Primary Ovarian InsufficiencyENCODENCT06866119
Effects of Estrogen on Heart Health in Women With Primary Ovarian Insufficiency
An observational study of Primary Ovarian Insufficiency and Premature Menopause, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The goal of this observational study is to study the effects of treating women with Primary Ovarian Insufficiency (POI) with estrogen replacement therapy to bolster the evidence backing cardiometabolic preventive care in women with POI. Read more about this study
- Who is it for?
- Ages 30 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Primary Ovarian Insufficiency, Premature Menopause, Metabolic Complications
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jun 2026to 30 Jun 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 30 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: The study population is comprised of women newly diagnosed with POI (within 6 months) who are planning to clinically initiate hormonal replacement with 100mcg transdermal 17beta-estradiol twice weekly and micro-ionized progesterone (either 200mg cyclically or 100mg daily). For comparison, healthy women without POI matched 1:1 on age, BMI, and PREVENT™ risk score category (low-high risk) will also be studied.
Who may be able to join
- female sex
- age 30-40
- CASE PARTICIPANTS ONLY: clinically documented POI diagnosis within 6 months
- CASE PARTICIPANTS ONLY: planning to clinically initiate 100mcg transdermal 17beta-estradiol twice weekly and micro-ionized progesterone (either 100mg daily or 200mg cyclically)
- CONTROL PARTICIPANTS ONLY: regular menstrual cycles every 21-35 days
Who cannot join
- CASE PARTICIPANTS ONLY: genetic POI etiology
- CASE PARTICIPANTS ONLY: any prior initiation of ERT
- systemic estrogen, progesterone or testosterone therapy within the past 6 months (including contraception, except for locally acting intrauterine devices - IUDs)
- lipid lowering therapy within the past 6 months
- use of antihypertensive medication within the past 6 months
- current treatment with prescription, systemic (oral, IV, or IM) steroids or anti-inflammatory/immune suppressant medical therapies (excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDS) for autoimmune/inflammatory diseases (psoriasis, RA, IBD, lupus), post-transplant care, asthma, or pain syndromes
Show all 19Show fewer
- use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for >7 days within the past 1 month
- use of IV or IM steroids or IV or IM anti-inflammatory/immune suppressant medication within the past 3 months
- self-reported history of breast and/or estrogen dependent malignancy
- self-reported history of deep vein thromboembolism, pulmonary embolism or stroke
- self-reported severe liver disease such as cirrhosis
- self-reported hypercoagulable disorder
- uncontrolled hypertension at baseline Visit #1- systolic blood pressure (SBP) ≥180 and/or diastolic blood pressure (DBP) ≥110
- tobacco use within 6 months
- self-reported history of myocardial infarction, stroke, coronary revascularization or diabetes as a CVD risk equivalent
- stable or unstable angina
- self-reported history of heart failure
- pregnancy or breastfeeding
- concurrent enrollment in conflicting research study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Lauren Maldonado, MD, MPH, 617-643-4420, LYMALDONADO@MGH.HARVARD.EDU
About this study
Official title: Effects of Estrogen Replacement on Cardiometabolic Endpoints in Women With Primary Ovarian Insufficiency
The goal of this observational study is to study the effects of treating women with Primary Ovarian Insufficiency (POI) with estrogen replacement therapy to bolster the evidence backing cardiometabolic preventive care in women with POI. The main question it aims to answer is:
Does 6 months of estrogen replacement therapy for women with POI improved markers of heart health?
Women newly diagnosed with POI (within 6 months) who are planning to start estrogen replacement therapy from their clinical provider will undergo assessment of markers of heart health before and after 6 months of treatment. These markers will also be compared to those obtained from healthy women without POI.
