PCOS: The Insulin-Androgen Connection

The Metabolic Root Beneath the Reproductive Surface

Polycystic ovary syndrome affects 8-13% of reproductive-age women worldwide, making it the most common endocrine disorder in this population. But here is the clinical pivot that changes everything: PCOS is a metabolic disorder first, reproductive disorder second. Roughly 70% of women with PCOS have insulin resistance as the primary driver. The ovaries are downstream. The cysts are consequences, not causes.

In the IFM Matrix, PCOS sits at the intersection of hormonal and immune imbalances, with assimilation (gut health), biotransformation (detox capacity), and structural integrity all feeding into the picture. You cannot treat PCOS with birth control pills and metformin alone and call it medicine. You must ask: why are the androgens high? What is driving the insulin? What is inflaming the terrain?

Diagnostic Criteria: Rotterdam and Beyond

The Rotterdam criteria require 2 of 3:

1. Oligo-ovulation or anovulation — irregular or absent periods
2. Clinical or biochemical hyperandrogenism — acne, hirsutism, hair loss, or elevated testosterone/DHEA-S on labs
3. Polycystic ovaries on ultrasound — 12+ follicles per ovary or ovarian volume >10 mL

Critical point: not all PCOS looks the same. A lean woman with acne and irregular periods but no cysts on ultrasound still qualifies. A woman with cysts but regular periods and normal androgens does not. The name itself is misleading — many clinicians now prefer “metabolic reproductive syndrome.”

The Four Types of PCOS

Lara Briden’s clinical framework identifies four distinct phenotypes, each demanding a different therapeutic approach:

1. Insulin-Resistant PCOS (~70% of cases)

The most common type. Elevated insulin tells the ovaries to produce excess androgens (testosterone, androstenedione). The theca cells of the ovary have insulin receptors — when insulin is chronically high, these cells overproduce androgens. Simultaneously, high insulin suppresses sex hormone-binding globulin (SHBG) in the liver, freeing more testosterone into circulation.

Clinical markers: High fasting insulin (>8 uIU/mL), elevated HOMA-IR (>2.0), LH:FSH ratio >2:1 (drawn Day 3), acanthosis nigricans (dark velvety skin on neck, axillae, groin), central adiposity, sugar cravings, energy crashes. HbA1c may still be normal because the pancreas is compensating — insulin is the early warning signal, not glucose.

2. Inflammatory PCOS

Normal insulin sensitivity, but elevated inflammatory markers. hs-CRP is elevated. These women often have headaches, joint pain, fatigue, skin issues (eczema, urticaria), and digestive complaints. The inflammation drives the ovaries to overproduce androgens through inflammatory cytokines (TNF-alpha, IL-6) that stimulate adrenal and ovarian androgen production.

Root causes: gut dysbiosis, intestinal permeability (leaky gut), food sensitivities (gluten, dairy), environmental toxin exposure (BPA, phthalates, pesticides), chronic infections.

3. Adrenal PCOS

Elevated DHEA-S with normal testosterone — the androgens are coming from the adrenals, not the ovaries. This represents about 10% of PCOS cases. These women are often slim, stressed, anxious, sleep-deprived. The HPA axis is in overdrive, producing excess adrenal androgens as a byproduct of the cortisol cascade.

Key distinction: ovarian ultrasound may be normal. Testosterone is not elevated. DHEA-S tells the story. Treatment must focus on the stress response, not on insulin or inflammation.

4. Post-Pill PCOS

A temporary condition following discontinuation of oral contraceptives. The pill suppresses the HPO (hypothalamic-pituitary-ovarian) axis for years. When stopped, there is a rebound surge of LH and androgens as the system recalibrates. Periods become irregular, acne flares, and labs can mimic true PCOS.

Differentiating factor: this woman had regular periods before the pill. Labs will normalize within 3-12 months if the underlying terrain is healthy. Support the transition; do not diagnose a lifelong condition based on a temporary hormonal reset.

