Hormone replacement therapy prevents coronary artery disease in ovariectomized cholesterol‐fed rabbits

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Abstract
The prevention of coronary artery disease in women is of considerable importance. We have therefore investigated the influence of oestrogen monotherapy and oestrogen‐progestogen replacement therapy on coronary artery disease using a simple morphometric method. We studied sixty‐three cholesterol‐fed rabbits for nineteen weeks. They were randomized to either ovariectomy (51 rabbits) or a sham operation (12 rabbits). The ovariectomized rabbits were randomized to receive either 17 β‐estradiol, 17 β‐estradiol plus norethisterone acetate, 17 β‐estradiol plus levonorgestrel, or placebo. The rabbits with the sham operation received placebo. The hormone therapies reduced the development of coronary artery disease compared to placebo (p<0.0001). Furthermore, the coronary artery disease was attended by atherosclerosis in the more distal parts of the coronary arteries (p< 0.0001), the thoracic aorta (p<0.0001) and the abdominal aorta (p<0.0001), and by a reduced relative heart weight (p<0.05). We conclude that coronary atherosclerosis can be determined quantitatively by morphometry in rabbit arteries. Estradiol monotherapy reduces coronary atherosclerosis in cholesterol‐fed rabbits and the addition of norethisterone acetate or levonorgestrel does not attenuate this beneficial effect.