What is amenorrhoea, and how are primary and secondary defined?
Amenorrhoea is the absence of menstruation. It is a symptom, not a diagnosis — the exam task is always to find the level of the defect. StatPearls uses these working definitions:
| Type | Definition | Also evaluate when |
|---|---|---|
| Primary | No menstruation by 15 years of age, or 3 years after thelarche | No breast development or other secondary sexual characteristics by 13 years (delayed puberty work-up) |
| Secondary | No menses for ≥ 3 months in a woman with previously regular cycles, or ≥ 6 months in any woman who has menstruated at least once | Any unexplained change in a previously regular cycle |
Breast budding (thelarche) normally starts between 8 and 10 years, and menarche follows within 2 to 3 years. In the US only about 2% of adolescent girls have not reached menarche by 15.
How are the causes of amenorrhoea classified by compartment?
Normal menstruation needs four working parts: the hypothalamus (pulsatile GnRH), the anterior pituitary (FSH and LH), the ovary (oestradiol and, after ovulation, progesterone) and the outflow tract (endometrium, cervix and vagina). A defect at any level stops bleeding. Almost every cause except natural menopause can present as either primary or secondary amenorrhoea.
| Compartment | FSH / oestradiol | Primary-amenorrhoea examples | Secondary-amenorrhoea examples |
|---|---|---|---|
| Hypothalamus | Low / low (hypogonadotropic hypogonadism) | Constitutional delay, Kallmann syndrome, functional hypothalamic amenorrhoea | Functional hypothalamic amenorrhoea (stress, weight loss, exercise), TB or other infection |
| Pituitary | Low / low | Pituitary tumours, hypopituitarism | Prolactinoma, Sheehan syndrome |
| Ovary | High / low (hypergonadotropic hypogonadism) | Turner syndrome (45,X), pure gonadal dysgenesis incl. Swyer (46,XY) | Primary ovarian insufficiency; PCOS (chronic anovulation, FSH usually normal) |
| Outflow tract | Normal / normal | Imperforate hymen, transverse vaginal septum, MRKH, CAIS | Asherman syndrome, cervical stenosis |
What are the commonest causes of primary amenorrhoea?
StatPearls lists three big groups for primary amenorrhoea: gonadal dysfunction (about 43%), constitutional delay of growth and puberty (about 14%) and Müllerian agenesis (10–15%). Gonadal dysfunction is most often gonadal dysgenesis, classically Turner syndrome (45,X or a mosaic).
- Turner syndrome — 45,X; about 1 in 2,000 to 2,500 live female births. Short stature with no secondary sexual characteristics is the hallmark of gonadal dysgenesis. Look for a low hairline, high-arched palate, webbed neck, widely spaced nipples, multiple pigmented naevi, cubitus valgus and a short fourth metacarpal. Ovaries are streak gonads, so FSH is high.
- Swyer syndrome — 46,XY pure gonadal dysgenesis. The testes never work, so there is no anti-Müllerian hormone (AMH) and no testosterone in utero: the girl has a uterus and tubes, female external genitalia and streak gonads.
- Kallmann syndrome — congenital hypogonadotropic hypogonadism with anosmia or hyposmia. GnRH neurons fail to migrate from the olfactory placode to the hypothalamus, so FSH and LH stay low.
- Constitutional delay of growth and puberty and functional hypothalamic amenorrhoea — the commonest central causes; both reduce GnRH and can be hard to tell apart.
- Outflow obstruction — imperforate hymen, transverse vaginal septum, vaginal agenesis or cervical atresia, typically with cyclic abdominal pain and normal breasts.
How do you tell MRKH syndrome from complete androgen insensitivity?
Both present as a teenager with normal breasts, a blind vaginal pouch and no uterus. The difference is the karyotype and the gonad. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is Müllerian agenesis in a 46,XX girl with normal ovaries. Complete androgen insensitivity syndrome (CAIS) is a 46,XY individual with functioning testes whose androgen receptors do not respond.
| Feature | MRKH (Müllerian agenesis) | CAIS (testicular feminisation) |
|---|---|---|
| Karyotype | 46,XX | 46,XY |
| Gonads | Normal ovaries — ovulation occurs | Testes (abdominal or inguinal) |
| Breasts | Normal (ovarian oestrogen) | Well developed (testosterone aromatised to oestrogen) |
| Pubic and axillary hair | Normal | Sparse or absent |
| Uterus / upper vagina | Absent or rudimentary | Absent (AMH from testes) |
| Serum testosterone | Normal female range | Elevated |
| Associated anomalies | Urinary tract anomalies, e.g. unilateral renal agenesis | Gonadal tumour risk — gonadectomy, often delayed to early adulthood |
| Share of primary amenorrhoea | 10–15% | Less common |
What causes secondary amenorrhoea?
