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

NCT06866119 | Not Yet Recruiting

• 2 other identifiers: 2025P000601GR1000466
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

primary ovarian insufficiency; premature menopause; estrogen replacement therapy; cardiovascular disease prevention; POI; ERT

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (2)

• Metabolic biomarkers

  6 months

• Immune/inflammatory biomarkers

  6 months

Study Arms (2)

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.

Eligibility Criteria

• Age: 30 Years - 40 Years
• Gender Eligibility Details: Individuals assigned female at birth are eligible to participate in the study regardless of gender. However, participants may not be on systemic estrogen, progesterone or testosterone therapy, aside from the relevant prescribed estrogen replacement therapy for those with POI.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Primary Ovarian Insufficiency; Menopause, Premature

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Markella V. Zanni, MD

  MGH/HMS

  STUDY CHAIR

Central Study Contacts

Sara L. Stockman, MD, PhD

CONTACT

617-643-4420; sstockman@mgh.harvard.edu

Markella V. Zanni, MD

CONTACT

617-726-7948; mzanni@mgh.harvard.edu

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Endocrine Fellow

Study Record Dates

• First Submitted: March 4, 2025
• First Posted: March 10, 2025
• Study Start: March 1, 2026
• Primary Completion: April 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• 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.

Locations

US (1)