BACKGROUND: Circulating concentrations of estrogen throughout the menstrual cycle contribute to the cyclic increase in vascular function in healthy women. Evidence in animals; however, has identified a vasoconstrictive role of estrogen in the presence of diabetes. The present investigation sought to determine the role of estrogen throughout the menstrual cycle on vascular function and the impact of hormonal birth control (HBC) on vascular function in premenopausal women with type 1 diabetes (T1D). METHODS: 33 women with T1D (HbA1c =8.5±1.7%, age=26±8 years, BMI=27.1±5.6 kg/m2 ) and 20 healthy women (HbA1c =5.2±0.3%, age=25±7 years, BMI=23.9±3.8 kg/m2 ) participated in this study. A subgroup of 9 women with T1D taking oral HBC (HbA1c =8.3±2.1%, age=25±7 years, BMI=29.0±6.4 kg/m2 ) and 9 demographically matched women with T1D not taking HBC (HbA1c =8.3±2.1%, age=23±6 years, BMI=25.7±5.0 kg/m2 ), was then analyzed. In all participants, a venous blood sample was collected to determine circulating concentrations of estrogen. Flow-mediated dilation (FMD), the gold standard for measuring endothelial function non-invasively, was performed during menses and the late follicular phase of the menstrual cycle to represent periods of low and high estrogen, respectively. Menses was confirmed by a positive hemolytic urological multistix test, and the late follicular day was determined using an ovulation predictor kit for those not on HBC. For those on HBC, baseline was conducted during their placebo week, and the "late follicular" day was conducted during the second week of the HBC pills. RESULTS: A similar increase was observed in estrogen from menses to late follicular in both the T1D and control group. (Δ estradiol: T1D=74.5±85.4 pg/mL, controls= 88.2±79.1 pg/mL, p=0.561). A significant interaction (p=0.044) was observed between FMD across the menstrual cycle. Specifically, FMD was significantly greater (p=0.043) during late follicular phase in controls compared to T1D, albeit having a similar (p=0.666) FMD during menses. Within the subgroup analysis, there was no interaction between FMD and menstrual cycle between both T1D groups (p=0.555); however, there was a significant (p=0.04) menstrual cycle phase main effect indicating that vascular function overall was greater in women with T1D on HBC compared to women with T1D not on HBC. CONCLUSION: These data suggest that estrogen decreases vascular function in the presence of diabetes. In addition, HBC may reduce cardiovascular disease risk in premenopausal women with T1D.