Estrogen DeficiencyNCT00572858
Estrogen Deficiency and Cardiovascular Disease in Premenopausal Women
An observational study of Estrogen Deficiency, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
For unexplained reasons, young premenopausal women with heart disease have twice the rate of death compared to men of the same age. Animal experiments have shown that stress can reduce ovary function in females monkeys due to reductions in brain hormones. Read more about this study
- Who is it for?
- Ages Up to 55 years, women only
- Conditions the study is for
- Estrogen Deficiency
- What is being tested?
- Blood test, Ultrasound of neck arteries and Saliva test
- Type of treatment
- Surgery or procedure
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Oct 2020
- Phase
- Observational
- 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 Up to 55 years
- Women only
- No healthy volunteers
- Child, Adult
Study population: Premenopausal Women
Who may be able to join
- Premenopausal by WISE criteria
- English speaking (for the purposes of complete psychosocial assessment)
- Able to give informed consent
- Clinically-indicated coronary angiography within the last 24 months prior to enrollment with no interim change in symptoms, hospitalization, or events.
- Non-English speaking patients will be consented but will not undergo psychosocial assessment as part of the study.
Who cannot join
- Pregnant or intention of becoming pregnant during study period.
- Current hormonal therapy (oral contraceptives, hormone replacement therapy, designer estrogens or phytoestrogens)
- History of bilateral salpingoophorectomy
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Women's Heart Center
Los Angeles, California, 90048
About this study
For unexplained reasons, young premenopausal women with heart disease have twice the rate of death compared to men of the same age. Animal experiments have shown that stress can reduce ovary function in females monkeys due to reductions in brain hormones. This stress and reduced brain hormone levels lead to low estrogen levels and can cause menstrual cycles to become irregular, leading to reductions in fertility. These monkeys are also more likely to develop heart disease. In order, to better understand this relationship the investigators would like to study estrogen levels in premenopausal women with heart disease.
Premenopausal women who have recently undergone a study of their coronary (heart) arteries will have their blood hormone levels measured over one menstrual cycle. The investigators will correlate the blood hormone levels with coronary angiography results and with other markers of heart disease, such as a test that uses noninvasive, painless ultrasound waves to study the thickness of the arteries in the neck (carotid arteries). In addition blood cholesterol levels, blood sugar levels and other blood tests have been shown to correlate with heart disease will be measured.
Read more
Another aim of the study is to evaluate a potential link between environmental stress and hormone levels. Each patient will be given multiple questionnaires to evaluate stress, anxiety and depression and the investigators will be measuring the stress hormone (cortisol) levels in saliva for additional information.
The results of the study will further explore a possible link between low estrogen levels and heart disease in young premenopausal women and help pave the way for larger research studies to define better ways of preventing heart disease in these women.
Read the detailed description
Specific Aims
- To document that estrogen deficiency of hypothalamic (central brain) origin is a stable trait, when measured over one menstrual cycle or an approximate thirty days apart in premenopausal women undergoing angiography for coronary ischemia.
- To document a relationship between estrogen deficiency, other reproductive hormones and environmental stress in premenopausal women.
- To measure prevalence of angiographic coronary artery disease among premenopausal women and correlate it with noninvasive markers of coronary artery disease and the genetic relationship of estrogen in cardiovascular disease through genotyping and analysis of genes related to estrogen metabolism and pathways.
We are recruiting female patients who have undergone coronary angiography and are under the age of 55. After subject has signed the informed consent, we will screen her by testing her blood for two hormones to see if subject is premenopausal. If she is, she will be enrolled in the study and scheduled to return for a baseline visit on day 12-18 of the following menstrual cycle or 22-30 days later.
During the baseline visit we will measure height, weight, blood pressure, heart rate and waist-hip ratio. Subject will have to be fasting and we will draw blood for cholesterol, glucose and insulin levels and levels of various hormones, including but not limited to estrogen. Subject's saliva will be collected to test for cortisol levels. If subject agrees, a tablespoon of your blood will also be collected for genetic testing. Subject will be asked to fill out a separate consent form. Participation in the study does not mandate participation in genetic testing. Subject also will be given multiple questionnaires including questions regarding medical history, family history, medication use, stress, anxiety, and depression. They should be filled out within 48 hours of the blood draw to correlate findings. Neck arteries will be examined by ultrasound waves to measure the thickness of the arteries. This test can be performed on your second of third visit.
The final exit visit will be timed 26-33 days from your baseline visit. It will include all the tests that subjects underwent during their baseline visit except for the ultrasound, which will only be done once.
