Amenorrhoea Workup
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Direct answer
Pregnancy test first — always — because secondary amenorrhoea (no menses for 3 months if previously regular, or 6 months if irregular) is physiologically pregnancy until excluded. Thereafter the workup runs on four anatomical levels: uterus and outflow tract (Asherman syndrome, imperforate hymen), ovary (PCOS as the commonest cause; premature ovarian insufficiency with FSH above roughly 25–30 IU/L on two occasions), pituitary (prolactinoma, Sheehan) and hypothalamus (functional hypothalamic amenorrhoea from weight loss, exercise or stress). The standard first-line panel is a pregnancy test, TSH, prolactin and FSH with oestradiol; the progesterone challenge test then sorts the rest — withdrawal bleeding proves oestrogen present and outflow intact, no bleeding demands oestrogen-plus-progesterone to separate uterine from hormonal causes. Primary amenorrhoea (no menses by age 15, or by 13 with no secondary sexual characteristics) adds Turner syndrome and Müllerian agenesis to the differential.
What you must remember
- Definitions: primary — no menarche by 15 (or 13 without breast development); secondary — 3 months absent after regular cycles or 6 months after irregular ones.
- First-line tests for every patient: urine/blood pregnancy test, TSH, prolactin, FSH with oestradiol.
- Four-level framework: uterine/outflow — ovarian — pituitary — hypothalamic; localise before listing causes.
- PCOS is the commonest cause of secondary amenorrhoea with normal-low FSH; POI (menopause before 40) shows high FSH (above ~25–30 IU/L) twice, 4–6 weeks apart.
- Progesterone challenge: bleeding after medroxyprogesterone means anovulation with adequate oestrogen and patent outflow (classic PCOS); no bleeding means hypo-oestrogenism or uterine/outflow disease.
- Hyperprolactinaemia and thyroid disease reverse with treatment of the cause — treat, do not induce cycles over them.
- Turner syndrome (45,X): primary amenorrhoea, short stature, webbed neck, shield chest, streak gonads, coarctation — karyotype confirms.
- Asherman syndrome: amenorrhoea after dilatation and curettage or endometrial infection — in Indian practice, genital tuberculosis is an important cause of intrauterine adhesions and a standard viva answer.
How the pathway plays out in practice
A 26-year-old with nine months of absent menses after stopping combined pills. Step one: pregnancy excluded. Step two: she is normoprolactinaemic and euthyroid; FSH 4.2 IU/L — the axis runs but does not ovulate — and she is overweight with acne and polycystic ovaries: PCOS. Medroxyprogesterone 10 mg for 10 days produces heavy withdrawal bleeding — oestrogen adequate, uterus intact — and management proceeds along PCOS lines (weight, cycle regulation, endometrial protection).
Contrast a 24-year-old marathon runner with 11 months of amenorrhoea, BMI 17, FSH 2.1, oestradiol low: functional hypothalamic amenorrhoea — under-drive, not ovarian failure. The treatment is calories and reduced training with bone-density assessment, because oestrogen deficiency at peak bone-building age is the real injury; combined pills produce withdrawal bleeds but do not restore bone or fertility.
The silent-uterus lesson: a woman has amenorrhoea after a suction evacuation; hormones are entirely normal, but neither progesterone nor oestrogen-plus-progesterone produces bleeding — the endometrium itself is scarred. Hysteroscopy confirms Asherman syndrome, and in India genital tuberculosis must be excluded before adhesiolysis.
Where students slip
The classic sequence error is ordering a full androgen panel before excluding pregnancy and thyroid/prolactin disease — expensive, and it skips the two causes with specific treatment. The second slip is misreading the challenge test: no bleeding after progesterone is attributed to "severe PCOS", when it actually signals hypo-oestrogenism or uterine pathology and demands the next step. Third, treating functional hypothalamic amenorrhoea with cyclic pills and calling it cured — the pathology is energy deficiency, and the fracture risk remains until weight recovers. Fourth, forgetting POI is not menopause: it warrants karyotype (under 30), fragile-X premutation testing, and hormone replacement until natural menopause age for bone protection.
Frequently asked questions
What is the first investigation in any case of secondary amenorrhoea?
A pregnancy test — inexpensive, immediate and decisive — followed by TSH, prolactin and FSH with oestradiol as the first-line panel once pregnancy is excluded.
How is the progesterone challenge test interpreted?
Withdrawal bleeding within about a week of finishing progesterone confirms oestrogen-primed endometrium and patent outflow — usually anovulation such as PCOS; absent bleeding points to hypo-oestrogenism or uterine/outflow pathology, clarified by a subsequent oestrogen-plus-progesterone course.
How is premature ovarian insufficiency diagnosed and worked up?
Amenorrhoea before age 40 with FSH above roughly 25–30 IU/L on two occasions 4–6 weeks apart, low oestradiol; then karyotype in young women, fragile-X premutation testing, autoimmune screen, and bone health assessment.
Why does functional hypothalamic amenorrhoea need more than pills?
The driver is energy deficiency suppressing GnRH; recovery requires nutrition, weight gain and training modification. Hormonal therapy produces bleeds and may protect bone partially but does not correct the underlying disorder or restore fertility.
Which causes of amenorrhoea relate to the uterus rather than hormones?
Asherman syndrome (intrauterine adhesions after curettage, endometrial tuberculosis or infection), cervical stenosis, and developmental outflow obstruction such as imperforate hymen or transverse vaginal septum — hormone levels are typically normal, and imaging or hysteroscopy defines the anatomy.