American Chemical Society Meeting,
New York, September 2003

Oestrogen chemistry hints at HRT harm

HELEN PEARSON

Before 2002 around 6 million US women were prescribed HRT. © Digital Vision

A quarter of women have hormonal chemistry that may put them at greater risk of health problems from hormone-replacement therapy (HRT), say chemists.

Two major clinical trials, in 2002 and 2003, revealed that women taking prolonged courses of oestrogen and progesterone are more likely to suffer breast cancer, heart disease and stroke. Why is not clear.

One answer may lie in oestrogen's chemical fate, said delegates at this week's American Chemical Society meeting in New York City. Chemists already knew that cells convert oestrogen in HRT into damaging compounds called catechols - one of these morphs into a cancer-causing substance called a quinone. An enzyme inactivates catechols alleviating some of the damage. Its name is catechol-O-methyltransferase or COMT.

But one form of COMT is itself more susceptible to inactivation, and is weaker at fighting catechols, James Yager of Johns Hopkins University in Baltimore, Maryland, and his colleagues revealed at the meeting.

One in four women carries two copies of the gene that encodes this susceptible variant of COMT. They might be at greater risk of breast cancer after HRT, Yager speculates.

But COMT may be just one of many proteins that are important in creating the side-effects of HRT, warns Judy Bolton, who studies oestrogen chemistry at the University of Illinois at Chicago. "Until we get a large study [in humans], we can't pinpoint which is important," she says.

Two camps

Before 2002, around six million post-menopausal women in the United States were prescribed HRT to alleviate menopausal symptoms and, it was assumed, to cut the risk of osteoporosis, heart disease and dementia.

In July of that year, a large US trial called the Women's Health Initiative was halted when the treatment's health risks became clear. Another study involving a million British women, published in August this year, backed up these findings.

Until we get a large study in people we can't pinpoint which protein is important Judy Bolton University of Illinois, Chicago

One way to explore HRT's impact is to screen the blood of women from the trials for telltale genes or metabolites, says Sylvia Wassertheil-Smoller of Albert Einstein College of Medicine in New York, who led the Women's Health Initiative. "It may be a clue to the mechanism," she says.

Chemistry aside, many biologists assume that oestrogen causes its side-effects by binding to receptors on the cell's surface and boosting the activity of cancer-causing genes. "These two camps traditionally don't talk to each other," says Bolton.

© Nature News Service / Macmillan Magazines Ltd 2003