Polycystic Ovary Syndrome
(PCOS)
A Comprehensive Pathophysiological
& Clinical Overview
Introduction to PCOS
• - PCOS is a complex endocrine disorder
affecting 5-15% of reproductive-aged women.
• - Characterized by ovulatory dysfunction,
hyperandrogenism, and polycystic ovarian
morphology.
• - Strong association with metabolic syndrome,
insulin resistance, and increased
cardiovascular risk.
Epidemiology & Risk Factors
• - Affects 1 in 10 women globally, with
increased prevalence in South Asian and
Hispanic populations.
• - Genetic predisposition with familial
clustering.
• - Environmental factors: Obesity, diet,
sedentary lifestyle.
• - Epigenetic modifications due to prenatal
androgen exposure.
Pathophysiology of PCOS -
Overview
• - Disruption of the Hypothalamic-Pituitary-
Ovarian (HPO) axis.
• - Hyperandrogenism due to ovarian and
adrenal dysfunction.
• - Insulin resistance and compensatory
hyperinsulinemia.
• - Chronic low-grade inflammation contributing
to metabolic dysfunction.
HPO Axis Dysfunction in PCOS
• - Increased GnRH pulse frequency leads to
preferential LH secretion over FSH.
• - Elevated LH levels stimulate ovarian theca
cells to produce excessive androgens.
• - Low FSH impairs follicular maturation,
leading to anovulation.
• - Result: Irregular menstrual cycles, infertility,
and hormonal imbalance.
Ovarian Androgen Excess in PCOS
• - Theca cells overproduce androgens
(testosterone, androstenedione) due to high
LH.
• - Impaired granulosa cell function prevents
aromatization of androgens to estrogens.
• - Leads to hyperandrogenic symptoms:
Hirsutism, acne, androgenic alopecia.
• - Excess androgens cause follicular arrest,
leading to multiple small cysts in ovaries.
Insulin Resistance &
Hyperinsulinemia
• - Peripheral insulin resistance leads to
compensatory hyperinsulinemia.
• - Insulin acts synergistically with LH to
enhance theca cell androgen production.
• - Suppression of hepatic SHBG production
increases free testosterone levels.
• - Hyperinsulinemia contributes to metabolic
syndrome and Type 2 diabetes risk.
Chronic Low-Grade Inflammation
in PCOS
• - Increased levels of inflammatory markers:
TNF-α, IL-6, CRP.
• - Pro-inflammatory cytokines exacerbate
insulin resistance.
• - Oxidative stress contributes to ovarian
dysfunction and metabolic dysregulation.
• - Inflammation-linked epigenetic changes may
influence disease progression.
Rotterdam Criteria for PCOS
Diagnosis (2003)
• - Diagnosis requires at least 2 out of 3 criteria:
• 1. Oligo/anovulation (irregular menstrual
cycles)
• 2. Clinical or biochemical hyperandrogenism
(hirsutism, high testosterone)
• 3. Polycystic ovarian morphology on
ultrasound (>12 follicles, increased ovarian
volume)
Diagnostic Tests in PCOS
• - **Hormonal tests**: LH:FSH ratio, total/free
testosterone, DHEA-S, SHBG.
• - **Metabolic tests**: Fasting glucose, OGTT,
lipid profile, fasting insulin.
• - **Imaging**: Pelvic ultrasound showing
multiple small antral follicles.
• - **Differential Diagnosis**: Exclude Cushing’s
syndrome, CAH, thyroid dysfunction.
Management - Lifestyle
Modifications
• - **First-line therapy for all PCOS patients.**
• - **Weight loss (5-10%)** improves insulin
sensitivity and restores ovulation.
• - **Dietary approach**: Low-GI foods, high-
fiber, anti-inflammatory diet.
• - **Exercise**: At least 150 minutes/week of
moderate-intensity physical activity.
Pharmacological Management
• - **Menstrual regulation**: Combined oral
contraceptives (OCPs).
• - **Hyperandrogenism**: Anti-androgens
(spironolactone, flutamide, finasteride).
• - **Insulin resistance**: Metformin, myo-
inositol.
• - **Ovulation induction**: Letrozole (first-
line), clomiphene citrate, gonadotropins.
Complications & Long-Term Risks
• - **Reproductive**: Infertility, pregnancy
complications.
• - **Metabolic**: Type 2 diabetes,
cardiovascular disease, NAFLD.
• - **Endometrial cancer risk** due to chronic
anovulation.
• - **Mental health**: Depression, anxiety,
eating disorders.