Exploring new treatments for hot flushes in postmenopausal estrogen deficiency

Vasomotor symptoms (VMS; ‘hot flushes’) affect 50-80% of women during menopause, yet the majority remain untreated due to concerns surrounding traditional hormone replacement therapy (HRT). Once widely used for ~ half a century, HRT utilization drastically declined following the Women's Health Initiative (WHI) studies reported in the early 2000s, which revealed substantial risks including blood clots, strokes, and various cancers. This shift has left a considerable treatment gap, with current management strategies insufficiently addressing the need for effective and risk-free interventions.

Central to understanding and treating VMS are the pathophysiological changes of KP neurons in the mediobasal hypothalamus. After menopause, these neurons undergo robust morpho-functional changes, characterized by conspicuous hypertrophy, increased neuropeptide biosynthesis and hyperactivity. Our research program uses high-throughput RNA-Sequencing of kisspeptin neurons isolated from the human hypothalamus with laser capture microdissection (LCM) to characterize menopausal alterations. Then, animal models of menopause are used in studies to explore the therapeutic potentials of i) brain selective estrogen therapy and ii) its non-hormonal alternatives.