Coronary Artery Disease in Postmenopausal Women with Hypothyroidism: Interaction of Estrogen Deficiency and Thyroid Insufficiency

Abstract

Objective: to systematize data on the mechanisms by which estrogen deficiency and thyroid insufficiency potentiate coronary artery disease (CAD), and to summarize available evidence on the cardiovascular significance of subclinical hypothyroidism in postmenopausal women. Materials and methods: a structured narrative review was conducted using PubMed, Scopus, eLIBRARY.RU and CyberLeninka databases for the period 2000–2024. Search terms included: hypothyroidism, menopause, coronary artery disease, estrogen deficiency, dyslipidemia, endothelial dysfunction. Inclusion criteria: cohort and case-control studies (n ≥ 100), meta-analyses (≥ 5 primary studies), systematic reviews with described methodology. A total of 23 sources were included in the final analysis. Results: overt hypothyroidism increases total cholesterol by up to 50%; subclinical hypothyroidism raises it by 10–20%. Concurrent estrogen and thyroid hormone deficiency suppresses LDL receptor expression through independent promoter elements (ERE and TRE), reducing LDL clearance by 60–70% in hepatocyte experiments. The Rotterdam Study (n = 1,149 women over 55 years) demonstrated a twofold increase in CAD risk associated with subclinical hypothyroidism (OR 2.3; 95% CI 1.3–4.0) after adjustment for traditional risk factors. Conclusions: the synergism of two hormonal deficiencies elevates cardiovascular risk to a clinically meaningful level. Standard risk scores (Framingham, SCORE) do not incorporate thyroid status and may underestimate prognosis in this population. Prospective RCTs stratified by menopausal status and TSH level are needed.