MASLD coexisting with PCOS increases cardiometabolic risk.
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BACKGROUND AND AIMS: In women in their reproductive years, metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) are the most common chronic liver and endocrine disorders, respectively. MASLD and PCOS are associated with longer-term risk of cardiometabolic complications. We aimed to determine whether PCOS coexisting with MASLD (PCOS + MASLD) predicts greater risk of future cardiometabolic adverse parameters than either condition alone after 10 years in a longitudinal study of adolescents in the Raine Study. METHOD: A total of 199 community-based female adolescents participating in the Raine Study had assessments for both PCOS and MASLD, including anthropometry, blood tests, and pelvic and abdominal ultrasound. Using updated diagnostic criteria, diagnoses of PCOS at age 14 years and MASLD at age 17 years, were retrospectively determined. At age 27 years, 148 participants had further anthropometry and cardiovascular and fasting blood assessments. RESULTS: At age 17 years, 37 (18.6%) had MASLD, 32 (16.1%) had PCOS, 20 (10.1%) had PCOS without MASLD, and 142 (71.4%) had neither. Among adolescents with PCOS, 12/32 (37.5%) had PCOS + MASLD, associated with obesity, higher serum remnant lipoprotein cholesterol, and free and total testosterone, but lower SHBG, compared with those with only MASLD, PCOS, or neither (P < .05 for all). By age 27 years, those with PCOS + MASLD (10/148) during adolescence were more insulin resistant and had higher serum remnant lipoprotein cholesterol and triglyceride/high-density lipoprotein cholesterol ratio (P < .05 for all), compared with those with only PCOS or MASLD or neither. PCOS without MASLD or obesity in adolescence did not predict future insulin resistance. CONCLUSION: PCOS + MASLD in adolescents, but not PCOS alone, increases the likelihood of obesity, insulin resistance and an adverse cardiometabolic phenotype during adulthood.