Abstract 3496: Sex Hormone Levels differ in Pre-Menopausal Women with Type 1 Diabetes Compared to Women without Diabetes, and are Associated with Coronary Artery Calcium Progression
Type 1 diabetes (T1D) increases Coronary Artery Disease (CAD) risk, and pre-menopausal (PreM) women with T1D appear to lose their natural protection against CAD. We hypothesize that this may be mediated by lower estrogen and higher testosterone levels in women with T1D, who report more menstrual dysfunction than women without diabetes (non-DM). The purpose of this study was to determine whether sex hormone levels differ by T1D status, and if sex hormones are associated with coronary artery calcification (CAC) progression - a marker of severity of subclinical CAD. Study participants were 311 PreM women (160 T1D, 151 non-DM) who completed two study visits, on average 2.5 ± 0.4 years apart. Sex hormone levels by menstrual cycle phase (MCP) are shown in the table⇓. Total testosterone (T) was 9.6 ng/dl higher (p = 0.002), sex hormone binding globulin (SHBG) was 41 nmol/l higher (p < 0.001), and free estradiol index (FEI, calculated free estradiol) was 0.32 lower (p = 0.006) in T1D women compared to non-DM women, adjusted for age, BMI, and MCP. In logistic regression, progression of CAC was inversely associated with FEI (Standardized OR [95% CI], 0.43 [0.25– 0.77], p = 0.004) and positively associated with SHBG (1.8 [1.2–2.6], p = 0.006) and FSH (1.7 [1.1–2.6], p = 0.02), adjusted for age, baseline CAC, follow-up time and MCP. Adjustment for FEI and SHBG each significantly attenuated the association between T1D and progression of CAC (OR 3.9 vs. 2.8, p = 0.002 and OR 3.9 vs. 2.3, p = 0.004, respectively). In conclusion, sex hormone levels differ significantly by T1D status across the menstrual cycle. Women with T1D have higher T and similar estradiol, but higher SHBG results in a similar mean free androgen index (FAI) and lower FEI compared to non-DM women. Lower FEI and higher SHBG were associated with CAC progression. These results suggest that PreM women with T1D are more likely to be free estrogen deficient due to increased SHBG than non-DM women, possibly explaining part of their increased CAD risk.