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American Chemical Society Meeting, New York, September 2003

Oestrogen chemistry hints at HRT harm
Metabolism might explain cancer risk of hormone-replacement therapy.
9 September 2003

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

http://www.nature.com/nsu/030908/030908-3.html