In summary, subjects will make three to four visits, the total study duration will be three to four months.
We will evaluate your hormone levels and other blood markers with respect to your coronary angiogram and thickness of the neck arteries. We will also assess whether your hormone levels are related to stress, anxiety and depression. And finally, we will measure the variability in your hormone levels over the testing period.
- Conditions
- Estrogen Deficiency
- Being tested
- Blood test, Ultrasound of neck arteries, Saliva test
- Keywords
- Hypo E
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood testProcedure or surgery
for cholesterol, glucose and insulin levels and levels of various hormones, including but not limited to estrogen
Blood testGenetic
Blood test for genetic testing
Ultrasound of neck arteriesProcedure or surgery
Non-invasive test using ultrasound waves to measure the thickness of the arteries
Saliva testProcedure or surgery
Saliva test for cotisol levels
| Study group | Role | What they receive |
|---|---|---|
| Premenopausal women | Female patients who have undergone coronary angiography and are under the age of 55 Receives: Procedure: Blood test; Genetic: Blood test; Procedure: Ultrasound of neck arteries; Procedure: Saliva test |
What is being measured
The primary outcome is the main question the study is designed to answer.
estrogen deficiency of hypothalamic (central brain) origin
at Baseline and Exit Visits (Baseline visit on day 12-18 of the following menstrual cycle; Final exit visit will be timed 26-33 days from the baseline visit).
Measured: 51 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2007 (estimated)
- Study startJan 2005
- Primary completionOct 2020
- Study completionOct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Estrogen DeficiencyStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Noel Bairey Merz, Cedars-Sinai Medical Center
- Investigators
- C.Noel Bairey-Merz, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00572858
- Sponsor's protocol ID
- IRB 6326
- Status last verified
- Oct 2020
- First submitted
- 12 Dec 2007
- Last updated
- 8 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Demissie S, Cupples LA, Shearman AM, Gruenthal KM, Peter I, Schmid CH, Karas RH, Housman DE, Mendelsohn ME, Ordovas JM. Estrogen receptor-alpha variants are associated with lipoprotein size distribution and particle levels in women: the Framingham Heart Study. Atherosclerosis. 2006 Mar;185(1):210-8. doi: 10.1016/j.atherosclerosis.2005.06.008. Epub 2005 Jul 7.
PubMed 16005459Gold B, Kalush F, Bergeron J, Scott K, Mitra N, Wilson K, Ellis N, Huang H, Chen M, Lippert R, Halldorsson BV, Woodworth B, White T, Clark AG, Parl FF, Broder S, Dean M, Offit K. Estrogen receptor genotypes and haplotypes associated with breast cancer risk. Cancer Res. 2004 Dec 15;64(24):8891-900. doi: 10.1158/0008-5472.CAN-04-1256.
PubMed 15604249Herrington DM, Howard TD. ER-alpha variants and the cardiovascular effects of hormone replacement therapy. Pharmacogenomics. 2003 May;4(3):269-77. doi: 10.1517/phgs.4.3.269.22686.
PubMed 12718718Schuit SC, de Jong FH, Stolk L, Koek WN, van Meurs JB, Schoofs MW, Zillikens MC, Hofman A, van Leeuwen JP, Pols HA, Uitterlinden AG. Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women. Eur J Endocrinol. 2005 Aug;153(2):327-34. doi: 10.1530/eje.1.01973.
PubMed 16061840Schuit SC, Oei HH, Witteman JC, Geurts van Kessel CH, van Meurs JB, Nijhuis RL, van Leeuwen JP, de Jong FH, Zillikens MC, Hofman A, Pols HA, Uitterlinden AG. Estrogen receptor alpha gene polymorphisms and risk of myocardial infarction. JAMA. 2004 Jun 23;291(24):2969-77. doi: 10.1001/jama.291.24.2969.
PubMed 15213208Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone. 2004 Jan;34(1):195-202. doi: 10.1016/j.bone.2003.10.001.
PubMed 14751578Shearman AM, Cupples LA, Demissie S, Peter I, Schmid CH, Karas RH, Mendelsohn ME, Housman DE, Levy D. Association between estrogen receptor alpha gene variation and cardiovascular disease. JAMA. 2003 Nov 5;290(17):2263-70. doi: 10.1001/jama.290.17.2263.
PubMed 14600184Shearman AM, Demissie S, Cupples LA, Peter I, Schmid CH, Ordovas JM, Mendelsohn ME, Housman DE. Tobacco smoking, estrogen receptor alpha gene variation and small low density lipoprotein level. Hum Mol Genet. 2005 Aug 15;14(16):2405-13. doi: 10.1093/hmg/ddi242. Epub 2005 Jul 13.
