Menstrual Dysfunction Is Associated With Elevated Liver Enzymes in Adolescent Females: A United States Population-Based Study.

PURPOSE: Polycystic ovary syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD) both emerge during adolescence; however, it remains unknown whether menstrual abnormalities and hyperandrogenism signals increased hepatic risk.

METHODS

We analyzed 2011-2020 National Health and Nutrition Examination Survey data for 1,651 females aged 12-19 years in the United States who were at least 2 years postmenarche. Amenorrhea was defined as self-reported absence of menses in the past 12 months. Biochemical hyperandrogenism was defined as free androgen index ≥5. Elevated alanine aminotransferase (ALT; >22 U/L) was the primary hepatic outcome; suspected MASLD was defined as elevated ALT plus ≥1 cardiometabolic risk factor. Survey-weighted logistic regression models adjusted for age, race and ethnicity, and body mass index (BMI) percentile.

RESULTS

Amenorrhea was reported by 2.8% of participants and was associated with higher odds of elevated ALT (adjusted odds ratio 2.5, 95% confidence interval 1.1-5.7). Biochemical hyperandrogenism was also associated with elevated ALT (adjusted odds ratio 2.6, 95% confidence interval 1.4-4.8). The positive association between insulin resistance and ALT was stronger among adolescents with amenorrhea (β = 2.7 vs. 1.1). Although ALT levels rose with increasing BMI, adolescents with amenorrhea had consistently higher ALT prevalence, including those with a normal BMI.

DISCUSSION: Amenorrhea and hyperandrogenism, hallmark features of polycystic ovary syndrome, are independently associated with elevated ALT and suspected MASLD in adolescent females. These findings support ALT screening for youth with menstrual dysfunction, even in the absence of obesity, to enable earlier detection and more integrated endocrine-hepatic care.