Amenorrhoea

Medicine > Endocrine & metabolic

Differential Diagnosis Schema 🧠

Primary Amenorrhoea

Congenital anatomical abnormalities: Müllerian agenesis, imperforate hymen.
- Müllerian agenesis (Rokitansky-Küster-Hauser syndrome) involves the absence of the uterus and upper part of the vagina but normal ovaries and secondary sexual characteristics.
Genetic disorders: Turner syndrome (45,X), androgen insensitivity syndrome.
- Turner syndrome typically presents with short stature, webbed neck, and lack of secondary sexual characteristics.
- Androgen insensitivity syndrome presents with a female phenotype despite XY karyotype.
Endocrine disorders: Hypothalamic amenorrhoea, pituitary failure, congenital adrenal hyperplasia.
- Hypothalamic amenorrhoea is often associated with stress, excessive exercise, or weight loss.
- Pituitary failure can result from conditions like Sheehan’s syndrome.
- Congenital adrenal hyperplasia often presents with virilization and ambiguous genitalia.

Secondary Amenorrhoea

Pregnancy: Most common cause of secondary amenorrhoea, should always be excluded first with a pregnancy test.
Hypothalamic causes: Stress, significant weight loss, excessive exercise.
- These conditions lead to reduced GnRH secretion, which results in decreased stimulation of the pituitary gland.
Pituitary causes: Prolactinoma, Sheehan’s syndrome, pituitary apoplexy.
- Prolactinoma causes elevated prolactin levels leading to amenorrhoea and galactorrhoea.
- Sheehan’s syndrome involves postpartum pituitary necrosis.
Ovarian causes: Polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI).
- PCOS is often associated with hirsutism, acne, and obesity.
- POI involves early menopause before age 40.
Uterine causes: Asherman’s syndrome, endometrial atrophy.
- Asherman’s syndrome, typically post-D&C, involves intrauterine adhesions.

Other Systemic Causes

Thyroid dysfunction: Hyperthyroidism, hypothyroidism.
- Both hyperthyroidism and hypothyroidism can cause menstrual irregularities, including amenorrhoea.
Chronic systemic illness: Diabetes, coeliac disease, chronic kidney disease.
- Chronic illnesses can lead to hypothalamic suppression and amenorrhoea due to the body being in a catabolic state.
Medications: Antipsychotics, chemotherapy, contraceptives.
- Antipsychotics can cause hyperprolactinaemia, leading to amenorrhoea.
- Chemotherapy and contraceptives can directly affect the menstrual cycle.

Key Points in History 🥼

Menstrual History

Age of menarche: Delayed menarche may suggest congenital or genetic conditions like Turner syndrome.
Cycle regularity and flow: Irregular cycles or absent cycles can indicate PCOS, hypothalamic amenorrhoea, or thyroid disorders.
Associated symptoms: Consider hirsutism (suggestive of PCOS), galactorrhoea (suggestive of prolactinoma), or hot flushes (suggestive of POI).

Background

Past medical history: Previous surgeries (D&C may suggest Asherman’s syndrome), chronic illnesses like diabetes or thyroid disease.
Drug history: Use of antipsychotics, contraceptives, or chemotherapy.
Family history: Family history of premature ovarian insufficiency, genetic disorders.
Social history: Lifestyle factors such as stress, exercise, diet (e.g., eating disorders), and substance use.

Possible Investigations 🌡️

Laboratory Tests

Pregnancy test: First-line investigation in any case of amenorrhoea.
Hormone levels: FSH, LH, oestradiol, prolactin, TSH, free T4.
- Elevated FSH and LH with low oestradiol may suggest POI, while elevated prolactin can indicate prolactinoma.
Androgen levels: Testosterone and DHEAS levels are useful in suspected PCOS or androgen-secreting tumours.
Genetic testing: Karyotyping may be needed in cases of primary amenorrhoea to rule out Turner syndrome or other genetic causes.

Imaging Studies

Pelvic ultrasound: To assess the uterus, ovaries, and endometrial thickness. Helps in diagnosing PCOS, Müllerian agenesis, and ovarian tumours.
MRI of the brain: Useful for evaluating the pituitary gland if a prolactinoma or pituitary apoplexy is suspected.
Hysteroscopy: Consider in suspected Asherman’s syndrome for direct visualization of intrauterine adhesions.

Other Tests

Progesterone challenge test: To assess oestrogen status and endometrial function. A withdrawal bleed suggests anovulation; absence of bleed suggests a problem with oestrogen or the outflow tract.
Hysterosalpingography: May be used to evaluate for uterine abnormalities, especially in cases of suspected Asherman’s syndrome.

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