Functional hypothalamic amenorrhoea

Definition

• Functional hypothalamic amenorrhoea is chronic anovulation with absent menses without any identifiable organic cause, resulting from disrupted pulsatile secretion of hypothalamic gonadotrophin-releasing hormone.

Classification

• Three types are recognised: weight loss-related, stress-related and exercise-related hypothalamic amenorrhoea.

Occurrence & epidemiology

Epidemiology

• It is one of the most common causes of secondary amenorrhoea, accounting for about 20–35% of cases.
• It is more common in athletes; sports such as ballet, running or gymnastics favour low energy availability.

Aetiopathogenesis

Aetiology and pathogenesis

• Triggers are caloric restriction and weight loss, excessive exercise and psychological stress; in athletes, low energy availability develops when energy expenditure exceeds energy intake.
• Increased activity of the stress axis with raised cortisol secretion, together with low leptin and raised ghrelin levels, is involved.

Clinical features

• Anovulation and profound oestrogen deficiency predominate; reduced bone mineral density with osteopenia and osteoporosis is regarded as the main long-term complication.
• Athletes may show the female athlete triad of disordered eating, amenorrhoea and reduced bone density up to osteoporosis.

Diagnosis

• It is a diagnosis of exclusion that requires genetic and organic causes to be ruled out.
• Baseline tests include a pregnancy test and FSH, LH, oestradiol, AMH, prolactin, TSH and free T4; typical findings are low or low-normal LH, normal FSH and reduced oestradiol and progesterone levels.
• A progestin challenge test assesses oestrogen exposure of the endometrium and patency of the outflow tract.

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Further reading (selection)

1. Functional hypothalamic amenorrhea and its influence on women's health (J Endocrinol Invest 2014, PubMed Central)
2. Neuroendocrine disturbances in women with functional hypothalamic amenorrhea: an update and future directions (Endocrine 2024, PubMed Central)
3. MSD Manual Professional: Amenorrhea

Cross-references