|
Should you take HRT?
Hello and welcome to our next newsletter. Before we go on, I have a favour to ask. If you value these comprehensive newsletter’s, our service and our consistent efforts to help the local community through health education and support, we would be very grateful if you would write a review: Click here to write your review.
Thanks for all your great feedback on the last two newsletters concerning mental health and Big Tech. The topic is terrifying and most people, understandably found the video on the last one hard to watch and digest. The future habits, behaviours and beliefs of young people are being shaped by a very small cohort of white, privileged, Ivy League educated, mostly American tech fanatics who are generally under 35 years old. That’s not a population with diversity or experience.
In this newsletter we will begin a journey into the murky world of HRT. Its a question that repeatedly comes up in clinical practice: What are your thoughts on HRT?
The stimulus behind this question doesn’t seem to be the mood swings, night sweats, or irregular periods. It is when the the menopause comes for your brain that the alarm bell’s seem to ring.
Once HRT is used, the transformation can be quite impressive. The big questions are: is this the product of age-related hormonal deficiency or are people jumping on the latest well-being bandwagon, making a big fuss about a natural life stage that would soon pass? And, importantly, are you protecting your long-term health by taking HRT or risking it? To further complicate issues, what about women who suffer from polyps, fibroids, PCOS, endometriosis pain, ovarian tumours, etc. who produce too much oestrogen so HRT may impact their physiology negatively?
These are considerations that scientists have been grappling with for more than 80 years, ever since the first HRT was approved by the US Food and Drug Administration. Premarin, made from oestrogens extracted from the urine of pregnant horses, was licensed in the early 1940s for the treatment of hot flushes and night sweats, the most common menopausal symptoms. There are many others, ranging from heart palpitations and joint pain to brain fog, anxiety and depression. Let’s investigate this with the help of a video below by Avrum Bluming, MD, hematologist and medical oncologist, and a Master of the American College of Physicians. Dr Bluming is also the author of our recommended further reading featured at the end of the newsletter.
Overall, the symptoms of menopause are eminently treatable with HRT. Yet its use has been controversial ever since 2002, when a large, randomised, controlled trial of HRT was stopped after early data suggested the combined oestrogen and progesterone treatment may be associated with an increased risk of breast cancer, heart attacks and stroke. The Million Women Study, published the following year, concluded that HRT had accounted for 20,000 more breast cancer cases in a decade. The chart below gives an update on those outcomes, take some time to study it.
The media storm that followed persuaded millions of people in the midst of menopause to bin their prescriptions and made doctors reluctant to write new ones. HRT uptake crashed by half over the next five years the world over and remains low to this day.
‘While an estimated 75 per cent of people who go through the menopause actually experience symptoms, only around 14 per cent take HRT in the UK’.
– Dr Louise Newson, family doctor and menopause specialist.
Menopause symptoms
This would be understandable if the scare stories were justified, but in the years since, both studies’ methods have been called into question and new research has put the risks into context by comparing them with other lifestyle factors, such as alcohol intake and obesity. But the question of whether to use HRT is about more than just statistics. It is wrapped up in wider social debates about the over or under-medicalisation of “women’s problems”, in which, as gynaecology researcher Martha Hickey at the University of Melbourne in Australia puts it, “everyone is taking the feminist high ground”. It is no wonder we are so confused.
At this point it is also worth describing why obesity is the biggest single risk factor by a huge margin for breast cancer and actually why weight loss drugs or gastric bands don’t really have the long term impact on chronic avoidable disease we are led to believe. Recall from our Insulin Resistance series we discussed obesity as something more complex than just overeating. That it is actually cellular failure by not too muchfood but the wrong type of food and that it is a global, body wide issue that affects all cells in your body – joint cells (osteoarthritis), neurological cells (dementia) and importantly immune cells (cancer and autoimmune disease).
That right there is why there is an association with obesity and chronic disease. A failing immune system cannot keep rogue cancer cells in check, fat or made chemically/mechanically thin, you are still Insulin Resistant. This is the fundamental basis of why we get cancer and avoidable chronic disease.
