Is this the pill to end hot flushes?
Trials for a non-hormonal menopause treatment have produced startling results, says the project leader, Dr Julia Prague
When I advertised for women to take part in our clinical trial of a drug to combat hot flushes, Elaine Barker from Princes Risborough was typical of those keen to take part. Daily and nightly flushes and sweats were making the 61-year-old’s life a misery, and she had never taken HRT because she had previously had a suspected blood clot. “Anything that could improve the quality of my life would be worthwhile,” she told me.
She’s just one of 70 per cent of menopausal women who experience hot flushes, 10 per cent of whom describe them as “intolerable”.
On average, the menopause lasts seven years, and despite all the symptoms women experience, including poor sleep, low libido, fatigue, mood swings and weight gain, we and other researchers have found that the flushes bother them most because they directly impact every aspect of their lives including their careers.
The most prescribed treatment is hormone replacement therapy (HRT) but, due to its links with an increased risk of breast cancer and blood clots, many women choose to avoid it – or even seeing a doctor altogether.
As an endocrinologist I appreciated the problem that women with breast cancer had with HRT, but it was only when I did this research that I became aware how many menopausal women suffer such debilitating symptoms in silence. The persistent taboo around the menopause means that many feel they can’t talk about their experiences, while those who do often find they are met with stereotypical responses and jokes, reinforcing the taboo.
Many of the hundreds of women I spoke to felt as if they were “going mad”, as no one else told them they felt like that, too, or were “being feeble” when someone said dismissively: “It’s just the menopause.”
They tried to ignore their symptoms as much as possible and carry on with their busy lives, complete with careers and families. Some of these women had suffered seven years of sleep deprivation and embarrassing, sweaty daytime encounters.
Unsurprisingly, this had taken its toll on them, both physically and mentally, with some women at the peak of their careers finding themselves so exhausted they had to reduce their hours, or even give up work altogether.
For the first time in years, these women finally have hope in the form of a new drug. Unlike HRT, this new treatment relieves flushes but does not increase oestrogen levels, meaning it carries less long-term risk for all women and is an option for those who cannot take HRT. Our clinical trial at Imperial College found it can reduce hot flushes in menopausal women by almost 75 per cent, while remaining flushes were also less severe.
The new drug compound, called MLE4901, works by blocking a hormone in the brain called Neurokinin B, normally involved in reproduction. Naomi Rance, an eminent scientist in Arizona who has been looking into this for 20 years, found that it increases in response to falling oestrogen levels in the menopause, and is involved in activating the brain pathway that controls temperature regulation, making it an important mediator of hot flushes. Further work at Imperial, led by Professor Waljit Dhillo, led us to believe that if we could use a drug to stop Neurokinin B acting, we might be able to stop menopausal hot flushes without needing to increase oestrogen levels. Last February, in collaboration with AstraZeneca and Millendo Therapeutics, and funded by the Medical Research Council and National Institute for Health Research, we started a clinical trial to see whether we could relieve hot flushes with the oral drug MLE4901, taken twice daily.
Twenty-eight women took part, and during their weekly visits, they took the active drug and a dummy drug for a total of four weeks each, in random order. Their lives were transformed. As they took the new drug, their flushes diminished to the point where they spoke about feeling “human again”.
They described with great glee how they were able to put on make-up to go out, secure in the knowledge that it wouldn’t be sliding down their faces within an hour. They could style their hair as they pleased, confident that it wouldn’t be sticking to the back of their necks with sweat. One woman was thrilled to be able to plan a party outfit with sleeves, something that had been impossible for years, as she’d be far too hot during a flush to have her arms covered. Others didn’t need to carry a flannel with them in their handbags, or have a fan on their desk at work. They noticed the difference, as did their partners and colleagues.
For these women, hope is on the horizon. Though our drug still needs further trials, and would not be available on the market for a number of years yet, it heralds optimism that safe, non-hormonal treatments can exist. HRT remains an option for some women but the decision must be carefully considered with a doctor examining the risks and benefits. Though it’s effective in treating flushes, if it’s taken for longer than five years, HRT can lead to an increased risk of breast cancer, ovarian cancer, blood clots and stroke. If a woman has a history of anyy of these conditions, she’s advised d never to take it.
Other options tions include antidepressants, s, which aren’t given to menopausalusal women because they’re suffering ering depression, but becausee they can be helpful in reducing educing flushes in the way they y work on the brain. Yet, like ike other existing treatments, including gabapentin and herbal remedies, there here are limitations or side effects.
What really lly needs to happen is for the menopause enopause taboo to end, with discussion iscussion among both men and women, omen, from partners and friends to work colleagues and medical practitioners, rs, about what the menopause is really like and what could be done to help those who suffer from its symptoms. During the trial, I realised that all of the women involved had gone through at least one very significant life event, mainly because they’re at the stage of life where they’re at the very centre of their families. Some have elderly parents, young grandchildren, partners or close friends suffering ill health or young adult children who still depend on them. My admiration for them has no bounds: although they often said they found it difficult to manage everything, I felt they did the complete opposite, meeting endless challenges with amazing fortitude, in spite of exhaustion from constantly interrupted sleep. Women will only be truly supported through the menopause when they have access to more effective, safer treatments such as the one we are working on. Seeing these women leave misery behind and finding themselves feeling vibrant and human again has been rewarding beyond measure.
‘I have seen them leave misery behind and feel vibrant and human again’