Postmenopausal SyndromeEstrogenNCT00565916
Evaluating the Roles of Estrogen and Progesterone in Heart Metabolism
A study testing Estrogen and Progesterone in people with Postmenopausal Syndrome, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Estrogen and progesterone are two main female sex hormones. When a woman goes through menopause, the body's production of estrogen and progesterone significantly decreases. Recent studies have shown that the breakdown of fatty acids in cardiac muscle is important in maintaining a healthy heart, and that estrogen may… Read more about this study
- Who is it for?
- Ages 55 to 75 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postmenopausal Syndrome
- What is being tested?
- Estrogen and Progesterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Jan 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 to 75 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy postmenopausal woman
- Body mass index less than 30
- Practices normal eating habits
- Stops hormone replacement therapy at least 6 months prior to study entry
Who cannot join
- Currently taking hormone replacement therapy
- History of cardiovascular disease
- Family history of coronary artery disease
- Recent history of smoking, high blood pressure, or hyperlipidemia
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63366
About this study
Official title: Role of Estrogen/SERMS on Cardiac Fatty Acid Metabolism (Aim #1- Human Studies)
Estrogen and progesterone are two main female sex hormones. When a woman goes through menopause, the body's production of estrogen and progesterone significantly decreases. Recent studies have shown that the breakdown of fatty acids in cardiac muscle is important in maintaining a healthy heart, and that estrogen may enhance this process. Also, cardiovascular disease (CVD) occurs more frequently in postmenopausal women than in premenopausal women. This study will determine in postmenopausal women whether estrogen increases the heart's ability to use fats as energy and whether progesterone decreases this effect.
Read the detailed description
Menopause is a natural event that generally occurs in women between the ages of 45 and 55. During menopause, the body starts producing less estrogen and progesterone until menstruation eventually stops. Estrogen and progesterone are involved in many important functions in a woman's body, and the drastic decline of these hormones in menopause leads to significant changes in the body. Along with such changes, postmenopausal women are at a higher risk than premenopausal women for certain health problems, such as CVD. Previous studies have revealed that alterations in the breakdown of fatty acids in cardiac muscle play a key role in a variety of cardiac disorders. In studies involving human skeletal muscle, estrogen has been shown to increase the breakdown of fatty acids, while progesterone lessens this effect. This study will determine in postmenopausal women whether estrogen increases the heart's ability to break down fats for energy use and whether progesterone decreases this effect. This study will also analyze ovariectomized mice to determine if the candidate specific estrogen receptor modulators (SERMs) raloxifene and tamoxifen increase the heart's ability to use fats as energy and whether the increase is similar to that seen with estrogen. Study investigators will also create estrogen receptor knock-out mice (mice with estrogen receptors removed) to further explore the roles of estrogen and SERMs in heart metabolism.
Participation in this double-blind study will last up to 1 month and will include three study visits. During Visit 1, participants will undergo three standard clinical evaluations. The first evaluation, a medical screening, will include a medical history exam and blood tests to measure estrogen and progesterone levels, liver and kidney function, cholesterol levels, and blood sugar and insulin levels. For the second evaluation, participants will undergo a body composition study to measure total body fat and muscle content using a dual-energy x-ray absorptiometry (DEXA) scan. During the third evaluation, participants will undergo an electrocardiogram (ECG) and an echocardiogram (ECHO), each performed immediately before and after walking on a treadmill. The ECG will measure electrical activity of the heart, and the ECHO will involve imaging the heart with an ultrasound.
Visits 2 and 3, occurring 3 days apart, will each include two imaging tests of the heart: a positron-emission tomographic (PET) scan and a resting ECHO. Throughout both tests an ECG and blood pressure cuff will be used to monitor heart rhythm and blood pressure, respectively. During the PET scan, participants will lie flat in an imaging machine for three 45- to 60- minute intervals. Blood will be drawn and radioactive tracers will be injected via intravenous lines placed in the arms. The ECHO test will also be done during the PET scan.
