New US research has revealed that a by-product of the breakdown of cholesterol can interfere with the mechanism by which oestrogen helps to ward off heart disease.
Senior author David Mangelsdorf believes that the results could help explain why hormone replacement therapy fails to protect some women from heart disease.
"This model may help explain why women are better protected than men from cardiovascular disease until they reach menopause," said Dr Mangelsdorf.
The researchers found that a molecule called 27-hydroxycholesterol (27HC) binds to the same receptors as oestrogen in the heart's network of blood vessels.
Whereas oestrogen keeps the blood vessel walls dilated and elastic, 27HC inhibits the production of nitric acid, which has been shown to relax muscles in blood vessels and aid cell growth and repair.
"In the Women's Health Initiative research program, the women who began taking HRT were an average of 13 years postmenopause," Dr Manglesdorf said.
"By the time they started taking this oestrogen again, the damage caused by 27HC binding to the estrogen receptors in the cardiovascular system may already have occurred. Once you lose oestrogen's protection for such an extended period of time, you can't get it back."