Once pregnancy and lactation are excluded, StatPearls notes that most non-physiological secondary amenorrhoea comes from a handful of conditions. In one large breakdown, about 30–40% have chronic anovulation (mostly PCOS), about 35% functional hypothalamic amenorrhoea, about 10% hyperprolactinaemia and about 10% primary ovarian insufficiency. Intrauterine adhesions make up most of the rest.
| Cause | Typical clue | Key test |
|---|---|---|
| PCOS | Hirsutism, acne, obesity; the commonest cause when there is androgen excess | Androgens, pelvic ultrasound |
| Functional hypothalamic amenorrhoea | Eating disorder, heavy exercise, major stress — a diagnosis of exclusion | Low or normal FSH/LH, low oestradiol |
| Hyperprolactinaemia | Galactorrhoea, headache, peripheral field loss (prolactinoma); antipsychotics or opiates | Serum prolactin, then pituitary MRI |
| Primary ovarian insufficiency | Hot flushes, age under 40 | FSH in the menopausal range on two occasions |
| Sheehan syndrome | Severe postpartum haemorrhage, then failure to lactate | Pituitary hormone panel |
| Asherman syndrome | Amenorrhoea after a D&C, especially postpartum or post-miscarriage | Hysteroscopy (gold standard) |
| Thyroid disease | Hypo- or hyperthyroid features | TSH |
What are Asherman syndrome and primary ovarian insufficiency?
Asherman syndrome is intrauterine adhesion formation after the basal layer of the endometrium is destroyed, so the endometrium cannot grow despite normal hormones. It follows a dilatation and curettage for termination of pregnancy, missed or incomplete miscarriage or retained placenta; tuberculosis and schistosomiasis are less common causes. It may follow up to 13% of first-trimester terminations and 30% of D&Cs after a late miscarriage. Ultrasound misses it; hysteroscopy is the gold standard for diagnosis and allows treatment at the same sitting.
Primary ovarian insufficiency (POI) is loss of ovarian function before 40 years. It affects about 1–2% of women under 40 and about 0.1% under 30. StatPearls describes diagnosis after 4–6 months of amenorrhoea with two FSH values in the menopausal range (above 40 IU/L) about a month apart and low oestradiol. Causes include Turner syndrome and mosaics, autoimmune ovarian failure, gene mutations, chemotherapy and radiotherapy.
What is the step-wise work-up, including the progestin challenge test?
- History and examination — weight change, exercise, stress, drugs (antipsychotics, opiates, contraceptives), galactorrhoea, headache or visual change, hirsutism, previous D&C or postpartum haemorrhage; Tanner staging of breasts and pubic hair; look for Turner stigmata.
- Urine pregnancy test in every patient.
- Baseline hormones — FSH, LH, oestradiol, prolactin and TSH; androgens if there are signs of excess.
- Pelvic ultrasound — is there a uterus? Are the ovaries normal, polycystic or streaks? (In primary amenorrhoea this is part of the first round.)
- Karyotype when FSH is high in primary amenorrhoea, or when the uterus is absent; pelvic MRI if anatomy is unclear.
- Hormone challenge tests if the picture is still unclear (below).
| Test | How it is done | Bleed occurs | No bleed |
|---|---|---|---|
| Progestin challenge | Oral medroxyprogesterone acetate 5–10 mg daily for 10 days | Endogenous oestrogen is adequate and the outflow tract works — think anovulation (PCOS) | Too little oestrogen (POI, hypothalamic or pituitary failure), damaged endometrium (Asherman) or outflow obstruction |
| Oestrogen + progestin challenge | About 3 weeks of combined oestrogen and progestin (usually a combined pill), then stop | Endometrium and outflow are normal — the problem is lack of oestrogen (ovary or above) | Endometrial damage (Asherman) or outflow obstruction |
How does outflow tract obstruction present?
Girls with an obstructed outflow tract usually present around the expected age of menarche with cyclic lower abdominal pain, otherwise normal puberty and no bleeding. Menstrual blood collects behind the obstruction (haematocolpos in the vagina, haematometra in the uterus).
- Imperforate hymen — about 1 in 1,000 female births. Examination shows a bulging, bluish membrane at the introitus without a hymenal fringe that distends on Valsalva.
- Transverse vaginal septum — failure of the junction between the Müllerian ducts and the vaginal plate; no bulge at the introitus.
- Vaginal agenesis / cervical atresia — failure of canalisation.
- A patent vagina and a normal cervix on examination exclude vaginal agenesis, CAIS and outflow obstruction.
Which amenorrhoea traps keep appearing in NEET PG and INI-CET?
- Anosmia + amenorrhoea = Kallmann syndrome (low FSH/LH), not Turner (high FSH).
- Short stature + absent breasts + high FSH = Turner syndrome — order a karyotype.
- 46,XY with a uterus = Swyer syndrome (no AMH); 46,XY without a uterus and with breasts = CAIS.
- Amenorrhoea after a D&C with normal hormones and no withdrawal bleed even to oestrogen + progestin = Asherman syndrome; diagnose and treat by hysteroscopy.
- Failure to lactate after PPH = Sheehan syndrome — the first symptom.
- Galactorrhoea on antipsychotics = drug-induced hyperprolactinaemia; check prolactin and TSH.
- Use 15 years (or 3 years after thelarche) for primary amenorrhoea, and 13 years with no secondary sexual characteristics as the trigger for a delayed-puberty work-up.