The aim of this study was to investigate whether transdermal estrogen hormone therapy could eliminate the adverse effects of oral estrogen on the size of low-density lipoprotein (LDL) particles in post-menopausal women who had been treated with estrogen either orally (0.625mg conjugated equine estrogen daily) or transdermally (17-β-estradiol patch – 50 µg/daily). This involved measuring the plasma concentrations of lipids, the size of LDL particles and susceptibility of LDL particles to oxidative modification. Transdermal estrogen administration was associated with a decrease in plasma concentration of triglyceride and an increase in size of LDL particles. Overall this suggests that transdermal delivery has the potential to ameliorate the adverse effects caused by oral estrogen hormone therapy on size and oxidative susceptibility of LDL particles, properties which are associated with an increased risk of coronary heart disease.