Secondary Amenorrhoea

Secondary amenorrhoea is absence of menstruation for 3 months in a woman who had regular cycles, or 6 months in a woman who had irregular cycles.

Pregnancy is the commonest cause, followed by polycystic ovary syndrome, hypothalamic causes (weight loss, stress, exercise), hyperprolactinaemia, premature ovarian insufficiency, thyroid disease, contraceptive effect (depot medroxyprogesterone), uterine adhesions (Asherman syndrome), Sheehan syndrome and chronic illness.

It matters because it may signal oestrogen deficiency with bone loss, endometrial hyperplasia from unopposed oestrogen, or an underlying tumour.

• Risk factors: pregnancy risk, low body weight, intense exercise, previous uterine surgery or curettage, postpartum haemorrhage, chemotherapy, pelvic radiotherapy, autoimmune disease, family history of early menopause.
• Pregnancy must be excluded before any other test.
• Measuring hCG, prolactin, thyroid stimulating hormone and follicle stimulating hormone together identifies most causes.

Women have missed periods with symptoms that depend on the cause:

• Hot flushes and vaginal dryness in ovarian insufficiency.
• Hirsutism, acne and weight gain in polycystic ovary syndrome.
• Galactorrhoea and headache in hyperprolactinaemia.
• Weight loss in hypothalamic amenorrhoea.
• Fatigue after postpartum haemorrhage in Sheehan syndrome.

• Body mass index, hirsutism, acne, goitre, galactorrhoea, visual fields.
• Atrophic vaginal mucosa in oestrogen deficiency.
• Differential diagnosis: pregnancy, polycystic ovary syndrome, hypothalamic amenorrhoea, hyperprolactinaemia, premature ovarian insufficiency, hypothyroidism, hyperthyroidism, Asherman syndrome, Sheehan syndrome, contraceptive related amenorrhoea, ovarian or adrenal tumour, Cushing syndrome.
• Complications: infertility, osteoporosis, endometrial hyperplasia or cancer in polycystic ovary syndrome, cardiovascular risk, depression, loss of libido.

The approach is a stepwise assessment starting with pregnancy and then hormone tests.

• Urine or serum hCG; thyroid stimulating hormone, prolactin, follicle stimulating hormone, luteinising hormone, oestradiol; testosterone and sex hormone binding globulin if hirsute.
• Pelvic ultrasound for polycystic ovaries (12 or more follicles of 2 to 9 mm in an ovary), endometrial thickness and uterine anatomy.
• Progestogen challenge: medroxyprogesterone 10 mg oral once daily for 10 days; withdrawal bleeding within 7 days indicates adequate oestrogen and a patent outflow tract.
• Pituitary MRI for prolactin above 1000 mIU/L (about 47 ng/mL) or visual symptoms; hysteroscopy or sonohysterography for suspected adhesions; morning cortisol and thyroid function if Sheehan syndrome is suspected.

The principle is to treat the cause, protect the endometrium and bone, and manage fertility wishes.

• Supportive: lifestyle changes (weight loss of 5 to 10 percent in obesity, weight gain in underweight, reduced intensive exercise); calcium 1000 mg and vitamin D 800 to 1000 IU oral daily; counselling; stress management.
• Pharmacological:
• Pregnancy: antenatal care.
• Polycystic ovary syndrome: combined oral contraceptive pill with ethinylestradiol 30 micrograms and levonorgestrel 150 micrograms oral once daily for 21 days then 7 days free, or medroxyprogesterone 10 mg oral once daily for 10 to 14 days every 1 to 3 months. Add metformin 500 mg oral once daily increased weekly to 500 mg 3 times daily (maximum 2000 mg daily) for metabolic features.
• Hyperprolactinaemia: cabergoline 0.25 mg oral twice weekly increased every 4 weeks to a maximum of 1 mg twice weekly (or bromocriptine 1.25 mg oral at night increased to 2.5 mg twice daily).
• Hypothyroidism: levothyroxine 50 micrograms oral once daily increased every 4 to 6 weeks to normalise thyroid stimulating hormone.
• Premature ovarian insufficiency: oestradiol valerate 2 mg oral once daily with medroxyprogesterone 10 mg oral once daily for 12 days each month, or the combined oral contraceptive pill, until about age 50 years.
• Asherman syndrome: oestradiol valerate 2 mg oral twice daily for 30 days with medroxyprogesterone 10 mg oral once daily for the last 10 days, after adhesiolysis.
• Ovulation induction when pregnancy is desired: letrozole 2.5 mg oral once daily on days 3 to 7 of a withdrawal bleed, increased by 2.5 mg each cycle to 7.5 mg, or clomifene 50 mg oral once daily on days 2 to 6, increased to 100 and 150 mg.
• Procedures: hysteroscopic adhesiolysis for uterine adhesions; surgical removal of a pituitary adenoma that fails medical therapy or compresses the optic chiasm; ovarian drilling for polycystic ovary syndrome with failed drug therapy.
• Special groups: women with premature ovarian insufficiency have bone density scan and hormone replacement until the natural age of menopause. Women wanting pregnancy with hyperprolactinaemia continue cabergoline until pregnancy is confirmed. Women on depot medroxyprogesterone are counselled that amenorrhoea is expected and may last up to 12 months after the last injection.
• Red flags: visual field loss or severe headache, virilisation, rapid hirsutism, galactorrhoea with high prolactin, hypotension after haemorrhage, endometrial thickness above 12 mm, unexplained weight loss.
• Follow-up: review at 3 months with repeat hormones; bone density scan if amenorrhoea lasts over 12 months with low oestrogen; yearly review of metabolic risk in polycystic ovary syndrome; endometrial assessment if no withdrawal bleed in 3 months.