The Early versus Later Intervention Trial with Estradiol (ELITE) is a randomized, double-blind, placebo- controlled, serial arterial imaging (carotid artery intima-media thickness) trial designed to test the """"""""timing hypothesis"""""""" which posits that there is a differential effect of hormone therapy (HT) on atherosclerosis progression according to when HT is initiated in relation to menopause. ELITE is a 2x2 factorial trial in which healthy postmenopausal women without pre-existing cardiovascular disease were randomized to 172-estradiol or placebo according to their time since menopause, <6 years or >10 years. Since initially proposed 6 years ago, the scientific evidence for the timing hypothesis has grown substantially. ELITE was randomized ahead of schedule, the dropout rate is lower than initially projected, compliance with the study intervention remains >94% and adverse effects are low. This Renewal Application is submitted for 2 specific purposes: 1) to broaden the trial imaging end point to subclinical atherosclerosis of the coronary arteries through contrast and non-contrast cardiac computed tomography to validate and extend recent findings that HT potentially reduces coronary artery disease in young postmenopausal women;and, 2) to extend the intervention period of ELITE to sufficiently increase power to detect a smaller treatment interaction between time since menopause strata than originally designed since ELITE remains the only randomized controlled trial specifically designed to test the timing hypothesis. To determine whether the biologic response to 172-estradiol is different in younger versus older postmenopausal women (defined as time since menopause) remains the long-term and primary goal of this trial.

Public Health Relevance

With the growing number of women entering menopause (approximately 50% of U.S. women will be >45 years old by 2015) and with the introduction of new hormonal products into the marketplace, use of postmenopausal hormone therapy (HT) will continue. Therefore, understanding the effect of HT on the progression of subclinical atherosclerosis, especially in young postmenopausal women who are likely to initiate these products for menopausal symptoms (primarily for flushing since there are no comparably effective alternatives) continues to be an important and timely public health issue.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG024154-07
Application #
8085742
Study Section
Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Hannah, Judy S
Project Start
2004-09-30
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
7
Fiscal Year
2011
Total Cost
$2,173,159
Indirect Cost
Name
University of Southern California
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Herrera, Alexandra Ycaza; Hodis, Howard N; Mack, Wendy J et al. (2017) Estradiol Therapy After Menopause Mitigates Effects of Stress on Cortisol and Working Memory. J Clin Endocrinol Metab 102:4457-4466
Kurita, Keiko; Henderson, Victor W; Gatz, Margaret et al. (2016) Association of bilateral oophorectomy with cognitive function in healthy, postmenopausal women. Fertil Steril 106:749-756.e2
Rettberg, Jamaica R; Dang, Ha; Hodis, Howard N et al. (2016) Identifying postmenopausal women at risk for cognitive decline within a healthy cohort using a panel of clinical metabolic indicators: potential for detecting an at-Alzheimer's risk metabolic phenotype. Neurobiol Aging 40:155-163
Karim, Roksana; Dang, Ha; Henderson, Victor W et al. (2016) Effect of Reproductive History and Exogenous Hormone Use on Cognitive Function in Mid- and Late Life. J Am Geriatr Soc 64:2448-2456
Hodis, Howard N; Mack, Wendy J; Henderson, Victor W et al. (2016) Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med 374:1221-31
Karim, Roksana; Stanczyk, Frank Z; Brinton, Roberta D et al. (2015) Association of endogenous sex hormones with adipokines and ghrelin in postmenopausal women. J Clin Endocrinol Metab 100:508-15
Hodis, Howard N; Mack, Wendy J; Shoupe, Donna et al. (2015) Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis. Menopause 22:391-401
Hodis, Howard N; Mack, Wendy J (2014) Hormone replacement therapy and the association with coronary heart disease and overall mortality: clinical application of the timing hypothesis. J Steroid Biochem Mol Biol 142:68-75
Gatto, Nicole M; Henderson, Victor W; Hodis, Howard N et al. (2014) Components of air pollution and cognitive function in middle-aged and older adults in Los Angeles. Neurotoxicology 40:1-7
Hodis, Howard N; Mack, Wendy J (2013) The timing hypothesis and hormone replacement therapy: a paradigm shift in the primary prevention of coronary heart disease in women. Part 2: comparative risks. J Am Geriatr Soc 61:1011-8

Showing the most recent 10 out of 27 publications