A new HRT study has been published in top medical journal The BMJ. (1) Once again the news headlines are screaming out a warning to women who are prescribed HRT. “Long term use of hormone therapy linked to increased Alzheimer’s risk,” claims the title of the press release. “Absolute risk is small but women should be informed,” say researchers.
The majority of women only take HRT if their symptoms are severe and their quality of life is significantly affected. It is well established that, following the HRT breast cancer scare in 2002, a large number of women are not getting the hormone treatment they need to lead healthy fulfilling lives as they age. HRT is a safe treatment that alleviates the symptoms of menopause and significantly improves quality of life for many women.
In the words of Oprah Winfrey: “after one day on bioidentical estrogen, I felt the veil lift. After three days, the sky was bluer, my brain was no longer fuzzy, my memory was sharper. I was literally singing and had a skip in my step.”
The research, conducted by Prof. Mikkola Tomi, MD, and colleagues at Helsinki University Hospital, Finland looked at a large group of nearly 85,000 women with Alzheimer’s and compared them to age matched controls. The researchers investigated HRT use in both groups and found that a slightly higher number of the women with Alzheimer’s had taken HRT. However, this type of study (an observational study) can only say that these two factors are associated with each other. There is no proven link.
Following the publication of these results I asked Prof Tomi what he would advise women. He said:
“The key message is that HRT is for treating moderate to severe symptoms. If a woman remains symptomatic after using HRT for 10 years, there is no reason why she could not continue. Overall, we need to treat women individually and consider all risks and benefits when we consult a woman, so that she can make an educated decision on using/discontinuing HRT.”
In addition, on reading the research in detail and interviewing the researchers I have listed ten reasons why you should not be concerned if you currently take HRT, or may wish to take HRT in the future:
1. There is already high-quality evidence that taking HRT is associated with significantly reduced risk of coronary artery disease and hip fracture/osteoporosis and also with increased longevity.(2)
Adapted from Lobo et al. 2017 (2)
2. The same researchers found in an earlier study that HRT was associated with significantly lower risk of both vascular dementia and Alzheimer’s disease.(3)
3. The best type of evidence comes from clinical trials. A recent review highlighted the fact that: “Further clinical trials of different HRT types, doses and routes of administration are urgently needed. … different metabolic effects of oral versus transdermal HRT administration routes may have different effects on coronary heart disease and venous thromboembolism. Few studies have performed direct comparisons, and none have compared a transdermal regimen with a new ultra-low-dose oral oestradiol/dydrogesterone combination.” (4)
4. The study just published is only an observational study – a type of study which does not provide a high level of evidence. For example, this evidence would only be considered good enough for inclusion in a medical guideline if it was supported by multiple other similar studies analysed together in a systematic review and meta-analysis.
5. The study included women who took the form of estrogen that is extracted from horse urine (conjugated equine estrogens or CEE) and known to be more likely to cause adverse effects. Newer body identical estrogen and progesterone and transdermal patches are yet to be studied to see what the effects are in the longer term, but early data shows far fewer adverse effects.
6. The researchers did not take any other factors into account (called confounders) such as smoking and obesity. Both of these factors, among many others, may increase the severity of menopause symptoms and may also be associated with increased Alzheimer’s risk. For the study to be meaningful such confounding factors must be taken into account.
7. The study was conducted on the Finnish population and has a very high rate of HRT use and with many women starting HRT at an unusually advanced age. In this study many women were starting HRT at age 60 or over which is not current best-practice. It was in these women commencing HRT at very advanced age that the very slightly increased Alzheimer’s risk was observed. The ‘estrogen window’ hypothesis suggests that women should commence HRT as soon as possible after menopause, and definitely before age 60.(5)
8. In women aged under 60 at first HRT use, who then used HRT for 10 years or more, there was a small association between HRT and Alzheimer’s showing that women with Alzheimer’s were 13% to 26% more likely to have used HRT. However, the incidence of Alzheimer’s is very low and therefore this represents an extremely small number of additional cases.
9. Finland has the highest rate of Alzheimer’s in the world with a death rate for women of 75.26 per 100,000. In comparison, the death rate in Australia is half that in Finland at only 35.32 per 100,000.(6) The risk of dying of Alzhemer’s is very, very small. The numbers in the study by Prof Tomi and colleagues would only increase the number of deaths (in women who have taken HRT for 10 or more years) by between 4 and 9 per 100,000 women (that equates to a 0.004 to 0.009% increase).
10. It is established that taking HRT is associated with living longer and in turn, living longer is associated with Alzheimer’s disease. It is possible that this has influenced the results of this study.
“We know that the overall increase in lifespan in both men and women increases the likelihood to get Alzheimer’s disease, as well as other forms of dementia. Theoretically HRT could play a role here as well but since we have a well conducted age-matched case-control study, our results hardly can be explained by this hypothesis. Furthermore, we have recently shown that HRT reduces vascular dementia mortality risk,” said Prof Tomi.
(1) Tomi et al. (2019) Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study BMJ 2019;364:l665 (Published 06 March 2019) Link to full article here.
(3) Tomi et al. (2017) J Clin Endocrinol Metab, March 2017, 102(3):870–877
(4) Gerval & Stevenson. (2017) Establishing the risk related to hormone replacement therapy and cardiovascular disease in women. Clinical Pharmacist 9(1) DOI: 10.1211/CP.2017.20202066
(5) Savolainen-Peltonen et al. (2016) The Journal of Clinical Endocrinology & Metabolism, Volume 101, Issue 7, 1 July 2016, Pages 2794–2801, https://doi.org/10.1210/jc.2015-4149