Longitudinal Study of Insulin Resistance and Sex Hormones over the Menstrual Cycle: The BioCycle Study

Context: Conflicting findings have been reported regarding the effect of menstrual cycle phase and sex hormones on insulin sensitivity. Objective: The aim was to determine the pattern of insulin resistance over the menstrual cycle and whether variations in sex hormones explain these patterns. Design: The BioCycle study is a longitudinal study that measured hormones at different phases of the menstrual cycle. Participants had up to eight visits per cycle; each visit was timed using fertility monitors to capture sensitive windows of hormonal changes. Setting: The study was conducted in the general community of the University at Buffalo (Buffalo, NY). Participants: A total of 257 healthy, premenopausal women (age, 27 +/- 8 yr; body mass index, 24 +/- 4 kg/m(2)) participated in the study. Main Outcome Measures: We measured fasting insulin, glucose, and insulin resistance by the homeostasis model of insulin resistance (HOMA-IR). Results: Significant changes in HOMA-IR were observed over the menstrual cycle; from a midfollicular phase level of 1.35, levels rose to 1.59 during the early luteal phase and decreased to 1.55 in the late-luteal phase. HOMA-IR levels primarily reflected changes in insulin and not glucose. After adjustment for age, race, cycle, and other sex hormones, HOMA-IR was positively associated with estradiol (beta = 0.082; P < 0.001) and progesterone (beta = 0.025; P < 0.001), and inversely associated with FSH (adjusted beta = -0.040; P < 0.001) and SHBG (beta = -0.085; P < 0.001). LH was not associated with HOMA-IR. Further adjustment for BMI weakened the association with SHBG (beta = -0.057; P = 0.06) but did not affect other associations. Conclusion: Insulin exhibited minor menstrual cycle variability. Estradiol and progesterone were positively associated with insulin resistance and should be considered in studies of insulin resistance among premenopausal women. (J Clin Endocrinol Metab 95: 5435-5442, 2010)