Dunaif 1997: PCOS and Insulin Resistance

Background

Dr. Andrea Dunaif from Northwestern University published this landmark review in Endocrine Reviews (PMID: 9408743), establishing the mechanistic link between polycystic ovary syndrome and insulin resistance.

Study Design

Comprehensive review synthesizing evidence from clinical studies, molecular biology, and genetics to explain why PCOS and insulin resistance are intimately connected.

Key Findings

Prevalence of insulin resistance in PCOS:

• •50-70% of women with PCOS have insulin resistance
• •Independent of obesity (lean PCOS women also affected)
• •Defect appears specific to insulin's metabolic actions

Feature	Insulin Resistance in PCOS
Skeletal muscle	Reduced glucose uptake
Adipose tissue	Reduced glucose uptake
Ovary	PRESERVED insulin sensitivity

Key paradox: The ovary remains insulin-sensitive while metabolic tissues are resistant.

Mechanistic Insights

Hyperinsulinemia (compensating for peripheral resistance) directly stimulates ovarian theca cells to produce androgens. Insulin:

1. •Enhances LH-stimulated androgen production
2. •Decreases hepatic SHBG (increasing free androgens)
3. •Augments adrenal androgen secretion

This explains why hyperandrogenism improves when insulin is lowered.

Clinical Implications

PCOS treatment should target insulin resistance:

• •Metformin improves ovulation and reduces androgens
• •Low-carbohydrate diets effective for PCOS symptoms
• •Weight loss improves fertility even without full weight normalization

Metabolic Health Perspective

PCOS is fundamentally a metabolic disease with reproductive manifestations. Addressing insulin resistance through carbohydrate restriction often resolves symptoms without hormonal medications.