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While CVD etiology is multifactorial, mitochondrial dysfunction, characterized by reduced content, impaired energy production, and increased oxidative stress, is an underlying contributor. These impairments reduce the ability of the heart and vasculature to support peripheral tissues. Estradiol, a key sex hormone with widespread physiological effects, supports mitochondrial function, lipid oxidation, vascular endothelial cell and smooth muscle function, and redox balance, contributing to its cardioprotective effects in women. Perimenopause is marked by hormonal variability and an overall decline in estradiol concentrations that may compromise mitochondrial quality and vascular function, increasing CVD risk. Mitochondrial quality and maintenance are largely controlled by the peroxisome proliferator\u2010activated receptor gamma coactivator\u20101 (PGC\u20101) family of transcriptional coactivators. Impairments in PGC\u20101 isoform expression have been linked to cardiovascular and metabolic decline and may be exacerbated by estradiol loss during the menopause transition. However, the mechanisms by which estradiol signaling regulates PGC\u20101 isoforms, and how this interaction contributes to mitochondrial dysfunction and CVD development following menopause, have not been comprehensively described. Thus, this review aims to highlight current evidence on the individual and overlapping roles of estradiol and PGC\u20101 isoforms and examine how their interaction may contribute to the development of CVD following menopause.<\/jats:p>","DOI":"10.14814\/phy2.71155","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:16:08Z","timestamp":1792646168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estradiol\u2014\n                    <scp>PGC<\/scp>\n                    \u20101 signaling in mitochondrial health: Implications for perimenopause and cardiovascular disease"],"prefix":"10.14814","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9067-9014","authenticated-orcid":false,"given":"Alyssa L.","family":"Parten","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Disease, Department of Medicine University of Alabama at Birmingham  Birmingham 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