Inappropriate conclusions by the Women’s Health Initiative (WHI) in 2002 have resulted in a disastrous reduction in the use of HRT (hormone replacement therapy) by perimenopausal women. The 2002 announcement led to widespread adverse publicity about HRT, and regulatory authorities issuing safety restrictions on its use throughout Europe and the USA. The effect of this was to dissuade both women and doctors from using HRT, with the result that thousands of women have subsequently suffered from menopausal complaints and may have done untold harm to their future health. It has been estimated that a million women in the UK are suffering unnecessarily having rejected HRT as a consequence of the scares. Prescriptions for HRT have fallen in the last six years from 6.3 million in 2001 to 3.4 million. Over the same period the number of women taking HRT has dropped from two million to one million.
Oestrogens are hormones produced predominantly by the ovaries during reproductive years. They are associated with egg development and release. Nature has understandably decreed that a woman should stop releasing eggs around the age of 50 when there is still time for her to raise her children. The cessation of egg release results in a significant fall in oestrogen production which in turn leads to menopausal symptoms, particularly hot flushes and night sweats, in around 80% of women.
The primary role of HRT has been to reduce menopausal symptoms. It subsequently became apparent that HRT could play a role in the reduction of some of the long-term consequences of the menopause including coronary heart disease and osteoporosis (bone thinning). HRT is available with and without progestogen. When the uterus is present, progestogen is necessary to prevent cancer. For women who have had a hysterectomy, oestrogen alone is appropriate.
Women have relatively few problems attributable to coronary heart disease before the menopause because oestrogens confer protection. Thus, the majority of heart attacks before the age of sixty occur in men. After the menopause nature’s protection (oestrogen) is lost. One study found that by the age of seventy, women are as likely to suffer a heart attack as men. When the ovaries are surgically removed before the menopause the oestrogen protection for the coronary arteries is suddenly lost and without hormone replacement therapy the likelihood of heart problems is increased.
In 1976, The American Nurses Health Study recruited 121,700 female registered nurses aged 30-55 years. These women are now aged 61 – 86 years. Heart attacks were reduced by 50% for those who took HRT.
One review of the literature found twenty studies all consistently demonstrating cardio-protection (cardio heart) associated with HRT following removal of the ovaries. When considering evidence from large studies we are always concerned that there may have been some hidden bias. It has been suggested, for example, that those nurses considered to be at particular risk of heart disease might have been advised not to take HRT twenty-five years ago heart disease was considered to be a contraindication. A study specifically designed to eliminate such possible bias investigated a case control analysis of 858 women presenting aged 45 – 69 between 1986 and 1990 with their first heart attack. The outcomes again showed that oestrogen replacement reduced the chance of heart attack.
There were several criticisms of the WHI 2002 paper and its conclusions. Most pertinent was the fact that the analysis was conducted for the whole group of 27, 000 women which included women starting HRT as late on as their seventies. The average age that HRT was initiated was 63. Some started the HRT more than 20 years after their menopause. Clearly by the age of 70 coronary artery disease may have been established. It was inappropriate to apply the observations made from women in their 70s and suggest this it could be applied to women in their later 40s and early 50s, the age when most women need to consider commencing HRT.
In April 2007, the WHI investigators published the combined results of their trials of HRT on cardiovascular disease, using oestrogen both with and without additional progestogen. This time they looked at their data for different age groups. They have confirmed, what was believed before 2002, namely that those women aged below 60 and less than 10 years past their menopause have a lower risk of coronary disease, a lower risk of death from any cause, and no increased risk for a stroke. It is only in the older age groups where increased risks are seen, ages at which it is unusual to commence HRT. Furthermore, the WHI provided the same dose of HRT to all women irrespective of their age, yet there are good reasons to believe that the dose was too high for the older women. The WHI investigators failed to comment on this important issue. Women taking oestrogen alone actually had a lower risk of breast cancer .
It is quite astonishing that the study which initially warned us of all the dangers of HRT is now showing us the opposite. But where is the publicity about this? And will the regulatory authorities act with the same speed as they did to warn against HRT to now correct their advice? There were calls from an International Consensus Group last year for them to revisit their recommendations. The British Menopause Society and Womens Health Concern request that the regulatory authorities, including the European Agency for the Evaluation of Medicinal Products (EMEA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) now do so as a matter of urgency.