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Case 24.3 – Polycystic Ovary Syndrome (PCOS)

Category: Medicine | Discipline: Obstetrics & Gynaecology | Setting: GP Surgery

Case

Miss Amira Khan, a 24-year-old student, presents to her GP with concerns about irregular periods and excessive facial hair growth. She has had irregular periods since menarche at age 13, with cycles varying from 35 days to 3-4 months. She sometimes goes 6 months without a period. When periods do occur, they are heavy and last 7-10 days.

Over the past 3 years, she has noticed increasing facial hair (upper lip, chin, sideburns), requiring weekly shaving. She also has acne on her face and back, which has not responded to over-the-counter treatments. She has gained 15kg over the past 2 years despite trying various diets. She feels self-conscious about dark patches of skin on the back of her neck.

She is not currently sexually active but is concerned about her future fertility. She denies galactorrhoea, hot flushes, or pelvic pain. Her mother was diagnosed with type 2 diabetes at age 45.

Past medical history is unremarkable. She takes no regular medications. She is a non-smoker and does not drink alcohol.

On Examination:

Investigations

Bedside: Bloods (Day 2-5 of cycle - follicular phase): Metabolic screen: Pelvic Ultrasound (transvaginal):

Questions

Question 1: What is PCOS, what are the Rotterdam criteria, and what are the long-term complications?

Definition: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting 5-20% of women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology.

Rotterdam Criteria for Diagnosis (2003 - International Consensus):

Diagnosis requires 2 out of 3 criteria:

  • 1. Oligo/anovulation: Irregular periods - cycles >35 days or <8 periods per year
  • 2. Clinical or biochemical hyperandrogenism:
    • Clinical: Hirsutism (Ferriman-Gallwey score ≥8), acne, male-pattern alopecia
    • Biochemical: Elevated testosterone, elevated free androgen index
  • 3. Polycystic ovaries on ultrasound:
    • ≥20 follicles (2-9mm diameter) in one ovary, OR
    • Ovarian volume >10cm³

Plus: Exclusion of other causes (hyperprolactinaemia, thyroid dysfunction, Cushing's, congenital adrenal hyperplasia, androgen-secreting tumours)

Pathophysiology:

  • Insulin resistance (central feature):
    • Hyperinsulinaemia → stimulates ovarian androgen production
    • Insulin ↓ SHBG → ↑ free testosterone
    • Present in 70-80% of PCOS (even in non-obese women)
  • Hyperandrogenism:
    • Excess ovarian testosterone production (stimulated by LH and insulin)
    • ↑ LH:FSH ratio (LH drives androgen production)
  • Anovulation:
    • High androgens inhibit follicle maturation
    • Multiple arrested follicles (2-9mm) → "polycystic" appearance on USS
    • No dominant follicle → no ovulation → irregular/absent periods

Clinical Features:

  • Menstrual: Oligomenorrhoea (\>35-day cycles), amenorrhoea, irregular heavy bleeding
  • Hyperandrogenism:
    • Hirsutism (70%) - excess hair in male-pattern distribution (face, chest, abdomen)
    • Acne (40%)
    • Male-pattern alopecia (androgenic alopecia)
  • Metabolic:
    • Obesity (50-80%, especially central/abdominal)
    • Acanthosis nigricans - dark, velvety skin (neck, axillae, groin) - marker of insulin resistance
  • Reproductive: Infertility/subfertility (anovulation), increased miscarriage risk

Long-Term Complications of PCOS:

1. Metabolic complications:

  • Type 2 diabetes: 4-7x increased risk
    • Screen with HbA1c/fasting glucose at diagnosis, then annually
    • Insulin resistance is key driver
  • Cardiovascular disease: Increased risk of hypertension, dyslipidaemia, atherosclerosis, MI
    • Check BP and lipids annually
  • Metabolic syndrome: Clustering of central obesity, hypertension, dyslipidaemia, insulin resistance
  • Non-alcoholic fatty liver disease (NAFLD): Common in PCOS

2. Reproductive complications:

  • Infertility: Anovulation is leading cause (treatable with ovulation induction)
  • Pregnancy complications: Gestational diabetes, pre-eclampsia, preterm birth, increased miscarriage risk

3. Endometrial complications:

  • Endometrial hyperplasia: Unopposed oestrogen (due to anovulation) → endometrial proliferation
  • Endometrial cancer: 3-4x increased risk (especially if prolonged amenorrhoea/obesity)
    • Regular withdrawal bleeds (with COCP or cyclical progestogens) protect endometrium

4. Psychological:

  • Depression, anxiety (2-3x higher prevalence)
  • Poor body image, low self-esteem (hirsutism, acne, obesity)

This patient's features consistent with PCOS:

  • ✓ Oligo/anovulation: Irregular periods since menarche (cycles 35 days to 6 months)
  • ✓ Hyperandrogenism: Clinical (hirsutism FG score 16, acne) + Biochemical (testosterone 3.2, LH:FSH >2:1)
  • ✓ Polycystic ovaries on USS: >20 follicles per ovary, ovarian volume >10cm³
  • Exclusions met: Normal prolactin, normal TSH, pregnancy excluded
  • Metabolic features: Obesity (BMI 32), acanthosis nigricans (insulin resistance), prediabetic HbA1c
  • Diagnosis: PCOS confirmed (meets all 3 Rotterdam criteria)
Question 2: How is PCOS managed?

