Estrogens as antioxidants – reducing heart disease in younger postmenopausal women

HRT could be used to protect younger postmenopausal women from heart disease. An article published in the journal Lipids in Health and Disease shows that estrogens commonly used in HRT reduce the build up of harmful oxidised lipoproteins, which can lead to heart disease, by acting as antioxidants.

It is well known that high-density lipoproteins (HDL) protect against heart disease while low-density lipoproteins (LDL) promote it. However, recent research has shown that the relationship is not that simple. The effectiveness of both types of lipoprotein change when they are oxidised by free radicals – highly reactive by-products of metabolism. If LDL becomes oxidised its ability to cause heart disease increases. If HDL becomes oxidised its ability to protect against heart disease is lessened.

Researchers from St. Michael’s Hospital, part of the University of Toronto, have shown that estrogens can act as antioxidants, which neutralise free radicals, and hence protect HDL from oxidation. In addition, high levels of HDL are able to protect LDL from oxidation, and this ability is strongly enhanced when estrogens are present.

Dr Bhagu Bhavnani’s team, who carried out the research, write, “The inhibition of HDL oxidation and the enhancement provided by estrogens toward the inhibition of LDL oxidation may be another way in which estrogens reduce the risk of coronary heart disease in healthy young postmenopausal women.”

Although recent randomised control trials have shown that HRT in older women may not reduce the incidence of coronary heart disease, Dr. Bhavnani believes that this is not the whole story. Although his team carried out experiments in test tubes rather than in human subjects they saw that estrogen had beneficial effects at concentrations lower than those found in women on HRT. He urges that, “randomised control trials using lower doses of HRT, different estrogens and progestins, and in younger postmenopausal women, from 50 to 60 years, are urgently needed to resolve the confusion created by recent studies”.

The research team used blood taken from men and postmenopausal women to carry out experiments in vitro. They measured the resistance of HDL to oxidation in the presence or absence of increasing concentrations of eleven different estrogens. All of these estrogens are components of a combined estrogen supplement that is commonly used for HRT by postmenopausal women. They then assessed whether the presence of HDL increased the resistance of LDL to oxidation, and if this resistance was further enhanced by the addition of estrogen.

They found that all the estrogens tested were able to protect HDL from oxidation and to enhance HDL’s ability to protect LDL from oxidation. They also found that different estrogens had different potencies as antioxidants, with an estrogen called Equilenin being the most effective.

According to recent data from the British Heart Foundation, women are five times less likely to suffer from coronary heart disease than men. This reduced risk can only partly be explained by differences in behaviour, such as smoking or stress levels. As women’s risk of heart disease increases after menopause it has been suggested that ovarian hormones such as estrogen play a role in protecting younger women from the disease. The research from Bhavnani’s team supports this idea.