The Complete Testing Panel

Incomplete testing is the single biggest reason PCOS is mismanaged. Order all of the following, ideally on Day 3 of the menstrual cycle (or any day if periods are absent):

Insulin and Metabolic:

• Fasting insulin (most important single test — often overlooked)
• Fasting glucose
• HOMA-IR calculation (fasting insulin x fasting glucose / 405)
• HbA1c
• Lipid panel with triglyceride-to-HDL ratio (>2.0 suggests insulin resistance)

Androgens:

• Total testosterone
• Free testosterone (calculated or direct)
• DHEA-S (adrenal androgen)
• Androstenedione
• SHBG (low = high free androgens)

Reproductive Hormones:

• LH and FSH (Day 3 — LH:FSH ratio >2:1 is classic)
• AMH (anti-Mullerian hormone — often elevated in PCOS, reflects follicle count)
• Estradiol (Day 3)
• Progesterone (Day 21 or 7 days post-ovulation — confirms ovulation if >5 ng/mL)
• Prolactin (to rule out prolactinoma)

Inflammation and Nutrients:

• hs-CRP
• Vitamin D (25-OH)
• Full thyroid panel (TSH, free T4, free T3, TPO antibodies — hypothyroidism mimics PCOS)

Insulin-Resistant PCOS Protocol

This is the most evidence-based natural protocol in reproductive endocrinology, with multiple RCTs supporting each intervention:

Inositol: The Cornerstone

Myo-inositol and D-chiro-inositol in a 40:1 ratio — this mirrors the physiological ratio found in the body. Dose: 4g myo-inositol + 100mg D-chiro-inositol daily, divided into two doses.

Inositol is a second messenger in insulin signaling. In PCOS, inositol metabolism is deranged — the conversion of myo-inositol to D-chiro-inositol is impaired in ovarian tissue. Supplementation restores insulin sensitivity, lowers androgens, improves ovulation, and regulates menstrual cycles. The research from Unfer, Genazzani, and others shows inositol is as effective as metformin for insulin-resistant PCOS — without the GI side effects, B12 depletion, or lactic acidosis risk.

Supporting Insulin Sensitizers

• Berberine: 500mg 2-3x/day with meals. Activates AMPK (the same pathway as metformin), reduces fasting glucose and insulin, improves lipid profile. Multiple RCTs show comparable efficacy to metformin. Caution: can interact with medications metabolized by CYP enzymes.
• Chromium picolinate: 200-1000mcg/day. Enhances insulin receptor sensitivity. Meta-analysis shows significant reduction in fasting glucose and insulin in PCOS.
• NAC (N-acetyl cysteine): 600mg 3x/day. The Rizk 2005 study showed NAC improved ovulation rates and reduced testosterone comparable to metformin. Also replenishes glutathione, supporting detoxification.

Anti-Androgenic Support

• Zinc: 30mg/day (with copper 2mg to prevent depletion). Zinc is a potent 5-alpha reductase inhibitor — the enzyme that converts testosterone to the more potent DHT, which drives acne and hair loss.
• Saw palmetto: 320mg/day standardized extract. Another 5-alpha reductase inhibitor, well-studied for its anti-androgenic effects on skin and hair.
• Spearmint tea: 2 cups daily. The Akdogan 2007 and Grant 2010 studies demonstrated significant reductions in free testosterone with regular spearmint tea consumption. A simple, pleasant intervention.
• DIM (diindolylmethane): 100-200mg/day. Supports healthy estrogen metabolism via the 2-OH pathway, reducing estrogenic load.

Anti-Inflammatory and Nutrient Support

• Omega-3 fatty acids: 3g/day (combined EPA + DHA). Reduces androgens, improves insulin sensitivity, lowers inflammation. Choose triglyceride form for better absorption.
• Vitamin D: 5000 IU/day, targeting serum levels of 50-70 ng/mL. Vitamin D receptors exist on ovarian tissue. Deficiency worsens insulin resistance and anovulation. Multiple studies show repletion improves ovulation rates.

Dietary Strategy

The dietary approach for insulin-resistant PCOS is not about calorie restriction — it is about glycemic management:

• Protein-first at meals: Start every meal with protein (20-30g) before carbohydrates. This blunts the glucose spike by 40-60% (Shukla et al., Cornell).
• Low glycemic load: Eliminate refined sugars, white flour, processed carbohydrates. Emphasize whole foods, vegetables, legumes, nuts, seeds.
• Remove dairy (especially A1 casein from conventional cow’s milk): A1 beta-casein increases IGF-1, which amplifies insulin signaling and androgen production. Goat, sheep, and A2 dairy are better tolerated.
• Time-restricted eating: 16:8 can improve insulin sensitivity — but only for insulin-resistant PCOS. Avoid fasting in adrenal PCOS (cortisol is already dysregulated).
• Seed cycling: Days 1-14 (follicular phase): 1 tbsp each ground flaxseed + pumpkin seeds daily. Days 15-28 (luteal phase): 1 tbsp each sesame seeds + sunflower seeds. Flax provides lignans that modulate estrogen; pumpkin provides zinc; sesame and sunflower support progesterone production.

