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Hormone therapy's verdict hinged on timing
Revisiting the early studies
Those studies are apparently flawed: the conclusions did not match the data, or the studies were not done correctly, and in many cases therapy was started too late. Therapies started early enough, in menopause or perimenopause, showed beneficial effects that weren't popularized from the actual data, while therapies started too late showed some evidence of detrimental effects, perhaps. Researchers are now re-evaluating the data and running new studies on the best timing and on the different forms of hormone therapy.
Hormones and brain circuits
Perimenopause and menopause bring large swings in estrogen, progesterone, and testosterone, and sometimes hormones rise because they regulate each other. Hormones have strong effects on neurons in circuits including the hypothalamus, which regulates hunger, sleep, and body temperature and is involved in anxiety through the hypothalamic pituitary adrenal axis that governs cortisol. A change in hormones changes how active those circuits are.
Anxiety and sleep links
Tracing a change in anxiety to a single hormone works in some cases and not in many others, because so many mechanisms overlap. A mechanistic basis exists to suspect a link even where a direct one isn't established. Sleep suffers for many people at this stage, with night sweats and waking in the night, and hormone therapies may get at the foundation of those issues.
Why did the early hormone studies matter?
The Women's Health Initiative was a large US trial whose estrogen-plus-progestin arm was stopped early in 2002 after reports of increased breast cancer and cardiovascular events. The average participant was about 63, many years past the onset of menopause. Later analyses examined whether the age or years since menopause at which therapy began changed the results, an idea called the timing hypothesis.
How does estrogen affect brain cells?
Estrogen receptors are found in the hippocampus, hypothalamus, and amygdala. In a 1990s study in the Journal of Neuroscience, Catherine Woolley and Bruce McEwen found that the density of dendritic spines on hippocampal neurons in female rats rose and fell across the estrous cycle with estrogen levels. Spines are the tiny structures on neurons that receive signals.
Why do hot flashes come with menopause?
Falling estrogen narrows the range of body temperature that the hypothalamus treats as comfortable. A small rise in core temperature can then trigger sweating and widening of skin blood vessels. Naomi Rance and colleagues at the University of Arizona found that a group of neurons in the hypothalamus called KNDy neurons enlarge and become more active after menopause.
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