Secondary Amenorrhoea Related to Neuro-Endocrinological Causes

Objective: To review the neuroendocrinological causes of secondary amenorrhoea, focusing on its pathophysiology, mediators, and management strategies.
Design: A comprehensive review of current evidence on physiological, pathological, and iatrogenic causes of secondary amenorrhoea, emphasizing functional hypothalamic amenorrhoea (FHA), hyperprolactinemia, and pituitary-related disorders.
Method: The review integrates findings from experimental studies, clinical observations, and expert consensus to outline the mechanisms underlying hypothalamic-pituitary-ovarian (HPO) axis dysregulation. Key mediators, including leptin, insulin, and fibroblast growth factor-21 (FGF-21), are explored, alongside conditions such as Sheehan’s syndrome, sellar lesions, and genetic mutations.
Results: Secondary amenorrhoea affects 3–4% of women globally, with over half of cases linked to HPO axis dysfunction. FHA emerges as a leading cause, driven by stressors such as malnutrition and chronic illness. Hyperprolactinemia, both physiological and pathological, significantly impacts gonadotropin secretion and ovarian function. Pathological conditions, including pituitary adenomas, hypothyroidism, and infiltrative diseases, further contribute to amenorrhoea. Iatrogenic factors, such as cranial irradiation and medication use, also play a role. Early diagnosis and targeted interventions, including hormone replacement therapy and addressing reversible causes, are crucial for restoring gonadotropin function and improving fertility outcomes.
Conclusion: Secondary amenorrhoea is a multifaceted condition often resulting from neuro-endocrinological disturbances. A multidisciplinary approach is essential to accurately diagnose and manage the condition, ensuring optimal reproductive and overall health outcomes.