Estrogen, Diabetes, and Endothelial Function

Vascular Disease, Inflammation and Hormones in Women With Type 1 Diabetes

This study planned to learn more about women and how the drop in estradiol levels during menopause may affect their cardiovascular risk. With aging, the arteries that are located around the heart get stiffer, and this increase in arterial stiffness can lead to a number of health problems such as high blood pressure and heart disease. In this study, the investigators examined whether a short-term drop in estrogen levels caused arteries to become stiffer, and explored potential reasons for stiffening arteries.

Participants completed two study visits. The baseline study visit occurred during the early follicular phase of the menstrual cycle, confirmed via take-home ovulation testing. On the day of the baseline study visit, all participants underwent ovarian sex hormone suppression with GnRHant therapy (cetrorelix acetate, 0.25 mg/day) delivered daily as subcutaneous injections for a 1-week period. Participants were randomized to one of two concurrent intervention groups: transdermal estradiol patch (0.075 mg/day) (+E2) or placebo patch (+PL) and returned for a follow-up visit after 1 week of the intervention. Both study visits included collection of anthropometric measures, a fasting blood sample, measures of arterial stiffness, flow-mediated dilation, and endothelial cells via an intravenous catheter.

Inclusion Criteria:

• Premenopausal
• Euthyroid
• Not currently planning to become pregnant
• Not currently breastfeeding
• No recent history of amenorrhea in the previous 6 months
• Consent to data and specimen banking
• No use of hormonal contraceptives

Inclusion Criteria, type 1 diabetes only:

• Diagnosis of type 1 diabetes for at least 5 years
• On insulin within a year of diagnosis
• Current insulin therapy
• Hemoglobin A1c < 9.5%
• No macroalbuminuria (AER < 200 ug/min)

Inclusion Criteria, non-diabetic controls only:

• Hemoglobin A1c < 5.7%

Exclusion Criteria:

• Pregnant and/or breastfeeding
• Have not had a menstrual cycle in the last 6 months