Management of PCOS - Individualized Based on Symptoms and Goals:

1. Lifestyle Modifications (FIRST-LINE for ALL patients):

  • Weight loss (if overweight/obese):
    • 5-10% weight loss significantly improves insulin resistance, ovulation, menstrual regularity, fertility
    • Diet: Calorie restriction, low glycaemic index (GI) diet
    • Exercise: 150 mins/week moderate activity
  • Dietary advice: Mediterranean diet, reduce refined carbohydrates, increase fiber
  • Smoking cessation, reduce alcohol

2. Medical Management - Tailored to Patient Goals:

A) For women NOT trying to conceive:

Menstrual irregularity + Endometrial protection:

  • Combined oral contraceptive pill (COCP) - First-line
    • Regulates menstrual cycle (regular withdrawal bleeds)
    • Protects endometrium (prevents hyperplasia/cancer from unopposed oestrogen)
    • Reduces androgens (↓ testosterone, ↑ SHBG)
    • Improves hirsutism and acne
    • Choose pills with anti-androgenic progestogen (e.g., Yasmin - drospirenone, co-cyprindiol)
  • Cyclical progestogens (alternative if COCP contraindicated):
    • Medroxyprogesterone 10mg or norethisterone 5mg daily for 10-14 days per month
    • Induces withdrawal bleed, protects endometrium
    • Does NOT improve hyperandrogenism
  • LNG-IUS (Mirena): Protects endometrium locally, but does NOT treat hyperandrogenism

Hirsutism and acne:

  • COCP (first-line) - takes 6-12 months for effect
  • Topical eflornithine (Vaniqa) - for facial hirsutism (slows hair growth)
  • Co-cyprindiol (Dianette): COCP with anti-androgen (cyproterone acetate)
    • Very effective for acne and hirsutism
    • Higher VTE risk - use for max 2 years, review regularly
  • Spironolactone: Anti-androgen (aldosterone antagonist)
    • 50-200mg daily
    • Reduces hirsutism and acne
    • Requires contraception (teratogenic)
  • Cosmetic treatments: Laser hair removal, electrolysis, waxing, threading
  • Acne treatments: Topical retinoids, benzoyl peroxide, antibiotics (standard acne management)

Insulin resistance / Metabolic risk:

  • Metformin 500mg BD/TDS (up to 1500-2000mg/day)
    • Improves insulin sensitivity
    • Modest weight loss (1-2kg)
    • May improve ovulation and menstrual regularity
    • Reduces risk of type 2 diabetes
    • Side effects: GI upset (nausea, diarrhoea) - start low, titrate slowly
    • Less effective than lifestyle changes for weight loss
  • Annual screening:
    • HbA1c/fasting glucose - diabetes screening
    • BP - hypertension screening
    • Lipid profile - CVD risk

B) For women TRYING to conceive (fertility management):

  • Stop COCP/hormonal contraception (suppresses ovulation)
  • Weight loss: Restore ovulation in 30-40% if BMI normalized
  • Metformin: May restore ovulation (off-label use)
  • Ovulation induction (if not conceiving after 6-12 months):
    • Clomifene citrate (first-line): Selective oestrogen receptor modulator (SERM), induces ovulation in 70-80%
    • Letrozole (aromatase inhibitor): Alternative to clomifene, may have higher live birth rate in PCOS
    • Gonadotropins (FSH injections): Second-line if clomifene fails
    • Risk of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS)
  • Laparoscopic ovarian drilling (LOD):
    • Surgical option if clomifene-resistant
    • Thermal/laser cautery destroys ovarian stroma → reduces androgens → restores ovulation
    • Avoids multiple pregnancy risk (unlike gonadotropins)
  • IVF: Third-line if other treatments fail

3. Psychological Support:

  • Screen for depression, anxiety, eating disorders
  • Refer to psychology/counselling if needed
  • PCOS support groups (e.g., Verity PCOS charity)

This patient's personalized management plan:

  1. Lifestyle modifications (essential):
    • Weight loss goal: 5-10% (3-5kg) over 6 months
    • Dietary advice: Low-GI diet, calorie deficit, referral to dietitian
    • Exercise: 150 mins/week moderate activity
  2. Metformin 500mg BD:
    • Improve insulin resistance, modest weight loss, reduce diabetes risk
    • Titrate to 1500mg/day over 2-4 weeks (GI tolerance)
  3. Combined oral contraceptive pill (e.g., Yasmin or co-cyprindiol):
    • Regulate menstrual cycle, protect endometrium
    • Reduce hirsutism and acne over 6-12 months
    • Explain VTE risk, ensure no contraindications
  4. Cosmetic treatments for hirsutism: Laser hair removal (most effective), eflornithine cream
  5. Annual metabolic screening:
    • HbA1c (prediabetic now - high risk T2DM)
    • BP (monitor for hypertension)
    • Lipid profile (CVD risk)
  6. Fertility counselling: Reassure that fertility treatments (clomifene, IVF) are highly effective when she is ready to conceive. Weight loss will significantly improve fertility.
  7. Psychological support: Screen for depression/anxiety, offer support

Key counselling points:

  • PCOS is a chronic condition but highly manageable
  • Weight loss is the most effective intervention (improves ALL symptoms)
  • Fertility is achievable with treatment (ovulation induction very successful)
  • Regular withdrawal bleeds are essential to protect endometrium from cancer risk
  • Long-term metabolic monitoring important (diabetes, CVD risk)

Key Learning Points