VMS and Menopause: KNDy Neurons, NK Receptors, and Practical Insights - Episode 3
Neurokinin and Estrogen Balance in Menopausal Hot Flashes for Primary Care
Panelists discuss how to simplify the physiology of KNDy neurons and neurokinin (NK) receptors for primary care physicians, explaining how NK3 antagonism reduces hot flashes, while NK1 antagonism helps alleviate sleep disturbances and night sweats, with fezolinetant and elinzanetant serving as key nonhormonal treatment options.
The following transcript has been edited for clarity, style, and length.
Mary Jane Minkin, MD: Let’s move on to practical insights for primary care physicians. Lisa, how can we simplify the physiology of KNDy neurons and their role in vasomotor symptoms (VMS) for our colleagues in primary care?
Lisa Larkin, MD: It’s important to emphasize that while estrogen plays a role, it’s not just about its loss. There’s a more complex interplay at work. The key is the balance between estrogen and neurokinin B (NKB) binding to KNDy neurons in the hypothalamus. When estrogen declines, NKB can more readily bind to these neurons, disrupting thermoregulation and triggering hot flashes. So, it’s not simply about low estrogen levels; it’s about this dynamic interaction.
Additionally, understanding that these KNDy neurons are crucial to thermoregulation—and that targeted therapies are now being developed to address this mechanism—helps us better explain the pathophysiology of VMS.
Minkin: You summed it up perfectly, Lisa. It’s crucial for clinicians to realize that if it were just about estrogen loss, every woman would experience hot flashes and poor sleep after menopause. But that’s not the case. While all women end up with low estrogen levels post-menopause, only some develop these symptoms, suggesting a more intricate mechanism.
Here’s a simplified analogy: in premenopausal women, estradiol occupies neurokinin receptors in the hypothalamus, effectively blocking NKB from binding. This keeps the thermoregulatory system stable. But once estrogen declines during menopause, those neurokinin receptors are no longer "occupied," allowing NKB to bind freely, disrupting thermoregulation and causing symptoms like hot flashes.
Larkin: That’s a great way to describe it, Mary Jane. It’s succinct and captures the essence of what’s happening.
Minkin: Exactly. So, the takeaway for primary care providers is that these symptoms aren’t just about estrogen levels. They’re the result of a broader neurochemical imbalance, and emerging therapies targeting neurokinin receptors offer promising solutions for our patients.
