February 28

Let’s Focus On Known Facts About HRT

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By the MenoClarity team

If you’re confused about the actual benefits and risks of HRT, you’re not alone. Exactly what are the facts about HRT? So much seems to be claimed about it. How much of that is true?

It’s standard practice to receive information about a medicine from your doctor. But in the case of HRT, it seems that anyone can take to social media and even established media outlets to convince you to take it. We’ve seen how this has gathered speed in recent years, even though in the UK, and many other countries, it’s still forbidden by law to promote prescription-only medicines (like HRT) to the general public.

Why is this allowed to happen? We at MenoClarity don’t know, but we are passionate about restoring clarity to the discussion around perimenopause and menopause. Women shouldn’t be made to worry by endless fear and misinformation that they need to take medicine. Unfortunately, in the case of HRT, women are now worried about NOT taking it.

Below, we highlight some claims that we’ve seen on social media. We analyze the science and research behind these ‘facts’ that are increasingly becoming accepted narratives. We are concerned that women are being driven into medicating midlife change based on misleading data. We are not denying that HRT can be helpful for some women in managing the menopause transition. Rather, we are concerned about some of the claims being made about it for disease prevention and the sources quoted to back up these claims.

For example, the following claims have been made on social media about how helpful HRT is, not just for menopause, but because it can supposedly reduce the risk of the following conditions by significant margins:

Diabetes (by 30%)

Coronary Heart Disease (by 50%)

Dementia (by 22-32%)

Age-Related Macular Degeneration (ARMD) (by 35%)

Depression (by 50%)

Osteoporosis (by 26-37%)

All-cause Mortality (by 30%)

When we see such absolute figures being presented as fact, we get curious about where those figures come from. How is it possible to be so categorical about the rate at which risk of a disease can be reduced by one drug, when the drug isn’t even licensed for that purpose? What research is this based on? What is the sample size? What is the ethnicity or national background of the sample researched? Is this for the world, or a small part of it? Is this supposed to be for all women? These questions are rarely answered and any context for the figures is rarely given. The nuance behind any research results is lost. Social media isn’t great on nuance.

Yet claims such as these are frequently made by menopause influencers even though they usually contradict national and international medical guidelines, and the guidance of menopause associations, which do not recommend HRT for disease prevention for women going through a natural menopause.

Sometimes, references are given to research papers that can apparently provide the scientific-backing to confirm the supposed disease-preventing benefits of HRT. But we know that for every research paper published, there is another one finding something very different. It is all about context; how the research was structured, who or what was researched, who was doing the research, when it was done, and on what form of HRT, in the context of hormone therapy etc.

Even the personal values of the researcher can impact research findings. In addition, research often fails to consider all the lifestyle and environmental factors that can impact how anyone responds to HRT. We could also get into a discussion of the presentation of absolute versus relative risk reduction and whether risks and benefits are being presented in the same way in that respect, but that’s a whole other article!

To ease our skepticism about these claims, our team of experts at MenoClarity, which include professors, doctors and researchers from the field of women’s health, got to work to check the references given.

Do these claims stand up to scrutiny based on the research reports quoted?

An analysis of the research papers referenced found that the data used to come up with the claims above was mostly either taken from weak and inconclusive studies, or from research that’s ONLY relevant to women who’ve had a hysterectomy. BUT most women go through natural menopause with their uterus intact.

We believe promoting prescription-only medicine like systemic HRT should continue to be prohibited when it comes to the general public, because we can’t expect consumers to be able to decipher the accuracy of claims about the benefits of any medicine. Suggesting, as was the case above, that HRT reduces the risk of depression by 50% on the basis of a study of 172 participants is, with an understanding of scientific methods, ridiculous. But how many women would actually go to the research paper to understand the validity of this figure? Many will see the social media post and believe it to be true. We believe that social media posts presenting information in this way are a disservice to women’s health.

Taking data from research carried out on women following the removal of a uterus and/or ovaries and claiming it’s relevant to all women, is a long-used tactic put in place to exaggerate the benefits of HRT.

Although a hysterectomy is considered a standard procedure, it comes with high risks, especially if a woman’s ovaries are removed along with her uterus. Following the procedure, women can experience the rapid onset of intense menopause symptoms and loss of bone density, as well as an increased risk of several diseases and conditions. As we’ll see from the research offered as evidence for the above claims of supposed HRT benefits, oestrogen-only therapy has been found to reduce some of the known risks for women who have had their uterus and/or ovaries removed.

