Amenorrhoea Evaluation
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Direct answer
Pregnancy is the first cause to exclude in any amenorrhoea — the commonest cause of secondary amenorrhoea by far — before any hormone panel is drawn: secondary amenorrhoea means no menses for three months in a previously regular cycle (six if irregular), and primary amenorrhoea means no menarche by 15 years with secondary sexual characteristics or 13 years without them. The first-line bloods are TSH and prolactin, plus FSH and oestradiol when chronic anovulation or ovarian failure is suspected; the progesterone challenge test then maps the uterus-outflow axis: medroxyprogesterone 10 mg daily for 5-7 days, and a withdrawal bleed confirms oestrogen-present, outflow-patent anovulation (polycystic ovary syndrome the leading answer), while no bleed prompts the combined oestrogen-progestin challenge — still no bleed means uterine or outflow pathology (Asherman syndrome, imperforate hymen, MRKH), whereas a bleed confirms hypo-oestrogenism, split by FSH: high FSH means ovarian failure (premature ovarian insufficiency, Turner), low or normal FSH means hypothalamic-pituitary causes (weight loss, exercise, prolactinoma, Sheehan).
What you must remember
- Definitions: primary — no menarche by 15 with secondary sexual characteristics (or by 13 without, or within three years of thelarche failing); secondary — three months absent in regular cyclers, six in irregular.
- Step one, always: pregnancy test — urine hCG — before anything else in secondary amenorrhoea; lactational amenorrhoea and perimenopause also sit in the "physiological" basket before pathology is chased.
- First-line bloods: TSH (both hypo- and hyperthyroidism amenorrhoea), serum prolactin (hyperprolactinaemia suppresses GnRH; grossly raised values demand pituitary MRI), FSH with oestradiol.
- Progesterone challenge: medroxyprogesterone acetate 10 mg daily x 5-7 days (or micronised progesterone 200 mg x 10 days) — withdrawal bleed within 7 days of stopping means adequate endogenous oestrogen and a patent outflow, with anovulation (most often PCOS) as the mechanism.
- No bleed to progesterone: give oestrogen-progestin; bleeding now means the outflow and endometrium are fine but endogenous oestrogen was lacking; still no bleed means uterine or outflow failure — hysteroscopy for Asherman (history of curettage), examination for imperforate hymen or transverse septum, and ultrasound or MRI for Müllerian agenesis (MRKH — primary amenorrhoea with normal 46XX karyotype and absent uterus).
- FSH interpretation in hypo-oestrogenism: high FSH (with low oestradiol) — ovarian: premature ovarian insufficiency (below 40 years; FSH above 25-30 on two occasions), Turner 45X in primary amenorrhoea with short stature; low or normal FSH — central: hypothalamic (weight loss, athlete's triad, stress, chronic illness) or pituitary (prolactinoma, Sheehan syndrome with failure of lactation postpartum).
- Hyperprolactinaemia sources: prolactinoma, drugs (antipsychotics, metoclopramide, opioids), hypothyroidism (TRH stimulation) — treat cause or with dopamine agonists (cabergoline, bromocriptine).
- PCOS numbers: Rotterdam two of three — oligo/anovulation, hyperandrogenism, polycystic ovarian morphology — with the LH:FSH ratio above 2 an older supporting clue the exam still quotes.
The progesterone challenge, step by step
Run the algorithm on a 27-year-old with nine months of absent menses, negative pregnancy test, normal TSH, and prolactin of 18 ng/mL. Day one to seven: medroxyprogesterone 10 mg nightly. Five days after the last tablet she reports a normal three-day bleed — oestrogen is present, the endometrium responds, the outflow works; the defect is ovulation, and the phenotype (hirsutism, BMI 29, 12-plus follicles per ovary on scan) closes the diagnosis as PCOS: lifestyle change, cyclical progestins or a combined pill, metformin where needed, fertility counselling later.
Rerun the algorithm with no bleed after progesterone. A two-month combined oestrogen-progestin course follows, and this time she does bleed — the anatomy is intact, the deficiency was oestrogen; FSH returns 68 mIU/mL with oestradiol 12 pg/mL in a 27-year-old: premature ovarian insufficiency, mandating karyotype, bone-density protection and hormone replacement until natural menopause age. Rerun once more with no bleed despite oestrogen: the uterus or its exit is at fault — her history of postpartum curettage points to Asherman syndrome, confirmed by hysteroscopy and treated by adhesiolysis with oestrogen therapy and a balloon stent. Three women, one test, three destinations — uterine, ovarian, central — which is precisely why this algorithm anchors the topic.
Where the marks hide
Recall questions live in the definitional numbers (15 and 13 years; 3 and 6 months) and in the challenge-test logic — "bleeds after progesterone" means oestrogen present (so FSH is not the emergency), "fails both progesterone and oestrogen" means uterine-outflow disease. Turner (45X, primary amenorrhoea, short stature, streak gonads, high FSH) versus MRKH (46XX, absent uterus, normal breasts, normal FSH) is the classic primary-amenorrhoea discrimination; Sheehan versus prolactinoma is the central pair — Sheehan's signature is postpartum lactation failure.
Frequently asked questions
What defines primary versus secondary amenorrhoea?
Primary: no menarche by 15 years with secondary sexual characteristics or 13 without; secondary: no menses for three months in a woman with regular cycles (six months if cycles were irregular).
What does a withdrawal bleed after the progesterone challenge indicate?
Adequate endogenous oestrogen, a responsive endometrium and a patent outflow — the cause is chronic anovulation, most commonly polycystic ovary syndrome.
How is failure to bleed after both progesterone and oestrogen interpreted?
Uterine or outflow tract pathology — Asherman syndrome, Müllerian agenesis or obstruction — requiring hysteroscopy, examination and imaging rather than more hormones.
What does a high FSH with low oestradiol signify in a woman under 40?
Premature ovarian insufficiency — confirmed on repeat testing, with karyotype and autoimmune screening, and hormone replacement to protect bone and cardiovascular health.
Which two hormones are the first-line tests in secondary amenorrhoea after pregnancy is excluded?
TSH and serum prolactin, since thyroid disease and hyperprolactinaemia both suppress GnRH pulsatility and are eminently treatable.