Menstrual Dysfunction in Girls From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study

J Clin Endocrinol Metab. 2018 Jun 1;103(6):2309-2318. doi: 10.1210/jc.2018-00132.


Context: Little is known about reproductive function in girls with youth-onset type 2 diabetes.

Objectives: To characterize girls with irregular menses and effects of glycemic treatments on menses and sex steroids in the Treatment Options for Type 2 Diabetes in Youth (TODAY) study.

Design: Differences in demographic, metabolic, and hormonal characteristics between regular- vs irregular-menses groups were tested; treatment group (metformin with or without rosiglitazone, metformin plus lifestyle) effect on menses and sex steroids over time in the study was assessed. This is a secondary analysis of TODAY data.

Setting: Multicenter study in an academic setting.

Patients: TODAY girls not receiving hormonal contraception and those at least 1-year postmenarche were included. Irregular menses was defined as three or fewer periods in the prior 6 months.

Results: Of eligible participants with serum measurement of sex steroids (n = 190; mean age, 14 years), 21% had irregular menses. Those with irregular vs regular menses had higher body mass index (BMI) (P = 0.001), aspartate aminotransferase (AST) (P = 0.001), free androgen index (P = 0.0003), and total testosterone (P = 0.01) and lower sex hormone-binding globulin (SHBG) (P = 0.004) and estradiol (P = 0.01). Differences remained after adjustment for BMI. There was no treatment group effect on menses or sex steroids at 12 or 24 months, and no association of sex steroids was seen with measures of insulin sensitivity or secretion.

Conclusions: Menstrual dysfunction is common in girls with recently diagnosed type 2 diabetes and associated with alterations in sex steroids, SHBG, and AST but not with alteration in insulin sensitivity or β-cell function and did not improve with 2 years of antihyperglycemic treatment.

Trial registration: NCT00081328.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Androgens / blood
  • Aspartate Aminotransferases / blood
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Therapy, Combination
  • Estradiol / blood
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin Resistance / physiology*
  • Life Style
  • Menstruation Disturbances / blood
  • Menstruation Disturbances / complications*
  • Metformin / therapeutic use
  • Rosiglitazone / therapeutic use
  • Sex Hormone-Binding Globulin / metabolism
  • Testosterone / blood


  • Androgens
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sex Hormone-Binding Globulin
  • hemoglobin A1c protein, human
  • Rosiglitazone
  • Testosterone
  • Estradiol
  • Metformin
  • Aspartate Aminotransferases

Associated data