However, women who go through natural menopause are on a different path and have different needs. Natural menopause is not a trigger that increases the risk of disease or all-cause mortality. Women in natural menopause who choose to take HRT for symptom relief will be offered oestrogen and progesterone, with the latter given to protect a woman’s uterus from the risk of cancer.

Since the 1960s, certain interests have tried to convince women who journey through natural menopause that hormone therapy is needed to reduce the risk of disease. However, large randomized controlled trials (considered the gold standard in medical research and the most robust research currently available) have not found this to be true.

To get some clarity on what is actual fact with regard to the benefits of HRT for disease prevention for women in natural menopause, let’s take a look at the references given to back up the figures we have quoted above.

Diabetes

To back up the claim that HRT reduces the risk of diabetes by 30%, the following research paper was referenced: 

Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women – PubMed (nih.gov) (2006)

This research paper is a meta-analysis (looking at past studies) taking data from trials conducted between the years 1966-2004. For most of those years, oestrogen only therapy was the standard hormone therapy treatment offered to women, since the risks of endometrial (uterine) cancer were not taken into account. The research found that the addition of a progestin to oral oestrogen decreased any perceived beneficial or adverse effects. (Combined HRT is now standard for all those still having a womb.) Conjugated estrogens tended to produce larger effects, positive and negative, than esterified oestrogens. Neither of these formulations are currently widely prescribed in the UK. The lead researcher reported that they served as a consultant to Wyeth Pharmaceutical and were paid by the hour.

Conclusion: Inconclusive research on out of date HRT formulations and delivery methods to back the claim for most women in natural menopause now. Potential issues with impartiality of the research referenced.

Coronary Heart Disease 

To back up the claim that HRT reduces the risk of coronary heart disease (CHD) by 50%, the following paper was referenced: 

Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It’s About Time and Timing – PMC (nih.gov) (2022)

This is a review of literature and studies, highlighting research mainly in the field of cardiovascular disease (CVD) prevention. There is no information on how studies were selected for review nor any information on the review process. This paper does not appear to have been through a peer review process which is standard for academic research.

In medicine, large randomized controlled trials are considered the most robust method to test the efficacy and possible risks of a product. Observational studies are considered less reliable.

This research states: “More than 40 observational studies show a consistent 30%–50% reduction in CHD in HRT users versus nonusers. On the other hand, RCTs (randomized controlled trials) have shown a null effect of HRT on CHD (chronic heart disease) in analyses of women over all ages, typically 45–90 years old when randomized to HRT versus placebo.”

If there are no randomized controlled trials to back your desired hypothesis, you can’t just turn the results of observational studies into scientific facts! The paper seeks to justify why it elevated the results of observational studies over RCTs, by highlighting some problems they found in the design of certain RCTs that they chose to review. 

Interestingly, the writers failed to review a significant recent RCT on CHD and all-cause mortality, an 18-year clinical trial published in The Journal of The American Medical Association (JAMA) in 2017, that can be found here: Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality (2017) This study found that “Among postmenopausal women who participated in 2 parallel randomized trials of estrogen plus progestin and estrogen alone, all-cause mortality rates for the overall cohort in the pooled trials were not significantly different for the hormone therapy groups vs the placebo groups.”

Conclusion:

Selective and inconclusive research referenced to back the claim.  Here are the UK NICE guidelines on HRT and cardiovascular disease. The North American Menopause Society said in 2022 “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on CHD and all-cause mortality when initiated in perimenopause or early postmenopause.”

Dementia 

To back up the claim that HRT reduces the risk of dementia by 22-32%, the following research paper was referenced: 

Frontiers | Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia (frontiersin.org)

This is a meta-analysis (looking at past studies) of what are considered more reliable randomized controlled trials and less reliable observational studies.

The results of this analysis show that only observational studies that investigated oestrogen-only therapy could show a reduction in risk of dementia. Meanwhile, randomized controlled trials showed an increased risk of dementia with combined HRT use when compared with placebo, and no significant impact of estrogen-only therapy. 

Conclusion:

This claim is certainly not relevant for women in natural menopause based on the research referenced. Furthermore, it ignores the results of more robust research and relies on weaker types of studies regarding women who had their uterus removed.

