Polycystic Ovary Syndrome

PCOS is the most common endocrine disorder affecting women of reproductive age (8-13%). It's a multisystem disorder with significant clinical relevance for UK finals, spanning gynaecology, endocrinology, and primary care. The diagnosis relies on the 2003 Rotterdam criteria: at least two of (1) clinical/biochemical hyperandrogenism, (2) oligo- or anovulation, and (3) polycystic ovaries on ultrasound (≥12 follicles per ovary or ovarian volume >10cm³). Understanding the underlying insulin resistance, even in non-obese individuals, is key to grasping its pathophysiology and long-term risks. These risks include Type 2 Diabetes Mellitus, cardiovascular disease, and endometrial hyperplasia/carcinoma due to unopposed oestrogen. Management is highly individualised, focusing on the patient's primary concerns (e.g., hirsutism, irregular cycles, subfertility). Crucially, lifestyle interventions, particularly weight loss (even 5-10%), can dramatically improve symptoms and metabolic parameters. Always consider the significant psychological impact of PCOS on patients.

The core pathophysiology involves a dysregulation of the hypothalamic-pituitary-ovarian axis and significant insulin resistance. High LH:FSH ratio stimulates ovarian theca cells to overproduce androgens (testosterone, androstenedione). Insufficient FSH prevents normal follicular maturation, leading to follicular arrest and the characteristic 'string of pearls' appearance on ultrasound. Insulin resistance, a hallmark of PCOS, leads to hyperinsulinaemia. High insulin reduces hepatic Sex Hormone-Binding Globulin (SHBG) production, increasing free, bioavailable testosterone. Insulin also directly enhances ovarian androgen production. This vicious cycle of hyperandrogenism and anovulation is further exacerbated by genetic and environmental factors. Understanding this interplay is vital for explaining symptoms (hirsutism, anovulation) and long-term risks (T2DM).

PCOS typically presents in adolescence/early adulthood. Key presentations for finals:
1. **Menstrual irregularities**: Oligomenorrhoea (<9 periods/year) or amenorrhoea.
2. **Hyperandrogenism**: Hirsutism (assess with Ferriman-Gallwey score), persistent acne, male-pattern hair loss.
3. **Infertility**: Often the presenting complaint, due to anovulation.
4. **Metabolic features**: Central obesity, acanthosis nigricans (neck, axillae, groin).
**Red Flags/Complications**:
- **Endometrial hyperplasia/cancer**: Due to chronic unopposed oestrogen. Any abnormal uterine bleeding in a PCOS patient warrants investigation.
- **Type 2 Diabetes Mellitus**: 2-3 fold increased risk; screen regularly (HbA1c/OGTT).
- **Cardiovascular disease**: Increased risk factors (dyslipidaemia, hypertension).
- **Psychological impact**: High rates of anxiety, depression, body image issues. Always address this in consultations.
**Differentials**: Thyroid dysfunction, hyperprolactinaemia, congenital adrenal hyperplasia (non-classical), androgen-secreting tumours (rare, consider if rapid onset severe hyperandrogenism).

Investigations aim to confirm diagnosis (Rotterdam criteria) and exclude differentials/screen for complications.
- **Bedside**: BMI, waist circumference, BP (for metabolic risk).
- **Bloods**:
- **Hormonal**: Total testosterone (often mildly elevated), SHBG (often low, leading to high Free Androgen Index - FAI), LH/FSH ratio (can be high, but not diagnostic alone), Prolactin (exclude hyperprolactinaemia), TSH (exclude thyroid disease), 17-OH Progesterone (exclude non-classical CAH - measure early follicular phase).
- **Metabolic**: HbA1c or Oral Glucose Tolerance Test (OGTT) for T2DM screening, Lipid profile.
- **Imaging**:
- **Transvaginal Ultrasound (TVUS)**: Preferred for ovarian morphology (≥12 follicles 2-9mm in diameter in one ovary, or ovarian volume >10cm³). Transabdominal if TVUS not appropriate (e.g., virginal). **Crucial OSCE point**: Do not diagnose PCOS based on ultrasound alone, especially in adolescents (within 8 years of menarche) as multifollicular ovaries are common and normal.

Management is tailored to the patient's primary concerns and long-term risk reduction.
- **Lifestyle**: **Weight loss (5-10% body weight)** through diet and exercise is paramount for overweight/obese patients. Improves insulin sensitivity, ovulation, and metabolic profile.
- **Menstrual Regulation & Endometrial Protection**:
- **Combined Oral Contraceptive Pill (COCP)**: First-line. Regulates cycles, reduces androgen symptoms (hirsutism, acne), and protects the endometrium from hyperplasia. Dianette (co-cyprindiol) is effective for severe hirsutism but has a higher VTE risk; Yasmin is an alternative with anti-androgenic effects.
- **Cyclical Progestogens**: (e.g., Medroxyprogesterone 10mg for 14 days every 3-4 months) if COCP contraindicated, to induce withdrawal bleeds and protect the endometrium.
- **Hirsutism/Acne**:
- **COCP** (as above).
- **Topical Eflornithine cream**: For facial hirsutism.
- **Spironolactone**: Anti-androgen, used off-licence, requires contraception.
- **Infertility**:
- **Weight loss**: First step.
- **Ovulation induction**:
- **Clomifene citrate**: First-line oral agent (anti-oestrogen). Requires specialist monitoring due to risk of multiple pregnancy.
- **Letrozole**: Aromatase inhibitor, increasingly used as first-line, potentially better outcomes than clomifene.
- **Metformin**: Can be used as an adjunct, especially in obese patients with insulin resistance, but not first-line for ovulation induction.
- **Laparoscopic Ovarian Drilling (LOD)**: Surgical option for clomifene-resistant cases.
- **Long-term Monitoring**: Annual screening for T2DM (HbA1c), cardiovascular risk factors (BP, lipids).