- Hot flashes treatment is shifting towards non-hormonal drug therapies
- Falling estrogen levels during menopause stimulate kisspeptin/neurokinin B/ dynorphin (KNDy) neuron complex, which leads to hot flashes
- Selective Serotonin Uptake Inhibitors (SSRIs) in low doses can reduce night sweats and hot flashes
Non-hormonal therapies that target the neuron complex are currently being developed. SSRIs at low doses can also be used to treat hot flashes.
During menopause the level of estrogen, which is important for regulation of the body temperature, starts to fall, and this leads to a sudden wave of mild or intense body heat called hot flashes.
A study conducted in North America showed that almost 75 percent of women take hormone replacement therapy to provide relief from hot flashes, which are also called vasomotor symptoms (VMS). In hormone replacement therapy, synthetic estrogen and progesterone are given to replace the falling estrogen levels and relieve vasomotor symptoms.
Dr. Reed specifically targeted the drugs which act on the kisspeptin/neurokinin B/dynorphin (KNDy) neuron complex in the hypothalamus. This neuron complex in the hypothalamus is important as they control reproduction and hormones.
As the estrogen level is falling during menopause, kisspeptin/neurokinin B/ dynorphin (KNDy) neurons are overstimulated, which leading to hot flashes.
Dr. Reed said,"When estrogen falls, it causes this KNDy neuron complex to just basically go bonkers. It's like turning on a gazillion fire hydrants, which spill over into the adjacent thermoregulatory center and cause thermoregulatory dysregulation, resulting in hot flashes. The thermoregulator center sends signals to the rest of the body to cool us when we are too hot (via hot flashes) and to warm us when we are too cool (shiver)." This thermoregulatory dysregulation at the normal core body temperature leads to hot flashes.
Currently, there is no FDA approved drug for treating menopause symptoms that target the KNDy neuron complex.
For her research, Dr. Reed collaborated with Dr. Robert Steiner of UW Medicine's obstetrics and gynecology and Dr. Charles Chavkin of pharmacology and pain medicine from UW and Dr. Victor Navarro from Harvard. They evaluated kappa agonists and NKB (Neurokinin B) antagonists, which showed promising results.
Dr. Reed said,"The KNDy neuron manipulation, is really exciting and holds great promise for rapid and efficacious treatment of menopausal symptoms. We're still looking at safety in the Phase 3 trials for the NKB antagonists (targeting the N in KNDy) but this treatment is up to 80 percent effective in amelioration of hot flashes, with improvement of other menopausal symptoms such as sleep and well-being."
The Neurokinin B (NKB) antagonists target the neurokinin B in the kisspeptin/neurokinin B/ dynorphin (KNDy) neuron complex. Minor adverse effects on liver function were observed, so further studies are being conducted to evaluate its safety.
Dr. Reed also worked on a study that looked at using low doses of a class of drugs called selective serotonin uptake inhibitors (SSRIs) to treat hot flashes. The research team found that SSRIs are normally used to treat depression, but in low doses, they could effectively reduce hot flashes and night sweats.
Yoga, omega 3, and exercise were also evaluated to see if they could provide relief from hot flashes but the study data did not support them, but it is important to remember that yoga and exercise help improve the overall quality of life and health and can be helpful for well-being in midlife.
Dr. Reed stated that in the future, research would focus on the vaginal microbiome of menopausal women as well as the brain area beside the hypothalamus, which regulates cold stimuli and body temperature.
She said,"We know there is a lot of crosstalk between the hypothalamic neurons in the reproductive center and the thermoregulatory center, and that they chat back and forth. Unlocking the key to how this area of the brain is controlled will be critical to our understanding of the etiology of menopausal symptoms so that we can best target future safe effective non-hormonal therapies."