Cassar · Human reproduction (Oxford, England) 2016 · systematic review and meta-analysis · n=28 studies

Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies.

Cited 403 times in the scientific literature.

Level 3 - non-randomized controlled study

Systematic review and meta-analysis of observational/case-control studies

PubMed 27907900 · doi:10.1093/humrep/dew243 · record verified 2026-08-29

What was done

A systematic review and meta-analysis following PRISMA guidelines was conducted across Medline and All EBM databases through May 30, 2015. Eligible studies compared premenopausal women diagnosed with polycystic ovary syndrome (PCOS) to control groups for insulin sensitivity (IS) measured using the gold-standard euglycaemic-hyperinsulinaemic clamp. Analysis utilized mixed modeling and magnitude-based inferences, reporting mean effect ± 99% CI against standardisation thresholds of -3.7% or 3.8%.

What was found

From 4,881 retrieved articles, 28 studies were included. Overall IS was lower in women with PCOS compared to controls (mean effect -27%, 99% CI ±6%; large, most likely lower). A higher BMI further worsened the reduction in IS by -15% (99% CI ±8%; moderate, most likely lower) in PCOS compared to control women. IS did not clearly differ between women diagnosed by original NIH criteria versus Rotterdam criteria. Low sex hormone-binding globulin (SHBG) was associated with reduced IS (-10%, 99% CI ±10%; small, very likely negative), unaffected by BMI confounding.

Why it matters

Using gold-standard clamp technique, this study confirms that insulin resistance is an inherent feature of PCOS independent of adiposity, while showing that elevated BMI further compounds this metabolic deficit.

Limits

The review inherited limitations from primary literature, including small sample sizes in individual studies, missing data (such as specific hormone measurements, waist and hip circumferences), and a lack of reporting on specific Rotterdam criteria phenotypes. Total participant numbers across the 28 included studies were not provided in the abstract.

Cited by