Estrogen, Diabetes, and Endothelial Function

Not Applicable

Completed

• Conditions: Type 1 Diabetes
• Interventions: Drug: Cetrorelix acetate, 0.25 mg/day; Drug: Estradiol Patch, 0.025 Mg/24 Hours Weekly Transdermal Film, Extended Release; Drug: Placebo patch

• Registration Number: NCT04418908
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study Start: 2010-11-24
• Primary Completion: 2018-10-22
• Study Completion: 2018-10-22
• Study First Submitted: 2020-05-26
• Status Verified: 2020-06
• Study First Submitted QC: 2020-06-02
• Last Update Submitted: 2020-06-02
• Study First Posted: 2020-06-05
• Last Update Posted: 2020-06-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 40

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%

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GnRHant + E2	Cetrorelix acetate, 0.25 mg/day	Participants in this arm received GnRHant and a transdermal estradiol patch (0.075 mg/day) for a period of 1 week.
GnRHant + E2	Estradiol Patch, 0.025 Mg/24 Hours Weekly Transdermal Film, Extended Release	Participants in this arm received GnRHant and a transdermal estradiol patch (0.075 mg/day) for a period of 1 week.
GnRHant + PL	Cetrorelix acetate, 0.25 mg/day	Participants in this arm received GnRHant and a placebo patch for a period of 1 week.
GnRHant + PL	Placebo patch	Participants in this arm received GnRHant and a placebo patch for a period of 1 week.

Primary Outcome Measures

Name	Time	Method
Flow-mediated dilation (FMD) at follow-up	1 week	FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.
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
Flow-mediated dilation (FMD) at baseline	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.
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