Effects of conventional or lower doses of hormone replacement therapy in postmenopausal women

Objective-The effects of hormone replacement therapy (HRT) can affect many aspects relevant to cardiovascular disease, including vasomotor function, inflammation, and hemostasis. Recent studies have demonstrated that current doses of HRT exert a mixture of both protective and adverse effects. In the current study, we compared the effects of lower doses of HRT (L-HRT) and conventional doses of HRT (C-HRT) on a variety of relevant cardiovascular parameters. Methods and Results-This randomized, double-blind, crossover study included 57 women who received micronized progesterone 100 mg with either conjugated equine estrogen 0.625 mg (C-HRT) or 0.3 mg (L-HRT) daily for 2 months. L-HRT showed comparable effects to C-HRT on high-density lipoprotein cholesterol and triglyceride levels, but not on low-density lipoprotein cholesterol levels. C-HRT and L-HRT significantly improved the percent flow-mediated dilator response to hyperemia from baseline values (both P < 0.001) by a similar degree (P = 0.719). C-HRT significantly increased high-sensitivity C-reactive protein (hsCRP) levels from baseline values (P < 0.001); however, L-HRT did not significantly change hsCRP (P = 0.874). C-HRT and L-HRT significantly decreased antithrombin III from baseline values (P < 0.001 and P = 0.042, respectively). C-HRT significantly increased prothrombin fragment 1 + 2 (F1 + 2) from baseline values (P < 0.001); however, L-HRT did not significantly change F1 + 2 (P = 0.558). Of interest, the effects of C-HRT and L-HRT on hsCRP, antithrombin III, and F1 + 2 were significantly different (all P < 0.001). C-HRT and L-HRT significantly reduced plasma PAI-1 antigen levels from baseline values (P = 0.002 and P = 0.038, respectively) to a similar degree (P = 0.184). Conclusions-Compared with C-HRT, L-HRT has comparable effects on lipoproteins, flow-mediated dilation, and PAI-1 antigen levels. However, L-HRT did not increase hsCRP or F1 + 2 levels, and it decreased antithrombin III less than C-HRT.