Sustained Metabolic Improvements with Low-Dose Metformin Combined with Oral Contraceptives in Female Adolescents with PCOS: A Single-Center Retrospective Cohort Study

Abstract

Introduction: This study aimed to evaluate metformin treatment's immediate and long-term efficacy in adolescent patients with polycystic ovary syndrome (PCOS) and hyperinsulinemia and the subsequent metabolic evolution post-treatment discontinuation.

Methods: This single-center, retrospective cohort study included 168 adolescent girls (12-17 years) diagnosed with PCOS between December 2018 and August 2024. All participants underwent an oral glucose tolerance test to evaluate insulin sensitivity and were stratified into two groups: patients with normal insulinemia (n = 21) and patients with hyperinsulinemia (n = 147). Patients with hyperinsulinemia were offered low-dose metformin (500 mg twice daily); 80 accepted and formed the treatment arm, while 53 declined and served as controls. Simultaneously, every subject received a continuous regimen of combined oral contraceptives (COCs) (30 µg ethinyl estradiol/3 mg drospirenone). Clinical, biochemical, and ultrasound assessments were conducted at baseline, at regular intervals during therapy, at the end of treatment, and at least 24 months after metformin discontinuation to evaluate immediate and long-term outcomes.

Results: Metformin therapy yielded favorable body mass index, insulin sensitivity, and androgenic profile outcomes. Remarkably, these benefits persisted beyond the cessation of treatment. Metformin responders showed a ≥ 20% decrease in the insulin area under the curve values post-treatment. Our investigation revealed a substantial reduction in insulin resistance indices, evident both after therapy (p < 0.001) and during post-therapy follow-up (p = 0.001) compared to baseline values. Furthermore, patients showed improvements in clinical hyperandrogenism and reductions in ovarian volume.

Conclusions: Our study highlights the effectiveness of low-dose metformin therapy in improving insulin resistance and metabolic parameters among adolescent patients with PCOS. Sustained benefits were observed even after treatment cessation. These findings underscore the potential for early intervention with metformin during adolescence to confer long-lasting advantages in managing metabolic abnormalities associated with PCOS.

Keywords: Adolescents; Hyperandrogenism; Insulin; Insulin resistance; Metformin; Ovary; PCOS.

Fig. 1

Study enrollment flow chart. PCOS polycystic ovary syndrome, OGTT oral glucose tolerance test, COCs combined oral contraceptives

Fig. 2

Area under the curve (AUC) values at baseline (b-AUC), at the end of therapy (e-AUC), and after the end of treatment (ae-AUC)