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

Abstract

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: ClinicalTrials.gov NCT00081328.

Figures

Figure 1.

CONSORT (Consolidated Standards of Reporting Trials) diagram for inclusion in analysis.

Figure 2.

Free androgen index at randomization by menstrual status in female youth with type 2 diabetes in the TODAY study: 39 girls with irregular menses and 151 girls with regular menses at randomization. There was a high frequency of elevated free androgen index (>6) in both groups, despite treatment with metformin for at least 2 months during the run-in period.

Figure 3.

Menstrual irregularity at annual visits. Proportion of TODAY girls not receiving hormonal contraception with irregular menses at baseline, 12 months, and 24 months. Prevalence of irregular menses over time did not significantly differ (P = 0.10). There was also no significant treatment effect on menstrual irregularity (data not shown; P = 0.60)

Figure 4.

Mean sex steroid levels at annual visits overall and by treatment group. In the overall cohort, there was a significant increase in testosterone (P = 0.0095), SHBG (P = 0.0017), and estradiol (P = 0.001) across treatment visits, but there were no effects of treatment group on sex steroids or SHBG over time. Blue lines, metformin only; red lines, metformin plus rosiglitazone; green lines, metformin plus lifestyle; black lines, overall.