Part of the reason for the confusion about HRT is that while menopause marks the end of fertility, the loss of oestrogen it brings has repercussions that go far beyond reproduction. In the run-up to age-related menopause, which is counted as a full year after the last menstrual period, the body goes on a hormonal roller coaster, as the ovaries start to run out of the egg follicles that release oestrogen and become less responsive to other hormones that stimulate ovulation. This is perimenopause. It is at this stage, when periods may still be going strong, that those affected may start to experience a bewildering range of symptoms. In people who have their ovaries surgically removed and are thrown directly into menopause, symptoms can appear overnight.
In age-related menopause, not everyone experiences severe symptoms, or indeed any at all. According to the British Menopause Society, 25 per cent of people who experience symptoms of the menopause describe them as severe. However, across Africa and Asia, there is huge variation in the experiences that people report.
The reason for this variation isn’t clear, but there is no doubt that the menopause can be debilitating. Now, a growing number of researchers and campaigners are demanding a fresh look at how we should deal with it. Ensure you take time to watch the superb video below.
Why Estrogen Matters….
Some see menopausal symptoms as a kind of biological cry for help. That is because, outside of its role in reproduction, oestrogen has a hand in many other important processes in the body, from maintaining the structure of bones and skin to regulating cholesterol and blood sugar levels. It also contributes to blood vessel flexibility, the growth and maintenance of connections in the brain and glucose metabolism in the brain.
Recall we investigated this in depth in the newsletters:
Understanding Menopause
Menopause Prep…
‘The symptoms of perimenopause are, in fact, neurological: hot flushes are the result of temperature regulation changes in the hypothalamus; sleep is governed by the suprachiasmatic nucleus; and mood and memory changes are largely related to the brain’.
– Roberta Diaz Brinton, PhD
Director of the UA Center for Innovation in Brain Science at the University of Arizona Health Sciences and leading neuroscientist in the field of Alzheimer’s, the aging female brain and regenerative therapeutics.
Brinton’s research shows that oestrogen helps to regulate glucose metabolism throughout the brain, with receptors for the hormone found everywhere, from regions that support memory to those that specialise in emotional regulation. In mice, a lack of oestrogen seriously dents their brains’ ability to make energy, leading to a 15 to 25 per cent drop in chemical activity in their brains.
Brain fog
Could this be behind the fatigue and mental fogginess that motivates the research for HRT. Brinton thinks it is a possibility. She says that cognitive symptoms could be the result of a brain that is struggling to function.
Brinton’s research suggests that if oestrogen isn’t replaced, the brain does eventually adapt, but at a cost. With less glucose being metabolised, the brain turns to fats for energy, one easy source of which is the brain’s own white matter, the myelin sheaths that insulate nerve cells and speed up processing across the brain. Her research with Lisa Mosconi at Cornell University in Ithaca, New York, has led them to suggest that this could contribute to some of the pathologies seen in Alzheimer’s disease.
When asked whether this means anyone with cognitive symptoms should take HRT to protect the brain from long-term damage, Brinton says it is a matter of personal choice, but she believes that toughing it out may not be in your best interests.
This all sounds alarming, but there is disagreement about what these changes in the brain’s metabolism actually mean. After all, it is certainly not the case that every person who goes through the menopause untreated gets dementia.
As for whether HRT helps the brain bypass this metabolic shift to reduce the risks of neurological conditions, Brinton and her team recently published research that suggested it does. They looked at the health of more than 350,000 women who had taken HRT and found HRT reduced the risk of Alzheimer’s disease, Parkinson’s, multiple sclerosis and motor neurone disease (also known as amyotrophic lateral sclerosis, or ALS) over five years.
But another piece of research, in a similar number of women from the UK Biobank study, suggests that, while spikes in oestrogen levels through adulthood – caused by things such as the use of contraceptive pills – did protect against Alzheimer’s disease, the addition of HRT either made no difference or slightly increased the risk of dementia overall.
So far, so confusing. Would the picture be any clearer for the increased risk of breast cancer? Since the 1980s, when taking extra oestrogen alone was shown to increase the risk of endometrial cancer, anyone who takes HRT is usually also prescribed progesterone to counteract the over-thickening of the uterus lining. However, this seems to add slightly to the risk of breast cancer.