PubMed 16014638
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estrogen Deficiency and Cardiovascular Disease in Premenopausal Women
- ClinicalTrials.gov ID
- NCT00572858
- Acronym / sponsor ID
- IRB 6326
- Conditions
- Estrogen Deficiency
- Keywords
- Hypo E
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Study start
- Jan 2005
- Primary completion
- Oct 2020 (actual)
- Study completion
- Oct 2020 (actual)
- First posted
- 13 Dec 2007 (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.
For unexplained reasons, young premenopausal women with heart disease have twice the rate of death compared to men of the same age. Animal experiments have shown that stress can reduce ovary function in females monkeys due to reductions in brain hormones. This stress and reduced brain hormone levels lead to low estrogen levels and can cause menstrual cycles to become irregular, leading to reductions in fertility. These monkeys are also more likely to develop heart disease. In order, to better understand this relationship the investigators would like to study estrogen levels in premenopausal women with heart disease.
Premenopausal women who have recently undergone a study of their coronary (heart) arteries will have their blood hormone levels measured over one menstrual cycle. The investigators will correlate the blood hormone levels with coronary angiography results and with other markers of heart disease, such as a test that uses noninvasive, painless ultrasound waves to study the thickness of the arteries in the neck (carotid arteries). In addition blood cholesterol levels, blood sugar levels and other blood tests have been shown to correlate with heart disease will be measured.
Another aim of the study is to evaluate a potential link between environmental stress and hormone levels. Each patient will be given multiple questionnaires to evaluate stress, anxiety and depression and the investigators will be measuring the stress hormone (cortisol) levels in saliva for additional information.
The results of the study will further explore a possible link between low estrogen levels and heart disease in young premenopausal women and help pave the way for larger research studies to define better ways of preventing heart disease in these women.
Detailed description
Specific Aims
- To document that estrogen deficiency of hypothalamic (central brain) origin is a stable trait, when measured over one menstrual cycle or an approximate thirty days apart in premenopausal women undergoing angiography for coronary ischemia.
- To document a relationship between estrogen deficiency, other reproductive hormones and environmental stress in premenopausal women.
- To measure prevalence of angiographic coronary artery disease among premenopausal women and correlate it with noninvasive markers of coronary artery disease and the genetic relationship of estrogen in cardiovascular disease through genotyping and analysis of genes related to estrogen metabolism and pathways.
We are recruiting female patients who have undergone coronary angiography and are under the age of 55. After subject has signed the informed consent, we will screen her by testing her blood for two hormones to see if subject is premenopausal. If she is, she will be enrolled in the study and scheduled to return for a baseline visit on day 12-18 of the following menstrual cycle or 22-30 days later.
During the baseline visit we will measure height, weight, blood pressure, heart rate and waist-hip ratio. Subject will have to be fasting and we will draw blood for cholesterol, glucose and insulin levels and levels of various hormones, including but not limited to estrogen. Subject's saliva will be collected to test for cortisol levels. If subject agrees, a tablespoon of your blood will also be collected for genetic testing. Subject will be asked to fill out a separate consent form. Participation in the study does not mandate participation in genetic testing. Subject also will be given multiple questionnaires including questions regarding medical history, family history, medication use, stress, anxiety, and depression. They should be filled out within 48 hours of the blood draw to correlate findings. Neck arteries will be examined by ultrasound waves to measure the thickness of the arteries. This test can be performed on your second of third visit.
The final exit visit will be timed 26-33 days from your baseline visit. It will include all the tests that subjects underwent during their baseline visit except for the ultrasound, which will only be done once.
In summary, subjects will make three to four visits, the total study duration will be three to four months.
We will evaluate your hormone levels and other blood markers with respect to your coronary angiogram and thickness of the neck arteries. We will also assess whether your hormone levels are related to stress, anxiety and depression. And finally, we will measure the variability in your hormone levels over the testing period.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Premenopausal women | – | Procedure: Blood test, Genetic: Blood test, Procedure: Ultrasound of neck arteries, Procedure: Saliva testFemale patients who have undergone coronary angiography and are under the age of 55 |
Who may qualify
- Ages
- Up to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Premenopausal Women
Key inclusion criteria (5 listed)
- Premenopausal by WISE criteria
- English speaking (for the purposes of complete psychosocial assessment)
- Able to give informed consent
- Clinically-indicated coronary angiography within the last 24 months prior to enrollment with no interim change in symptoms, hospitalization, or events.
