Altered oxidative and neuroendocrine reactivity to emotional stimuli in functional hypothalamic amenorrhea

Functional hypothalamic amenorrhea (FHA) is a reversible condition characterized by disruption of the hypothalamic-pituitary-ovarian axis, commonly associated with stress, energy deficit, and behavioral factors. Increasing evidence suggests that FHA involves broader systemic alterations, including oxidative stress, inflammation, and metabolic dysregulation, yet the interaction between emotional processing and these physiological systems remains poorly understood. Here, we investigated whether exposure to emotionally salient stimuli modulates redox, inflammatory, and metabolic markers in women with FHA compared with controls.

Eleven women diagnosed with FHA and ten healthy controls were exposed to highly emotional images. Saliva samples were collected before and after the task to assess reactive oxygen species (ROS), total antioxidant capacity, leptin, ghrelin, insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Cognitive performance and psychological traits were also evaluated.

FHA patients exhibited higher basal levels of ROS, IL-6, and 8-OH-dG, alongside lower leptin concentrations. Emotional image exposure induced a significant reduction in ROS and ghrelin levels selectively in the FHA group, whereas no changes were observed in controls. IGF-1 increased after stimulation irrespective of group, whereas other markers remained unchanged. Behaviorally, FHA patients showed increased impulsivity (i.e., more errors in a Go/No-Go task) but lower self-reported alexithymia.

FHA is associated with a state of oxidative stress, low-grade inflammation, and metabolic imbalance, which are dynamically modulated by emotional stimuli. These findings support a multidimensional model of FHA involving altered integration between emotional, neuroendocrine, and metabolic systems. Targeting stress-related and redox pathways may represent a promising avenue for therapeutic intervention.