48-year-old CEO goes red, gets hot flashes at meeting: Three gynaecologists on why a breakthrough menopause pill in the US offers hope

What’s a hot flash?

“The levels of the female hormone estrogen drop in the run-up to stoppage of periods or menopause. This directly impacts the body’s thermostat located in the brain called hypothalamus. This misinterprets slight increases in body temperature as overheating and initiates a series of cooling mechanisms, including a hot flash, to lower the body’s temperature,” she explains. Because a hot flash is an unusual response, it releases stress hormones like cortisol and elevates blood pressure too.

“That’s why my patient was complaining of heat around her neck and head. Since she was having hot flashes all too often, I gave her a blood pressure drug, called clonidine. This is prescribed for hot flashes, even in people who do not have high blood pressure, because it affects the brain’s temperature-regulating centre. This helps to reduce the frequency and severity of hot flashes by 46 per cent,” says Dr Rastogi. But it would make the corporate woman dry-mouthed and drowsy. “Besides, she would need a sleep pill as she could hardly sleep beyond three hours and very mild antidepressants, the kind that lower the body’s core body temperature by blocking certain receptors in the brain,” she says. Which is why a new oral, non-hormone pill, which takes care of all these symptoms rather than addressing them one by one, has been approved by the US Food and Drug Administration (FDA).

“Although not available in India yet and having a price tag, the drug elinzanetant, which hits the US in November under the brand name of Lynkuet by Bayer, is a significant breakthrough. It is a once-a-day pill that works without hormones to treat moderate and severe hot flashes in menopausal women. A similar drug was greenlighted by the FDA in 2013 but this one reduces hot flashes by 73 per cent. The earlier oral drug is available in Japan and might be available in India soon,” says Dr Rastogi. However, gynaecologists like her are looking at the pill as enabling a clinical management of hot flashes and encouraging further research into a condition that 80 per cent of women suffer from.

How effective is the new menopause drug?

It works by blocking brain chemicals that get triggered by estrogen drops and lead to hot flashes and night sweats. According to a Phase 3 clinical trial of elinzanetant, which included 628 post-menopausal women, those taking the drug for 12 weeks reported more than a 77 per cent reduction in the frequency of hot flashes and sweating symptoms. Those taking a placebo reported a 47 per cent reduction. Researchers say the effects lasted for over a year. They also slept better, thereby offering more benefits.

Elinzanetant was preceded by the FDA nod to fezolinetant in 2023. But while the first suppresses two brain receptors that have an effect on body heat regulation, fezolinetant works on one. Both are, however, limited in cases of those suffering from liver ailments. Both can work in the run-up to and after menopause.

Why hormone replacement therapy is not effective for everybody

“Usually in extreme cases, hormone replacement therapy (HRT) is recommended but every woman does not qualify for it. HRT is safe only in a certain set of women. We do not recommend these to those with underlying health conditions or histories, including certain cancers, those with a history of or at risk of blood clotting, those with a history of stroke or heart attack, those who experience heavy bleeding and those over 60 or who are more than 10 years past their last menstrual period, as risks of cardiovascular issues and stroke may then outweigh the benefits. Avoid HRT if you have liver or gallbladder disease,” says Dr Rastogi.

That’s why a non-hormonal pill could work in most women, who currently have to individualise their treatment.

The trouble with HRT

Dr Meenakshi Ahuja, senior director, obstetrics and gynaecology, Fortis La Femme, and president of the Delhi Menopausal Society, says HRT is safe when given in the proper context and among the right group of women. In fact, she believes, research in HRT should continue to see which women can benefit. “Early studies on HRT in 2000 were done on a group of women over 70, who had heart disease, obesity and co-morbidities. That group was not right for the test. Later analysis showed that starting HRT on women who are older or further from menopause increases cardiovascular risks because they are more likely to have underlying arterial disease. The lowest amount of HRT dose is safe, if it is judiciously used among women who do not have the risk of underlying conditions, heart disease or breast cancer history,” she says.

Current medical consensus holds that the benefits of HRT typically outweigh the risks for healthy women (free of risk factors) under 60 experiencing wild menopausal symptoms. The fear and subsequent drop in HRT goes back to the Women’s Health Initiative (WHI) studies, particularly the 2002 trial for combined estrogen and progestin therapy. Reportage focussed on relative risks rather than the small absolute risks. So a 29% relative risk of coronary heart disease (CHD) was misinterpreted as a 29% chance of developing the condition, when the actual increase was very small. The study used older, synthetic hormones that led to blood clots; the modern ones are more risk-proof.

What can Indian women do?

Dr Ahuja is particularly worried about women using unregulated herbal products in the non-hormone category. “Women use rhubarb root, ashwagandha or anything with phytoestrogens (plant-based compounds with estrogen-like properties). But as of now, there is no scientific evidence of their benefits or any attendant risks,” she says.

In the absence of non-hormone pills, both Dr Rastogi and Dr Mannan Gupta, Chairman & HOD, Obstetrics and Gynaecology, Elantis Healthcare, Delhi, say at the moment there can only be symptomatic relief and customising medication on a case-specific basis. “While hot flashes are the most observed symptom, women also complain of short, patchy sleep, a dry and itchy vagina and weak bones. So we have to give sleep inducing drugs, mood relaxants, vitamin D and calcium supplements as well. Let me say that all these have to be backed up with changes in diet, lifestyle and exercise,” says Dr Gupta.

Dr Rastogi is happy that more women are at least approaching her in the peri-menopausal stage. Otherwise, women consulted a doctor only during heavy bleeding or vaginal dryness. “Considering that women may go through a good five to seven-year period of hormonal changes and resultant symptoms in the run-up to menopause, and then a couple of years after it, means that menopause research needs to give us a cost-effective pill to manage the condition,” she says.

Worse are cases of surgical menopause, where ovaries are removed to treat or prevent ovarian cancer, severe endometriosis or recurrent cysts. “This leads to the worst hot flashes compared to natural menopause because the drop in estrogen is sudden and abrupt. A pill is effective here,” says Dr Rastogi.