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

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).