Overview

This trial is active, not recruiting.

Condition insulin resistance
Treatment estradiol
Sponsor University of Colorado, Denver
Collaborator National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Start date September 2011
End date August 2016
Trial size 55 participants
Trial identifier NCT01605071, 11-0788, R01DK088105

Summary

The aim of the current study is to test whether the effect of estrogen on insulin metabolism depends on the timing of treatment relative to when a woman went through menopause. The investigators hypothesize that estrogen will improve insulin sensitivity in early postmenopausal women, but decrease insulin sensitivity in late postmenopausal women.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model crossover assignment
Masking single blind (subject)
Arm
(Active Comparator)
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
estradiol Climara
1 week of transdermal estradiol (0.15mg) 1 week of transdermal placebo
(Active Comparator)
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
estradiol Climara
1 week of transdermal estradiol (0.15mg) 1 week of transdermal placebo

Primary Outcomes

Measure
insulin-mediated glucose disposal rate (hyperinsulinemic-euglycemic clamp)
time frame: after 1wk estradiol or placebo

Secondary Outcomes

Measure
fat and muscle estrogen receptor expression
time frame: after 1wk estradiol or placebo
24hr glycemic profile (continuous glucose monitoring)
time frame: after 1wk estradiol or placebo

Eligibility Criteria

Female participants from 45 years up to 70 years old.

Inclusion Criteria: - aged 45-70 yr - postmenopausal (no menses ≥12 mo or bilateral oophorectomy and FSH >30 IU/L) - ≤6yrs or ≥10yrs of menopause (last menses or oophorectomy) - BMI <30 kg/m2 and weight stable (±2kg in past 2mo) - non-smokers - sedentary to moderately active (<3 days/wk of structured exercise) - naïve to estrogen-based hormone therapies (previous use ≤6 months) - CBC, CMP and TSH values within normal ranges specified by lab Exclusion Criteria: - underwent a partial hysterectomy (i.e., one or both ovaries left intact) - underwent menopause (natural, chemical, or surgical) prior to age 45yr - are between >6yr and <10yr of menopause (last menses or oophorectomy) - previously used (>6 mo) or are currently using any formulation of estrogen-based HT (e.g., oral Premarin, transdermal 17beta-estradiol, selective estrogen receptor modulators) - have T2DM or are being treated with glucose-lowering/ insulin sensitizing medications - have uncontrolled hypertension (SBP>140 and/or DBP>90 mmHg) - have hypertriglyceridemia (>400 mg/dL) - have contraindications to estrogen therapy (history of venous thromboembolism, heart disease, myocardial infarction, hormone sensitive cancer) - have contraindications to biopsies (severe anemia, blood clotting disorders)

Additional Information

Official title Time Past Menopause, Duration of Estrogen Deficiency, and Insulin Action
Principal investigator Rachael E Van Pelt, PhD
Description Large clinical trials have shown a reduced incidence of type 2 diabetes in postmenopausal women randomized to estrogen-based hormone therapy compared to placebo. Moreover, studies suggest development of diabetes is reduced in postmenopausal women who used hormone therapy for a part of the postmenopausal period compared to women who never used hormone therapy. Consistent with this, our preliminary data suggest that the timing of estrogen treatment relative to the menopause may be an important determinant of whether there are favorable effects on insulin action. Our observations suggest that estrogen improves insulin sensitivity in early postmenopausal women, but may decrease insulin sensitivity in those more than 10 years past menopause. More and more studies suggest estrogens have divergent effects on cardiovascular risk when initiated close to the onset of menopause rather than distant from the menopause; we hypothesize this is also true for diabetes risk. The goal of this study is to determine whether the effects of estrogen on insulin metabolism are different in women who are early postmenopausal compared to late postmenopausal. To meet our goal, we propose to measure insulin sensitivity in women who are within 6 years of the onset of menopause or more than 10 years beyond the menopause and who have not used hormone therapy previously. All women will be studied on two separate occasions, one day with and one day without short-term (1 week) treatment with transdermal estradiol. We expect that estradiol will increase insulin sensitivity in early postmenopausal women and decrease insulin sensitivity in late postmenopausal women. We also expect that estrogen receptors in fat and muscle may change with increasing time after menopause. Thus, we will collect fat and muscle biopsies to compare changes in estrogen receptors between early and late postmenopausal women and in response to 1 week of estradiol treatment. We believe these studies will provide evidence for a benefit of estradiol on insulin sensitivity when administered early, but not late, after menopause; likely contributing to delayed onset of type 2 diabetes in postmenopausal women.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by University of Colorado, Denver.