Primary Amenorrhoea
On this page
Direct answer
Primary amenorrhoea is failure of menarche by age 15 years (or by 14 with no secondary sexual development, or within three years of thelarche in older classifications) — a girl of 15 with no periods and no breast budding needs workup at 14 or earlier. Evaluation sorts every case by two bedside questions: is the uterus present on ultrasound, and are breasts developed? Uterus absent with no breasts suggests gonadal dysgenesis (Turner syndrome 45,X — short stature, webbed neck, streak gonads, high follicle-stimulating hormone); uterus absent with normal breasts suggests Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) or complete androgen insensitivity (XY karyotype, testes, normal breasts, scanty pubic hair, high testosterone). Uterus present divides into outflow obstruction (imperforate hymen, transverse vaginal septum — cyclic pain with a haematocolpos) versus endocrine causes (hypothalamic, polycystic ovary syndrome, congenital adrenal hyperplasia, hyperprolactinaemia), sorted by follicle-stimulating hormone, prolactin, thyroid function and karyotype.
What you must remember
- Age cut-offs: evaluate by 15 with normal secondary sexual characteristics, by 14 if none — the current convention; menarche typically follows thelarche by 2-3 years.
- The two-question algorithm: uterus present or absent (ultrasound or magnetic resonance imaging) crossed with breast development (oestrogen present or absent) — this grid generates the differential before any endocrinology.
- Turner syndrome (45,X): the commonest cause overall with absent puberty — short stature (under 150 cm), webbed neck, wide carrying angle, streak gonads, follicle-stimulating hormone above 40 mIU/mL; karyotype confirms; cardiac and renal evaluation mandatory.
- Mayer-Rokitansky-Kuster-Hauser syndrome: second commonest with uterus absent and normal breasts — 46,XX, normal ovaries and hormones, absent or hypoplastic uterus and upper vagina; renal anomalies (unilateral agenesis) coexist frequently; treatment is progressive vaginal dilatation or vaginoplasty.
- Complete androgen insensitivity: 46,XY with testes producing testosterone (male range) and anti-Mullerian hormone — hence no uterus, normal breast development (aromatised oestrogen), scanty axillary and pubic hair; testes need removal after puberty for tumour risk, then oestrogen replacement.
- Uterus present with obstruction: imperforate hymen or transverse septum — primary amenorrhoea with monthly cyclic pain, cryptomenorrhoea, a bulging bluish hymen or haematocolpos on examination; treatment is hymenotomy or septoplasty, and delay causes endometriosis and damage.
- Uterus present, endocrine axis: follicle-stimulating hormone high — ovarian failure or dysgenesis; follicle-stimulating hormone normal or low — hypothalamic, polycystic ovary syndrome, hyperprolactinaemia (check prolactin), congenital adrenal hyperplasia (17-hydroxyprogesterone, androgen excess with clitoromegaly).
- Constitutional delay: the benign diagnosis — family history of late menarche, bone age delayed, normal everything else; watchful waiting with reassurance.
Running the algorithm on three girls
First, a 16-year-old, height 141 cm, no breast development, no periods. Follicle-stimulating hormone 85 mIU/mL — hypergonadotropic hypogonadism; karyotype 45,X confirms Turner. Management fans out: echocardiography for coarctation and bicuspid valve, renal ultrasound, growth-hormone discussion, and puberty induction with escalating oestrogen (unopposed first, then with progestogen).
Second, a 17-year-old with developed breasts, absent periods, no visible cervix and a short blind vagina. Ultrasound: no uterus, normal ovaries. Karyotype 46,XX, testosterone female-range — Mayer-Rokitansky-Kuster-Hauser. Renal imaging for associated agenesis, psychological support at disclosure (fertility involves surrogacy since ovaries are normal), and progressive perineal dilatation to create a functional vagina.
Third, a 15-year-old with normal breasts, absent periods and sparse pubic hair; the mother mentions a childhood hernia repair. No uterus on ultrasound, testosterone in the male range, 46,XY — androgen insensitivity. The testes are removed after breast development completes, with oestrogen replacement; the psychological framing (a disorder of androgen action, not of gender identity) matters as much as surgery.
Where students slip
The grid is the marks: candidates jump to karyotype without first localising by uterus and breasts, and one-best-answer stems punish that order. Specific slips: scanty pubic hair with normal breasts and absent uterus points to androgen insensitivity, not Mullerian agenesis (testosterone cannot act at the hair follicle); a high follicle-stimulating hormone means the gonad, a normal or low value points upstream; and cryptomenorrhoea is real menstruation behind an obstruction, so "primary amenorrhoea with cyclic pain" is the hymen/septum answer. The age cut-offs (15, or 14 without secondary sexual characteristics) are quoted verbatim in options.
Frequently asked questions
At what age is primary amenorrhoea investigated?
At 15 years with normal secondary sexual characteristics, or at 14 if there are no signs of puberty — earlier if other concerns exist.
Which two bedside findings organise the differential?
The presence or absence of the uterus on imaging, combined with the presence or absence of breast development, creating the four-quadrant differential before hormone tests.
How does Mullerian agenesis differ from androgen insensitivity?
Mayer-Rokitansky-Kuster-Hauser is 46,XX with normal ovaries and female-range testosterone; complete androgen insensitivity is 46,XY with testes, male-range testosterone, and sparse pubic hair — both have an absent uterus and normal breasts.
What causes primary amenorrhoea with cyclic pelvic pain?
Outflow obstruction — imperforate hymen or transverse vaginal septum — producing cryptomenorrhoea with haematocolpos; treatment is timely surgical release.
Why is follicle-stimulating hormone the first hormone to check?
An elevated value localises the fault to the gonad (gonadal dysgenesis or premature ovarian insufficiency) while normal or low values direct attention to hypothalamic, pituitary or local uterine causes.