Since as early as the 1940s, women of a certain age have had the option of hormone replacement therapy (HRT) to treat the symptoms of the menopause. When it was first introduced, it was heralded as the elixir of youth; a tablet that could keep women young and feminine for the rest of their lives.
But for 60 years it has been dogged by controversy and mixed messages from the medical community. All this came to a head in July 2002 with the publication of a report by the Women’s Health Initiative (WHI) linking it to breast cancer, strokes and heart attacks. But now a reassessment of the research has concluded that women and their doctors had been unnecessarily panicked by this study and as a result menopausal women had been warned against HRT without real reason. So what is the truth? Is HRT really safe?
This was not the first health scare associated with HRT. As early as the 1950s, doctors became concerned about reports suggesting that women taking HRT had increased risk of uterine cancer. Over time they came to realise that this was a result of oestrogen-only HRT and that these risks could be cancelled out by adding in progesterone, another female hormone. With this initial panic apparently dealt with, attention turned to the positive effects of HRT. Research showed that it was protective against heart disease and heart attacks as well as helping prevent osteoporosis — thinning of the bones — and associated risk of fractures.
People began taking HRT not for aesthetic reasons but for its apparent health benefits. The WHI study changed all this. It was the first large-scale, double-blind, placebo-controlled study into HRT, and followed more than 16,000 women, for an average of five and a half years. The women in the study were aged between 50 and 70, although most were over 60. Half of the women took a placebo, the other half HRT.
The study found a statistically significant increase in rates of breast cancer and strokes. It also showed a higher risk of heart attacks, contradicting previous research. So shocking were the findings that the study was halted three years early so that the results could be made public. Its publication provoked widespread panic. Doctors who had trumpeted HRT began advising caution, with many recommending against taking it all together. The number of prescriptions halved in the year following publication and has never recovered.
Following the WHI study, guidelines were drawn up stating that women in their fifties should use HRT for the shortest period possible and to limit it to five years. But the latest reassessment of the research by scientists — including two involved in conducting it to begin with — found that the results were ‘wrongly generalised’ to the whole population, when it had looked mainly at HRT in women over 60.
Another, UK study that appeared to support the WHI findings has also come under criticism for the way in which it was designed and interpreted. Indeed, subsequent research has shown that the benefits of HRT outweigh the risks in women under 60, or within ten years of the menopause: for these groups, it has been shown to reduce rates of bowel cancer, osteoporosis and heart disease, and indeed overall death rate. What the WHI study did show is that for women who are ten years or more past the menopause, the risks of taking HRT far outweighed the benefits.
This controversy teaches us several important lessons. First, it is a good illustration of the frustrating limits of research. Scientific understanding is constantly changing and evolving and new pieces of evidence support or challenge received wisdom. Uncertainty is inherent in medical knowledge.
In hindsight, it was an error for the medical profession to respond so quickly to the results of just one study.
Given the large numbers of people affected by the menopause, such research was bound to attract media attention, which can generate panic before a proper analysis is completed. But doctors and their patients must remember that while sometimes speedy action is warranted — sometimes, it undoubtedly saves lives — there’s also a risk of dismissing something on evidence that does not withstand in-depth scrutiny or is shown to be only part of a larger picture.
In this instance doctors were, of course, in an impossible situation. To ignore the study would have appeared negligent. But reacting before the results were evaluated, challenged and replicated has resulted in women being scared off a treatment that might have really helped them.
At the heart of the concern was one statistic that fuelled much of the backlash against HRT. The WHI study reported that it increased the risk of breast cancer by 26 per cent. But this terrifying-sounding statistic is not quite what it appears to be. There are different ways of presenting risk, and the approach chosen in the 2002 research — and the press releases about it — came in for criticism in the re-evaluation.
For example, if the risk of having a stroke is two in 100, and a medication increases it to three in 100, then it could be said that the treatment has increased the risk of strokes by 1 per cent (from 2 per cent to 3 per cent). This way of presenting the data is called the ‘absolute risk’.
However, it could equally be said that it has increased the risk of stroke by 50 per cent. This is called ‘relative risk’ — and it’s how the WHI study findings were reported. The problem is that the relative risk doesn’t really give us enough information to assess the actual risk of someone developing breast cancer while on HRT, because on its own it doesn’t tell us how many people would develop it anyway. In fact, in the case of breast cancer and HRT, while the relative risk is 26 per cent, the absolute risk is 0.4 per cent. This means there are four extra cases of breast cancer per 1,000 women taking HRT over a five-year period.
When you take into account that the study didn’t properly assess the risk and benefit on middle-aged women because they were under-represented in the sample, it becomes clear why the WHI study has been criticised. Like any treatment, HRT has risks and benefits. The doctor and patient need to weigh these up depending on the woman’s unique position and come to a decision about whether or not HRT is right for her.
What can be said for certain, however, is that academics and the media must remember to report scientific findings in a responsible manner and the general public and doctors must remember that one trial rarely provides enough information to assess fully the risks and benefits of a treatment for all patients.