PCOS and insulin resistance: how biochemistry restores hormonal balance

Polycystic ovary syndrome (PCOS) affects 10–13% of women of reproductive age and is under-treated in Estonia. Insulin resistance underlies more than 70% of cases – which is why lifestyle intervention often outperforms hormonal medication alone. This guide takes a biochemical view: why excess insulin turns the ovary into an androgen factory, which labs are clinically justified, and what steps restore ovulation in 12–16 weeks.

What PCOS is – and why it is not just “cysts”

PCOS is a hormonal and metabolic syndrome. Diagnosis uses the Rotterdam criteria: two of three features – 1) irregular or absent ovulation, 2) clinical or lab hyperandrogenism (acne, hirsutism, elevated testosterone), 3) polycystic ovarian morphology on ultrasound. Visible cysts are not required – the name is misleading. The 2023 international guideline (Teede et al., Fertility and Sterility 2023) is explicit: PCOS is primarily a metabolic disease, with reproductive symptoms as a consequence.

How insulin resistance feeds the androgens

The key mechanism: elevated insulin (a) stimulates ovarian theca cells to produce more testosterone and androstenedione, (b) suppresses hepatic SHBG production, raising free biologically active testosterone even higher, (c) arrests follicular maturation – ovulation fails. Nestler et al. (JCEM 2001) showed that lowering insulin with metformin reduced androgens and restored ovulation in about half of women with PCOS. Lifestyle intervention delivers a comparable or stronger effect through the same biochemistry (Legro et al., JCEM 2016).

Which labs actually matter

The standard PCOS panel I order:

• Fasting insulin + glucose → HOMA-IR (one of the measures used when assessing hidden hyperinsulinaemia; not a diagnosis on its own)
• HbA1c → long-term glycemic picture
• Total testosterone, SHBG → free-testosterone index (FAI)
• DHEA-S → adrenal-origin androgens
• LH and FSH (cycle days 2–5) → LH/FSH > 2 is classic but not required
• 17-OH-progesterone → to rule out congenital adrenal hyperplasia
• Prolactin, TSH, free T4, TPO-Ab → to distinguish look-alikes
• Extended lipids, ALT/AST → the metabolic side

A pelvic ultrasound on cycle days 2–5 is useful but not mandatory – the 2023 guideline permits a diagnosis without ultrasound if the other two criteria are clear. Ovarian appearance is a consequence, not a cause.

PCOS phenotypes – why one plan does not fit all

PCOS is divided into four phenotypes (Azziz et al., Nat Rev Dis Primers 2016). The commonest is phenotype A: hyperandrogenism + oligo-anovulation + polycystic ovarian morphology – and it carries the strongest insulin resistance (~80% of cases). Phenotype D is subtler: irregular cycles + polycystic ovaries without overt hyperandrogenism – insulin is less often the driver, and disrupted hypothalamic rhythm more so. That distinction changes the plan: phenotype A needs insulin lowering first; phenotype D needs sleep, training and stress regulation.

What lifestyle changes are clinically proven

Three lifestyle interventions carry high-quality evidence: 5–10% weight loss (if BMI > 25), carbohydrate quality and quantity, and strength training. The Moran et al. Cochrane meta-analysis (2011) showed that a 5% weight loss restores ovulation in about 30% of women, and 10% in about 60% – without medication. On carbohydrates, what matters is not low-carb per se but glycemic load: refined sugar, white flour and sweet drinks raise insulin the most and longest. Fiber, adequate protein and mono-saturated fats (Mediterranean or low-glycemic pattern) are the first choice. I do not require strict keto if BMI is near normal – it works, but long-term social sustainability matters more than strict biochemistry.