Polycystic Ovarian Syndrome (PCOS)
Summary
Polycystic Ovarian Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting ~10-15%. It is a syndrome of hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Beyond reproductive health, PCOS is strongly associated with metabolic syndrome (obesity, insulin resistance, type 2 diabetes, dyslipidaemia) and carries long-term risks including endometrial cancer and cardiovascular disease. Management is tailored to the patient's main concern (Menstrual regulation, Fertility, Hirsutism) with lifestyle modification (weight loss) being the cornerstone. [1,2]
Clinical Pearls
It's NOT About the Cysts: The name is misleading. The "cysts" are actually antral follicles that have arrested development. You can have PCOS without polycystic ovaries on ultrasound, and you can have polycystic ovaries without PCOS.
Weight Loss Restores Ovulation: In overweight/obese women with PCOS, losing just 5-10% of body weight can restore regular ovulation and improve fertility naturally.
Protect the Endometrium: Women with PCOS have chronic anovulation, meaning they produce oestrogen but no progesterone. This "unopposed oestrogen" stimulates the endometrium, increasing the risk of endometrial hyperplasia and cancer (3x risk). They need at least 4 periods per year (or progestogen withdrawal every 3 months) to protect the lining.
Screen for Metabolic Disease: All PCOS patients need screening for diabetes (OGTT or HbA1c), dyslipidaemia, and should be counselled on cardiovascular risk.
Demographics
- Prevalence: 8-13% of women of reproductive age (highest estimate ~20% using Rotterdam criteria).
- Age: Presents in adolescence (often post-menarche) or early adulthood. Symptoms may improve after menopause.
- Ethnicity: Similar prevalence across ethnicities, but phenotypic expression may differ.
Risk Factors / Associations
- Family History: Strong genetic component. First-degree relatives have increased risk.
- Obesity: Present in 40-80% of PCOS women. Worsens insulin resistance and hyperandrogenism.
- Insulin Resistance: Present in 50-70%, independent of BMI.
Mechanism
- Genetic Predisposition: Multiple genes involved (affecting gonadotropin secretion, steroidogenesis, insulin signalling).
- Hypothalamic-Pituitary Axis Dysregulation: Increased GnRH pulse frequency favours LH over FSH secretion.
- High LH/FSH Ratio: Elevated LH stimulates ovarian theca cells to produce Androgens (Testosterone, Androstenedione).
- Insulin Resistance & Hyperinsulinaemia:
- Insulin acts on Ovary: Stimulates theca cell androgen production (synergistic with LH).
- Insulin reduces SHBG: Free (active) androgen levels rise further.
- Hyperandrogenism: Excess androgens cause Hirsutism, Acne, and disrupt follicular development.
- Anovulation: Follicles arrest at the antral stage (appearing as "cysts" on ultrasound). No dominant follicle is selected. No ovulation occurs.
- Metabolic Consequences: Hyperinsulinaemia promotes weight gain, dyslipidaemia, NAFLD, and eventually Type 2 Diabetes.
| Condition | Key Features |
|---|---|
| Congenital Adrenal Hyperplasia (Non-Classic) | Elevated 17-Hydroxyprogesterone. Autosomal recessive. |
| Androgen-Secreting Tumour (Ovary/Adrenal) | Rapid onset, severe virilisation (Clitoromegaly, Voice change). Very high Testosterone (>5 nmol/L). |
| Cushing's Syndrome | Central obesity, Striae, Proximal weakness, Buffalo hump. Elevated 24h urinary cortisol. |
| Hyperprolactinaemia | Galactorrhoea, Elevated Prolactin. (Can mimic PCOS). |
| Thyroid Dysfunction (Hypo/Hyper) | Check TFTs. |
| Functional Hypothalamic Amenorrhoea | Low BMI, Excessive exercise, Stress. Low LH/FSH. |
| Premature Ovarian Insufficiency | Age less than 40. High FSH. Low Oestrogen. |
Symptoms (The Triad)
- Menstrual Irregularity: Oligomenorrhoea (less than 9 periods/year), Amenorrhoea, or Irregular cycles.
