Hormone therapy: will it help or harm your heart?

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 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 randomisedRandomization is the process of randomly dividing into groups the people taking part in a trial. One group (the intervention group) will be given the intervention being tested (for example a drug, surgery, or exercise) and compared with a group which does not receive the intervention (the control group).   control trialsClinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. randomising some women to HT and some to placeboAn intervention that appears to be the same as that which is being assessed but does not have the active component. For example, a placebo could be a tablet made of sugar, compared with a tablet containing a medicine. – 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 treatmentSomething done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. is started. The “Timing HypothesisAn unproved theory that can be tested through research. To properly test a hypothesis, it should be pre-specified and clearly articulated, and the study to test it should be designed appropriately.” 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 studyAn investigation of a healthcare problem. There are different types of studies used to answer research questions, for example randomised controlled trials or observational studies. 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 reviewCochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. 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 riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. 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 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 safetyRefers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. of HT when considering its use for the relief of menopausal symptoms.

Resources on menopause

The Editors have added these in April 2022. With thanks to @drhannahshort, GP Specialist in Menopause & Premenstrual Disorders, for her suggestions.

• You can find our other blogs on menopause here.
• Balance: Founded by Dr Louise Newson, “a GP and Menopause Specialist who works to increase awareness and knowledge of the perimenopause and menopause, and campaigns for better menopause care for all women”.
• British Menopause Society: tools for clinicians and Menopause Care Resources Toolkit 
• Daisy Network, a charity providing information and support to women with Premature Ovarian Insufficiency, also known as Premature Menopause.
• European Society of Human Reproduction and Embryology – Guideline on the management of premature ovarian insufficiency.
• Global Menopause Inclusion Collective 
• Healthtalk – Menopause. Here you can see videos of women in the UK talking about their menopause experiences.
• International AssociationA relationship between two characteristics, such that as one changes, the other changes in a predictable way. For example, statistics demonstrate that there is an association between smoking and lung cancer. In a positive association, one quantity increases as the other one increases (as with smoking and lung cancer). In a negative association, an increase in one quantity corresponds to a decrease in the other. Association does not necessarily mean that one thing causes the other. for Premenstrual Disorders: Surgery and surgical menopause for premenstrual disorders.
• Rock My Menopause (created on behalf of the Primary Care Women’s Health Forum)
• NICE guideline – Menopause: diagnosis and management.
• NHS – Menopause
• Women’s Health Concern factsheets

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 ReviewsIn systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. 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