- Non-English speaking patients will be consented but will not undergo psychosocial assessment as part of the study.
Key exclusion criteria (3 listed)
- Pregnant or intention of becoming pregnant during study period.
- Current hormonal therapy (oral contraceptives, hormone replacement therapy, designer estrogens or phytoestrogens)
- History of bilateral salpingoophorectomy
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 |
|---|---|---|
| Blood testfor cholesterol, glucose and insulin levels and levels of various hormones, including but not limited to estrogen | Procedure or surgery | Premenopausal women |
| Blood testBlood test for genetic testing | Genetic | Premenopausal women |
| Ultrasound of neck arteriesNon-invasive test using ultrasound waves to measure the thickness of the arteries | Procedure or surgery | Premenopausal women |
| Saliva testSaliva test for cotisol levels | Procedure or surgery | Premenopausal women |
Primary outcome
estrogen deficiency of hypothalamic (central brain) origin
Time frame: 51 days
at Baseline and Exit Visits (Baseline visit on day 12-18 of the following menstrual cycle; Final exit visit will be timed 26-33 days from the baseline visit).
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 8 Oct 2020.
- Background: PubMed 16005459Demissie S, Cupples LA, Shearman AM, Gruenthal KM, Peter I, Schmid CH, Karas RH, Housman DE, Mendelsohn ME, Ordovas JM. Estrogen receptor-alpha variants are associated with lipoprotein size distribution and particle levels in women: the Framingham Heart Study. Atherosclerosis. 2006 Mar;185(1):210-8. doi: 10.1016/j.atherosclerosis.2005.06.008. Epub 2005 Jul 7.
- Background: PubMed 15604249Gold B, Kalush F, Bergeron J, Scott K, Mitra N, Wilson K, Ellis N, Huang H, Chen M, Lippert R, Halldorsson BV, Woodworth B, White T, Clark AG, Parl FF, Broder S, Dean M, Offit K. Estrogen receptor genotypes and haplotypes associated with breast cancer risk. Cancer Res. 2004 Dec 15;64(24):8891-900. doi: 10.1158/0008-5472.CAN-04-1256.
- Background: PubMed 12718718Herrington DM, Howard TD. ER-alpha variants and the cardiovascular effects of hormone replacement therapy. Pharmacogenomics. 2003 May;4(3):269-77. doi: 10.1517/phgs.4.3.269.22686.
- Background: PubMed 16061840Schuit SC, de Jong FH, Stolk L, Koek WN, van Meurs JB, Schoofs MW, Zillikens MC, Hofman A, van Leeuwen JP, Pols HA, Uitterlinden AG. Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women. Eur J Endocrinol. 2005 Aug;153(2):327-34. doi: 10.1530/eje.1.01973.
- Background: PubMed 15213208Schuit SC, Oei HH, Witteman JC, Geurts van Kessel CH, van Meurs JB, Nijhuis RL, van Leeuwen JP, de Jong FH, Zillikens MC, Hofman A, Pols HA, Uitterlinden AG. Estrogen receptor alpha gene polymorphisms and risk of myocardial infarction. JAMA. 2004 Jun 23;291(24):2969-77. doi: 10.1001/jama.291.24.2969.
- Background: PubMed 14751578Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone. 2004 Jan;34(1):195-202. doi: 10.1016/j.bone.2003.10.001.
- Background: PubMed 14600184Shearman AM, Cupples LA, Demissie S, Peter I, Schmid CH, Karas RH, Mendelsohn ME, Housman DE, Levy D. Association between estrogen receptor alpha gene variation and cardiovascular disease. JAMA. 2003 Nov 5;290(17):2263-70. doi: 10.1001/jama.290.17.2263.
- Background: PubMed 16014638Shearman AM, Demissie S, Cupples LA, Peter I, Schmid CH, Ordovas JM, Mendelsohn ME, Housman DE. Tobacco smoking, estrogen receptor alpha gene variation and small low density lipoprotein level. Hum Mol Genet. 2005 Aug 15;14(16):2405-13. doi: 10.1093/hmg/ddi242. Epub 2005 Jul 13.
- Individual participant dataSharing planned: Yes
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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.
C.Noel Bairey-Merz, MD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Estrogen Deficiency, run by Cedars-Sinai Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. 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 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
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.
What does the primary outcome measure?
estrogen deficiency of hypothalamic (central brain) origin (time frame: 51 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00572858, which also lists 8 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 8 Oct 2020.