To make sense of all this, consider the baseline risk of being diagnosed with breast cancer. According to the British Menopause Society, between the ages of 50 and 55, without HRT, this risk is in the region of 13 in every 1000 women. According to the most recent analyses, adding combined oestrogen and progesterone HRT into the equation increases that risk by an extra 3 to 7 cases per 1000 over five years of use. With oestrogen-only HRT, the risk is either reduced by 3 in a 1000 or increased by 2 in 1000, depending on which study you look at.
‘The chances of avoiding breast cancer are high, with or without HRT. In short, HRT slightly increases the risk of being diagnosed with breast cancer. That risk is very small, but it is there and cannot be ignored’.
– Professor John Stevenson
Consultant metabolic physician at Guy’s Hospital
Emeritus reader at the National Heart and Lung Institute, Imperial College London
It should, however, be taken in context with other lifestyle factors that affect breast cancer risk. For instance, consuming 4 to 6 units of alcohol a day adds 8 to 11 additional cases per 1000, while being obese adds 10 cases per 1000, both over five years. Healthy lifestyle choices can reduce risk by the equivalent of a few cases per 1000 over the same period.
Plus, analysis of follow-up data from the 2002 study that caused controversy has shown that despite any increase in cancer risk, there is no increased risk of dying from any cause in the 18-year period after the study was stopped.
Other research backs this up, and analysis of HRT hints at potential protective effects on cardiovascular disease, particularly when started before the age of 60. In addition, a drop in oestrogen increases risk of osteoporosis and HRT has been shown to reduce bone fractures in people who are post-menopausal. Does this mean that everyone going through menopause should take it, regardless of whether or not they have symptoms?
Stevenson says no: “For someone who is asymptomatic and at no increased risk for future osteoporosis or cardiovascular disease, then there would be no advantages in taking HRT, only the risks.” Newson thinks differently. “If you were to say, we’ve got this drug that reduces mortality from cardiovascular disease, reduces osteoporosis, reduces clinical depression and it’s really cheap. Everyone would think ‘why aren’t we all having it?’” she says.
One thing that everyone agrees on is that anyone seeking out HRT should be given unbiased, up-to-date information and allowed to make their own decision. This sounds simple, but conveying the complexities isn’t easy. In England, the first official guidelines for GPs only came along in 2015. Even now, says Newson, many people who want HRT are still being refused by their doctors. Here are the NHS guidelines Click Here
Key Facts
(Click on any line for the appropriate supporting research)
Heart Disease
A women is 7 times more likely to die of heart disease then breast cancer
In every decade of a women’s life starting at 40, her risk of dying from heart disease is greater than her risk if dying from cancer
Even amongst the population of women diagnosed with breast cancer the main cause of death is heart disease not breast cancer
Repeated studies have found that oestrogen reduces the risk of heart disease by 40 – 50% – much more reliably than statins
Osteoporotic Hip Fracture
The number of women who die from osteoporotic hip fracture each year is similar to the number who die from breast cancer
Calcium and vitamin D administered to postmenopausal women who are not on HRT do not decrease the risk of these fractures
Long term HRT is more effective than bisphosphonates (like aredia, zometa or prolia) in prevention of hip fractures
Postmenopausal oestrogen therapy reduces the risk of osteoporotic hip fracture by 30 to 50%
Brain
In 1900, only 5% of all American women lived beyond their 50thbirthday; today their life expectancy is close to 80 years
A women in her 60’s is twice as likely to develop Alzheimer’s disease as she is to develop breast cancer
While 90% of newly diagnosed patients with breast cancer will be cured, there is no current effective treatment for Alzheimer’s disease
The only known effective treatment is oestrogen which, when started within 10 years of the menopause, has been found to reduce the risk of dementia by 24 – 65%
Lifespan
Over 20 years ago, Dr Nananda Col estimated that nearly all postmenopausal women would benefit from taking HRT as measured by deceased rates of disease and improved longevity – by up to 3 years
A 2017 study by Dr Roger Lodo as the Columbia Collage of Physicians and Surgeons found a 20 – 40% reduction in overall mortality rates for women on HRT
A 20 year follow up report from the Women’s Health Initiative found women receiving postmenopausal oestrogen were:
Non-hormone treatments
Future research will help to further clarify the risks and benefits. A major criticism of many of the studies on which risk assessments are currently made is that they were done in people who were already post-menopausal and may not account for other risk factors like obesity and smoking. However, some recent studies indicate that starting HRT in your mid to late 40s may have a better risk/benefit profile, particularly for cardiovascular disease. Brinton also has preliminary results that suggest early HRT may be good for the brain, too.