Between Visits 2 and 3, participants will be randomly assigned to one of two hormone replacement therapy (HRT) regimens: estrogen plus placebo or estrogen plus progesterone. All participants will wear a patch containing estrogen and take a pill of either placebo or progesterone for the 3 days leading up to Visit 3. All participants will be asked for permission to store a sample of their blood for up to 10 years to be used in future research studies.
- Conditions
- Postmenopausal Syndrome
- Being tested
- Estrogen, Progesterone, Placebo
- Keywords
- Post-Menopausal, PET, Estrogen, Progesterone, Heart Metabolism, Cardiovascular Disease
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstrogenDrug
Also called Estradiol
Estrogen only plus placebo: estradiol topical patch 0.3 mg placed on the lower abdomen for 3 days plus an oral placebo.
Other procedures: heart metabolism tests which includes a positron-emission tomography (PET) scan, an electrocardiogram (ECG), and an echocardiogram (ECHO).
ProgesteroneDrug
Also called prometrium
Estrogen plus progesterone: estradiol with oral progesterone (Prometrium, 200 mg/day) for 3 days, instead of placebo. Progesterone therapy involves taking a daily oral pill of 200 mg Prometrium for the same 3 days that the estradiol is taken.
PlaceboDrug
Also called Inactive Drug
Placebo progesterone therapy involves taking a daily placebo pill for the same 3 days that the estradiol is taken.
| Study group | Role | What they receive |
|---|---|---|
| estrogen plus progesterone | Experimental | Hormone replacement therapy (HRT): estrogen plus progesterone Receives: Drug: Estrogen; Drug: Progesterone |
| estrogen plus placebo | Active comparator | Hormone replacement therapy (HRT): estrogen plus placebo Receives: Drug: Estrogen; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Had an Increase in Myocardial Fatty Acid Utilization.
Measurements of myocardial fatty acid utilization and oxidation with C[11]-Palmitate and PET in healthy postmenopausal women who take either estrogen alone or with progesterone. The primary outcome measure was designed to determine prospectively whether estrogen will increase the heart's fatty acid utilization and whether progestins will attenuate this effect, in a manner similar to what was seen in an observational study of hormone replacement therapy (HRT) in post-menopausal women. To this end, we had anticipated enrolling 30 healthy post-menopausal women for assessment of cardiac fatty acid metabolism using positron emission tomography (PET) and radioactive C[11]-Palmitate both before and after 3 days of hormone replacement therapy. These volunteers were to be randomized to receive either estrogen alone (E) or combined estrogen/progesterone (EP).
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2007 (estimated)
- Study startAug 2004
- Primary completionJan 2008
- Study completionJan 2008
Why it stopped: Atypically high dropout rate.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Postmenopausal SyndromeStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Robert Wood Johnson Foundation
- Responsible party
- Sponsor
- Investigators
- Pablo Soto, MD, Principal investigator, Washington University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00565916
- Sponsor's protocol ID
- 489
- Other IDs
- K23HL077179, IRB# 04-0812, RDRC# 538F, GCRC# 966
- Acronym
- Estrogen
- Status last verified
- Sep 2018
- First submitted
- 29 Nov 2007
- Last updated
- 16 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Castelli WP. Cardiovascular disease in women. Am J Obstet Gynecol. 1988 Jun;158(6 Pt 2):1553-60, 1566-7. doi: 10.1016/0002-9378(88)90189-5.
PubMed 3377033Bokhari S, Bergmann SR. The effect of estrogen compared to estrogen plus progesterone on the exercise electrocardiogram. J Am Coll Cardiol. 2002 Sep 18;40(6):1092-6. doi: 10.1016/s0735-1097(02)02111-3.
PubMed 12354433Babiker FA, De Windt LJ, van Eickels M, Grohe C, Meyer R, Doevendans PA. Estrogenic hormone action in the heart: regulatory network and function. Cardiovasc Res. 2002 Feb 15;53(3):709-19. doi: 10.1016/s0008-6363(01)00526-0.
PubMed 11861041Petrie MC, Dawson NF, Murdoch DR, Davie AP, McMurray JJ. Failure of women's hearts. Circulation. 1999 May 4;99(17):2334-41. doi: 10.1161/01.cir.99.17.2334. No abstract available.
