Donna Adams-Pickett, PhD, MD, FACOG, a board-certified obstetrician-gynecologist at Augusta Women’s Health & Wellness Center, discusses what KNDy neurons are and why they’re essential for effective menopause care.
KNDy (kisspeptin, neurokinin B, and dynorphin) neurons are hypothalamic neurons that help regulate reproductive hormones, body temperature, and metabolism. As estrogen levels decline during menopause, these neurons can become dysregulated, contributing to common symptoms such as hot flashes, temperature instability, and metabolic changes that may impact insulin sensitivity.
For clinicians, understanding the biological mechanisms that drive menopause — including the role of KNDy neuron dysregulation — is key to choosing the most effective treatments and helping patients navigate this significant hormonal shift.
When there’s an adequate amount of estrogen being made by the ovary, the KNDy neurons recognize that there’s enough estrogen there, and they’re pretty quiet. But when their estrogen levels begin to fall, the kidney neurons in the hypothalamus trigger the pituitary to make follicle-stimulating hormone, FSH, and luteinizing hormone, LH. Once the pituitary makes the FSH and the LH, they send down the signal to the ovary: “Ovary, we need you to make estrogen.” The ovary makes the estrogen, and it feeds it on back to the hypothalamus, and the kidney neurons stay quiet.
In menopause, the ovary does not respond to the FSH and the LH. Estrogen levels go very, very, very low. And once they go low, the signal back to the hypothalamus is, “Hey, we need estrogen.” The KNDy neurons begin to work overtime, trying to trigger the pituitary to trigger the ovary to make the estrogen — but it doesn’t happen, and that constant triggering makes the KNDy complex in the hypothalamus become hypertrophic — basically enlarged. That enlargement is what triggers the dysregulation of the body temperature and even sleep patterns.
We now know that if we really want to control at least those two aspects of menopausal health, we need to address what the KNDy neurons are doing. It’s very important that clinicians understand the pathway for diagnosing and treating menopausal symptoms, because typically, our approach to menopausal care is hormone therapy only. But there are patients who are not candidates for hormone therapy. So when we find those patients who are not candidates for hormone therapy, then we need to focus our emphasis on the symptoms.
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