The future may also see the advent of targeted hormone and non-hormone-based therapies (see Alternatives to HRT below), designed to bypass particular oestrogen receptors found in the breast while still targeting those in other organs. Brinton sees the future of HRT as moving towards personalised medicine that takes into account a person’s risk factors and treats their symptoms directly. “We really need to bring precision medicine to women’s health, so it’s not either/or, but what works best,” she says.
For now, the best advice for anyone approaching menopause seems to be to weigh up the pros and cons of taking hormones – perhaps even before symptoms start – with your doctor and pick the option that feels least scary. For many, the scariest option is going back to a place where they don’t have the energy to think about it.
You should consult your doctor before starting medical treatment. Links to studies mentioned can be found in the links above or contact me directly for more detail.
Alternatives to HRT
Are there any evidence-based alternatives to hormonal replacement therapy for the menopause? According to a recent meta-analysis, there is evidence in favour of some plant-based supplements. Several studies suggest that an extract from the black cohosh plant can reduce hot flushes and night sweats compared with a placebo – although its mechanisms are unclear.
Soya extracts, which act in a similar way to oestrogen in the body, also show promise. More than 30 milligrams per day of the soya plant-derived compound genistein was effective for reducing hot flushes, although researchers warn that the effects take at least 12 weeks to reach half of their maximum effect (compared with three weeks for traditional hormone replacement therapy). There is also some evidence that the effect of soya extracts is dependent on the make up of the gut microbiome.
A combination of 400 to 600 international units of vitamin D per day and between 1200 and 2500 mg of calcium is recommended by the North American Menopause Society during perimenopause and menopause to help protect bone health. However, I feel, based on the current groundswell of research suggesting very little impact on bone health with vitamin D that this will be changing soon. For more on bone health, review the following newsletters where I wrote extensively about bone density, osteopenia and osteoporosis:
Is Osteoporosis really a disease of Calcium Deficiency?
Bone Density, Balance and the Brain
Also, here are two interesting articles on the efficacy of bone scans:
DXA and clinical challenges of fracture risk assessment in primary care
The challenges of diagnosing osteoporosis and the limitations of currently available tools
Finally, reframing the experience can help. A study by Myra Hunter and Joseph Chilcot at King’s College London has shown that cognitive behavioural therapy reduces the impact of symptoms and improves sleep and quality of life.
What is the ‘manopause’?
The menopause directly affects half of the human population. But what about the other half? Men and some trans women and non-binary people may also see an age-related decline in their dominant sex-related hormone, testosterone. This is linked with changes in mood and strength, as well as a loss of libido, coined the “manopause”.
The difference, though, is that testosterone levels decline very slowly, at the rate of about 1 per cent per year around the age of 40, and only about 1 to 2 per cent of people report symptoms that are directly related to the drop in the hormone. For these people, testosterone replacement therapies may be offered.
For others, the lack of energy and libido that can accompany midlife is difficult to link with the gradual decline in testosterone. Obesity, diabetes and other lifestyle factors like stress, smoking, doing less exercise and alcohol might account for at least some of the symptoms. What’s more, the drop in testosterone isn’t a change that signals the end of these people’s reproductive lives.
In short, a lack of testosterone can cause problems in some people, but does not come near what occurs with oestrogen issues.
Thanks for taking the time to read this newsletter, I hope you have enjoyed it and it was helpful. As ever your thoughts are always appreciated.
Recommended further reading: the new book Estrogen Matters is fantastically helpful and insightful.
|
