ELITE: Early Versus Late Intervention Trial With Estradiol

NCT ID: NCT00114517

Last Updated: 2023-01-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

643 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-07-31

Study Completion Date

2013-03-05

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to examine the effects of oral 17B-estradiol (estrogen) on the progression of early (subclinical) atherosclerosis and cognitive decline in healthy postmenopausal women.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The primary hypothesis to be tested is that 17B-estradiol (estrogen) will reduce the progression of early atherosclerosis if initiated soon after menopause when the vascular endothelium (lining of blood vessels) is relatively healthy versus later when the endothelium has lost its responsiveness to estrogen. Ultrasonography will be used to measure the rate of change in the thickness of the carotid artery and cardiac computed tomography (CT) will be used to measure coronary artery calcium and coronary artery lesions. The second hypothesis to be tested is that 17B-estradiol (estrogen) will reduce the progression of cognitive decline if initiated soon after menopause when healthy brain tissue remains responsive to estrogen versus later when brain tissue has lost its responsiveness to estrogen.

A total of 643 (actual; 504 initially proposed) postmenopausal women were randomized according to their number of years since menopause, less than 6 years or 10 years or more, to receive either oral 17B-estradiol 1 mg daily or matching placebo. Women with a uterus will also use vaginal progesterone gel 4% (or placebo gel) the last ten days of each month. The vaginal progesterone will be distributed in a double-blinded fashion along with the randomized treatment so that only women exposed to active treatment will receive active progesterone. As initially proposed, participants will undergo ultrasonography at baseline and every 6 months throughout the 2 to 5 years (average 3 years) of randomized treatment. Participants will also undergo cognitive testing at baseline and after 3 years of randomized treatment. The trial has been extended for an additional 2 to 2.5 years of randomized treatment (overall average randomized treatment of 5 years and range of 2 to 8.5 years). Ultrasonography will continue to be collected every 6 months and upon completion of randomized treatment, participants will undergo cardiac CT for coronary artery calcium and coronary artery lesion measurements. Participants will also undergo a third cognitive testing at the completion of randomized treatment.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Atherosclerosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

17B-estradiol

Oral 17B-estradiol 1 mg daily

Group Type ACTIVE_COMPARATOR

17B-estradiol

Intervention Type DRUG

Oral 17B-estradiol 1 mg daily

Placebo

Matching oral 17B-estradiol placebo daily

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matching oral 17B-estradiol placebo daily

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

17B-estradiol

Oral 17B-estradiol 1 mg daily

Intervention Type DRUG

Placebo

Matching oral 17B-estradiol placebo daily

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Estrace Estrogen Estrogen replacement therapy Hormone replacement therapy Hormone therapy Menopausal hormone replacement therapy Matching placebo

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Women with a serum estradiol level 25 pg/ml or less
* No period for 6 months or more
* Postmenopausal less than 6 years, OR 10 years or longer

Exclusion Criteria

* Clinical signs, symptoms, or personal history of cardiovascular disease
* Women who have had a hysterectomy only and no oophorectomy (since time from menopause cannot be determined)
* Diabetes mellitus or fasting serum glucose 140 mg/dL or greater
* Uncontrolled hypertension (diastolic blood pressure 110 mmHg or greater)
* Thyroid disease (untreated)
* Serum creatinine greater than 2.0 mg/dL
* Plasma triglyceride levels greater than 500 mg/dL
* Life threatening disease with prognosis less than 5 years
* Cirrhosis or liver disease
* History of deep vein thrombosis or pulmonary embolism
* History of breast cancer
* Current hormone replacement therapy (HRT)
Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Howard N. Hodis, M.D.

Harry J. Bauer and Dorothy Bauer Rawlins Professor of Cardiology, Professor of Medicine, Population and Public Health Sciences, and Molecular Pharmacology and Toxicology, Director, Atherosclerosis Research Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Howard N. Hodis, M.D.

Role: PRINCIPAL_INVESTIGATOR

Atherosclerosis Research Unit, University of Southern California

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Atherosclerosis Research Unit, University of Southern California

Los Angeles, California, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Hodis HN, Mack WJ, Shoupe D, Azen SP, Stanczyk FZ, Hwang-Levine J, Budoff MJ, Henderson VW. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis. Menopause. 2015 Apr;22(4):391-401. doi: 10.1097/GME.0000000000000343.

Reference Type BACKGROUND
PMID: 25380275 (View on PubMed)

Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, Li Y, Feng M, Dustin L, Kono N, Stanczyk FZ, Selzer RH, Azen SP; ELITE Research Group. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med. 2016 Mar 31;374(13):1221-31. doi: 10.1056/NEJMoa1505241.

Reference Type RESULT
PMID: 27028912 (View on PubMed)

Henderson VW, St John JA, Hodis HN, McCleary CA, Stanczyk FZ, Shoupe D, Kono N, Dustin L, Allayee H, Mack WJ. Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis. Neurology. 2016 Aug 16;87(7):699-708. doi: 10.1212/WNL.0000000000002980. Epub 2016 Jul 15.

Reference Type RESULT
PMID: 27421538 (View on PubMed)

Chen IJ, Stanczyk FZ, Sriprasert I, Karim R, Shoupe D, Kono N, Hodis HN, Mack WJ. Sex steroid hormones and subclinical atherosclerosis progression in postmenopausal women. Eur J Endocrinol. 2025 Mar 3;192(3):248-256. doi: 10.1093/ejendo/lvaf032.

Reference Type DERIVED
PMID: 39980346 (View on PubMed)

Lin F, Pa J, Karim R, Hodis HN, Han SD, Henderson VW, St John JA, Mack WJ. Subclinical carotid artery atherosclerosis and cognitive function in older adults. Alzheimers Res Ther. 2022 May 7;14(1):63. doi: 10.1186/s13195-022-00997-7.

Reference Type DERIVED
PMID: 35526057 (View on PubMed)

Sriprasert I, Mert M, Mack WJ, Hodis HN, Shoupe D. Use of oral estradiol plus vaginal progesterone in healthy postmenopausal women. Maturitas. 2021 Dec;154:13-19. doi: 10.1016/j.maturitas.2021.09.002. Epub 2021 Sep 5.

Reference Type DERIVED
PMID: 34736575 (View on PubMed)

Sriprasert I, Kono N, Karim R, Hodis HN, Stanczyk FZ, Shoupe D, Mack WJ. Factors Associated With Serum Estradiol Levels Among Postmenopausal Women Using Hormone Therapy. Obstet Gynecol. 2020 Oct;136(4):675-684. doi: 10.1097/AOG.0000000000004006.

Reference Type DERIVED
PMID: 32925623 (View on PubMed)

Sriprasert I, Mack WJ, Hodis HN, Allayee H, Brinton RD, Karim R. Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women. Am J Cardiol. 2019 Oct 1;124(7):1031-1037. doi: 10.1016/j.amjcard.2019.06.022. Epub 2019 Jul 15.

Reference Type DERIVED
PMID: 31362877 (View on PubMed)

Sriprasert I, Hodis HN, Karim R, Stanczyk FZ, Shoupe D, Henderson VW, Mack WJ. Differential Effect of Plasma Estradiol on Subclinical Atherosclerosis Progression in Early vs Late Postmenopause. J Clin Endocrinol Metab. 2019 Feb 1;104(2):293-300. doi: 10.1210/jc.2018-01600.

Reference Type DERIVED
PMID: 30272234 (View on PubMed)

Karim R, Stanczyk FZ, Brinton RD, Rettberg J, Hodis HN, Mack WJ. Association of endogenous sex hormones with adipokines and ghrelin in postmenopausal women. J Clin Endocrinol Metab. 2015 Feb;100(2):508-15. doi: 10.1210/jc.2014-2834. Epub 2014 Nov 18.

Reference Type DERIVED
PMID: 25405497 (View on PubMed)

Henderson VW. Aging, estrogens, and episodic memory in women. Cogn Behav Neurol. 2009 Dec;22(4):205-14. doi: 10.1097/WNN.0b013e3181a74ce7.

Reference Type DERIVED
PMID: 19996872 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R01AG024154

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AG0025

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Estrogen, HDL, and Coronary Heart Disease in Women
NCT00083824 COMPLETED PHASE2/PHASE3
Effect of Estradiol Topical Products
NCT05645393 COMPLETED EARLY_PHASE1