Jan 12
23
Menopause and the Double “M”: Mood & Memory
Most of us usually think of menopause as hot flashes, night sweats, and insomnia fostered by changes in the ovaries and uterus. During perimenopause, a variable time 2 to 10 years or more before the final menstrual period, the ovaries lose their rhythmic pattern of estrogen and progesterone release. It is the time of fluctuating estrogen that underlies the production of the typical menopausal symptoms—hot flashes and so on. However, it is not the ovaries that regulate temperature, sweating, and sleep. These are all functions of the brain.
It is an interesting situation because doctors define the clinical problems of menopause as ovarian and uterine, but the symptoms of menopause that annoy women are defined by problems related to their brain. Hot flashes and night sweats are a disturbance of the hypothalamus, a small region of the brain tasked to thermoregulation. Estrogen has direct effects on neurons in the hypothalamus; and when estrogen peaks and troughs in perimenopause, it causes some of the hypothalamic cells to go a little haywire: triggering hot flashes and night sweats, termed vasomotor symptoms. Similarly, changes in estrogen disturb sleep by disrupting the complex interaction of brain neurons that drive normal sleep patterns.
Since estrogen has considerable influence on thermoregulation and sleep, it comes to no surprise that estrogen has effects on other brain functions, particularly mood and memory. Erratic estrogen production in perimenopause makes thermoregulation and sleep worse, not better, and the same goes for mood and memory. We affectionately call 
that “Mood Matters” and “Meno Fog”. For many women, the perimenopausal disruption of mood and concentration outweighs the annoyance of hot flashes; and for some women, mood and memory problems are their only complaint.
Depressive symptoms are common during perimenopause affecting over 50% of women. In some ways, it’s reasonable to think of this as “normal” aging, since all women who live long enough reach menopause. For many women, however, the symptoms adversely affect their quality of life (and their family’s) and should be medically treated. Typically, perimenopausal women say they have “PMS all the time,” low energy, poor concentration, sadness, and irritability. Major depressive disorder may also be increased during perimenopause, especially in women who have had a prior depressive event.
The risk factors for midlife depressive symptoms include: hot flashes, insomnia, surgical menopause, high BMI, smoking, low education, and the stress found in life events, both financial and personal. One belief that links estrogen to mood is the “cascade theory”. In this theory, changes in estrogen lead to hot flashes, which lead to insomnia, which result in depression, sort of a domino sequence. Other evidence points more toward a direct effect of estrogen on neurons determining mood, rather than just through the mechanism of insomnia. More on that later.
Memory, usually referred to as cognition: the ability to remember, think, and perform spatial navigation, declines with normal aging. Sorry, it’s a fact. Interestingly, many of the risk factors for dementia parallel the risk factors for most other deadly diseases such as heart disease, stroke, and cancer; can you say lifestyles! Anything that you can think of that increases heart disease also increases dementia: smoking✔obesity✔hypertenision✔ diabetes ✔sedentary life ✔high saturated fat diet✔. You get the idea. The other risks are also important to consider. Being a woman is a significant risk (3 times that of men)—what is it about women? Age, genetic factors, family history, stress/depression also increase the risk. There is evidence that the more a brain is pushed, the less the risk because those with higher educational attainment and those with more job complexity suffer less dementia.
The hippocampus is an area of the brain where critical processing of information takes place for the consolidation of information to form memories. Estrogen has been shown to preserve hippocampal neurons by several different mechanisms. Estrogen stimulates cerebral blood flow, stimulates nerve cell branching (dendritic outgrowth), protects against oxidative stress, improves nerve cell survival and slows neuronal death, and modulates neurotransmitter release and transmitter receptors. When mapped with MRI scanning, estrogen preserves the volume of neuronal 
tissue in the hippocampus. Whew.
It is now known that estrogen is important in how the brain uses energy. The brain comprises only 2% of body weight, but it consumes over 25% of the body’s energy source: glucose. Most of the brain’s energy consumption is burned in cognitive processing. In other words, it takes a lot of fuel to think. Estrogen plays a critical role in many steps of brain energy utilization, promoting glucose uptake by neurons and transport to the mitochondria (the cell’s power plant) for the generation of ATP. During perimenopause, when there are times of low circulating estrogen, the brain is actually starved for lack of energy with resulting derangement of mood and memory. Withdrawal of estrogen is like a stun gun to the brain. During hot flashes, there are also demonstrable reductions of blood flow to areas of the brain that are involved in cognition.
Menopausal hormone therapy reduces the incidence of dementia by 65% or more in large population based studies. However, like a good punch line, timing is everything. If hormone therapy is initiated at or near the time of the final menstrual period (preferably during perimenopause), there is a profound neuroprotective effect. If initiation of hormone therapy is delayed until age 65, then there is actually a worsening of dementia risk. The healthy cell theory suggests that when a woman is in her forties or 
fifties, her nerve cells are still healthy and can respond well to estrogen. After age 65 or so, the neurons are already damaged, and estrogen does not help them but in fact, can harm them. Most menopause experts believe that if a woman began hormone therapy at the usual age (40 to 60), and continues to feel that it helps her, then it is safe to continue hormone therapy indefinitely. It is prudent to discuss continuation of hormone therapy at yearly intervals to access current health status, benefits, and risks.
Estrogen therapy for depressive symptoms, during the “P times”: PMS, postpartum, and perimenopause, is as effective as anti-depressants. In addition to its effects on serotonin, Estrogen further modulates increases in available norepinephrine by stimulating synthesis and decreasing turnover. Estrogen works much faster than standard antidepressants. Measurable improvements are apparent with estrogen in one week rather than 6 to 8 weeks as seen for standard antidepressants. Estrogen is a more natural way to treat depressive symptoms triggered by perimenopausal estrogen withdrawal. A mental health care specialist should evaluate major depressive disorder.
There is no dispute about the effectiveness of hormone therapy in eliminating hot flashes, night sweats, and menopausal insomnia. The idea that hormones play a role in mental health is a relatively new and important field of investigation. In addition to thermoregulation and sleep, there is substantial data that hormone therapy for menopause, estrogen therapy, normalizes mood and memory functions as well. Problems with Mood and Memory, the “Double M,” contribute to substantial impairments for midlife women and beyond. Hormone therapy poses few risks for healthy menopausal women and provides substantial benefits.
Find complete information about all things menopause in our new book:WOMENOPAUSE: STOP PAUSING AND START LIVING
