OBJECTIVE: Recent large, prospective, randomized studies show that hormone therapy (HT) does not confer a protective effect against cardiovascular disease (CVD) but may in fact increase cardiovascular events. Low plasma adiponectin levels are considered to be related to the development of atherosclerosis and CVD. The purpose of this study was to determine the effect of long-term hormone therapy on plasma adiponectin levels in postmenopausal women. METHODS: We recruited a total of 88 postmenopausal women aged 55-69 years old. Our sample consisted of 44 women who had undergone estrogen plus progestogen therapy (EPT) for more than 5 years and 44 age-matched women who had not received HT. We measured plasma adiponectin levels, the serum levels of their lipid profiles, high-sensitivity C-reactive protein (hs-CRP), fasting glucose levels, fasting insulin levels and estradiol levels. Their medical histories including their age at menopause, vitamin use, exercise, alcohol ingestion and cigarette smoking were also assessed by a questionnaire. RESULTS: The mean duration (mean+/-S.D.) of HT was 8.4+/-2.4 years. The mean serum estradiol level (mean+/-S.D.) of the HT group was 47.9+/-36.8 pg/L, significantly higher than that of the non-HT group (p<0.01). Plasma adiponectin levels were significantly lower in the HT group than in the non-HT group (p<0.05). Plasma adiponectin levels were inversely correlated to cholesterol, triglycerides and HOMA-IR (r=-0.33, p<0.05; r=-0.40, p<0.01 and r=-0.30, p<0.05, respectively) in the non-HRT group, but such correlations were not seen in the HT group. In the multivariate analysis, hormone therapy and serum estradiol levels were the independent factors associated with plasma adiponectin levels after adjustments were made for potential confounders. CONCLUSION: Plasma adiponectin levels were significantly lower in postmenopausal women with long-term HT than in those without HT, suggesting that long-term HT may modulate plasma adiponectin level in postmenopausal women.