Exercise

• Resistance training 3-4x/week: Increases GLUT4 transporter expression on muscle cells, improving glucose uptake independent of insulin. This is the single most effective exercise modality for insulin-resistant PCOS.
• Daily walking: 30 minutes post-meal walks reduce post-prandial glucose by 30%.
• Avoid overtraining: Excessive HIIT or endurance training raises cortisol, worsening adrenal PCOS and potentially stalling weight loss through HPA axis dysregulation.

Adrenal PCOS Protocol

This phenotype requires a fundamentally different approach — the opposite of aggressive dieting and intense exercise:

• Ashwagandha (Withania somnifera): 300-600mg KSM-66 extract daily. Reduces cortisol by 30% (Chandrasekhar 2012), lowers DHEA-S, improves sleep and anxiety.
• Rhodiola rosea: 200-400mg standardized extract. Adaptogen that modulates the HPA axis response to stress.
• Magnesium glycinate: 400mg before bed. Calms the nervous system, supports sleep, acts as a natural muscle relaxant.
• No fasting: These women need regular meals to stabilize cortisol. Skipping meals triggers the stress response.
• Gentle exercise only: Yoga, walking, swimming, Pilates. No HIIT, no CrossFit, no marathon training until the HPA axis is restored.
• Sleep optimization: 8+ hours, consistent sleep-wake cycle, blue light blocking after sunset, melatonin 0.5-1mg if needed.
• Nervous system regulation: Breathwork (4-7-8 breathing, box breathing), meditation, vagal toning.

Inflammatory PCOS Protocol

Address the fire before addressing the hormones:

• Elimination diet: Remove gluten, dairy, sugar, corn, soy, eggs for 30 days. Reintroduce systematically. Many inflammatory PCOS cases resolve with dietary change alone.
• Gut healing 5R protocol: Remove pathogens, Replace digestive support, Reinoculate with probiotics, Repair with glutamine/zinc carnosine/colostrum, Rebalance lifestyle.
• Curcumin: 500-1000mg/day (with piperine or liposomal for absorption). NF-kB inhibitor, reduces hs-CRP, anti-androgenic.
• Quercetin: 500mg 2x/day. Mast cell stabilizer, anti-inflammatory, reduces insulin resistance.
• Environmental detox: Filter water, switch to glass containers, avoid plastic food contact, use clean personal care products (EWG Skin Deep database). Endocrine disruptors (BPA, phthalates, parabens) directly worsen PCOS.

Fertility Considerations

For women with PCOS trying to conceive:

• Letrozole over Clomid: The landmark NICHD RCT (Legro 2014, NEJM) demonstrated letrozole produces higher ovulation and live birth rates than clomiphene in PCOS, with fewer multiple pregnancies.
• Inositol improves IVF outcomes: Meta-analyses show improved oocyte quality, lower gonadotropin requirements, and better fertilization rates.
• Weight loss of 5-10% can restore ovulation in overweight women with PCOS — often this alone is sufficient.
• Progesterone support: PCOS women who do ovulate often have inadequate luteal phase progesterone. Consider bioidentical progesterone (200mg vaginal or oral) in the luteal phase.
• Monitor thyroid: Subclinical hypothyroidism (TSH >2.5 in fertility context) impairs ovulation and increases miscarriage risk. Optimize before conception.

The Bigger Picture

PCOS is not a life sentence. It is a signal — from the body’s metabolic and hormonal terrain — that something in the environment, diet, stress load, or gut ecosystem is out of balance. The functional medicine approach does not suppress symptoms with synthetic hormones. It asks why the system is producing excess androgens, and it addresses the upstream drivers: insulin, inflammation, stress, toxins, and gut health.

When you resolve the root cause, the ovaries remember what they were built to do.