杏吧原创

THE mood swings I could handle. Ditto the night sweats, irregular periods and a听libido that swung between randy teenager and old maid. Then the menopause came for my brain and enough was enough. If听ageing 鈥渘aturally鈥� meant giving up the job I love because I could no longer think, I was out. Bring on the hormone replacement therapy.

Within weeks, I found energy reserves that I had forgotten I had. The urge to crawl into bed mid morning disappeared and was replaced with a clear head and renewed zest for life.

It was quite the transformation. So much so听that one of the first things I wanted to do with my new mental clarity was to dig in to the听science behind what was happening to me. Was I experiencing an age-related hormonal deficiency that I had, sensibly, nipped in the bud? Or was I guilty of jumping on the latest well-being bandwagon, making a big fuss about a natural life stage that would soon pass?听And, importantly, am I protecting my long-term health by taking HRT or risking it?

These are questions 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.

These symptoms 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 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, says Louise Newson at Newson Health in Stratford-upon-Avon, UK, who is a family doctor and menopause specialist.

Menopause symptoms

This would be understandable if the scare stories were justified, but in the years since, both studies鈥� 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 鈥渨omen鈥檚 problems鈥�, in which, as gynaecology researcher Martha Hickey at the University of Melbourne in Australia puts it, 鈥渆veryone is taking the feminist high ground鈥�. It is no wonder we are听so confused.

Part of the reason for the confusion 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听a听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. But Hickey says that this isn鈥檛 universal. Across Africa and Asia, there is huge variation in the experiences that people report.

The reason for this variation isn鈥檛 clear, but听there is no doubt that the menopause can听be debilitating. Now, a growing number of researchers and campaigners are demanding a fresh look at how we should deal with it.

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 . It also contributes to blood vessel flexibility, the growth and maintenance of connections in the brain and glucose metabolism in the brain. It is this last function that听most concerns Roberta Brinton at the University of Arizona in Tucson.

Brinton points out that most of 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. Brinton鈥檚 research shows that , with receptors for the hormone found everywhere, from regions that听support memory to those that specialise in emotional regulation. In mice, a seriously dents their brains鈥� 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 sent me to the doctor? Brinton thinks it is a possibility. She says that cognitive symptoms could be the result of a brain that is struggling to function.

Brinton鈥檚 research suggests that if oestrogen isn鈥檛 replaced, the brain does eventually adapt,听but at a cost. With less glucose being metabolised, the brain turns to fats for energy,听one easy source of which is the brain鈥檚 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听York, has led them to suggest that this could contribute to some of the pathologies seen in听Alzheimer鈥檚 disease.

When asked whether this means anyone with cognitive symptoms should take HRT to听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 our best interests.

This all sounds alarming, but there is disagreement about what these changes in the听brain鈥檚 metabolism actually mean. After all,听not 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鈥檚 disease, Parkinson鈥檚, 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 , suggests that, while spikes in oestrogen levels through adulthood 鈥� caused by things such as the use of contraceptive pills or pregnancy 鈥� did protect against Alzheimer鈥檚 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 , 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听risk is either reduced by 3 in a 1000 or increased by 2 in 1000, depending on which study you look at. John Stevenson, a consultant endocrinologist at the Royal Brompton Hospital in London, points out that 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, says Stevenson, is 鈥渧ery small, but it is there and cannot be ignored鈥�.
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听.

Plus, analysis of follow-up data from the 2002 study that caused controversy has shown that despite any increase in cancer risk, there is of dying from in the 18-year period after the study was stopped.

Other , and analysis of听HRT hints at potential protective effects on听cardiovascular disease, particularly . In addition, a drop in oestrogen increases risk of osteoporosis and HRT has been shown to . Does this听mean that everyone going through menopause should take it, regardless of whether or not they have symptoms?

Non-hormone treatments

Stevenson says no: 鈥淔or 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.鈥� Newson thinks differently. 鈥淚f you were to say, we鈥檝e got this drug that reduces mortality from cardiovascular disease, reduces osteoporosis, reduces clinical depression and it鈥檚 really cheap. Everyone would think 鈥榳hy aren鈥檛 we all having it?鈥欌�� 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鈥檛 easy. In England, the first official guidelines for听GPs only came along in 2015. Even now, says听Newson, many people who want HRT are听still being refused by their doctors.

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. Some more recent studies indicate that starting HRT in your mid to late 40s may have听a听better risk/benefit profile, particularly for cardiovascular disease. Brinton also has preliminary results that suggest early HRT may听be good for the brain, too.

The future may also see the advent of targeted hormone and (see 鈥淎lternatives to HRT鈥�), 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鈥檚 risk factors and treats their symptoms directly. 鈥淲e really need to bring precision medicine to women鈥檚 health, so it鈥檚 not either/or, but what works best,鈥� she says.

For now, the best advice for anyone approaching menopause seems to be to weigh up the pros and cons of taking hormones 鈥� perhaps even before symptoms start 鈥� with your doctor and pick the option that feels least scary. For me, the scariest option is going back to a place where I don鈥檛 have the energy to think about it. So, for me at least, HRT is very much worth the risks.

You should consult your doctor before starting medical treatment. Links to studies mentioned can be found in the online version of this article

听

Caroline Williams is a journalist and听author of Move!: The new science of body over mind