July 12, 2007
Medical News Today

More Research Confirms Danger Of HRT For Older Women

A new study from the UK, Australia and New Zealand confirms the findings of American research, that women who start on hormone replacement therapy (HRT) many years after the menopause increase their risk of major heart problems and blood clots.

The study is published in the early online issue of the British Medical Journal (BMJ).

The project was called the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) and started in 1999, with researchers drawn from Australia's University of Adelaide, the Wellington School of Medicine and Health Sciences in New Zealand, and the UK's Medical Research Council.

The researchers set up a multicentre, randomized, double blind placebo controlled trial in 384 general practices in the UK, 91 in Australia and 24 in New Zealand. A double blind trial is one where neither the patient nor the drug administrator knows whether they are given the active agent or a placebo.

Over 5,500 healthy women started treatment from a screened pool of over 56,000.

The purpose of the trial was to assess the risks and benefits, in the longer term, of a combined HRT against placebo or oestrogen only HRT.

The patients were randomly assigned to one of three groups: combined HRT, oestrogen only HRT, and placebo.

Their average age was 62.8, with most of them aged between 58 and 67.6 years.

The combined HRT group took a daily oral dose of 2.5 mg of conjugated equine oestrogens plus 5.0 mg of medroxyprogesterone acetate. The oestrogen only HRT group took a daily oral dose of 0.625 mg of oestrogen.

The original plan was that the trial would last for 10 years, until 2009, but it was stopped early, when the large scale Women's Health Initiative (WHI) study in the US, which was similar in design, was stopped in 2002 after it became clear that it was putting the health of patients at risk.

The WISDOM trial had produced enough data however for a meaningful and valid analysis.

The results showed that:
There was a significant increase in number of major cardiovascular events (7 versus 0) and venous thromboembolisms (22 versus 3) in the combined HRT group (2,196 patients) compared to the placebo group (2,189 patients).
There were no statistically significant differences in incidence of breast and other cancers, cerebrovascular events, fractures and overall deaths between the same two groups.
There was no significant differences between the outcomes of combined versus oestrogen only HRT.
The researchers concluded that:

"Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause."

They said the results were consistent with the findings of the WHI study in the US as well as secondary prevention studies.

More research would be needed to determine the effect of starting HRT nearer to the menopause, suggesting it could yield a different result, they added.

In an editorial in the same issue of the BMJ, Dr Helen Roberts from the University of Auckland, New Zealand, said that "postmenopausal hormone therapy has come full circle". In fact this is the title of her article.

She said that HRT was first used to treat the symptoms of the menopause: hot flashes, night sweats and vaginal dryness. But then doctors started prescribing it to prevent heart problems, and now it has come back full circle to its original purpose, to treat the symptoms of menopause. She said it is still the best treatment available for these symptoms.

However, she reminded readers that women should only use the lowest dose necessary to relieve the symptoms, most of which are self-limiting in any case. And the dose should not be open-ended but stopped as soon as sufficient relief is gained.

She said that healthy women at the start of menopause are not at high risk and taking HRT for a few years to relieve the symptoms of menopause is unlikely substantially to increase it.

As always, the advice to a woman considering taking HRT is talk to your doctor and make sure that he or she includes a review of the risks that are relevant to your individual situation, while being aware of the latest research.

HRT use fell by 50 per cent in the UK following the publication of the WHI study.