Relative energy deficiency in sports (RED-S): elucidation of endocrine changes affecting the health of males and females

The purpose of this review is to present a different perspective of the relative energy deficiency syndrome, to improve understanding of associated endocrine alterations, and to highlight the need for further research in this area. The term "female athlete triad" was coined over 25 years ago to describe three interrelated components: disordered eating, menstrual dysfunction, and low bone mass. The syndrome's etiology is attributed to energy intake deficiency relative to energy expenditure required for health, function, and daily living. Recently, it became clear that there was a need to broaden the term, as the disorder is not an issue of only three interrelated problems but of a whole spectrum of insults resulting from low energy availability (LEA; i.e., insufficient energy availability to cover basic physiological demands) that can potentially affect any exerciser, irrespective of gender. The new model, termed relative energy deficiency in sport (RED-S), has received greater scrutiny in sports medicine due to its effects on both health and performance in athletes of both sexes. RED-S results from low-energy diets (intentional or unintentional) and/or excessive exercise. Energy deficiency reduces hypothalamic pulsatile release of gonadotropin-releasing hormone, this impairing anterior pituitary release of gonadotropins. In women, reduced FSH and LH pulsatility produces hypoestrogenism, causing functional hypothalamic amenorrhea and decreased bone mass. In men, it reduces testosterone and negatively affects bone health. Moreover, LEA alters other hormonal pathways, causing physiological consequences, such as alteration of the thyroid hormone signaling pathways, leptin levels, carbohydrate metabolism, the growth hormone/insulin-like growth factor-1 axis, and sympathetic/parasympathetic tone. This review explains and clarifies the effects of RED-S in both sexes.