- Hyperandrogenism:
- Hirsutism (Excess terminal hair in male pattern: Face, Chest, Abdomen).
- Acne (Often treatment-resistant).
- Alopecia (Male pattern androgenic alopecia).
- Infertility / Subfertility: Due to anovulation.
Signs
Metabolic Associations
Psychological
Diagnostic Criteria (Rotterdam Criteria - Need 2 of 3)
- Oligo- or Anovulation: Irregular or absent periods.
- Clinical AND/OR Biochemical Hyperandrogenism: Hirsutism/Acne OR Raised Total/Free Testosterone.
- Polycystic Ovaries on Ultrasound: >12 antral follicles (2-9mm) per ovary OR Ovarian volume >10ml.
Laboratory Tests
- Testosterone (Free/Total): Usually mildly elevated (2-5 nmol/L). Very high levels (>5) suggest tumour.
- SHBG: Low (due to insulin and androgens).
- LH/FSH: LH elevated, FSH normal/low. LH:FSH ratio >2:1 (Classic but not essential for diagnosis).
- 17-Hydroxyprogesterone: To exclude Non-Classic CAH.
- Prolactin: Exclude Hyperprolactinaemia.
- TFTs: Exclude Thyroid dysfunction.
Metabolic Screening (All Patients)
- OGTT (75g) or HbA1c: Screen for Impaired Glucose Tolerance / Diabetes.
- Fasting Lipid Profile.
- Blood Pressure.
Ultrasound
- Transvaginal US: Polycystic morphology. "String of pearls" appearance (Peripheral follicles).
- Note: Not required for diagnosis if other 2 criteria are met.
Management Algorithm
PCOS DIAGNOSED
(Rotterdam 2 of 3)
↓
WHAT IS THE MAIN CONCERN?
┌─────────┬──────────┬──────────┐
↓ ↓ ↓ ↓
MENSTRUAL FERTILITY HIRSUTISM METABOLIC
IRREGULARITY /ACNE RISK
↓ ↓ ↓ ↓
COCP or WEIGHT COCP WEIGHT LOSS
CYCLICAL LOSS +/- METFORMIN
PROGESTOGEN FIRST ANTI- STATINS
(Protect ↓ ANDROGEN OGTT SCREEN
Endometrium) OVULATION ↓
INDUCTION EFLORNITHINE
- Letrozole (Topical)
- Clomiphene
- Gonadotrophins
- Metformin
1. Lifestyle Modification (FIRST LINE for ALL)
- Weight Loss: 5-10% loss improves metabolic profile, restores ovulation in many, and enhances response to fertility treatments.
- Diet: Low glycaemic index diet, reduced refined carbohydrates.
- Exercise: Regular aerobic exercise (improves insulin sensitivity).
2. Menstrual Regulation / Endometrial Protection
- Combined Oral Contraceptive Pill (COCP): First-line. Provides regular withdrawal bleeds. Suppresses ovarian androgens and raises SHBG.
- Preferred: Contains anti-androgenic progestogen (e.g., Drospirenone, Cyproterone acetate).
- Cyclical Progestogen: If COCP contraindicated. Medroxyprogesterone acetate for 12-14 days every 1-3 months.
- Mirena IUS: Provides endometrial protection but doesn't treat hyperandrogenism.
3. Fertility / Ovulation Induction
- Letrozole: Aromatase inhibitor. Now first-line for ovulation induction (higher live birth rate than Clomiphene).
- Clomiphene Citrate: SERM. Second-line.
- Metformin: Improves ovulation, can be used alone or with Clomiphene. Most beneficial in obese/insulin-resistant women.
- Gonadotrophins / IVF: If first-line fails.
- Laparoscopic Ovarian Drilling (LOD): Alternative to gonadotrophins. Less used now.
4. Hirsutism / Acne
- COCP: Suppresses androgens, increases SHBG.
- Co-Cyprindiol (Dianette): COCP with Cyproterone acetate (Anti-androgen). Use for limited duration (VTE risk).
