Menopause Hormones

The hypothalamus contains neurons that secrete kisspeptin, neurokinin B (NKB), and dynorphin. They are referred to as the KNDy neurons. When estrogen levels decline during menopause, KNDy neurons hypertrophy and become hyperactive. These hyperactive neurons express increased levels of not only NKB but also substance P.  The NK1 receptor and substance P appear to modulate sleep and may also play a role in peripheral vasodilation. 

Over-expression of KNDy neurons is responsible for the vasomotor symptoms (VMS) caused by declining estrogen levels during menopause. Antagonism of the NK3 receptor alone reduces the vasomotor symptoms (VMS)  that occur during menopause.. Fezolinetant, a NK3 receptor antagonist, was the first novel drug approved by the FDA in May 2023 for for VMS management. 

Antagonism of the NK1 receptor has been shown to be effective for treatment of primary insomnia not related to menopause and for improvement of sleep disturbances related to menopause. Elinzanetant is a dual NK1 and NK3 receptor antagonist for the treatment of moderate to severe VMS associated with menopause. 

Reference

Faubion SS, Shufelt CL. A New Era in Menopause Management? JAMA. 2024;332(16):1335–1337. doi:10.1001/jama.2024.15118