Relative Energy Deficiency in Sport (REDs): Endocrine Manifestations, Pathophysiology and Treatments

Abstract

Research on lean, energy-deficient athletic and military cohorts has broadened the concept of the Female Athlete Triad into the Relative Energy Deficiency in Sport (REDs) syndrome. REDs represents a spectrum of abnormalities induced by low energy availability (LEA), which serves as the underlying cause of all symptoms described within the REDs concept, affecting exercising populations of either biological sex. Both short- and long-term LEA, in conjunction with other moderating factors, may produce a multitude of maladaptive changes that impair various physiological systems and adversely affect health, well-being, and sport performance. Consequently, the comprehensive definition of REDs encompasses a broad spectrum of physiological sequelae and adverse clinical outcomes related to LEA, such as neuroendocrine, bone, immune, and hematological effects, ultimately resulting in compromised health and performance. In this review, we discuss the pathophysiology of REDs and associated disorders. We briefly examine current treatment recommendations for REDs, primarily focusing on non-pharmacological, behavioral, and lifestyle modifications that target its underlying cause – energy deficit. We also discuss treatment approaches aimed at managing symptoms, such as menstrual dysfunction and bone stress injuries, and explore potential novel treatments that target the underlying physiology, emphasizing the roles of leptin and the activin-follistatin-inhibin axis, the roles of which remain to be fully elucidated, in the pathophysiology and management of REDs. In the near future, novel therapies leveraging our emerging understanding of molecules and physiological axes underlying energy availability or lack thereof may restore LEA-related abnormalities, thus preventing and/or treating REDs-related health complications, such as stress fractures, and improving performance.

Effects of a Ketogenic Diet on Body Composition in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial

“…Consequently, the potential reduction in FFM remains a notable concern associated with ketogenic diets, even in the presence of concurrent resistance training [42]. Importantly, the risks associated with the loss of lean mass, primarily muscle mass, along with fat mass in female athletes, include decreased muscle strength and performance, increased risk of hormonal imbalance, menstrual irregularities, compromised immune function, sports injuries, decreased bone density, stress fractures, and long-term osteoporosis [44]. Therefore, female athletes should carefully consider these risks if adhering to a ketogenic LCHF diet.…”

Total and H-specific GDF-15 levels increase in caloric deprivation independently of leptin in humans

“…To address these questions, we performed post-hoc analyses to explore the physiological role of GDF-15 during acute complete and chronic mild energy deprivation, with and without leptin administration in lean participants. Chronic energy deprivation was studied in participants with relative energy deficiency in sport syndrome (REDs), previously defined as hypothalamic amenorrhea due to insufficient caloric intake or excessive energy expenditure, altering several physiological and metabolic functions [19][20][21] . To measure GDF-15, we used two GDF-15 ELISAs.…”