Amenorrhoea, hyperprolactinaemia and polycystic ovary syndrome

Overview

Amenorrhoea is the absence of periods. It is a symptom, not a diagnosis. The approach is the same every time:

1. Rule out pregnancy.
2. Decide primary or secondary.
3. Find the level of the problem: hypothalamus, pituitary, ovary, or uterus and outflow tract.

Polycystic ovary syndrome (PCOS) is the commonest cause of oligomenorrhoea and the commonest endocrine disorder in women of reproductive age, so it gets its own section.

Definitions

Causes by level

Hypogonadotrophic vs hypergonadotrophic

• Hypogonadotrophic hypogonadism (central): low FSH, LH and oestrogen. Causes are hypothalamic or pituitary.
• Hypergonadotrophic hypogonadism (gonadal failure): the ovary does not respond, so FSH and LH are high and oestrogen low. Causes include Turner syndrome, gonadal dysgenesis and premature ovarian insufficiency.

Primary amenorrhoea: think by findings

• Imperforate hymen: early teenage girl with cyclical lower abdominal pain, a pelvic mass and a bulging membrane at the introitus; treated by incision and drainage.
• MRKH (Müllerian agenesis): somewhere between 1 in 5,000 and 1 in 40,000 girls; normal ovaries so normal breasts and hair; often associated renal anomalies. Vaginal dilators create a vagina; genetic children are possible by egg retrieval and a surrogate.

Specific causes worth remembering

• Kallmann syndrome: X-linked, GnRH deficiency because GnRH neurons fail to migrate with olfactory neurons; anosmia with delayed puberty.
• Sheehan syndrome: pituitary necrosis after massive obstetric haemorrhage with hypotension; failure to lactate, then amenorrhoea and other pituitary failure.
• Asherman syndrome: intrauterine adhesions after vigorous curettage (especially postpartum or with infection), endometrial TB or surgery; normal hormones, hypomenorrhoea or amenorrhoea, subfertility. Treated by hysteroscopic adhesiolysis with an IUD left in.

• Post-pill amenorrhoea usually lasts no more than about 6 months; longer than this needs investigation (often PCOS is unmasked).

History and examination

• Developmental history, age of menarche, previous cycle pattern.
• Weight change, exercise, stress, eating disorder.
• Galactorrhoea, headache, visual disturbance (pituitary tumour).
• Hirsutism, acne, alopecia, weight gain (PCOS); hot flushes (POI).
• Cyclical pain without bleeding (outflow block).
• Previous curettage, postpartum haemorrhage, chemotherapy, radiotherapy.
• Drugs: antipsychotics, progestogens, opioids.
• Examine BMI, Tanner stage, signs of androgen excess and Cushing syndrome, visual fields, external genitalia and vagina.

Investigations

• A progestogen challenge is a classic bedside test: a withdrawal bleed means the endometrium is oestrogen-primed and the outflow is open (for example PCOS). No bleed even after oestrogen plus progestogen points to the endometrium or outflow (for example Asherman).

Management by cause

Hyperprolactinaemia (summary)

• Causes: pregnancy, breastfeeding, stress, dopamine antagonists (antipsychotics, metoclopramide), primary hypothyroidism, renal failure, prolactinoma, stalk compression.
• Features: oligo- or amenorrhoea, galactorrhoea, subfertility, low libido; headache and bitemporal hemianopia with macroadenomas.
• Mechanism: prolactin suppresses GnRH pulses, so FSH and LH fall.
• Treatment: cabergoline (or bromocriptine); check TSH and drug history first.

Polycystic ovary syndrome (PCOS)

Basics

• Affects about 8-15% of women of reproductive age.
• Polycystic-looking ovaries on scan are seen in about 25% of all women; most of them do not have the syndrome.
• Strong family tendency (genetic).

Pathophysiology (what explains the exam facts)

• Fast GnRH pulses → relative excess LH → theca cells make excess androgen.
• Insulin resistance with high insulin: insulin works with LH on theca cells to raise androgens, and lowers liver SHBG, so more testosterone is unbound.
• Many small follicles (2-9 mm) start to grow but no dominant follicle is selected, so ovulation fails.
• No ovulation means no progesterone: the endometrium is exposed to unopposed oestrogen.

Clinical features

• Oligomenorrhoea or amenorrhoea (up to 75%), from chronic anovulation.
• Hirsutism, acne, male-pattern hair loss.
• Subfertility.
• Obesity (at least 40%), difficulty losing weight.
• Acanthosis nigricans (velvety dark skin in the axillae and flexures), a sign of insulin resistance.
• Anxiety and depression are common.
• Some women have no symptoms.

Diagnosis: Rotterdam criteria (2 of 3)

1. Ovulatory dysfunction (oligo- or amenorrhoea).
2. Clinical or biochemical hyperandrogenism.
3. Polycystic ovaries on ultrasound.

• Ten Teachers describes the polycystic ovary as having eight or more small subcapsular follicles under 10 mm with increased stroma. Different guidelines quote different follicle counts as scanners have improved, so read the options carefully.
• Ovarian appearance alone does not make the diagnosis.
• Other causes of the same picture must be excluded: thyroid disease, hyperprolactinaemia, non-classic congenital adrenal hyperplasia (raised 17-hydroxyprogesterone), Cushing syndrome and androgen-secreting tumours.

Long-term risks

• Gestational and type 2 diabetes.
• Endometrial hyperplasia and cancer (unopposed oestrogen).
• Cardiovascular disease, dyslipidaemia, hypertension.
• Obstructive sleep apnoea.
• Depression and anxiety.

Management

1. Lifestyle (for everyone)

• Weight loss, diet and exercise. Even modest weight loss can restore ovulation and improve insulin resistance and hirsutism.

2. Endometrial protection (women not seeking pregnancy)

• Combined oral contraceptive pill (first line): regular bleeds, contraception, and it raises SHBG, which lowers unbound testosterone.
• Cyclical oral progestogen to cause regular withdrawal bleeds.
• LNG-IUS for local protection.

3. Androgen symptoms and metabolic features

• Hirsutism: eflornithine cream; cyproterone acetate (in some pills); laser or electrolysis.
• Metformin: improves insulin resistance, androgen excess, ovulation and acne, and helps weight loss.
• Inositol may help metabolic features but has little effect on ovulation.

4. Fertility

• The combined pill must be stopped when trying to conceive.
• Ovulation induction carries a risk of multiple pregnancy and needs ultrasound follow-up.

5. Surgery and other

• Bariatric surgery may help in severe obesity.
• Screen for and treat mood problems.

Quick revision

• Pregnancy test first in every case.
• Primary: none by 16; secondary: none for over 6 months.
• High FSH = ovary failed; low FSH = hypothalamus or pituitary.
• Breasts present + no uterus: MRKH (XX) or CAIS (XY).
• Asherman = adhesions after curettage; Sheehan = pituitary necrosis after PPH.
• Prolactin high: check drugs and TSH; treat with cabergoline.
• PCOS: 2 of 3 (anovulation, androgen excess, polycystic ovaries).
• PCOS treatment: lifestyle, pill or progestogen, metformin; letrozole for fertility.

Written by The House Job from standard references (Gynaecology by Ten Teachers; Guyton and Hall Textbook of Medical Physiology).

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