The importance of shared decision making
Dr. Shifren: As with any important health care decision, women should be involved in an individualized discussion of risks and benefits, with shared decision making about whether HT is the right choice. Women also should be involved in ongoing decisions regarding HT formulation, dose, and duration of use.
A nonhormonal option for hot flashes
OBG Management: How many women experience VMS around the time of menopause?
Dr. Genevieve Neal-Perry, MD, PhD: About 60% to 70% of individuals will experience hot flashes around the time of the menopause.6 Of those, about 40% are what we would call moderate to severe hot flashes—which are typically the most disruptive in terms of quality of life.7 The window of time in which they are likely to have them, at typically their most intense timeframe, is 2 years before the final menstrual period and the year after.7 In terms of the average duration, however, it’s about 7 years, which is a lot longer than what we previously thought.8 Moreover, there are disparities in that women of color, particularly African American women, can have them as long as 10 years.8
OBG Management: Can you explain why the VMS occur, and specifically around the time of menopause?
Dr. Neal-Perry: For many years we did not understand the basic biology of hot flashes. When you think about it, it’s completely amazing—when half of our population experiences hot flashes, and we don’t understand why, and we don’t have therapy that specifically targets hot flashes.
What we now know from work completed by Naomi Rance, in particular, is that a specific region of the brain, the hypothalamus, exhibited changes in number of neurons that seemed to be increased in size in menopausal people and smaller in size in people who were not menopausal.9 That started the journey to understanding the biology, and eventual mechanism, of hot flashes. It took about 10-15 years before we really began to understand why.
What we know now is that estrogen, a hormone that is made by the ovaries, activates and inactivates neurons located in the hypothalamus, a brain region that controls our thermoregulation—the way your body perceives temperature. The hypothalamus controls your response to temperature, either you experience chills or you dissipate heat by vasodilating (hot flush) and sweating.
The thermoregulatory region of the hypothalamus houses cells that receive messages from KNDy neurons, neurons also located in the hypothalamus that express kisspeptin, neurokinin, and dynorphin. Importantly, KNDy neurons express estrogen receptors. (The way that I like to think about estrogen and estrogen receptors is that estrogen is like the ball and the receptor is like the catcher’s mitt.) When estrogen interacts with this receptor, it keeps KNDy neurons quiet. But the increased variability and loss of estrogen that occurs around the time of menopause “disinhibits” KNDy neurons—meaning that they are no longer being reined in by estrogen. In response to decreased estrogen regulation, KNDy neurons become hypertrophied with neurotransmitters and more active. Specifically, KNDy neurons release neurokinin, a neuropeptide that self-stimulates KNDy neurons and activates neurons in the thermoregulatory zone of the brain—it’s a speed-forward feed-backward mechanism. The thermoregulatory neurons interpret this signal as “I feel hot,” and the body begins a series of functions to cool things down.
ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT
Continue to: Treatments that act on the thermoregulatory region