Cardiovascular DiseasesPhase 3NCT00000559
Women's Estrogen/Progestin Lipid Lowering Hormone Atherosclerosis Regression Trial (WELL-HART)
A Phase 3 study testing estrogen replacement therapy, hormone replacement therapy and estradiol in people with Cardiovascular Diseases and Coronary Disease, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial summary
To determine the effects, in postmenopausal women, of hormone replacement therapy on progression/regression of coronary heart disease, as measured by quantitative angiography. Read more about this study
- Who is it for?
- Ages 45 to 75 years, women only
- Conditions the study is for
- Cardiovascular Diseases, Coronary Disease, Heart Diseases
- What is being tested?
- estrogen replacement therapy, hormone replacement therapy and estradiol
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Mar 1995to Aug 2001
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Postmenopausal women with angiographically-documented coronary disease. Approximately 70 percent minority
About this study
To determine the effects, in postmenopausal women, of hormone replacement therapy on progression/regression of coronary heart disease, as measured by quantitative angiography.
Read the detailed description
BACKGROUND:
The trial was a logical extension of preceding observational and cross-sectional studies on estrogen replacement therapy. Overall, the studies suggested a 50 percent reduction in risk of coronary heart disease in current estrogen users compared to non-users. In spite of such striking findings, most studies had been prone to a number of biases. One major criticism of observational studies had been that women receiving estrogen were generally healthier and more compliant than non-estrogen users.
There was a very large body of observational data suggesting that the use of estrogen in postmenopausal women reduced coronary heart disease mortality by approximately 45 percent. At the same time, there had been some concern that replacement therapy increased the likelihood of uterine cancer and perhaps breast cancer as well, although it was generally accepted that this risk was probably significantly less than the benefits obtained from the reduction of coronary heart disease mortality.
DESIGN NARRATIVE:
Randomized, double-blind, placebo-controlled. After baseline angiograms, patients were randomized to one of three arms: micronized 17-beta estradiol, 1 milligram per day; 17-beta estradiol plus medroxyprogesterone, 5 milligrams per day for twelve days per month; and placebo. Subjects in all three arms received lipid-lowering therapy, low fat/low cholesterol diet, and the HMG-CoA reductase inhibitor, pravastatin, in sufficient dosage to reduce low density lipoprotein (LDL) cholesterol levels below 130 mg/dl. The primary endpoint was progression/regression of coronary obstructive disease as measured by angiography, including the expert human panel and quantitative computer analysis. The secondary endpoint was carotid media-intima thickness determined by ultrasound. Clinical measures included lipids, lipoproteins, apolipoproteins, estradiol and medroxyprogesterone levels, urinary prostanoid metabolites, and insulin/glucose metabolism. Subjects were recruited at three centers with active coronary angiography units. Several core facilities supported the study: a Core Lipid Lab, a Reproductive Endocrine Lab, the Biostatistics Lab (Data Coordinating Center) and the Angiographic Imaging Laboratory.
The study completion date listed in this record was obtained from the "Completed Date" entered in the Query View Report System (QVR).
- Conditions
- Cardiovascular Diseases, Coronary Disease, Heart Diseases, Myocardial Ischemia, Postmenopause
- Being tested
- estrogen replacement therapy, hormone replacement therapy, estradiol, medroxyprogesterone
- Medical subject headings
- Cardiovascular Diseases, Coronary Disease, Heart Diseases, Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
estrogen replacement therapyDrug
hormone replacement therapyDrug
estradiolDrug
medroxyprogesteroneDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 1999 (estimated)
- Study startMar 1995
- Study completionAug 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Howard Hodis, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000559
- Sponsor's protocol ID
- 103
- Status last verified
- May 2005
- First submitted
- 27 Oct 1999
- Last updated
- 12 Jul 2016
- Results posted
- No
Publications
Slater CC, Zhang C, Hodis HN, Mack WJ, Boostanfar R, Shoupe D, Paulson RJ, Stanczyk FZ. Comparison of estrogen and androgen levels after oral estrogen replacement therapy. J Reprod Med. 2001 Dec;46(12):1052-6.
PubMed 11789085Wilcox JG, Hwang J, Hodis HN, Sevanian A, Stanczyk FZ, Lobo RA. Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoprotein. Fertil Steril. 1997 Jan;67(1):57-62. doi: 10.1016/s0015-0282(97)81856-0.
PubMed 8986684Hodis HN, Mack WJ, Azen SP, Lobo RA, Shoupe D, Mahrer PR, Faxon DP, Cashin-Hemphill L, Sanmarco ME, French WJ, Shook TL, Gaarder TD, Mehra AO, Rabbani R, Sevanian A, Shil AB, Torres M, Vogelbach KH, Selzer RH; Women's Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial Research Group. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med. 2003 Aug 7;349(6):535-45. doi: 10.1056/NEJMoa030830.
PubMed 12904518Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, Hodis HN. Unopposed estradiol therapy in postmenopausal women: results from two randomized trials. Obstet Gynecol. 2007 Mar;109(3):581-7. doi: 10.1097/01.AOG.0000251518.56369.eb.
