Clinical trial NCT06866119: Effects of Estrogen on Heart Health in Women with Primary Ovarian Insufficiency
Official title: Effects of Estrogen Replacement on Cardiometabolic Endpoints in Women with Primary Ovarian Insufficiency
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
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
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2025-03-10
Enrollment: 45
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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).

Eligibility criteria: Inclusion criteria (I):

* 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

Exclusion criteria (E):

* 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
* stable or unstable angina
* self-reported history of heart failure
* pregnancy or breastfeeding
* concurrent enrollment in conflicting research study

Primary outcomes:
measure: Brachial artery Flow Mediated Vasodilation (FMD)
timeFrame: 6 months
Secondary outcomes:
measure: Metabolic biomarkers
timeFrame: 6 months
measure: Immune/inflammatory biomarkers
timeFrame: 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: MGH/HMS
name: Markella V. Zanni, MD
role: STUDY_CHAIR
References: