Hormone replacement therapy (HRT), possibly the most controversial medicine ever invented, will not kill you. That was the conclusion this week of a big, respectable study in the United States that was one of the first to flag up the risk of breast cancer. Women who took the tablets to alleviate the hot flushes and night sweats that assail them, prevent them sleeping and can make life intolerable were no more likely to be dead 18 years later than women who did not.
That’s good news and it was loudly celebrated. Gynaecologists who have been frustrated and dismayed by the bad press HRT has had, leaving them groping in the dark for something else to give the distressed woman in the consulting room who doesn’t want hormones, said this is proof of its safety. The risks are low. Women must be told about them, but they should not be deterred by any thought that HRT could shorten their life.
And yet. The long-term results from the Women’s Health Initiative study are about mortality. In one way they don’t change a thing. HRT still increases the chances that a woman will get breast cancer and ovarian cancer and possibly heart disease and stroke in those over 60 – she just won’t die as a result. Treatment is better these days. But that woman sobbing in the doctor’s consulting room, waking up in bed soaked with sweat, trying to get through a meeting at work with heat pounding her body and afraid everybody must be noticing her flushed face, still has a difficult decision to make.
HRT works. It can be like magic for women who feel their life is wrecked. Mariella Frostrup said she got her life back and hit out at “the shroud of secrecy and shame” around the menopause that prevents women getting the relief of HRT. Woman’s Hour presenter Jenni Murray, however, who developed breast cancer after ten years of HRT following an early menopause, said she would never have taken it if she had known then what she knows now.
Most women go through the menopause between the ages of 45 and 55, although for some it happens prematurely and others are thrown into it by cancer treatment to stop the body producing oestrogen, as the hormone feeds breast and ovarian cancers.
The first oestrogen pill was introduced in 1942, and HRT became available to women in the UK in 1965, without the sort of trials that would be done today to look at the side-effects. The rationale was clear: the pills replaced the oestrogen women were losing. The sales pitch was paternalistic and played on women’s fears of ageing. Without any evidence, the suggestion was planted that HRT would restore both vigour and beauty. “When a woman develops hot flashes, sweats, wrinkles on her face, she is quite concerned that she is losing her youth – that she may indeed be losing her husband,” said a drugmaker’s promotional film in 1972. New York gynaecologist Robert Wilson, who had links to the manufacturers, published a book called Feminine Forever, calling women who did not take hormones “castrates”.
The science came later and caused much dismay. The Women’s Health Initiative (WHI) was a huge study of nearly 162,000 women launched in 1991. The UK-based Million Women Study began in 1996. Both found an increased rate of breast and ovarian cancer. Thousands of women stopped taking HRT. Thousands more were anxious about starting it.
The pendulum has recently swung back the other way, with guidance from Nice, the National Institute for Health and Clinical Excellence, in November 2015. Millions of women should no longer have to suffer in silence, it said. An estimated 1.5 million women in the UK – 85% of all those going through menopause – suffer common symptoms such as hot flushes, insomnia and night sweats. Yet they don’t always get the help they need to manage the symptoms. HRT worked, Nice said, and should be considered. And now the WHI study has published its long-term findings showing women do not die from taking it.
“Data showing that mortality overall is not increased in all age groups is a very reassuring finding,” said Haitham Hamoda, consultant gynaecologist at Kings College Hospital and spokesman for the Royal College of Obstetricians and Gynaecologists. Hamoda is also on the medical advisory council of the British Menopause Society which has lobbied for HRT and disputed the risk findings in the past.
Hamoda says the breast cancer risk is not high. The WHI study puts it at one more case in 1,000. He prefers that to the observational Million Women Study, funded by Cancer Research UK, which says it is two women in 1,000. One in 1,000, Hamoda says “in medical and statistical terms is a small number. It is similar to the [breast cancer] risk of drinking a glass of wine a night.” The risk of breast cancer from being overweight is four times higher.
A more recent study, from the Institute of Cancer Research in London, found last year that among the 100,000 women taking part to look at the causes of breast cancer, those on HRT had a 2.7 times higher risk than those not taking hormones. “We found risks that were slightly higher than other people had been reporting,” said Dr Michael Jones of the ICR’s genetics and epidemiology unit. “Part of that we think is because we have good quality data and were able to tell when women started and stopped HRT.”
The risk is higher for woman taking the combined oestrogen and progesterone pill and lower for oestrogen only – but women need progesterone to protect against womb cancer unless they have had a hysterectomy.
Gynaecologists like Hamoda understand the need. “We see about 2,000 patients a year. The number of patients who come in saying it’s affecting my relationship, I go to a meeting and my brain goes blank. It really affects women’s lives. The average duration of symptoms is seven years but one in three go beyond that. There are no markers to show who will have the symptoms for six months and who is going to have them for 20 years,” he said.
Author Jeanette Winterson described two years of mental breakdown. She, like many others, decided to seek treatment with “bioidentical” hormones rather than those the NHS provides, which their supporters claim are natural. She wrote of the “impossible choice” that women have to make, between mental and physical wreckage and flooding their bodies with synthetic hormones.
But conventional doctors say there is no difference. Women are given oestrogen in the form of estradiol on the NHS, which Hamoda says is bioidentical – identical – to that made in the female body. The progesterone that most women get is synthetic, but bioidentical micronised progesterone, made from plants, is also available on the NHS.
The advice from the NHS is that each woman should sit down with her GP and talk through the options, based on what they know of her individual risk. There are no easy answers. Women at high risk of breast or ovarian cancer or those who have had them will not be advised to take HRT. For everyone else it is something of a guessing game. The odds of cancer are low and reduced if a woman takes the pills for a shorter length of time (no help to those who have symptoms for 20 years), but the risk exists.
There is a glimmer of hope on the horizon though. Maybe more than a glimmer. In April this year, the results of a trial of a new drug were published by Imperial College London. It involved women who were having seven or more hot flushes a day; the drug cut the number of hot flushes by 73%. Oestrogen deficiency causes a chemical in the brain called neurokinin B to increase and this causes menopausal flushing - the drug blocks neurokinin B from working, eliminating menopausal flushing.
It was a small and early study carried out with taxpayer’s money, funded by the Medical Research Council because the drug had already been tried and failed in other uses. But Big Pharma can now see the potential and has swooped to develop the molecule. Astellas paid $500m to buy Belgian biotech firm Ogeda, which was running a trial with similar results to Imperial’s.
Professor Waljit Dhillo, an endocrinologist and one of the leaders of the trial at Imperial, said they have been inundated with emails from women wanting the drug since news emerged of the results. “They are miserable and not sleeping and it is usually at a time when women are right at the top of their career and they are drenched in sweat and can’t go into meetings,” he said. HRT works and is very effective, he said, but there is a huge interest in an alternative for those who cannot or will not take it. It will be a couple of years before the new drug is on the market, but if the results of further trials are as good as theirs, it is going to do very well indeed.
The alternatives
Mood swings, hot flushes, night sweats and other unpleasant symptoms of the menopause are caused by the loss of oestrogen in the body as the ovaries run out of eggs in mid-life and stop producing it. HRT replaces that oestrogen. Too much oestrogen can cause endometrial cancer so to protect the lining of the womb, combined HRT is given which contains progesterone as well.
None of the alternatives offers an instant and complete end of the symptoms. They help some women and not others. They fall into three groups: the non-drug options, medicines designed for other conditions which have been found to reduce menopausal symptoms as a side-effect and alternative therapies, which are largely untested.
Non-drug:
• Yoga. The combination of relaxation and exercise helps some women, particularly with the mood swings that the menopause can bring and also in coping with what are technically called vasomotor symptoms – in other words, the surges of heat that cause the body to sweat and the skin to flush red. Stress makes the symptoms worse.
• Cognitive behaviour therapy (CBT). Several studies have shown that CBT can help women cope and reduce the symptoms.
• Lifestyle changes and weight loss. Getting fit, taking exercise and becoming healthier helps all medical conditions. Losing weight is good for bone health, which can be impaired by the loss of oestrogen during the menopause.
• Dietary changes. Caffeine, alcohol and spicy foods have all been known to trigger sweating and flushes. Giving up smoking can also help, according to NHS Choices.
Other medicines:
• Clonidine. This is a pill to treat high blood pressure, ADHD and anxiety, but among the side effects that have been found is a (small) reduction of menopausal flushing.
• Antidepressants. These are said to help reduce hot flushes, in a lower dose than is used for depression. Venlafaxine and other drugs of the SSRI class (of which Prozac is a member) are generally prescribed.
• Gabapentin. This is a drug against epilepsy. As a side-effect, it has been found to help hot flushes in some women but may cause tiredness and other side effects.
Alternative therapies:
• A variety of herbal medicines have been found to help some women, although not in formal randomised clinical trials. Nice mentions that there is some evidence for black cohosh and isoflavones, like soy, which are derived from the bean family and are phytoestrogens. But it warns that in the different strengths and packs available, their safety is uncertain and that they can interact with conventional medicines. Evening primrose oil, angelica, ginseng and St John’s Wort (effective for depression but interacts with other medicines) are all also sold in health food shops to alleviate menopausal symptoms.
• Acupuncture. A study last year found that it cut the numbers of hot flushes some women experienced, but not others.
