Effect of metformin on clinical and biochemical hyperandrogenism in adolescent girls with type 1 diabetes

J Pediatr Endocrinol Metab. 2019 May 27;32(5):461-470. doi: 10.1515/jpem-2018-0430.


Background Hyperandrogenism with or without polycystic ovarian syndrome is seen in adolescents with type 1 diabetes (T1D), especially those with suboptimal control. Objective To assess the effect of metformin on hyperandrogenism and ovarian function in adolescents with T1D. Methods This prospective study included 28 T1D females showing signs of hyperandrogenism. History taking (detailed diabetes history and menstrual history) and anthropometric measurements (weight, height, body mass index [BMI], waist and hip circumference) were initially performed, and then the patients were assessed for the manifestations of hyperandrogenism (acne, hirsutism as well as pelvic ultrasound [U/S] for ovarian morphology). Biochemical evaluation for ovulation (progesterone assessment during the luteal phase), sex steroids (estradiol, testosterone, dehydroepiandrosterone sulfate [DHEAS] and androstenedione), prolactin, glycemic control (hemoglobin A1c [HbA1c]) and gonadotropin levels (follicle stimulating hormone [FSH] and luteinizing hormone [LH]) was done. Patients were subjected to 500 mg metformin twice daily orally for 1 year, and then the patients were re-evaluated for clinical and biochemical parameters. Results Metformin therapy resulted in a significant reduction in weight (p = 0.001), BMI (p = 0.002), acne (p = 0.008), hirsutism score (0.007), LH (p = 0.008), testosterone (p < 0.001) and androstenedione levels (p = 0.028) in adolescent girls with T1D. Regarding menstrual irregularities, there was a significant reduction in the number of patients with oligomenorrhea (68%) with a p value of <0.001. However, there were no significant reduction in the daily insulin requirements (p = 0.782) or HbA1c (p = 0.068). Nausea and/or abdominal pain were the commonly reported side effects of metformin (64%). Conclusions Metformin as an insulin sensitizing agent improved the BMI and cycle regularity together with clinical and biochemical hyperandrogenism in T1D adolescent girls. However, it did not improve their glycemic control.

Keywords: adolescent girls; hyperandrogenism; metformin; polycystic ovary syndrome; type 1 diabetes.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis*
  • Child
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperandrogenism / chemically induced*
  • Hypoglycemic Agents / adverse effects*
  • Metformin / adverse effects*
  • Prognosis
  • Prospective Studies
  • Young Adult


  • Biomarkers
  • Hypoglycemic Agents
  • Metformin