Plasma insulin concentration in newborns and children and age at menarche

OBJECTIVE: To investigate the association of plasma insulin levels and their trajectories from birth to childhood with the timing of menarche. 

RESEARCH DESIGN AND METHODS: This prospective study included 458 girls recruited at birth between 1998 and 2011 and followed prospectively at the Boston Medical Center. Plasma non-fasting insulin concentrations were measured at two time points: at birth (cord blood) and in childhood (age 0.5-5 years). Age at menarche was obtained from a pubertal developmental questionnaire or abstracted from electronic medical records. 

RESULTS: 306 (67%) of the girls had reached menarche. The median (range) age at menarche was 12.4 (9-15) years. Elevated plasma insulin concentrations at birth (n=391) and in childhood (n=335) were each associated with an earlier mean age at menarche: approximately 2 months earlier per doubling of insulin concentration (mean shift, -1.95 months, 95%CI, -0.33 to -3.53 and -2.07 months, 95%CI, -0.48 to -3.65), respectively. Girls with overweight or obesity in addition to elevated insulin attained menarche about 11-17 months earlier on average than those with normal weight and low insulin. Considering longitudinal trajectories (n=268), having high insulin levels at both birth and childhood was associated with a roughly 6 months earlier mean age at menarche (mean shift, -6.25 months, 95%CI, -0.38 to -11.88), compared with having consistently low insulin levels at both timepoints. 

CONCLUSIONS: Our data showed that elevated insulin concentrations in early life, especially in conjunction with overweight or obesity, contribute to the earlier onset of menarche, suggesting the need for early screening and intervention.