Most observational studies indicate that hormone replacement therapy (HRT) protects women from cardiovascular disease. Two recent randomized trials, however, showed no reduction in coronary events with HRT in postmenopausal women. A randomized study evaluating subclinical atherosclerosis showed a beneficial effect of estrogen. In the current study we evaluated the association between HRT and coronary artery atherosclerosis, as quantified by coronary artery calcium score. Current users of HRT were significantly more likely to have a coronary artery calcium score less than 100 and were less likely to have a score greater than 400 than non-HRT users. After adjustment for cardiac risk factors, current use of HRT was associated with a significant reduction of coronary artery calcium score (-28; 95% confidence interval, -48 to -10). The average age of users was 59 yr, the mean duration of use was 9 yr, and the duration of HRT use was significantly associated with a reduction in coronary artery calcium. These results suggest that HRT suppresses atherosclerosis in the coronary arteries. The failure to modify the cardiovascular event rate in clinical trials could result from the adverse effect of HRT on complicated lesions. Additional mechanistic studies may help identify therapeutic strategies that could maximize a potential benefit of HRT on early atherogenesis while minimizing adverse proinflammatory and procoagulant effects on complicated plaque lesions.

To characterize further the impact of thyroid dysfunction on the transport of cholesterol in plasma, we studied plasma lipids and cholesteryl ester transfer (CET) in 10 hypothyroid women before and 3 months after thyroid replacement therapy. CET, estimated as the net mass transfer of CE from HDL to the apolipoprotein B-containing lipoproteins (very low density and low density lipoproteins) was significantly decreased at 4 h (P < 0.05) and 6 h (P < 0.001) when the patients were hypothyroid (T4, 2.01 +/- 1.4; TSH, 55.5 +/- 39.9 microIU/mL) and increased to normal levels after hormone replacement and restoration of eumetabolism. Plasma lipid levels in the hypothyroid state closely resembled those in a female reference group, although total plasma cholesterol fell significantly [pretreatment, 218 +/- 36 vs. posttreatment, 192 +/- 49 (P < 0.025); control, 218 +/- 28 mg/dL (mean +/- SD)] after treatment. Concentrations of cholesteryl ester transfer protein (CETP) were unchanged (pretreatment, 2.35 +/- 0.83 vs. posttreatment, 2.30 +/- 1.19 mg/dL). The results of recombination studies using different lipoprotein fractions suggest that decreases in CET during hypothyroidism may be secondary to acceptor lipoprotein (low density and very low density lipoprotein) changes in the hypothyroid state and not to changes in the concentration of CETP itself.

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