Read the detailed description
Primary Ovarian Insufficiency (POI) is known to adversely affect bone and CV health. Despite the established role for ERT in bone health and the potential cardioprotection suggested by recent studies, few women with POI receive treatment. In this proposed study, we aim to characterize potential salient short-term benefits of ERT on CV surrogates. We hypothesize that among women newly diagnosed with POI, clinical initiation of ERT with transdermal estrogen will improve cardiometabolic risk surrogates, including endothelial function. This study will enhance the body of evidence underpinning guideline-directed approaches to cardiometabolic preventive health care for women with POI.
For this observational study, women newly diagnosed with POI (within 6 months) who are planning to clinically initiate hormonal replacement with 100mcg transdermal 17beta-estradiol twice weekly and micro-ionized progesterone (either 200mg cyclically or 100mg daily) will undergo assessment of cardiometabolic endpoints before and after 6 months of treatment. For comparison, healthy women without POI matched 1:1 on age, BMI, and PREVENT™ risk score category (low-high risk) will undergo parallel assessments at baseline.
Participants will undergo a medical history, physical exam, anthropomorphic measurements, blood sampling, brachial artery flow-mediated dilation (FMD), as a measure of peripheral endothelial function relevant to development of incident CVD, and whole-body DXA to assess body composition. Case participants with POI will participate in two in-person study visits that occur just prior to initiation of ERT and 6-months into treatment. Healthy control participants only participate in a single baseline visit.
The primary endpoint will be brachial artery flow-mediated dilation (FMD). Secondary endpoints will include measures of metabolic dysregulation (possibly including, but not limited to, hemoglobin A1c, circulating lipid levels, HOMA-IR for insulin resistance and DEXA-derived visceral adipose tissue) and characterization of circulating immune/inflammatory biomarkers (possibly including, but not limited to, CRP and pro-inflammatory cytokines IL-6 and TNF-α).
- Conditions
- Primary Ovarian Insufficiency, Premature Menopause, Metabolic Complications, Endothelial Function (FMD), Estrogen Replacement Therapy
- Keywords
- primary ovarian insufficiency, premature menopause, estrogen replacement therapy, cardiovascular disease prevention, POI, ERT
- Medical subject headings
- Primary Ovarian Insufficiency, Menopause, Premature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Case participants with Primary Ovarian Insufficiency | This group is comprised of women (assigned female at birth), age 30-40yo who have a clinically documented diagnosis of primary ovarian insufficiency (POI) within 6 months and be planning to clinically initiate estrogen replacement therapy (with 100mcg transdermal 17beta-estradiol twice weekly and micro-ionized progesterone either 100mg daily or 200mg cyclically) with their own provider. Women in the group may not be on systemic estrogen, progesterone or testosterone therapy, have contraindications for estrogen administration or known atherosclerotic cardiovascular disease or equivalents. They must also not take lipid lowering therapy or antihypertensive or anti-inflammatory/immune suppressant medications or be pregnant or breastfeeding. After a telephone screen to determine eligibility, the group will engage in two in-person study visits. The first occurs prior to the initiating estrogen replacement therapy and the second after 6 months of treatment. | |
| Health control participants without Primary Ovarian Insufficiency | This group is compromised of women (assigned female at birth), age 30-40yo who have regular menstrual cycles every 21-35 days. Women in the group may not be on systemic estrogen, progesterone or testosterone therapy, have contraindications for estrogen administration or known atherosclerotic cardiovascular disease or equivalents. They must also not take lipid lowering therapy or antihypertensive or anti-inflammatory/immune suppressant medications or be pregnant or breastfeeding. After a telephone screen to determine eligibility, the group will in a single in-person study visit. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brachial artery Flow Mediated Vasodilation (FMD)
Brachial artery flow-mediated dilation (FMD) is a non-invasive measure of endothelial function relevant to the development of incident cardiovascular disease. Brachial artery FMD will be reported as a percentage (%FMD), calculated by comparing the change in brachial artery diameter during reactive hyperemia to the baseline diameter. %FMD will be compared between case participants with POI and healthy control participants at baseline. The change in %FMD after 6 months of estrogen replacement therapy will be determined for case participants with POI.