PubMed 17329508
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Women's Estrogen/Progestin Lipid Lowering Hormone Atherosclerosis Regression Trial (WELL-HART)
- ClinicalTrials.gov ID
- NCT00000559
- Acronym / sponsor ID
- 103
- Conditions
- Cardiovascular Diseases, Coronary Disease, Heart Diseases, Myocardial Ischemia, Postmenopause
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Mar 1995
- Study completion
- Aug 2001 (actual)
- First posted
- 28 Oct 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the effects, in postmenopausal women, of hormone replacement therapy on progression/regression of coronary heart disease, as measured by quantitative angiography.
Detailed description
BACKGROUND:
The trial was a logical extension of preceding observational and cross-sectional studies on estrogen replacement therapy. Overall, the studies suggested a 50 percent reduction in risk of coronary heart disease in current estrogen users compared to non-users. In spite of such striking findings, most studies had been prone to a number of biases. One major criticism of observational studies had been that women receiving estrogen were generally healthier and more compliant than non-estrogen users.
There was a very large body of observational data suggesting that the use of estrogen in postmenopausal women reduced coronary heart disease mortality by approximately 45 percent. At the same time, there had been some concern that replacement therapy increased the likelihood of uterine cancer and perhaps breast cancer as well, although it was generally accepted that this risk was probably significantly less than the benefits obtained from the reduction of coronary heart disease mortality.
DESIGN NARRATIVE:
Randomized, double-blind, placebo-controlled. After baseline angiograms, patients were randomized to one of three arms: micronized 17-beta estradiol, 1 milligram per day; 17-beta estradiol plus medroxyprogesterone, 5 milligrams per day for twelve days per month; and placebo. Subjects in all three arms received lipid-lowering therapy, low fat/low cholesterol diet, and the HMG-CoA reductase inhibitor, pravastatin, in sufficient dosage to reduce low density lipoprotein (LDL) cholesterol levels below 130 mg/dl. The primary endpoint was progression/regression of coronary obstructive disease as measured by angiography, including the expert human panel and quantitative computer analysis. The secondary endpoint was carotid media-intima thickness determined by ultrasound. Clinical measures included lipids, lipoproteins, apolipoproteins, estradiol and medroxyprogesterone levels, urinary prostanoid metabolites, and insulin/glucose metabolism. Subjects were recruited at three centers with active coronary angiography units. Several core facilities supported the study: a Core Lipid Lab, a Reproductive Endocrine Lab, the Biostatistics Lab (Data Coordinating Center) and the Angiographic Imaging Laboratory.
The study completion date listed in this record was obtained from the "Completed Date" entered in the Query View Report System (QVR).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
Who may qualify
- Ages
- 45 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| estrogen replacement therapy | Drug | – |
| hormone replacement therapy | Drug | – |
| estradiol | Drug | – |
| medroxyprogesterone | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2016.
- Background: PubMed 11789085Slater CC, Zhang C, Hodis HN, Mack WJ, Boostanfar R, Shoupe D, Paulson RJ, Stanczyk FZ. Comparison of estrogen and androgen levels after oral estrogen replacement therapy. J Reprod Med. 2001 Dec;46(12):1052-6.
- Background: PubMed 8986684Wilcox JG, Hwang J, Hodis HN, Sevanian A, Stanczyk FZ, Lobo RA. Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoprotein. Fertil Steril. 1997 Jan;67(1):57-62. doi: 10.1016/s0015-0282(97)81856-0.
- Background: PubMed 12904518Hodis HN, Mack WJ, Azen SP, Lobo RA, Shoupe D, Mahrer PR, Faxon DP, Cashin-Hemphill L, Sanmarco ME, French WJ, Shook TL, Gaarder TD, Mehra AO, Rabbani R, Sevanian A, Shil AB, Torres M, Vogelbach KH, Selzer RH; Women's Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial Research Group. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med. 2003 Aug 7;349(6):535-45. doi: 10.1056/NEJMoa030830.
- Derived from this study: PubMed 17329508Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, Hodis HN. Unopposed estradiol therapy in postmenopausal women: results from two randomized trials. Obstet Gynecol. 2007 Mar;109(3):581-7. doi: 10.1097/01.AOG.0000251518.56369.eb.
Related trials for Cardiovascular Diseases
Active, not recruiting
Developing a Learning COmmunity to Increase eNgagemeNt and Enrollment in Cardiovascular Clinical Trials (CONNECT)
Cardiovascular Diseases, Hypertension
RecruitingObservational study
Cardiovascular Disease Progression in Survivors of Community Acquired Pneumonia and Lung Infection by Covid-19.
Pneumonia, Community-Acquired, COVID-19 Pneumonia
RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
RecruitingPhase 1/2
Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia (HHT), Osler Weber Rendu Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Howard Hodis
University of Southern California
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing estrogen replacement therapy, hormone replacement therapy and estradiol in people with Cardiovascular Diseases and Coronary Disease, run by National Heart, Lung, and Blood Institute (NHLBI).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000559, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2016; AzTrials last refreshed its copy on 7 Nov 2026.