Alterations in the Menstrual Cycle as a Peculiar Sign of Type 1 Diabetes Mellitus: A Meta-analytic Approach

Background: Menstrual irregularities are present in >30% of women with type 1 diabetes mellitus (T1DM). These abnormalities will likely lead to reduced fertility and earlier menopause. T1DM management has changed over time, with even more emphasis on stringent levels of glycemic control. Thus, we investigated whether therapeutic T1DM changes have an influence on the proportion of menstrual disorders in women with T1DM. Methods: A meta-analysis was performed that included clinical trials in which menstrual abnormalities in women with T1DM were studied. The literature was checked for studies in which women with T1DM were compared with healthy, age-matched controls. Case-control, cohort, and cross-sectional studies were included. The primary endpoint was rate of menstrual dysfunction. Results: Menstrual dysfunction was higher in women with T1DM compared with controls (odds ratio 2.08, 95% confidence interval [CI] 1.43 to 3.03, p<0.001), even when sensitivity analysis was performed, considering only studies published after 2000. The age at menarche was higher for women with T1DM compared with controls (mean difference 0.53, 95% CI 0.32 to 0.74 year, p<0.001). The proportion of menstrual abnormalities in T1DM was inversely related to diabetes duration, but was unrelated to both body mass index and glycated hemoglobin. Conclusions: The meta-analytic approach used confirmed the correlation between T1DM and menstrual irregularities. T1DM menstrual dysfunction seemed unrelated to change in therapeutic management across years, as well as to glycemic control and body weight. The underlying pathogenetic mechanisms are not fully understood.