Hypothalamic Neuroinflammation as a Driver of Reproductive Axis Suppression in Chronically Stressed Women: An Investigation in Conflict-Affected Communities of Borno State

The mechanisms by which chronic psychosocial stress suppresses the hypothalamic-pituitary-gonadal axis remain incompletely understood, particularly the role of hypothalamic neuroinflammation as a mediating pathway. This study investigated hypothalamic neuroinflammatory signalling and reproductive axis suppression in chronically stressed women in conflict-affected communities in Borno State, North East Nigeria. A cross-sectional analytical design enrolled 90 women aged 18 to 40 years with confirmed chronic stress exposure and 45 low-stress-exposure controls from non-conflict-affected areas. Stress exposure was characterised by Combat Exposure Scale adaptation and Perceived Stress Scale. Reproductive axis function was assessed by serum gonadotropin-releasing hormone pulse frequency estimated through blood sampling at 20-minute intervals for four hours, along with oestradiol and luteinising hormone. Neuroinflammatory markers measurable peripherally, including interleukin-1 beta, tumour necrosis factor-alpha, and kisspeptin, were assayed as proxies for central neuroinflammatory tone. Structural equation modelling and logistic regression were applied. Results showed significantly suppressed gonadotropin-releasing hormone pulse frequency in high-stress women, accompanied by elevated inflammatory cytokines and reduced kisspeptin. Mediation analysis confirmed that interleukin-1 beta partially mediated the stress-reproductive axis suppression pathway. Kisspeptin suppression was an independent predictor of oligomenorrhoea. This study presents a theoretically original framework for stress-induced reproductive dysfunction through neuroinflammatory pathways, tested in a uniquely underrepresented population. Clinical and policy implications for women's reproductive health in conflict zones are discussed. Keywords: hypothalamic neuroinflammation, reproductive axis, kisspeptin, chronic stress, Borno State.