Hypothalamic Amenorrhoea

Hypothalamic amenorrhoea is loss of menstruation caused by suppression of gonadotrophin releasing hormone from the hypothalamus, in the absence of an organic cause. It results from low energy availability (weight loss, eating restriction, intense exercise) and psychological stress, and it is a common cause of amenorrhoea in young women. It matters because oestrogen deficiency causes bone loss, infertility and cardiovascular risk, and it is usually reversible.

• Risk factors: body mass index below 18.5 kg/m2, weight loss of 10 percent or more, intense athletic training, dieting, psychological stress, chronic illness, perfectionism.
• Diagnosis of exclusion after other causes are ruled out.
• Recovery needs restored energy balance.

Women have absent menses for 3 months or longer, with low or normal body weight, fatigue, cold intolerance, constipation, low mood, loss of libido and sometimes stress fractures. Examination may show low blood pressure, slow pulse, dry skin and fine body hair.

• Body mass index below 18.5 kg/m2 in many, normal in some.
• Hot flushes and vaginal dryness in prolonged oestrogen deficiency.
• Differential diagnosis: pregnancy, polycystic ovary syndrome, hyperprolactinaemia, premature ovarian insufficiency, thyroid disease, anorexia nervosa, coeliac disease, diabetes, Cushing syndrome, pituitary tumour, chronic infection, malignancy.
• Complications: low bone density and fractures, infertility, cardiovascular risk, depression, delayed growth in adolescents, relapse.

The approach is to exclude other causes and assess the severity of oestrogen deficiency.

• Urine or serum hCG; follicle stimulating hormone, luteinising hormone (both low or normal), oestradiol (low), prolactin, thyroid stimulating hormone, free thyroxine, testosterone.
• Progestogen challenge: medroxyprogesterone 10 mg oral once daily for 10 days; no bleed indicates profound oestrogen deficiency.
• Full blood count, electrolytes, urea, creatinine, glucose, coeliac antibodies, HIV test; ECG if low body weight or electrolyte disturbance.
• Bone density scan (DXA) after 6 to 12 months of amenorrhoea; pituitary MRI if prolactin is raised, headaches or visual symptoms.

The principle is restoration of energy balance and weight, with bone protection and psychological support.

• Supportive: increase energy intake by 300 to 600 kcal daily and reduce training by 10 to 20 percent; target body mass index of 20 kg/m2 or more; weight gain of 0.25 to 0.5 kg weekly; dietitian review; cognitive behavioural therapy for stress and eating concerns; sleep hygiene; calcium 1000 to 1300 mg and vitamin D 800 to 1000 IU oral daily; weight-bearing exercise in moderation.
• Pharmacological: if bone density is low (Z score below -1.0) or amenorrhoea lasts more than 6 to 12 months despite measures: transdermal oestradiol 100 micrograms/24 hours patch changed twice weekly with medroxyprogesterone 10 mg oral once daily for 12 days each month; or oestradiol valerate 2 mg oral once daily with medroxyprogesterone 10 mg oral once daily for 12 days each month; combined oral contraceptive pill is avoided as it does not restore bone density; for pregnancy wish: letrozole 2.5 mg oral once daily on days 3 to 7, increased to 7.5 mg, or gonadotrophin therapy under specialist care; thiamine 100 mg oral once daily during refeeding of the severely underweight.
• Procedures: none.
• Special groups: adolescents and young athletes with stress fractures need sports medicine and endocrine review and a longer period of reduced training; women with eating disorders or body mass index below 16 kg/m2, pulse below 40 per minute, systolic blood pressure below 90 mmHg or electrolyte disturbance need admission for monitored refeeding and psychiatric care.
• Red flags: body mass index below 16 kg/m2, bradycardia, syncope, low potassium or phosphate, stress fracture, suicidal thoughts, signs of an eating disorder, visual loss.
• Follow-up: review monthly until weight and training are stable, then every 3 months; return of menses is expected within 3 to 12 months of recovery; bone density scan every 1 to 2 years; counselling on contraception and fertility.