Measured: 6 months
Secondary outcomes (2)
Metabolic biomarkers
Urine and serum biomarkers relating to metabolism (including glucose and lipid metabolism, body composition)
Measured: 6 months
Immune/inflammatory biomarkers
Urine and serum biomarkers relating to inflammation and immune activation
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2025
- Study start22 Jun 2026
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Ovarian InsufficiencyStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Other
- Time perspective
- Prospective
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Markella V. Zanni,M.D., Massachusetts General Hospital
- Investigators
- Markella V. Zanni, MD, Study chair, MGH/HMS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06866119
- Sponsor's protocol ID
- 2025P000601
- Other IDs
- GR1000466
- Acronym
- ENCODE
- Status last verified
- Jan 2026
- First submitted
- 4 Mar 2025
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Plans are for IPD to be shared to the NIH BioLINCC data repository.
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Estrogen Replacement on Cardiometabolic Endpoints in Women With Primary Ovarian Insufficiency
- ClinicalTrials.gov ID
- NCT06866119
- Acronym / sponsor ID
- ENCODE / 2025P000601
- Conditions
- Primary Ovarian Insufficiency, Premature Menopause, Metabolic Complications, Endothelial Function (FMD), Estrogen Replacement Therapy
- Keywords
- primary ovarian insufficiency, premature menopause, estrogen replacement therapy, cardiovascular disease prevention, POI, ERT
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 22 Jun 2026 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 10 Mar 2025 (actual)
- 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.
The goal of this observational study is to study the effects of treating women with Primary Ovarian Insufficiency (POI) with estrogen replacement therapy to bolster the evidence backing cardiometabolic preventive care in women with POI. The main question it aims to answer is:
Does 6 months of estrogen replacement therapy for women with POI improved markers of heart health?
Women newly diagnosed with POI (within 6 months) who are planning to start estrogen replacement therapy from their clinical provider will undergo assessment of markers of heart health before and after 6 months of treatment. These markers will also be compared to those obtained from healthy women without POI.
Detailed description
Primary Ovarian Insufficiency (POI) is known to adversely affect bone and CV health. Despite the established role for ERT in bone health and the potential cardioprotection suggested by recent studies, few women with POI receive treatment. In this proposed study, we aim to characterize potential salient short-term benefits of ERT on CV surrogates. We hypothesize that among women newly diagnosed with POI, clinical initiation of ERT with transdermal estrogen will improve cardiometabolic risk surrogates, including endothelial function. This study will enhance the body of evidence underpinning guideline-directed approaches to cardiometabolic preventive health care for women with POI.
For this observational study, women newly diagnosed with POI (within 6 months) who are planning to clinically initiate hormonal replacement with 100mcg transdermal 17beta-estradiol twice weekly and micro-ionized progesterone (either 200mg cyclically or 100mg daily) will undergo assessment of cardiometabolic endpoints before and after 6 months of treatment. For comparison, healthy women without POI matched 1:1 on age, BMI, and PREVENT™ risk score category (low-high risk) will undergo parallel assessments at baseline.
Participants will undergo a medical history, physical exam, anthropomorphic measurements, blood sampling, brachial artery flow-mediated dilation (FMD), as a measure of peripheral endothelial function relevant to development of incident CVD, and whole-body DXA to assess body composition. Case participants with POI will participate in two in-person study visits that occur just prior to initiation of ERT and 6-months into treatment. Healthy control participants only participate in a single baseline visit.
The primary endpoint will be brachial artery flow-mediated dilation (FMD). Secondary endpoints will include measures of metabolic dysregulation (possibly including, but not limited to, hemoglobin A1c, circulating lipid levels, HOMA-IR for insulin resistance and DEXA-derived visceral adipose tissue) and characterization of circulating immune/inflammatory biomarkers (possibly including, but not limited to, CRP and pro-inflammatory cytokines IL-6 and TNF-α).
