Weight-Loss-Associated Amenorrhoea

Weight loss associated amenorrhoea is absence of menstruation caused by significant weight loss or a body mass index below 18.5 kg/m2, from reduced energy intake, increased energy use or chronic illness. Causes include anorexia nervosa, dieting, malnutrition, HIV, tuberculosis, malignancy, malabsorption (coeliac disease), diabetes with poor control and hyperthyroidism. It occurs when body weight falls by 10 to 15 percent of the ideal, and matters because the underlying cause may be serious and the oestrogen deficiency harms bone.

• Risk factors: eating disorder, food insecurity, chronic infection (HIV, tuberculosis), cancer, gastrointestinal disease, hyperthyroidism, excessive dieting, psychological stress.
• Menses usually return when body weight is restored to near ideal.
• Refeeding too fast causes dangerous electrolyte shifts.

Women have absent periods with weight loss, fatigue, cold intolerance, dry skin, hair loss, constipation, dizziness and low mood. Examination shows low body mass index, low blood pressure, slow pulse, lanugo hair and muscle wasting.

• Body mass index below 18.5 kg/m2, with severe thinness below 16 kg/m2.
• Features of the underlying disease (night sweats, cough, diarrhoea, lymph nodes, goitre).
• Differential diagnosis: pregnancy, anorexia nervosa, tuberculosis, HIV infection, malignancy, coeliac disease and malabsorption, hyperthyroidism, diabetes mellitus, hypothalamic amenorrhoea, polycystic ovary syndrome, premature ovarian insufficiency, hyperprolactinaemia, Addison disease.
• Complications: osteoporosis and fractures, infertility, bradycardia and arrhythmia, electrolyte disturbance, refeeding syndrome, immune suppression, death in severe disease.

The approach is to measure weight, find the cause of weight loss and assess hormones and bone.

• Weight, height, body mass index, blood pressure (lying and standing), pulse, temperature; examination for signs of chronic disease.
• Urine or serum hCG; follicle stimulating hormone, luteinising hormone, oestradiol, prolactin, thyroid stimulating hormone, free thyroxine, glucose.
• HIV test, Xpert MTB/RIF on sputum, chest X-ray, full blood count, ESR, electrolytes, urea, creatinine, phosphate, magnesium, liver enzymes, albumin, coeliac antibodies; ECG.
• Bone density scan (DXA) after 6 to 12 months of amenorrhoea; stool tests and imaging for suspected malabsorption or cancer.

The principle is to treat the cause of weight loss, restore weight safely, and protect bone health.

• Supportive:
  • Nutritional rehabilitation with a dietitian, aiming for weight gain of 0.25 to 0.5 kg weekly in outpatients and 0.5 to 1 kg weekly as an inpatient, to a body mass index of 20 kg/m2 or more.
  • Slow staged refeeding in severe malnutrition with monitoring of potassium, phosphate, magnesium and glucose daily for the first week.
  • Psychological therapy for eating disorders; treat infections.
  • Calcium 1000 to 1300 mg and vitamin D 800 to 1000 IU oral daily; reduce exercise.
• Pharmacological:
  • Thiamine 100 mg oral 8-hourly (or 200 mg IV daily in severe cases) before and during the first 10 days of refeeding.
  • Multivitamin oral once daily.
  • Potassium chloride 600 mg to 1200 mg oral 8-hourly, phosphate and magnesium supplements guided by levels.
  • Tuberculosis: rifampicin 10 mg/kg (usual 600 mg) plus isoniazid 5 mg/kg (usual 300 mg) plus pyrazinamide 25 mg/kg (usual 1500 mg) plus ethambutol 15 mg/kg (usual 1200 mg) oral once daily for 2 months then rifampicin plus isoniazid for 4 months. Give pyridoxine 25 mg oral once daily.
  • HIV: tenofovir 300 mg, lamivudine 300 mg and dolutegravir 50 mg oral once daily (dolutegravir 50 mg twice daily during rifampicin treatment).
  • Hyperthyroidism: carbimazole 20 to 40 mg oral once daily, reduced to 5 to 15 mg when controlled.
  • Coeliac disease: gluten free diet.
  • If bone density is low (Z score below -1.0) after weight restoration is begun and amenorrhoea persists for more than 12 months: transdermal oestradiol 100 micrograms/24 hours patch changed twice weekly with medroxyprogesterone 10 mg oral once daily for 12 days each month.
• Procedures: nasogastric feeding for severe malnutrition or refusal to eat, under supervised care; endoscopy or imaging for suspected malabsorption or cancer.
• Special groups: women with anorexia nervosa and heart rate below 40 per minute, systolic blood pressure below 90 mmHg, potassium below 3.0 mmol/L, glucose below 3.0 mmol/L or body mass index below 15 kg/m2 need admission with cardiac monitoring. Women with HIV, tuberculosis or malignancy are treated for those conditions together with nutritional support.
• Red flags: heart rate below 40 per minute, syncope, potassium below 3.0 mmol/L, phosphate below 0.5 mmol/L, glucose below 3.0 mmol/L, body mass index below 15 kg/m2, suicidal thoughts, hypothermia.
• Follow-up: weight, pulse, blood pressure and electrolytes weekly during refeeding; review monthly until weight is stable; menses usually return after 6 to 12 months of weight restoration; bone density scan every 1 to 2 years; psychiatric follow-up.