Effects of Estrogen on Heart Health in Women with Primary Ovarian Insufficiency

Not yet recruiting

• Conditions: Primary Ovarian Insufficiency; Premature Menopause; Metabolic Complications; Endothelial Function (FMD); Estrogen Replacement Therapy

• Registration Number: NCT06866119
• Lead Sponsor: Massachusetts General Hospital

Brief 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. 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 Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-04
• Study First Submitted QC: 2025-03-04
• Last Update Submitted: 2025-03-04
• Study First Posted: 2025-03-10
• Last Update Posted: 2025-03-10
• Study Start: 2025-04-15
• Primary Completion: 2026-04
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 45

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Brachial artery Flow Mediated Vasodilation (FMD)	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.

Secondary Outcome Measures

Name	Time	Method
Metabolic biomarkers	6 months	Urine and serum biomarkers relating to metabolism (including glucose and lipid metabolism, body composition)
Immune/inflammatory biomarkers	6 months	Urine and serum biomarkers relating to inflammation and immune activation

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States