- Spironolactone: Anti-androgen. Off-label. Requires contraception.
- Eflornithine Cream (Vaniqa): Topical for facial hirsutism. Slows hair growth.
- Physical Methods: Laser hair removal, Electrolysis.
5. Metabolic Risk
- Metformin: Insulin sensitiser. Useful for metabolic syndrome, especially in obese/prediabetic women.
- Screen and Treat: Hypertension, Dyslipidaemia.
Short-Term
- Anovulatory Infertility.
- Psychological distress.
Long-Term
- Endometrial Cancer: 3x increased risk due to unopposed oestrogen.
- Type 2 Diabetes: 5-10x increased risk.
- Cardiovascular Disease: Increased risk (though hard evidence of clinical events is debated).
- Gestational Diabetes / Pre-eclampsia: Increased risk in pregnancy.
- Obstructive Sleep Apnoea: Increased prevalence.
- NAFLD: Non-Alcoholic Fatty Liver Disease.
- PCOS is a lifelong condition, though symptoms may improve post-menopause.
- With lifestyle modification and appropriate treatment, fertility rates approach those of normal population.
- Lifelong metabolic screening is essential.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| PCOS | International Evidence-Based (2018/2023) | Rotterdam Criteria for diagnosis. Letrozole first-line for ovulation induction. Lifestyle first-line for all. |
| PCOS | NICE NG137 (2023) | Endometrial protection. Metformin for metabolic/fertility. |
| Ovulation Induction | ESHRE | Letrozole first-line. |
Landmark Evidence
1. Legro RS (NEJM 2007) - Clomiphene vs Metformin
- Clomiphene superior to Metformin for ovulation induction. Combination not better than Clomiphene alone.
2. Letrozole vs Clomiphene (NEJM 2014)
- Letrozole resulted in significantly higher ovulation and live birth rates than Clomiphene.
What is PCOS?
Polycystic Ovarian Syndrome (PCOS) is a common hormonal condition that affects how your ovaries work. Your ovaries produce too many male hormones (androgens), which can stop eggs from developing properly and cause irregular periods, excess hair growth, acne, and difficulty getting pregnant.
Why is it called "Polycystic"?
The ovaries often have lots of small fluid-filled sacs (follicles) that contain immature eggs. These look like tiny cysts on an ultrasound, but they are not true cysts.
Is it serious?
PCOS itself isn't dangerous, but it's linked to other health problems:
- Difficulty getting pregnant (which can often be treated).
- Higher risk of diabetes and heart disease (especially if overweight).
- Higher risk of womb cancer if periods are very infrequent (the lining builds up).
How is it treated?
- Lifestyle: Losing weight (even 5-10%) is the most effective treatment. It can restore regular periods and improve fertility.
- Pill: The contraceptive pill regulates periods and protects the womb lining.
- Fertility drugs: If you want to get pregnant, we can give you tablets (like Letrozole or Clomiphene) to help you ovulate.
- Hair growth: Creams, laser, or sometimes tablets can help.
Primary Sources
- Teede HJ, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018 (Updated 2023).
- NICE. Polycystic ovary syndrome (NG137). 2023.
- Legro RS, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014.
Common Exam Questions
- Criteria: "How do you diagnose PCOS?"
- Answer: Rotterdam Criteria (2 of 3): Oligo/Anovulation, Hyperandrogenism, Polycystic Ovaries on US.
- Complications: "Why does PCOS increase endometrial cancer risk?"
- Answer: Chronic anovulation leads to unopposed oestrogen stimulation of the endometrium.
- Pharmacology: "First-line for ovulation induction in PCOS?"
- Answer: Letrozole (Aromatase Inhibitor).
- Management: "First-line treatment for all PCOS?"
- Answer: Lifestyle modification (Diet, Exercise, Weight loss).
Viva Points
- LH:FSH Ratio: Classically >2:1, but not required for diagnosis.
- Metformin: Explain its role as an insulin sensitiser and when it is useful (Obese, Metabolic syndrome, Adjunct for fertility).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.