HRT has been sold to women as a miraculous cure for the diseases of old age.
But none of the claims for it really stand up to close scrutiny.
It’s official: the menopause is an illness. According to the Amarant Trust a charity which uncritically promotes the use of hormone replacement therapy the fall in estrogen levels that accompanies the end of a woman’s fertility is a “deficiency disease”.
It asserts that menopause is “no different in principle from diabetes”, an argument which conveniently overlooks the difference between a disease state like the inability to produce insulin and an entirely normal event in a woman’s life.
If the menopause is a disease, then clearly we need a cure which is where hormone replacement therapy comes in. The Amarant Trust, and many in the medical profession, believe that the symptoms of menopause hot flushes, depression, falling libido, brittle bones are all due to the body ceasing to produce “enough” of the female hormone estrogen.
The solution, therefore, is to “replace” this “missing” hormone by administering HRT (nowadays usually a combination of estrogen and progesterone) either in the form of tablet, cream or skin patch.
Even fans of HRT have to concede that it has been shown to substantially increase the likelihood of breast and endometrial cancer (see our earlier Special Report, WDDTY vol 1 no 9, for a full round up of these particular dangers). However, they argue that these risks are more than set off by the benefits the drug confers. These supposed benefits include not only preventing the unpleasant and dangerous effects of the menopause, in particular bone loss (osteoporosis), but the added bonus of increased protection from Alzheimer’s and heart disease.
Such claims of the benefits of HRT crumble under close scrutiny. The latest results of an ongoing study of women in Framingham, Massachusetts (New Eng J Med, 14 October 1993), shows that HRT fails to protect women from osteoporosis therefore eliminating at a stroke one of the main reasons for its use.
Researchers looked at 670 women, 212 of whom were taking estrogen therapy. They concluded that HRT preserves bone mass only when it is taken for upwards of seven years far longer than most women stay on the drug. “Only women who had taken estrogen for seven to nine years or for 10 or more years had significantly higher bone mineral density than women who had taken estrogen,” they concluded.
However, even those on the treatment for 10 years were still not protected from fractures. As soon as they stopped taking HRT, bone mineral density declined rapidly so that by 75 it was only 3.2 per cent higher than in women who had never taken estrogen.
Most women have their menopause in their fifties, yet they are not at greatest risk of hip fractures until some 30 years later, when they reach their eighties. Therefore, HRT taken around the time of the menopause is “protecting” them from osteoporosis at a time when they are not going to suffer from it anyway, and fails to have any effect at the time when they really may be at risk.
This study shows that HRT will prevent osteoporosis only if women take it for the rest of their lives something which, in a display of massive understatement, a New England Journal editorial concedes “reduces the appeal of this preventative strategy”.
But before you let your doctor talk you into spending your whole life on this drug, remember that numerous studies show that the longer HRT is used, the greater the risk of breast and endometrical cancer a trebling of endometrical cancer risk (Br J Ob Gyn, July 1987) and a quadrupling of breast cancer risk (N E J of Med, 3 Aug 1989).
Claims that HRT protects against coronary heart disease are equally spurious. Most of the evidence supposedly proving this association is conflicting or hopelessly flawed. Proponents of HRT would have us believe that while estrogen in the contraceptive pill is known to increase the risk of cardiovascular disease, in HRT, it prevents this condition. As the BMJ puts it (5 December 1992): “Many doctors have been surprised to discover that a hormonal treatment they had learnt to avoid in women at risk of cardiovascular disease is now being specifically advised in this situation.”
The prevailing wisdom about its preventative effect is based on some fairly flimsy evidence. In the latest study, one group of researchers simply selected 4958 post menopausal women from various parts of the American South and Midwest, and performed numerous tests on them, measuring cholesterol levels and many other factors to supposedly determine their cardiovascular risks. After comparing the test results of those on HRT, versus those not on HRT, these epidemiologists made the astounding conclusion, “after making certain assumptions”, that, HRT, “if causal”, would reduce the risk of heart disease by 42 per cent (our italics) (New Eng J Med, 15 April 1993).
