Does Hormone Therapy (formerly known as Hormone Replacement Therapy) for postmenopausal women help or harm the heart? This is a question that’s been asked over several decades and this updated Cochrane review brings new evidence to light and gets us closer to answering the question.
Tackling uncertainty
Many studies have tried to answer this already but the picture has been confusing. First questionnaire based studies suggested a benefit. Then randomised control trials randomising some women to HT and some to placebo – this suggested no benefit and possible harm. More recently researchers have picked apart these studies and found that the benefit may vary according to age when treatment is started. The “Timing Hypothesis” that researchers have developed suggests that before 60 it is overall beneficial for the heart, after 60 then it may be harmful. However the evidence was not clear cut and there was a lot of uncertainty amongst both specialists and women considering HT.
In 2012 the longest study looking at HT and heart disease was published. The Danish Osteoporosis Prevention Study (DOPS) included 1006 women who had recently had their menopause and showed reduced heart disease in those who took HT. It reawakened the debate on HT and heart disease and got people talking about it again.
Could timing be important?
We have updated a Cochrane review which brings together the best available evidence on HT and its effects on the heart. We now have evidence from over 40,000 women in 19 trials based across the world, including the DOPS. We also looked at the timing of HT, to see if it could be beneficial in a subgroup of women who started it close to their menopause. The review included randomised control trials comparing oral hormone therapy, either oestrogen alone or in combination with progestogen. It did not include hormone therapy administered as patches, creams or by other non-oral routes.
Here’s what we found in looking at women of all ages:
- No reduction in heart disease in women taking HT (whether we looked at women free of heart disease, women with heart disease or all women together)
- Increased risk of stroke (by a quarter) and blood clots (double) in women taking HT
But when we looked at the results according to the age of women, or by how long since their menopause that they started treatment, we found that in women who started HT less than 10 years after their menopause or who were younger than 60:
- Moderate quality evidence of a small reduction in the risk of dying
- Moderate quality evidence of a small reduction in the risk of heart disease
- High quality of evidenceThe certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty. Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach More of a small increase in the risk of blood clots
- Probable small increase in the risk of stroke
If these results were confirmed, this would mean that if 1000 women under 60 started HT we would expect 6 fewer deaths, 8 fewer episodes of heart disease and 5 extra blood clots over 7 years compared to 1000 similar women who did not start HT.
Where does this leave us?
These exciting findings need to be carefully considered. It is complicated when the same treatment offers benefits in some people but harm in others.
It is also important to consider that these trials were not designed to assess the effect of HT on different ages, this was looked at after the studies were finished and therefore we must be more cautious in accepting the results than if the study had been designed to answer this question.
The evidence is not yet strong enough to recommend HT for the primary purpose of reducing a woman’s risk of cardiovascular disease. However this may come when further trial (ELITE) is published in the near future. At present, this review allows women to be better informed on the cardiovascular safety of HT when considering its use for the relief of menopausal symptoms.
Links:
Boardman HMP, Hartley L, Eisinga A, Main C, Roqué i Figuls M, Bonfill Cosp X, Gabriel Sanchez R, Knight B. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database of Systematic Reviews 2015, Issue 3 . Art. No.: CD002229. DOI: 10.1002/14651858.CD002229.pub4.
The Cochrane Library, Wiley Press Room [online]. 2015. Hormone Replacement Therapy for postmenopausal women: does it help or harm your heart? [press release]. 10 March 2015. Available from: http://eu.wiley.com/WileyCDA/PressRelease/pressReleaseId-116682.html
Page last updated: 14 May 2019
It’s good to know more about hormone therapy. I like how you said that this is good on a case-by-case basis. Just like any other treatment, it’s smart to make sure it’s safe for you specifically. I’ve heard a lot of good things about hormonal replacement therapy, but I’ll still tell my wife to get a few different opinions on it.
It’s essential in these overviews to tell us a bit more what kind of HRT you are writing about. Reading the above is a bit like reading a summary of the effect of painkillers that doesn’t distinguish between aspirin and morphine…Were subjects in these trials taking testosterone, what kind of oestrogen? Also, I’ve commented on twitter I’d like to see women feeding into choice of HRT research topics. Key factors in my decision to take HRT (oestrogen gel, progestogen pessary, testosterone gel) was reading mortality rate for women with fractured neck of femur (terrible) and the positive effect HRT has on my yoga practice which keeps me both mentally and physically balanced. We need more research on the general wellbeing effects of HRT for women to make informed choices about the risks and benefits.
Suzanne,
Thank you for your comments. This review focused on oral hormone therapy which includes oetrogen by itself or in combination with progestogen. I think you are absolutely right that for women with moderate to severe menopausal symptoms hormone therapy can be enormously beneficial. I think it is important for each woman with the help of their GP to make an individual decision, weighing up their own potential benefits and risks. I would encourage you to get involved with helping to direct research into areas which are relevant to patients. The James Lind Alliance is a useful starting point (http://www.lindalliance.org/).