In an article in Brainwork J. Kinoshita speculated in the kind of way that inspires drug houses to finance the running of large-scale clinical trials, in this case of the effects of estrogen given in the post menopausal age on the incidence of Alzheimer’s disease. Elderly women are more prone than men to Alzheimer’s, but some physicians report anecdotally that those who receive estrogen do not develop the disease. Estrogen is said to enhance cognitive function. What this actually means is that some GPs think that some of their older female patients might not have developed Alzheimer’s because they were on replacement estrogen. They have no idea which ones these might be or whether they would ever have developed Alzheimer’s or whether some other factor such as non-exposure to environmental estrogen poisons might be involved.
Once a large-scale trial has been set up it has its own momentum. A positive correlation of smoking with incidence of Alzheimer’s has recently been observed. As for estrogen, it is said to have an effect on human cognitive function. But the only evidence is from short-term administration of estrogen to small mammals in the laboratory, animals not normally noted for intricacy of brain function.
Sex steroids can hardly be expected to be neutral in their effect on behavior, mood, cognitive function and so forth, especially if we consider that the pharmacologic versions of sex steroids are administered at much higher levels than those occurring naturally. We are also beginning to realize that there are reciprocal interactions between steroids and behavior. In other words, as hormones influence behavior, so behavior influences hormones. The more expert the endocrinologist, the more respect she/he has for the synergistic interactions of body chemicals; unfortunately most health practitioners have only an elementary understanding of endocrinology and are far too ready to believe in quick-fix remedies for perceived malfunction.
What is claimed for Alzheimer’s is also claimed for cancers, except those of the endometrium and breast, which are considered estrogen-dependent. The data are difficult to interpret. Women on replacement estrogen are three times as likely to develop endometrial cancer as women who are not, but opposing the estrogen with progestogens is thought to control the risk factor. British doctors believe that after stopping HRT women should continue to take progestogens for two years but American doctors have yet to be convinced of the usefulness of opposing estrogen at all. Women on HRT have twice the rate of breast cancer after nine years, and women on combined regimes are four times as likely to have breast cancer after six years. HRT used to be denied to women who have had a brush with the disease, but now HRT users may also take tamoxifen if the risk of breast cancer is considered significant. The constant crying up of HRT has the effect of making women who are denied the therapy feel hard done by, when the truth is that most women who could use replacement estrogen don’t. The latest cross-national study of HRT users in Europe calculated current users as only one-third of women actually going through menopause and no more than 13 per cent of post-menopausal women. About a quarter of post-menopausal women reported use at some time.
Still fortunes are to be made and professional clout to be accumulated by setting up large-scale cohort trials to track the incidence of the diseases of ageing in a post-menopausal population that faithfully persists in dosing itself with estrogen. The difficulty will be to find that population, because if current trends persist women will use HRT during the period of menopausal discomfort as a symptomatic treatment and then abandon it. The drug houses, who anticipated easy pickings as women remained on their product for the term of their unnatural lives, are perplexed. They want explanations of this poor compliance. They blame voices like my own crying in the wilderness, effortlessly overcoming the booming sound of their endless promotion of their product in the medical press, and the equally energetic distribution of free samples to GPs. The truth is that selling estrogen as a panacea was a miscalculation. Nobody knows better than women that biology offers no free lunches. In women with wombs and ovaries estrogen has got to be opposed by progestogens if uterine hyperplasia is not to result. This results in administration regimes that are onerous, especially when the adverse effects of exogenous progestogens, bloating, headaches, mood swings, etc., are taken into account. Then there is the question of monthly bleeding. Every year the drug houses present new methods of administration, tacitly admitting that they have not got the mixture right. There will be no definitive large-scale cohort trial of the prophylactic effects of post-menopausal estrogen because there are insufficient examples of long-term use of any single method.