Mentoring is a critical component of the career of a patient-oriented-researcher, and essential for a successful career in patient-oriented research. The PI has a successful record of mentoring a number of fellows and trainees in the complex techniques of metabolic and bone health assessment in a large population of young athletes, particularly those with associated amenorrhea. The scientific aims of the application are based on the candidate's successfully funded R01, investigating: 1) whether low fat mass and altered levels of adipokines and fat regulated hormones determine alterations in LH pulsatility patterns in amenorrheic athletes (AA), that differentiate them from eumenorrheic athletes (EA) and non-athletes, and 2) treatment strategies to optimize bone accrual and structure in AA over a 12-month period. Several new directions are proposed in the current application, and it is hypothesized (1) that bone strength [assessed using finite element analysis (FEA)] is lower in AA compared with EA and non-athletes 14-21 y at baseline and decreases prospectively over a one- year duration in AA, whereas bone strength increases in EA over the same duration, (2) that greater visceral adipose tissue (VAT) and marrow fat are associated with lower bone density, impaired microarchitecture and lower bone strength, and (3) that in young AA, compared to oral estradiol or no treatment, transdermal estradiol replacement will increase bone strength to approximate that in controls, associated with decreases in marrow fat and no changes in regional body composition. Detailed assessment of regional body composition and bone strength will be performed. Adipocytokines will be measured and related to changes in bone density, structure and strength in longitudinal studies, controlling for traditional risk factrs. The mentoring goals of this proposal include the development of a comprehensive multidisciplinary mentoring and training program, in which trainees will be selected, based on their interest in patient oriented research, work habits and ethical standards. Projects will be selected that are unique and achievable, and significant time will spent by the PI guiding trainees in protocol design, regulatory requirements, didactic coursework, and funding opportunities. Trainees will be exposed to detailed techniques of body composition and bone strength assessment. This K-24 proposal is critical to support the PI's significant time spent in mentoring. The training environment at the PI's institution is outstanding in terms of didactic resources and availability of techniques to assess complex metabolic endpoints. Importantly, the PI enjoys significant support from her Unit and Division Chiefs, who have enthusiastically endorsed her successful mentoring efforts to date and the plans in the current proposal. Taken together, the proposed K-24 application offers a strong mentoring program in patient oriented research that is based on the teaching of important principles of endocrinology and metabolism. The studies are to be carried out in a population at significant risk for impaired bone accrual, with which the PI has significant expertise. The Midcareer Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support to reduce clinical and administrative responsibilities, and ensure the candidate's continued success as a mentor and clinical researcher.