Advances in the Relationship between Low Energy Availability and Functional Hypothalamic Amenorrhea

doi:10.12280/gjszjk.20260145

Abstract

Abstract:

Functional hypothalamic amenorrhea (FHA) is a central, non-organic, and reversible form of amenorrhea, resulting from the suppression of hypothalamic-pituitary-ovarian (HPO) axis induced by various intrinsic and extrinsic factors, such as insufficient energy intake, excessive physical activity, psychological stress, and genetic susceptibility. In recent years, low energy availability (LEA) has provided a unifying theoretical framework for understanding the pathophysiology of FHA. Under LEA, the body initiates adaptive responses that prioritize vital physiological functions while suppressing energy-demanding reproductive processes. These adaptations are characterized by the alterations in peripheral metabolic signals and impaired function of hypothalamic Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, ultimately leading to the disrupted gonadotropin-releasing hormone (GnRH) pulsatility and the attenuation of HPO axis function. Based on improving LEA, strategies for treating the FHA primarily focus on restoring energy availability. First-line management mainly involves lifestyle interventions, including nutritional support, appropriate exercise modification, and psychological intervention. In addition, the targeted therapies involving Kisspeptin and its receptor have also shown a potential therapeutic prospect.

Key words: Low energy availability, Amenorrhea, Functional hypothalamic amenorrhea, Kisspeptin/neurokinin B/dynorphin neurons, Gonadotropin-releasing hormone, Hypothalamo-hypophyseal system

ZHANG Yu, DING Xue-song, GUO Ying-ying, XUE Wei, WANG Yang, SUN Ai-jun. Advances in the Relationship between Low Energy Availability and Functional Hypothalamic Amenorrhea[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(4): 336-341.

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