Amenorrhoea

Definitions

Primary amenorrhoea — no menarche by:

• 13yrs without breast development, OR
• 15yrs with normal growth/breast development, OR
• 5 years after thelarche, if breast development began before age 10

Secondary amenorrhoea — no menstruation for:

• >3 months in previously regular cycles
• >6 months in previously irregular cycles

Oligomenorrhoea (<9 cycles/year) requires assessment once >2 years post-menarche (cycles are often physiologically irregular in that window).

Classifying by hormone axis

• Hypogonadotrophic (low/normal FSH+LH): hypothalamic or pituitary cause reducing gonadotrophin drive to the ovaries.
• Hypergonadotrophic (elevated FSH+LH): primary ovarian failure — reduced negative feedback drives FSH/LH up (e.g. Turner syndrome, POI).

Causes

Primary amenorrhoea

Category	Causes
Hypogonadotrophic	Constitutional delay (~30% — normal variant, often familial); functional hypothalamic amenorrhoea (stress, excessive exercise, illness, eating disorders, low body weight); isolated GnRH deficiency (Kallmann syndrome); hypopituitarism; prolactinoma
Hypergonadotrophic	Turner syndrome/gonadal dysgenesis (streak gonads); premature ovarian insufficiency
Outflow tract	Müllerian agenesis (absent vagina/uterus); imperforate hymen
Androgen-related	Androgen insensitivity; 5-alpha-reductase deficiency; (less commonly) PCOS or non-classical CAH

Secondary amenorrhoea

Category	Causes
Common	Pregnancy; perimenopause (≥45yrs); PCOS
Hypogonadotrophic	Functional hypothalamic amenorrhoea; pituitary tumour/hyperprolactinaemia; hypopituitarism
Hypergonadotrophic	Premature ovarian insufficiency; early menopause
Uterine	Intrauterine adhesions (Asherman syndrome)
Other endocrine	CAH, hyper/hypothyroidism
Medications	Hypothalamic/pituitary suppression: opioids, corticosteroids, COC, depot medroxyprogesterone, goserelin. Hyperprolactinaemia: antipsychotics, metoclopramide, domperidone, verapamil, ranitidine, SSRIs, tricyclics

Investigations

Initial work-up (all amenorrhoea/oligomenorrhoea): pregnancy test, FSH, LH, oestradiol, TSH, prolactin, pelvic ultrasound (transvaginal preferred; transabdominal if declined/unavailable — particularly useful for follicle counts in suspected POI/PCOS). Repeat FSH/LH at 4–6 weeks if results are borderline/inconclusive.

• Low FSH+LH + low oestradiol → hypothalamic/pituitary cause (functional hypothalamic amenorrhoea, chronic illness, hypopituitarism)
• Normal FSH+LH, variable oestradiol → hypothalamic/pituitary cause, excess androgen production (PCOS, CAH, ovarian/adrenal tumour), or a uterine cause (Asherman syndrome, endometritis, cervical stenosis)
• Elevated FSH+LH + low oestradiol → premature ovarian insufficiency

Primary amenorrhoea: history/exam should assess breast development, pubic hair, and (if appropriate) vaginal length/uterine palpability. Complete/partial absence of uterus or vagina, an elevated prolactin, or abnormal TSH all warrant direct specialist referral for interpretation — primary amenorrhoea always needs specialist referral for further work-up and management, even though initial investigations can be done in general practice.

Management

• Treat the underlying cause (eating disorder, prolactinoma, PCOS, thyroid disease etc.) — see the relevant condition-specific pages.
• Review and stop/switch causative medications where feasible.
• Oestrogen therapy is often needed for hypothalamic/pituitary-driven amenorrhoea, and is recommended for all with POI — a COC or vaginal ring if contraception is also wanted, otherwise combined oestrogen/progestogen MHT at a medium-to-high oestrogen dose. Progestogen is required for endometrial protection with an intact uterus. COC/vaginal ring/MHT can mask return of spontaneous ovulation — MHT itself is not contraceptive; make sure patients understand this distinction.
• Bone health: check BMD in prolonged secondary amenorrhoea. Oestrogen therapy partially offsets bone loss; in functional hypothalamic amenorrhoea, correcting the underlying energy deficit (weight, nutrition) is also needed for bone recovery.
• Cardiovascular risk: review modifiable risk factors — increased CV risk is seen with POI/early menopause, hypothalamic/pituitary causes, and PCOS.

Turner syndrome

Most present with primary amenorrhoea, short stature, and absent breast development (a minority menstruate initially, then develop secondary amenorrhoea). Growth hormone in childhood; oestrogen added for pubertal induction, escalated over 2–3yrs to adult replacement dose, with cyclical (or continuous) progestogen added once breakthrough bleeding occurs or after ~2yrs. Continue hormone therapy until at least the median natural menopause age (~51yrs).

MHT formulations are preferred over COC/vaginal ring in Turner syndrome: they avoid an oestrogen-free interval, use more physiological progestogen (especially cyclical micronised progesterone), give better bone protection, and — importantly — native estradiol is less likely to raise blood pressure than ethinylestradiol. Turner syndrome carries an increased risk of aortic dilatation/dissection, so ethinylestradiol- containing COC/vaginal ring is contraindicated if hypertensive (data on newer estradiol-containing pills in this context is still lacking). If contraception is needed in a normally-menstruating (usually mosaic) Turner patient, continuous COC/ring is an option provided BP is normal. Refer to a fertility specialist if pregnancy is desired. Turner syndrome also needs its own screening programme (thyroid, hearing, cardiac, glucose, lipids, BP, renal structure, BMD) — see the International Turner Syndrome Consensus guidance.