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Friday, 29 March, 2002, 05:19 GMT
Gene determines HRT heart benefit
Doctors can test cholesterol levels
Doctors can test cholesterol levels
Levels of "good" cholesterol could be boosted in women taking hormone therapy - if they have a certain gene mutation, US researchers suggest.

Identifying the genetic difference could lead to a test to help determine whose heart health would benefit from the therapy.

Good cholesterol - high-density lipoprotein (HDL) - is believed to help prevent heart disease, especially in women.

Whether hormone replacement therapy prevents or slows heart disease in postmenopausal women has proved a controversial subject in recent years.


Our research suggests that genetics may identify some women who respond more favourably to hormone replacement therapy than others

Professor David Herrington, Wake Forest University Baptist Medical Center
This latest research suggests genetics may play a part in determining who does benefit.

However, the researchers say it is too soon for doctors to begin testing for the gene variant and they should continue to follow expert guidance on the use of oestrogen and other therapies for preventing heart disease in women.

Genetic predisposition

Doctors at Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina looked at 309 women with heart disease who took HRT or a dummy version.

They discovered that women who took HRT who had a common mutation in the oestrogen receptor alpha gene had dramatic increases in good cholesterol.

The increase in HDL was more than twice as much as in women without the gene variant.

Around 18% of women had the genetic predisposition to high levels of HDL cholesterol when taking oestrogen.

The increase seen was two or three times what is normally achieved with cholesterol drugs used to raise HDL, the researchers said.

Previous research into cholesterol drugs show that raising HDL to this extent might reduce heart disease events by 25 to 40%.

David Herrington, a professor of cardiology who led the research, said: "Studies with oestrogen haven't shown the same connection between HDL raising and heart disease benefit, but it's possible this was because we were focusing on all women, rather than the sub-group with this gene variant."

Sensitive genes

He added: "Our research suggests that genetics may identify some women who respond more favourably to hormone replacement therapy than others."

But he added: "More research is needed to see if the higher HDL levels translate into fewer heart attacks.

"We also need to know if women with the gene variant are more sensitive to oestrogen's other effects.

"But, this finding is exciting because it shows the potential for doctors to use genetic testing to improve decisions about drug therapy."

Professor Herrington said scientists also needed to look at whether women with this gene variant are also more sensitive to beneficial effects of oestrogen, such as maintaining bone mineral density and reducing hot flashes, and negative ones, such as formation of blood clots in the legs.

"It makes sense that if one area, cholesterol, is affected, others might be too," he said.

Alison Shaw, medical spokesperson for the British Heart Foundation, told BBC News Online: "There is increasing evidence that HRT may help increase the levels of protective cholesterol in the body.

"This research suggests that some women may have a gene that makes them more responsive to HRT.

"This may lead to an increase in the manufacture of good cholesterol which has a protective effect against coronary heart disease (CHD).

But she added: "Although some research shows that HRT may help reduce the risks of CHD, it is still not usually prescribed for that sole purpose.

"As the researchers themselves suggest, further research regarding the link between high levels of good cholesterol and the reduction of heart attacks is needed.

"Until further studies have been carried out, the current guidelines for prescribing HRT for women should be adhered to."

The research is published in the New England Journal of Medicine.

See also:

23 Jul 01 | Health
HRT heart treatment 'caution'
17 Apr 00 | Health
HRT 'reduces heart disease risk'
29 Aug 99 | Health
HRT may not protect the heart
07 Nov 01 | Health
Tests boost HRT 'alternative'
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