果将超过口服雌激素或不治疗的效果。此外，初步数据表明，低脂肪量和脂肪相关激素的变化可能会导致运动员骨生成率降低，这一点将在本研究中得到证实。总而言之，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生成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经期，而停经会对骨骼健康产生有害影响。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调的影响，以及在这个关键时刻增加骨密度的策略。