HRT on Trial?

Posted on by Mark

Few if any things have had such a pharmaceutical roller-coaster ride than Hormone Replacement Therapy (HRT).  Let’s just look at the last 15 years.

In the mid- to late nineties, HRT was the flavour of the month.  Eminent writers, such as John Guilbaud, could write in their text-books that a women taking HRT was up to 50% less likely to suffer a myocardial infarction (MI) than one who was not.  It was even advocated that positive decisions should be made to prescribe HRT to women at risk of an MI.

Why did he say this?  Well it was based on the findings of a huge Observational Trial called the American Nurses Study.  Like all such studies, the investigators, as the name suggests, merely observed what was happening and did not intervene in any way at all.  They noted a large reduction in cardiovascular events in those nurses who were taking HRT.

However, ten years ago, there was a cataclysmic event: the reporting of the Women’s Health Initiative and, later, the Million Women Study (a now discredited observational study).  This was an interventionist trial looking at women taking and not taking HRT with an average age of 63.  It not only found no cardiovascular event benefit from taking HRT but a small increase in cancers.

The result of this was shattering and prescriptions for HRT plummeted so that today, half the number of people are taking HRT that were taking it ten years ago.  Everyone assumed that, in the American Nurses Trial, those taking HRT were less at risk of cardiovascular disease for other reasons (perhaps they smoked less).

Even at this time, some of the more thoughtful experts expressed doubts about the wisdom extrapolating results from women in their mid-sixties to those of the age at which women normally started taking HRT; in other words late forties and early fifties.  Some experts said that not only was the œstrogen/progesterone dose far higher than is currently used but the results were affected by the number of problems occurring in those over 70.  Few people in the real world in this age group take HRT.

Nevertheless, we were all persuaded to be much more guarded in whether we recommend a patient to take HRT.  This advice is currently reflected in our own course, Women’s Health Management in Primary Care.  Over a million women in the UK stopped taking HRT.

Now the situation has been blown apart with the publication of a new report from Denmark where over 1,000 people were randomly allocated into a group taking HRT and another group who were not.  It ran for a remarkable 16 years.

After 10 years, the figures showed that in the group who were not taking HRT, 33 had either died from or had suffered a myocardial infarction whereas in the group taking HRT, the figure was just 16.  Those taking HRT were then encouraged to stop taking the drug(s).  Even in this period, the women who had never taken HRT were 40% more likely to suffer a myocardial infarction or die.

There was no difference in either group in the number of stroke, blood clots or any type of cancer.  The number of those with breast cancer were less in the treated group.

The investigators and many commentators point to the importance of this study as the only long-term prospective randomised trial of HRT in women at or near the menopause.  It provides “direct and compelling evidence that the benefits of preventing chronic disease outweigh the risks even when HRT is used for more than 10 years”.

It was further pointed out that “limiting women to the lowest dose of HRT for the shortest period… prevented women from realising the benefits”.

The lesson from what can only be described as a debâcle is one that has been demonstrated over and over again – that results in one defined population CAN NOT be transferred to another group without very careful consideration.

However, the final thought is an extremely sombre one.  If the research is valid (and there is no reason to believe it is not), by extrapolating the figures, it is possible to work out that maybe 16,000 women in the UK alone have died or suffered a myocardial infarction who would not have done so had they continued to take HRT.

BMJ October 2012
Reported in the Daily Telegraph 10 Oct