Does low energy availability disrupt HPA axis function and cortisol secretion patterns?

Low energy availability (LEA) occurs when the body lacks sufficient energy to support its essential physiological functions after accounting for the energy expended during exercise. In a 41-year-old female, this state triggers a cascade of neuroendocrine adaptations designed to prioritize immediate survival over metabolic processes deemed non-essential, such as reproduction and growth.

Clinical evidence and HPA axis function

Extensive research on Relative Energy Deficiency in Sport (RED-S) and Functional Hypothalamic Amenorrhea (FHA) confirms that LEA is a significant metabolic stressor that alters the hypothalamic-pituitary-adrenal (HPA) axis.

• Hypercortisolemia: Studies demonstrate that when energy availability falls below a critical threshold (often cited as 30 kcal/kg of fat-free mass), basal cortisol levels increase significantly. This rise in cortisol is a compensatory mechanism to stimulate glucose production (gluconeogenesis) and mobilize fat stores.
• HPA overactivity: In clinical populations experiencing chronic energy deficits, such as those with FHA, researchers consistently find higher integrated 24-hour cortisol secretion. For example, individuals with FHA often exhibit cortisol levels 20-30% higher than age-matched controls.
• Diurnal rhythm disruption: LEA is associated with a "flattening" of the diurnal cortisol curve. This includes elevated evening cortisol and a blunted Cortisol Awakening Response (CAR), indicating a loss of the normal rhythmic sensitivity of the HPA axis.

Mechanistic explanations

The transition from LEA to HPA axis dysregulation is mediated by complex hormonal signaling:

• The Leptin Signal: LEA causes a rapid decline in leptin, a hormone produced by fat cells that signals energy sufficiency. Reductions of 50-60% in leptin levels signal the hypothalamus to activate the HPA axis as part of a starvation response.
• CRH Activation: The drop in leptin and glucose availability triggers the paraventricular nucleus of the hypothalamus to release Corticotropin-Releasing Hormone (CRH). Chronic CRH elevation leads to a sustained increase in adrenocorticotropic hormone (ACTH) and subsequent cortisol release.
• Feedback Desensitization: Prolonged LEA can lead to glucocorticoid receptor resistance. This impairs the brain's ability to "turn off" the stress response, resulting in persistent elevations of cortisol and a reduced ability to respond to acute stressors.

Bottom line

The evidence strongly supports the link between low energy availability and neuroendocrine adaptations that disrupt HPA axis function. This typically manifests as chronically elevated cortisol levels and a blunted diurnal rhythm, representing a systemic shift toward a catabolic state to maintain energy homeostasis.