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case participants with Primary Ovarian Insufficiency | – | –This group is comprised of women (assigned female at birth), age 30-40yo who have a clinically documented diagnosis of primary ovarian insufficiency (POI) within 6 months and be planning to clinically initiate estrogen replacement therapy (with 100mcg transdermal 17beta-estradiol twice weekly and micro-ionized progesterone either 100mg daily or 200mg cyclically) with their own provider. Women in the group may not be on systemic estrogen, progesterone or testosterone therapy, have contraindications for estrogen administration or known atherosclerotic cardiovascular disease or equivalents. They must also not take lipid lowering therapy or antihypertensive or anti-inflammatory/immune suppressant medications or be pregnant or breastfeeding. After a telephone screen to determine eligibility, the group will engage in two in-person study visits. The first occurs prior to the initiating estrogen replacement therapy and the second after 6 months of treatment. |
| Health control participants without Primary Ovarian Insufficiency | – | –This group is compromised of women (assigned female at birth), age 30-40yo who have regular menstrual cycles every 21-35 days. Women in the group may not be on systemic estrogen, progesterone or testosterone therapy, have contraindications for estrogen administration or known atherosclerotic cardiovascular disease or equivalents. They must also not take lipid lowering therapy or antihypertensive or anti-inflammatory/immune suppressant medications or be pregnant or breastfeeding. After a telephone screen to determine eligibility, the group will in a single in-person study visit. |
Who may qualify
- Ages
- 30 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- The study population is comprised of women newly diagnosed with POI (within 6 months) who are planning to clinically initiate hormonal replacement with 100mcg transdermal 17beta-estradiol twice weekly and micro-ionized progesterone (either 200mg cyclically or 100mg daily). For comparison, healthy women without POI matched 1:1 on age, BMI, and PREVENT™ risk score category (low-high risk) will also be studied.
Key inclusion criteria (5 listed)
- female sex
- age 30-40
- CASE PARTICIPANTS ONLY: clinically documented POI diagnosis within 6 months
- CASE PARTICIPANTS ONLY: planning to clinically initiate 100mcg transdermal 17beta-estradiol twice weekly and micro-ionized progesterone (either 100mg daily or 200mg cyclically)
- CONTROL PARTICIPANTS ONLY: regular menstrual cycles every 21-35 days
Key exclusion criteria (19 listed)
- CASE PARTICIPANTS ONLY: genetic POI etiology
- CASE PARTICIPANTS ONLY: any prior initiation of ERT
- systemic estrogen, progesterone or testosterone therapy within the past 6 months (including contraception, except for locally acting intrauterine devices - IUDs)
- lipid lowering therapy within the past 6 months
- use of antihypertensive medication within the past 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Brachial artery Flow Mediated Vasodilation (FMD)
Time frame: 6 months
Brachial artery flow-mediated dilation (FMD) is a non-invasive measure of endothelial function relevant to the development of incident cardiovascular disease. Brachial artery FMD will be reported as a percentage (%FMD), calculated by comparing the change in brachial artery diameter during reactive hyperemia to the baseline diameter. %FMD will be compared between case participants with POI and healthy control participants at baseline. The change in %FMD after 6 months of estrogen replacement therapy will be determined for case participants with POI.
2 secondary outcomes
Metabolic biomarkers
Time frame: 6 months
Immune/inflammatory biomarkers
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
- Individual participant dataSharing planned: Yes. Plans are for IPD to be shared to the NIH BioLINCC data repository.
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Gonadotropin-releasing Hormone Agonist (GnRHa) in Ovarian Preservation in SLE Subjects Receiving Cyclophosphamide as Determined by Questionnaires
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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.
Markella V. Zanni, MD study chair
MGH/HMS
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 Primary Ovarian Insufficiency and Premature Menopause, run by Massachusetts General Hospital 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 19 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: looking for participants now, as of the sponsor's last update on 8 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lauren Maldonado, MD, MPH (617-643-4420, LYMALDONADO@MGH.HARVARD.EDU), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brachial artery Flow Mediated Vasodilation (FMD) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Sep 2026.