Dr. JoAnn V. Pinkerton is the Mamie A. Jessup Professor of Obstetrics and Gynecology, division director for midlife health, and founder of the University of Virginia Midlife Health Center in Charlottesville, Virginia. She presented 'The effect of NKB antagonism beyond the hot flash: sleep, bone and cognition' at The Menopause Society 2026 Annual Meeting, held October 20 to 24 in San Diego, California. Her talk was part of the plenary symposium 'Beyond hormones: emerging and established pharmacologies in perimenopause and menopause management.'
Dr. Pinkerton began with a hypothetical link: menopausal symptoms, particularly vasomotor symptoms, may affect risk factors for heart disease, osteoporosis, or cognition. Neurokinin antagonists may therefore help, she suggested. Fezolinetant blocks neurokinin 3 (NK3) receptor, while elinzanetant blocks both NK3 and the neurokinin 1 (NK1) receptor. Unlike some older nonhormonal options, neither drug causes weight gain or changes in body composition.
How neurokinin antagonists may improve sleep in menopause
Both drugs improve sleep, partly because fewer night sweats mean fewer awakenings. But 'up to 54 percent of the sleep disruption was independent of those vasomotor symptoms,' Dr. Pinkerton said. Elinzanetant's added NK1 blockade may act directly on arousal pathways in the brain. 'By using both the NK1 and the NK3, you're actually having a balance both to temperature and to sleep,' she explained.
Fezolinetant's sleep results in trials were mixed, but women in a large real-world study reported better sleep.
What neurokinin antagonists may mean for mood, the brain, and bone
These drugs are not primary treatments for clinical depression, Dr. Pinkerton noted. But frequent hot flashes leave women exhausted and irritable, so better sleep and fewer hot flashes may ease mood and improve quality of life.
She asked whether the drugs might also improve 'some of the memory, the brain fog, the concentration.' It is too early to claim a causal link, she cautioned, but 'it's exciting to think about.' Fezolinetant was neutral on bone, and women taking elinzanetant lost less bone than those on placebo, which she called 'very reassuring.'
For women with breast cancer, who often cannot use hormone therapy, elinzanetant reduced hot flashes within a week during endocrine therapy, and the effect lasted a year.
'I love it that we're menopause heroes, that we like to treat hot flashes and night sweats,' Dr. Pinkerton said. 'But I also think we need to think longer than that.' Women at menopause 'are more than just their hot flashes and their night sweats,' she concluded, and paying attention to 'all those risk factors' may help them live longer, healthier lives.
NK3, neurokinin 3; NK1, neurokinin 1.