MON-176 Impact of Pharmacotherapy on Metabolic Health in Adolescents with PCOS: Findings from the Clinical Adolescent Polycystic Ovary (CALICO) Database

Abstract Disclosure: C.M. Burt Solorzano: None. H. Vanden Brink: None. T. Vigers: None. G. Carey: None. M. Garant: None. A.B. Sopher: None. R. Shah: None. C. Branstetter: None. A. Coren: None. L.C. Torchen: None. J. Snell-Bergeon: None. D.H. Geller: None. M.G. Cree: None. T. CALICO Consortium: None. Introduction: PCOS is a prevalent endocrinopathy characterized by anovulation and hyperandrogenism in adolescence with increased risk of comorbidities, such as insulin resistance, Type-2 Diabetes, and Metabolic Dysfunction–Associated Steatotic Liver Disease. Estrogen-containing contraceptives (EC) and metformin are recommended therapies for PCOS, but their metabolic impact in youth is unclear. This longitudinal analysis studied the effect of EC and metformin on adolescent PCOS metabolic outcomes.Methods: Participant data (n=899) was extracted from the CALICO Database, which represents 17 US sites of adolescents with PCOS diagnosed using the 2018 international guidelines. Participants taking weight loss, continuous progesterone-only, or atypical antipsychotic medications were excluded. Outcomes were High Density Lipoprotein (HDL), Triglycerides (TG), alanine aminotransferase (ALT), HbA1c, and Systolic Blood Pressure (SBP). Linear mixed effects models evaluated the differences in metabolic outcomes over time between Ever EC Users (pill, patch, or ring, n=458) vs Never EC Users (n=441) and Ever Metformin Users (n=503) vs Never Metformin Users (n=396). All models were adjusted for age, race, and insurance status. EC models were adjusted for metformin use, and vice versa. Full models were adjusted for baseline weight; secondary models were conducted by weight subgroup (BMI 5-84%, BMI 85-94%, BMI ≥95%). Analyses were performed using R version 4.4.2. Results: No differences in trajectory of HbA1c, ALT, or SBP were observed between EC users vs non-users (p>0.05). EC users experienced greater increase in HDL over time versus non-users (0.05 [-0.03, 0.13] mg/dL/month vs -0.04 [-0.11, 0.04] mg/dL/month, P=0.03). For metformin-users vs non-users, no differences in trajectory of HbA1c, ALT, SBP, or HDL were observed (P>0.05). Metformin use was associated with a greater increase in TG over time versus non-users (0.68 [0.08, 1.28] vs 0.08 [-0.45, 0.60], P=0.03). When evaluating data by BMI category, HDL increased more slowly over time in metformin users with a BMI 85-94% versus non-users (0.35 [-0.16, 0.86] vs 0.61 [0.09, 1.12] mg/dL/month, P=0.01]). HDL also increased over time in EC users with BMI ≥ 95% versus non-users (0.11 [0.02, 0.19] vs 0.01 [-0.02, 0.19] mg/dL/month, P=0.025). Individuals with BMI 5-84% showed no differences in metabolic outcomes in medication users vs non-users.Conclusions: EC and metformin use were associated with different lipid trajectories among adolescents with PCOS, which varied by BMI. Use of estrogen-containing medications may be beneficial in adolescents for PCOS to increase HDL, particularly among adolescents with obesity. Any use of metformin or ECs did not significantly affect the trajectory of glycemic control, liver function, or blood pressure outcome measures when compared to never users, even in those with elevated BMI. Presentation: Monday, July 14, 2025