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Effects of Estrogen Replacement on Cardiovascular Risk in Women with Primary Ovarian Insufficiency

Award Number: F32HL182155
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2025
PERIOD OF PERFORMANCE END DATE: 09/29/2026

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Effects of Estrogen Replacement on Cardiovascular Risk in Women with Primary Ovarian Insufficiency - PROJECT SUMMARY/ABSTRACT Primary ovarian insufficiency (POI) is a condition of accelerated reproductive aging, resulting in hypergonadotropic hypogonadism and, often, cessation of menses before age 40. POI is associated with significant comorbidities, including reduced bone mineral density and greater cardiovascular disease (CVD). Compared to women who experience menopause at the median age of 51, those with POI are at a greater risk of ischemic heart disease, ischemic stroke, and cardiovascular mortality. Current guidelines recommend that women with POI undergo estrogen replacement therapy (ERT) from diagnosis until the median age of natural menopause to mitigate the effects of deficient endogenous estrogen during this “vulnerable period.” These recommendations are primarily based on evidence that ERT preserves bone density and improves CVD risk surrogates. However, there is no longitudinal outcome data to confirm that ERT prevents CVD in women with POI. Despite the established role for ERT in bone health and potential cardioprotective effects suggested by recent studies, ERT remains underutilized among women with POI. Only about half of women with POI ever initiate ERT, and even fewer continue therapy for the recommended duration. Barriers to ERT uptake may include uncertainty regarding the impact on CV outcomes. While early trials of ERT in older postmenopausal women raised concerns about CVD risks, more recent studies find that newer ERT formulations, prescribed to younger women closer to the age of natural menopause, have neutral to beneficial effects on CV health. To optimize the health of women with POI throughout the lifespan, it is critical to address the gaps in evidence supporting ERT for CVD prevention. In Aim 1, we will leverage electronic health data from Mass General Brigham to identify women with POI at risk of ERT under-prescription and quantify long-term CVD risk in relation to ERT use. In Aim 2, we will conduct a prospective physiology study to evaluate the effects of 6 months of physiologic, transdermal ERT on cardiometabolic risk markers, including endothelial function, in women with POI compared to healthy matched controls. These findings will strengthen the evidential basis for guideline-driven cardiometabolic preventive care in women with POI. Aligned with my training plan and supported by a robust mentorship team, this work, facilitated by the Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship, will contribute to my overarching goal of becoming an independent endocrine physician-scientist dedicated to improving cardiometabolic health outcomes for women.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$88,060 )
2026	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	12/9/2025	NEW	-$88,060
														Subtotal = -$88,060

Issue Date FY: 2025 ( Subtotal = $88,060 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	8/18/2025	NEW	$88,060
														Subtotal = $88,060

Grand Total All Awards = $0

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Effects of Estrogen Replacement on Cardiovascular Risk in Women with Primary Ovarian Insufficiency

Award Number: F32HL182155

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2025

PERIOD OF PERFORMANCE END DATE: 09/29/2026

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