NCT00114517

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
643

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2004

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2004

Completed
12 months until next milestone

First Submitted

Initial submission to the registry

June 15, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 16, 2005

Completed
7.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 12, 2013

Completed
21 days until next milestone

Study Completion

Last participant's last visit for all outcomes

March 5, 2013

Completed
4.3 years until next milestone

Results Posted

Study results publicly available

June 8, 2017

Completed
Last Updated

January 18, 2023

Status Verified

December 1, 2022

Enrollment Period

8.6 years

First QC Date

June 15, 2005

Results QC Date

April 17, 2017

Last Update Submit

December 21, 2022

Conditions

Atherosclerosis

Keywords

atherosclerosisCADcardiac computed tomographycardiovascular diseasecarotid artery intima-media thicknesscognitive functioncomputed tomographycoronary artery calciumcoronary artery diseasecoronary artery lesionsCVDestrogenestrogen therapyhormone therapypostmenopausalsubclinical vascular diseasetiming hypothesisultrasonographymenopausal hormone replacement therapymenopausepreventionintervention

Outcome Measures

Primary Outcomes (1)

  • Progression of Subclinical Atherosclerosis

    Rate of change in distal common carotid artery (CCA) far wall intima-media thickness (mm per year) in computer image processed B-mode ultrasonograms that were obtained at two baseline examinations (averaged to obtain the baseline CIMT value) and every 6 months during trial follow-up.

    Baseline x 2 and then every 6 months up to 6.7 years

Secondary Outcomes (2)

  • Change in Neurocognitive Function (Global Cognition)

    Baseline and at 2.5 years and 5 years

  • Coronary Artery Calcium

    End of randomized treatment, up to 6.7 years

Study Arms (2)

17B-estradiol

ACTIVE COMPARATOR

Oral 17B-estradiol 1 mg daily

Drug: 17B-estradiol

Placebo

PLACEBO COMPARATOR

Matching oral 17B-estradiol placebo daily

Other: Placebo

Interventions

17B-estradiolDRUG

Oral 17B-estradiol 1 mg daily

Also known as: Estrace, Estrogen, Estrogen replacement therapy, Hormone replacement therapy, Hormone therapy, Menopausal hormone replacement therapy
17B-estradiol
PlaceboOTHER

Matching oral 17B-estradiol placebo daily

Also known as: Matching placebo
Placebo

Eligibility Criteria

Sexfemale
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Atherosclerosis Research Unit, University of Southern California

Los Angeles, California, 90033, United States

Location

Related Publications (11)

  • 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.

    PMID: 25380275BACKGROUND

  • 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.

    PMID: 27028912RESULT

  • 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.

    PMID: 27421538RESULT

  • 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.

    PMID: 39980346DERIVED

  • 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.

    PMID: 35526057DERIVED

  • 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.

    PMID: 34736575DERIVED

  • 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.

    PMID: 32925623DERIVED

  • 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.

    PMID: 31362877DERIVED

  • 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.

    PMID: 30272234DERIVED

  • 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.

    PMID: 25405497DERIVED

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

    PMID: 19996872DERIVED

MeSH Terms

Conditions

AtherosclerosisCardiovascular DiseasesCoronary Artery Disease

Interventions

EstradiolEstrogensEstrogen Replacement TherapyHormone Replacement Therapy

Condition Hierarchy (Ancestors)

ArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCoronary DiseaseMyocardial IschemiaHeart Diseases

Intervention Hierarchy (Ancestors)

EstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic CompoundsEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and UsesDrug TherapyTherapeutics

Results Point of Contact

Title
Howard N. Hodis, M.D., Director, Atherosclerosis Research Unit
Organization
University of Southern California
athero@usc.edu
323-442-1478

Study Officials

  • Howard N. Hodis, M.D.

    Atherosclerosis Research Unit, University of Southern California

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
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

Study Record Dates

First Submitted

June 15, 2005

First Posted

June 16, 2005

Study Start

July 1, 2004

Primary Completion

February 12, 2013

Study Completion

March 5, 2013

Last Updated

January 18, 2023

Results First Posted

June 8, 2017

Record last verified: 2022-12

Locations

US(1)