Type 1 Diabetes
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGPlacebo patch
Placebo patch designed to match active Climara patches.
DRUGCetrorelix acetate, 0.25 mg/day
All participants self-administered GnRHant daily between the baseline and follow-up visits (cetrorelix acetate, 0.25 mg/day).
DRUGEstradiol Patch, 0.025 Mg/24 Hours Weekly Transdermal Film, Extended Release
Active estradiol transdermal patch.
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants were randomized to either receiving a gonadotropin-releasing antagonist (GnRHant) with estradiol add-back (+E2) or placebo (+PL). Investigators and participants were blinded to randomization status until the study was completed.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow-mediated dilation (FMD) at baseline | 1 week | FMD will be measured following an intravenous saline infusion and ascorbic acid infusion. |
| Flow-mediated dilation (FMD) at follow-up | 1 week | FMD will be measured following an intravenous saline infusion and ascorbic acid infusion. |
| Change in flow-mediated dilation (FMD) | Baseline and 1 week | FMD will be measured following an intravenous saline infusion and ascorbic acid infusion at baseline and follow-up. |
| Quantitative immunuofluorescence of endothelial cell proteins at baseline | Baseline | Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells |
| Quantitative immunuofluorescence of endothelial cell proteins at follow-up | 1 week | Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells |
| Change in quantitative immunuofluorescence of endothelial cell proteins | Baseline and 1 week | Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells |
Outcome results
None listed