Age-Related Macular Degeneration  (ARMD) 

To back up the claim that HRT reduces the risk of Age-Related Macular Degeneration by 35%, the following research paper was referenced: 

Inverse Association of Female Hormone Replacement Therapy with Age-Related Macular Degeneration and Interactions with ARMS2 Polymorphisms | IOVS | ARVO Journals (2010)

This trial made no reference to the type of HRT used. It found that HRT and oral contraceptives have protective effects for women with AMD but that it had no significant effect on the occurrence of moderate AMD. In addition, it was a relatively small study, and the authors state that further studies replicating the effects in an independent cohort are necessary to validate the findings.

Conclusion:

Inconclusive research referenced to back the claim.

Depression

To back up the claim that HRT reduces the risk of depression by 50%, the following research paper was referenced: 

Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition: A Randomized Clinical Trial – PubMed (nih.gov) (2018)

This trial involved 172 participants over 12 months, in the US, with a mean household income of $39-$63k. 76% of the participants were white. This is not a large or broad enough trial to be considered scientifically significant for such a bold claim.

Conclusion:

Inconclusive research referenced to back the claim.

Osteoporosis

To back up the claim that HRT reduces the risk of osteoporosis by 26-37%, the following research paper was referenced:

Effect of hormone therapy on the risk of bone fractures: a systematic review and meta-analysis of randomized controlled trials – PubMed (nih.gov) (2016)

This was a meta-analysis (looking at past studies published pre 2014) reviewing different types of hormone therapy, CEE (conjugated equine estrogens) or estradiol to reduce risk of bone fractures. The studies used different formulations of HRT, had different lengths of follow-up, study population and therapy regimen. Researchers admit that their study did not have “enough power to investigate the occurrence of rare but serious adverse events in HT treatment, such as stroke, myocardial infarction, different types of cancers, and so on”. The studies appear to have included estrogen only HT which is not advised for women who still have their uterus, the majority of women.

Conclusion:

Given the above limitations of this study and its focus on estrogen-only HRT, there is inconclusive evidence in this research, to back up this claim for most women in natural menopause.

Note: HRT is considered as first-line intervention in the UK for the prevention and treatment of osteoporosis in women with premature ovarian insufficiency (POI) and early menopause. Women in natural menopause are not expected to experience osteoposis at midlife and any change to bone density is ONLY “maintained while HRT is taken,” as explained in the NICE Guidelines (2022).

All-cause mortality

To back up the claim that HRT reduces the risk of all-cause mortality by 30%, the following research paper was referenced: 

Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It’s About Time and Timing – PMC (nih.gov) (2022)

This is the same research paper that was given as a reference for chronic heart disease. 

In the case of all-cause mortality, the authors of this review relied on two meta-analyses of RCTs carried out from 1966 through to 2002/4. Women taking oestrogen-only therapy and oestrogen plus progestin therapy were included in the trials, but the results were grouped together in a non-specific manner. As a result, we cannot draw conclusions on how all-cause mortality can be impacted by HRT for women going through natural menopause or surgical menopause.

Conclusion:

Inconclusive research referenced to back the claim for most women in natural menopause. The North American Menopause Society said in 2022 “More clinical trial data are needed to confirm or refute
the potential beneficial effects of hormone therapy on CHD and all-cause mortality when initiated in perimenopause or early postmenopause.”


We hope this has proved a useful analysis of the research referenced to make certain social media claims and what we actually know or don’t know conclusively in terms of facts about HRT. Well done if you’ve got this far!

Research itself is always open to interpretation, even when done in the most robust manner. It’s complicated and context is everything. We can’t just make big bold statements based on random interpretation that suits a certain narrative. That is not demonstrating a duty of care to women. It is disingenuous. 

It’s worth noting that the authors of one of the most recent large randomized controlled trials on Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality (JAMA, 2017) concluded that they “would not support use of hormone therapy for reducing chronic disease or mortality.” That is also the stance taken by menopause societies around the world. The British Menopause Society said in in 2022 “HRT should not be recommended for the primary or secondary prevention of chronic disease in women experiencing the menopause in keeping with national and international guidelines.”

HRT can be helpful for treatment of (mainly vasomotor and genitourinary) symptoms of menopause but there is inconclusive evidence for many other claims. Please question what you see on social media and ask why anyone is making the claims they do. Let’s stick to what we actually know when it comes to facts about HRT.


Tags

Age Related Macular Degeneration, Coronary heart disease, dementia, Depression, Diabetes, hormone replacement therapy, menopause, Osteoporosis, perimenopause


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