Women taking part in two hormone replacement therapy trials in the United Kingdom and the United States have been informed that preliminary data from the US trial suggest a possible increase in risk of cardiovascular disease in early treatment. The women are being urged to stay in the trials.
The new data come from the Women's Health Initiative (WHI) study, which includes 27,000 women. They suggest a small increase in heart attack and stroke in women taking HRT, compared with those taking placebo, in the first two years of treatment.
In the UK, the Medical Research Council, which is co-ordinating the WISDOM (women's international study of long duration oestrogen after menopause) trial, says that its data monitoring committee has assessed the new US data and concluded that it provides no basis for stopping WISDOM.
While observational studies have raised hopes that long-term HRT will reduce the risk of cardiovascular disease, two recent randomised trials, both from the US, have already raised some doubts about this. The heart and estrogen/progestin replacement (HERS) study, which reported in 1998, found slightly more heart attacks in the HRT group in the first year of treatment. Over the whole four years of the study there was no excess of cardiovascular events in the HRT group, but neither was there any convincing evidence of the expected benefits. Last month, another study, the estrogen replacement and atherosclerosis (ERA) trial reported no difference between placebo and HRT in rate of progression of coronary artery narrowing (PJ, March 18, p431).
Both HERS and ERA involved women with established heart disease. In contrast, most of the women in the WHI and the WISDOM studies do not have heart disease.
Discussing the WHI findings at the 5th Cardiovascular Disease Prevention conference in London on April 6, Professor Elizabeth Barrett-Connor (professor of epidemiology, University of California, San Diego) said that she hoped that women would choose to continue with the WHI trial as it was important to be able to collect long-term data.
Asked by a general practitioner at the conference whether she would now recommend that he stopped a woman's HRT, Professor Barrett-Connor said: "If the woman is happy, her bones are being protected and her quality of life is good, then I would not stop the HRT." But she would not continue HRT with the aim of preventing heart disease. Measuring lipids and use of statins could be more appropriate. "I don't want to say that oestrogen is not the answer to the male/female difference in heart disease, but it is not clear yet," Professor Barrett-Connor said. "We may have been using the wrong doses or the wrong drugs," she added.
The HRT being used in both the WHI and the WISDOM studies is conjugated oestrogen, with and without medroxyprogesterone acetate.
There are no data yet from the placebo-controlled WISDOM study, which has so far enrolled around 1,000 of the planned 22,000 UK women. The MRC says that differences between active and placebo groups noted in the WHI study were small and could have been due to chance. "The WHI trial has told all of the women taking part about these findings and explained how this increasing uncertainty makes it even more important to find the answers about the long-term risks and benefits of HRT. MRC's independent assessment of the new data has reached the same conclusion," it says.