Introduction:
We have previously reported the favourable effect of transdermal estradiol (E2), relative to oral conjugated equine oestrogen (CEE), on ultrasensitive C-reactive protein after 12 months of treatment in a retinoid-placebo controlled two-by-two randomised breast cancer prevention trial (ref). Here we investigate the changes in lipids and clotting profile in patients of the same trial.
Methods and Results:
Recent postmenopausal women were randomised to either oral CEE 0.625 mg/d and placebo (n=55), CEE and fenretinide 200 mg/d (n=56), transdermal E2 50 µg/d and placebo (n=59), or E2 and fenretinide 200 mg/d (n=56). Sequential medroxyprogesterone acetate 10 mg/d was given in each group. After 12 months there was a statistically significant effect of the route of administration of hormone replacement therapy (HRT) on fibrinogen levels the median percent change being -5.7% with CEE and -1.1% with E2 (P=0.012). Total cholesterol decreased in all arms (P<0.0001). HDL-C decreased significantly with transdermal E2 (P=0.006) compared to oral CEE and with fenretinide relative to placebo (P<0.001). Triglycerides exhibited an opposite modulation by HRT route, with a 21.4% median increase with oral CEE and an 8.6% reduction with transdermal E2 (P<0.0001). Antithrombin-III showed a 4% borderline significant reduction in the fenretinide arm relative to placebo, irrespective of HRT administration route (P=0.055).
Conclusions:
Our data indicate that transdermal E2 may be preferable to oral CEE based on its safer cardiovascular risk profile. Fenretinide modified some cardiovascular risk biomarkers and confirmed a safer profile compared to other retinoids.
Further information:
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