Despite their enthusiasm, the researchers are forced to concede that there are serious flaws in their methodology. For one thing, the study wasn’t randomized, so there could have been what researchers term “selection bias”; only the healthiest women with a low incidence of heart disease could have been selected to take HRT. It also wasn’t prospective that is, it didn’t begin with a group of women and see what happened to them over 10 or 15 years.
An editorial in the same edition of the journal is critical of the study, saying: “The authors’ calculation of the overall benefit of the metabolic changes in their study a 42 per cent reduction in the risk of coronary artery disease is speculative, since it is not known whether these variables are ‘independent, additive and causal’.” By this they mean that we have no way of knowing whether HRT actually caused these changes, or whether they just occurred independently. And of course the entire study is based upon the assumption (now refuted see WDDTY vol 3 no 1) that a raised cholesterol level automatically leads to heart disease.
The New England Journal’s call for better research into HRT is nothing new. Two years earlier (12 September 1991), when it published a study which similarly concluded that HRT protects against heart disease, its accompanying editorial conceded: “There is always the lingering possibility that women who choose to take postmenopausal estrogens have other characteristics that explain their lower risk of ischemic heart disease.”
A 1991 review in the US of the evidence to date of HRT’s supposed protective effect against cardiovascular disease (JAMA, 10 April 1991) had similar reservations.
The review pointed out that women who take estrogen after the menopause are more likely to be white, educated, upper middle class and lean, and therefore naturally at lower risk of heart disease than women who don’t opt for HRT.
A review in the UK around the same time (The Lancet, 6 April 1991) also concludes that the evidence is either weak or non existent. In one major study, the effect of estrogens on deaths disappeared after the researchers had corrected their statistics for diseases already present when the study started. In two others, the study concluded, the effect was “non specific” and couldn’t be attributed to HRT.
Not all studies show decreased risk for HRT takers. In 1985, the Framingham, Massachusett Study (New Eng J Med 1985; 313: 1038-43) suggested that the risk of heart disease with HRT use was actually increased.
Finally, all these trials were conducted with oral estrogen alone, whereas most women now take an estrogen progestogen (progestin in the US) combination. The New England Journal (Sept 12, 1991) cautioned: “Since added progestins reverse at least some of the favorable effects of estrogen on serum lipoprotein cholesterol, it is possible that the beneficial effect [of HRT on heart disease] is reduced when progestins are added.”
Undeterred by such lingering questions, researchers are now experimenting with HRT to treat existing heart problems. So far, the studies have mainly looked at the effect of estrogen on animal arteries or human arteries obtained during cardiac transplants. In one study on 12 live women, German researchers from Hanover Medical School discovered that absorption of the drug was highly variable and that artery diameters remained unchanged in women with low absorption of estrogen. They also say that it’s still unclear whether the ability of estrogen to relax arteries actually means anything significant in terms of treating heart disease (The Lancet, 9 October 1993).
Another “fact” about HRT is that it reduces the risk of stroke, yet, again, there is no evidence to support this. The study of 48,470 women, referred to above, which was able to claim protection against heart disease, could find nothing to support protection from strokes. HRT “is not associated with any change in the risk of stroke”, concluded the researchers.
The Amarant Trust asserts in its literature that HRT can stop you becoming “seriously forgetful” in old age. “Institutions are full of old women who have become virtual cabbages due to senile decay (Alzheimer’s disease) which afflicts far more women than men. The latest research from America suggests that HRT can do a lot to prevent this.”
In fact, research from America suggests no such thing. Doctors looked at 800 women, aged between 65 to 95, almost half of whom had used estrogen at some time after their menopause, and a third of whom were current users (JAMA, 26 May 1993). They found that the reduction in “cognitive function” was the same regardless of whether the women were current, past or never users of estrogen. “These data do not support the hypothesis that estrogen use after the menopause preserves cognitive function in old age,” they baldly conclude.
The slaying of such HRT sacred cows is, however, unlikely to deter the most enthusiastic proponents. As each supposed benefit is exposed as unproven or baseless, medicine may simply find other uses for its pet drug. This process is already well underway. A report in the London Times (11 Nov 1993) suggests that HRT may have a role to play in the treatment of women with inflammatory bowel disease.