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Introduction

Hypothalamic amenorrhea, also known as functional hypothalamic amenorrhea (FHA), is the disruption of pulsatile hypothalamic GnRH secretion and the hypothalamic-pituitary-ovarian (HPO) axis, impairing follicular development and leading to low estradiol levels and amenorrhea (absence of menstruation).

Pathophysiology and risk factors

The menstrual cycle ( Figure 1) is controlled through the HPO axis ( Figure 2), which is a tightly regulated feedback loop that requires input from all 3 levels of the axis (hypothalamus, pituitary gland, and ovaries) to achieve normal, ovulatory menstruation:

  • The hypothalamus releases GnRH in a pulsatile fashion.
  • The anterior pituitary gland releases gonadotropins (FSH, LH) in response to GnRH.
  • The ovary releases estradiol from a cohort of developing follicles in response to FSH, resulting in ovulation.

FHA results from disruption at the level of the hypothalamus that causes diminished or abnormal GnRH release (

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