PubMed 10226101McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971 Dec 23;285(26):1441-6. doi: 10.1056/NEJM197112232852601. No abstract available.
PubMed 5122894
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Estrogen/SERMS on Cardiac Fatty Acid Metabolism (Aim #1- Human Studies)
- ClinicalTrials.gov ID
- NCT00565916
- Acronym / sponsor ID
- Estrogen / 489
- Conditions
- Postmenopausal Syndrome
- Keywords
- Post-Menopausal, PET, Estrogen, Progesterone, Heart Metabolism, Cardiovascular Disease
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Atypically high dropout rate.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Robert Wood Johnson Foundation
- Study start
- Aug 2004
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 30 Nov 2007 (estimated)
- Results
- Posted 16 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Estrogen and progesterone are two main female sex hormones. When a woman goes through menopause, the body's production of estrogen and progesterone significantly decreases. Recent studies have shown that the breakdown of fatty acids in cardiac muscle is important in maintaining a healthy heart, and that estrogen may enhance this process. Also, cardiovascular disease (CVD) occurs more frequently in postmenopausal women than in premenopausal women. This study will determine in postmenopausal women whether estrogen increases the heart's ability to use fats as energy and whether progesterone decreases this effect.
Detailed description
Menopause is a natural event that generally occurs in women between the ages of 45 and 55. During menopause, the body starts producing less estrogen and progesterone until menstruation eventually stops. Estrogen and progesterone are involved in many important functions in a woman's body, and the drastic decline of these hormones in menopause leads to significant changes in the body. Along with such changes, postmenopausal women are at a higher risk than premenopausal women for certain health problems, such as CVD. Previous studies have revealed that alterations in the breakdown of fatty acids in cardiac muscle play a key role in a variety of cardiac disorders. In studies involving human skeletal muscle, estrogen has been shown to increase the breakdown of fatty acids, while progesterone lessens this effect. This study will determine in postmenopausal women whether estrogen increases the heart's ability to break down fats for energy use and whether progesterone decreases this effect. This study will also analyze ovariectomized mice to determine if the candidate specific estrogen receptor modulators (SERMs) raloxifene and tamoxifen increase the heart's ability to use fats as energy and whether the increase is similar to that seen with estrogen. Study investigators will also create estrogen receptor knock-out mice (mice with estrogen receptors removed) to further explore the roles of estrogen and SERMs in heart metabolism.
Participation in this double-blind study will last up to 1 month and will include three study visits. During Visit 1, participants will undergo three standard clinical evaluations. The first evaluation, a medical screening, will include a medical history exam and blood tests to measure estrogen and progesterone levels, liver and kidney function, cholesterol levels, and blood sugar and insulin levels. For the second evaluation, participants will undergo a body composition study to measure total body fat and muscle content using a dual-energy x-ray absorptiometry (DEXA) scan. During the third evaluation, participants will undergo an electrocardiogram (ECG) and an echocardiogram (ECHO), each performed immediately before and after walking on a treadmill. The ECG will measure electrical activity of the heart, and the ECHO will involve imaging the heart with an ultrasound.
Visits 2 and 3, occurring 3 days apart, will each include two imaging tests of the heart: a positron-emission tomographic (PET) scan and a resting ECHO. Throughout both tests an ECG and blood pressure cuff will be used to monitor heart rhythm and blood pressure, respectively. During the PET scan, participants will lie flat in an imaging machine for three 45- to 60- minute intervals. Blood will be drawn and radioactive tracers will be injected via intravenous lines placed in the arms. The ECHO test will also be done during the PET scan.
