Primary Amenorrhoea

Primary amenorrhoea is the absence of menstruation by age 15 years in a girl with normal secondary sexual development, or by age 13 years with no breast development, or more than 3 years after the start of breast development without menses.

Causes are anatomical (imperforate hymen, transverse vaginal septum, Müllerian agenesis), chromosomal and gonadal (Turner syndrome, androgen insensitivity, gonadal dysgenesis), hypothalamic and pituitary (constitutional delay, hypogonadotropic hypogonadism, hyperprolactinaemia) and systemic (polycystic ovary syndrome, thyroid disease, congenital adrenal hyperplasia, chronic illness, malnutrition). It matters because it may signal a serious genetic or endocrine disorder, and it affects growth, bone health and fertility.

• Risk factors: family history of delayed puberty, chronic disease, low body weight, intense exercise, cranial irradiation, previous chemotherapy.
• Cyclical lower abdominal pain without bleeding suggests an obstructed outflow tract.
• Absence of the uterus with normal breasts suggests Müllerian agenesis or androgen insensitivity.

Girls have no menses with or without breast and pubic hair development, and may have short stature, webbed neck, cyclical pelvic pain, a bulging blue hymen, absent vagina, hirsutism, acne, galactorrhoea, headache or visual disturbance, depending on the cause.

• Breast stage (Tanner), pubic hair, height, arm span, weight and body mass index.
• Examination of the external genitalia and hymen; a short blind vagina in Müllerian agenesis or androgen insensitivity.
• Differential diagnosis: constitutional delay, Turner syndrome, hypogonadotropic hypogonadism, Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome), complete androgen insensitivity syndrome, imperforate hymen, transverse vaginal septum, polycystic ovary syndrome, hyperprolactinaemia, hypothyroidism, congenital adrenal hyperplasia, anorexia nervosa, pregnancy.
• Complications: infertility, osteoporosis, short stature, haematocolpos and haematometra with pain and urinary retention, cardiovascular disease in Turner syndrome, gonadoblastoma in girls with Y chromosome material, psychological distress.

The approach is to confirm pregnancy status, determine the pubertal stage and anatomy, and check hormones.

• Urine or serum hCG; follicle stimulating hormone, luteinising hormone, oestradiol (high FSH above 30 IU/L indicates ovarian failure; low or normal FSH suggests hypothalamic or pituitary cause); prolactin, thyroid stimulating hormone and free thyroxine; testosterone and 17-hydroxyprogesterone.
• Pelvic and abdominal ultrasound (uterus, ovaries, kidneys); MRI pelvis for complex anatomy; bone age X-ray of the left wrist.
• Karyotype (45,X in Turner syndrome; 46,XY in androgen insensitivity); anti-Müllerian hormone.
• Pituitary MRI for raised prolactin or hypogonadotropic hypogonadism; coeliac screen, HIV test, full blood count, urea, electrolytes.

The principle is to treat the cause, induce puberty or restore function with hormones when needed, and provide counselling on fertility and bone health.

• Supportive: explanation and counselling for the girl and family; nutritional rehabilitation to a body mass index of 20 kg/m2 or more; reduce excessive exercise; calcium 1000 mg and vitamin D 800 to 1000 IU oral daily; psychological support; vaginal dilator therapy for Müllerian agenesis.
• Pharmacological: constitutional delay: observation to age 15, or low dose oestradiol valerate 0.5 mg oral once daily for 3 to 6 months under specialist care; hypogonadism or Turner syndrome: oestradiol valerate 0.5 mg oral once daily, increased every 6 months to 1 mg, 1.5 mg and 2 mg daily over 2 to 3 years, then add medroxyprogesterone 10 mg oral once daily for 12 days each month (or norethisterone 5 mg oral once daily for 12 days each month) once breast development is established or bleeding occurs, continued until about age 50 years; hyperprolactinaemia: cabergoline 0.25 mg oral twice weekly increased to a maximum of 1 mg twice weekly; hypothyroidism: levothyroxine 50 micrograms oral once daily increased every 4 to 6 weeks to normalise thyroid stimulating hormone; polycystic ovary syndrome: combined oral contraceptive pill with ethinylestradiol 30 micrograms and levonorgestrel 150 micrograms oral once daily for 21 days then 7 days free; Turner syndrome: growth hormone 0.045 to 0.05 mg/kg/day subcutaneous at night under specialist care.
• Procedures: cruciate hymenotomy or excision for imperforate hymen; excision of a transverse vaginal septum; vaginal dilation for Müllerian agenesis (first line) or surgical neovagina; laparoscopic removal of gonads in girls with Y chromosome material (gonadoblastoma risk), timed after puberty in complete androgen insensitivity.
• Special groups: Turner syndrome needs echocardiography, renal ultrasound, thyroid function, coeliac screen, audiology and lifelong cardiology review; girls with Y chromosome material have gonadectomy after puberty and long term oestradiol replacement; adolescents with imperforate hymen have urgent drainage to relieve pain and retention.
• Red flags: cyclical pelvic pain with a bulging hymen, urinary retention, severe headache or visual loss, virilisation, galactorrhoea with visual field loss, signs of Turner syndrome with hypertension, a pelvic mass.
• Follow-up: review every 3 to 6 months during puberty induction; annual height, weight, blood pressure and bone health review; bone density scan at 18 years and every 2 to 3 years in hypogonadism; fertility counselling and referral for assisted conception or surrogacy.