The Colorado Specialized Center of Research Excellence (SCORE) on Sex Differences and Women’s Health is focused on Bioenergetic and Cardiometabolic Consequences of the Loss of Gonadal Function. The overarching scientific goal of the SCORE is to address gaps in knowledge of the impact of gonadal aging on the regulation of energy homeostasis and metabolism by conducting mechanistically driven research across the basic-to-clinical translational spectrum. The scientific premise is that gonadal aging, through the accompanying decline in sex hormones, mediates biological changes that increase risk for chronic disease. Importantly, because gonadal failure is inevitable in women in mid-life, but rare in men until much later in life, this meets the objective of the SCORE Program to study sex differences that impact women’s health. The Colorado SCORE is focused on the increased propensity for abdominal fat accumulation and the associated cardiometabolic dysfunction that are consequent to the loss of ovarian function. The overarching educational objective is to engage new investigators in research aligned with the focus of the SCORE. The SCORE will provide mentored career development and training on how to conduct research that appropriately addresses sex as a biological variable (SABV). These overarching objectives will be accomplished through the following Aims: 1) Advance novel translational research on mechanisms that are postulated to contribute to the abdominal adiposity and cardiometabolic dysfunction that accelerate following estradiol withdrawal. All projects include a focus on the kynurenine pathway because of the emerging evidence that it regulates energy homeostasis, metabolic function, and the aging process. The Colorado SCORE investigators are experts in these areas and are exceptionally well positioned to advance this research. 2) Attract and support outstanding early career investigators with research interests related to the SCORE and engage them in CEC training activities that will successfully advance their careers. The SCORE will support one Scholar and four Pilot Project Awardees each year. 3) Provide infrastructural support for the SCORE Research Projects, Scholars, and Pilot Awardees through the LAC, including biostatistics, data management, financial oversight, and administrative support. 4) Partner with and leverage resources provided by other programs at CU-AMC (Multidisciplinary Center on Aging, Ludeman Center for Women’s Health Research, Nutrition Obesity Research Center, Clinical and Translational Sciences Institute) to elevate the visibility and multi-disciplinary reach of women’s health research and the importance of investigating SABV. Activities will target both scientific and lay communities at local, regional, and national levels. Achieving these Aims will position the SCORE as a national leader in women’s health research, and the CEC as a model program for training the next generation of scientists to integrate SABV in th...