How is insulin level managed in Polycystic Ovary Syndrome (PCOS)?

Management of Insulin Levels in PCOS

All women with PCOS should be screened for insulin resistance and glucose intolerance with a fasting glucose level followed by a 2-hour oral glucose tolerance test after a 75-gram glucose load, and insulin resistance should be managed primarily through lifestyle modification as first-line therapy, with metformin as the preferred pharmacologic agent when medication is needed. 1, 2

Screening and Assessment

Screen every PCOS patient for metabolic dysfunction regardless of body weight, as insulin resistance occurs independent of BMI and affects both lean and overweight women. 1

• Obtain fasting glucose followed by 2-hour glucose level after 75-gram oral glucose load to detect type 2 diabetes and glucose intolerance 1, 2
• Measure fasting lipid profile including total cholesterol, LDL, HDL, and triglycerides, as insulin resistance drives dyslipidemia with elevated triglycerides, increased small dense LDL, and decreased HDL 1, 3
• Calculate BMI and waist-hip ratio to assess central obesity 1
• Look for acanthosis nigricans on physical exam (darkened, velvety skin patches in body folds), which indicates underlying insulin resistance 1, 2, 3

The oral glucose tolerance test is the most practical office-based method to assess insulin resistance while simultaneously detecting glucose intolerance, which carries greater prognostic and treatment implications than insulin resistance alone. 4

First-Line Management: Lifestyle Intervention

Initiate multicomponent lifestyle intervention before or concurrent with any pharmacologic therapy, as this is the foundation of the treatment hierarchy. 1

• Target weight loss of just 5% of initial body weight, which improves metabolic parameters, ovulation rates, and pregnancy outcomes 2
• Implement diet, exercise, and behavioral strategies together rather than any single component 1
• Emphasize regular exercise and weight control measures before considering drug therapy for dyslipidemia 1

The 2018 international evidence-based guideline established lifestyle management as first-line treatment with strong evidence supporting multicomponent interventions, though no specific diet is recommended over others. 1

Pharmacologic Management: Insulin-Sensitizing Agents

Use metformin as the preferred insulin-sensitizing agent when pharmacologic intervention is warranted, despite lack of FDA approval specifically for PCOS. 1, 2, 3

Metformin Benefits and Mechanism

• Improves insulin sensitivity by decreasing hepatic glucose production, decreasing intestinal glucose absorption, and increasing peripheral glucose uptake 5
• Decreases circulating androgen levels through improved insulin sensitivity 1
• Improves or maintains glucose tolerance over time 1
• Improves ovulation rates and metabolic outcomes 1, 2, 3
• Tends to decrease weight, unlike thiazolidinediones which increase weight 1

Metformin Dosing and Pharmacokinetics

• Typical dosing is 500 mg three times daily, titrated as needed 6
• Steady-state plasma concentrations reached within 24-48 hours 5
• Approximately 90% eliminated via renal route within 24 hours with plasma half-life of 6.2 hours 5
• Not metabolized hepatically and excreted unchanged in urine 5

Important Caveats About Insulin-Sensitizing Therapy

The severity of insulin resistance varies considerably in PCOS, with approximately 50-70% of women affected. 4, 7 Treatment should target specific metabolic or reproductive problems rather than universal application, as milder phenotypes may not require insulin-sensitizing drugs. 7

The role of insulin-sensitizing agents in primary or secondary prevention of cardiovascular disease in PCOS remains unknown, though metformin may reduce long-term diabetes risk. 1, 8

Integration with Other PCOS Treatments

When managing women not attempting conception, combination oral contraceptive pills remain first-line for menstrual regulation and androgen suppression, but be aware they may increase triglycerides and HDL cholesterol despite no evidence of increased cardiovascular events compared to the general population. 1, 2, 3

For fertility treatment, metformin can improve spontaneous or clomiphene-induced ovulation independently of weight loss by reducing ovarian 17α-hydroxyprogesterone production. 6

Common Pitfalls

• Do not assume all PCOS patients have clinically significant insulin resistance requiring pharmacologic treatment—assess severity and target specific metabolic or reproductive problems 7
• Do not overlook acanthosis nigricans, as it may indicate associated insulinoma or malignancy, particularly gastric adenocarcinoma 1
• Do not use thiazolidinediones as first-line agents given their tendency to increase weight and variable risk-benefit profiles compared to metformin 1
• Do not skip lipid screening—insulin resistance in PCOS creates a particularly atherogenic lipid profile requiring monitoring 1