An observational study in Primary Ovarian Insufficiency, Premature Menopause and Metabolic Complications, sponsored by Massachusetts General Hospital. Recruiting at 1 site in United States. Open to female participants aged 30 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-08.
Sponsored by Massachusetts General Hospital · Observational
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.
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).
181 studies on the registry are indexed under Primary Ovarian Insufficiency; 48 are open to participants now.
This study's planned enrollment of 45 is below the median of 100 across 61 observational studies indexed under Primary Ovarian Insufficiency.
Browse Primary Ovarian Insufficiency studies →Massachusetts General Hospital is the lead sponsor of 2,586 studies on the registry; 447 are open to participants now.
Of its 222 completed or terminated interventional studies of FDA-regulated products, 168 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion criteria (E):
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
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.
Time frame: 6 months
Metabolic biomarkers
Urine and serum biomarkers relating to metabolism (including glucose and lipid metabolism, body composition)
Time frame: 6 months
Immune/inflammatory biomarkers
Urine and serum biomarkers relating to inflammation and immune activation
Time frame: 6 months
Plan to share: Yes — Plans are for IPD to be shared to the NIH BioLINCC data repository.
Supporting information: Study protocol, Informed consent form
Time frame: Data will be made available 12 months after study completion and will remain available for a duration of time consonant with NIH policies.
Access criteria: Access criteria are as per the NIH BioLINCC data repository.
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