Between Visits 2 and 3, participants will be randomly assigned to one of two hormone replacement therapy (HRT) regimens: estrogen plus placebo or estrogen plus progesterone. All participants will wear a patch containing estrogen and take a pill of either placebo or progesterone for the 3 days leading up to Visit 3. All participants will be asked for permission to store a sample of their blood for up to 10 years to be used in future research studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| estrogen plus progesterone | Experimental | Drug: Estrogen, Drug: ProgesteroneHormone replacement therapy (HRT): estrogen plus progesterone |
| estrogen plus placebo | Active comparator | Drug: Estrogen, Drug: PlaceboHormone replacement therapy (HRT): estrogen plus placebo |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy postmenopausal woman
- Body mass index less than 30
- Practices normal eating habits
- Stops hormone replacement therapy at least 6 months prior to study entry
Key exclusion criteria (4 listed)
- Currently taking hormone replacement therapy
- History of cardiovascular disease
- Family history of coronary artery disease
- Recent history of smoking, high blood pressure, or hyperlipidemia
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 |
|---|---|---|
| EstrogenAlso: EstradiolEstrogen only plus placebo: estradiol topical patch 0.3 mg placed on the lower abdomen for 3 days plus an oral placebo. Other procedures: heart metabolism tests which includes a positron-emission tomography (PET) scan, an electrocardiogram (ECG), and an echocardiogram (ECHO). | Drug | estrogen plus placebo, estrogen plus progesterone |
| ProgesteroneAlso: prometriumEstrogen plus progesterone: estradiol with oral progesterone (Prometrium, 200 mg/day) for 3 days, instead of placebo. Progesterone therapy involves taking a daily oral pill of 200 mg Prometrium for the same 3 days that the estradiol is taken. | Drug | estrogen plus progesterone |
| PlaceboAlso: Inactive DrugPlacebo progesterone therapy involves taking a daily placebo pill for the same 3 days that the estradiol is taken. | Drug | estrogen plus placebo |
Primary outcome
Number of Participants That Had an Increase in Myocardial Fatty Acid Utilization.
Time frame: 3 days
Measurements of myocardial fatty acid utilization and oxidation with C[11]-Palmitate and PET in healthy postmenopausal women who take either estrogen alone or with progesterone. The primary outcome measure was designed to determine prospectively whether estrogen will increase the heart's fatty acid utilization and whether progestins will attenuate this effect, in a manner similar to what was seen in an observational study of hormone replacement therapy (HRT) in post-menopausal women. To this end, we had anticipated enrolling 30 healthy post-menopausal women for assessment of cardiac fatty acid metabolism using positron emission tomography (PET) and radioactive C[11]-Palmitate both before and after 3 days of hormone replacement therapy. These volunteers were to be randomized to receive either estrogen alone (E) or combined estrogen/progesterone (EP).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 3377033Castelli WP. Cardiovascular disease in women. Am J Obstet Gynecol. 1988 Jun;158(6 Pt 2):1553-60, 1566-7. doi: 10.1016/0002-9378(88)90189-5.
- Background: PubMed 12354433Bokhari S, Bergmann SR. The effect of estrogen compared to estrogen plus progesterone on the exercise electrocardiogram. J Am Coll Cardiol. 2002 Sep 18;40(6):1092-6. doi: 10.1016/s0735-1097(02)02111-3.
- Background: PubMed 11861041Babiker FA, De Windt LJ, van Eickels M, Grohe C, Meyer R, Doevendans PA. Estrogenic hormone action in the heart: regulatory network and function. Cardiovasc Res. 2002 Feb 15;53(3):709-19. doi: 10.1016/s0008-6363(01)00526-0.
- Background: PubMed 10226101Petrie MC, Dawson NF, Murdoch DR, Davie AP, McMurray JJ. Failure of women's hearts. Circulation. 1999 May 4;99(17):2334-41. doi: 10.1161/01.cir.99.17.2334. No abstract available.
- Background: PubMed 5122894McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971 Dec 23;285(26):1441-6. doi: 10.1056/NEJM197112232852601. No abstract available.
- Individual participant dataSharing planned: Undecided
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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.
Pablo Soto, MD principal investigator
Washington University Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Estrogen and Progesterone in people with Postmenopausal Syndrome, run by Washington University School of Medicine 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 4 inclusion and 4 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: stopped early, as of the sponsor's last update on 16 Oct 2018. 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?
Yes. Results are posted in the registry (first posted 16 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants That Had an Increase in Myocardial Fatty Acid Utilization. (time frame: 3 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 NCT00565916, which also lists 5 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 16 Oct 2018.