Moods And Menopause
There is definitely a hormonal component to our moods. This should not surprise any woman who is entering or is in menopause. The menopause transition is characterized by an initial fluctuation of estradiol production by the ovaries, evidenced by irregular menstrual cycles, but followed by a sustained estradiol decline resulting in the end of menses.
Why is estrogen important? Estrogen acts on blood vessels and neurons in many areas of the brain, but especially in the pre-frontal cortex, the center that mediates the highest level of cognitive function in primates, including humans. By stimulating the production of nitric oxide, a vasodilator, estradiol maintains blood flow to the brain. Estrogen inhibits the enzymes, monoamine oxidase and catechol-o-methyl transferase, that normally degrade and, therefore, reduce levels of serotonin, dopamine, and norepinephrine, our most important mood-altering proteins. By this enzyme-blocking action, estradiol helps to maintain a higher level of these hormones to boost and maintain our mood. Estrogen also protects our neurons from damage by oxidative free radicals and ischemic injury while helping to repair damaged nerves and stimulating growth factors to promote growth of dendritic spines (neuronal branches important for brain flexibility). This allows improved communications between neurons, which facilitates our performing complex learning tasks.
What happens as the brain experiences estrogen withdrawal? From animal studies, the cognitive performance of young animals is not affected, presumably reflecting flexibility (plasticity) of the youthful brain. Older animals, in contrast, demonstrate loss in performance and, on autopsy, demonstrate a dramatic decrease of dendritic spines. These findings correlate with human imaging studies demonstrating decreased blood flow to the brain and actual brain shrinkage. Many women report new onset or worsening anxiety and depression at perimenopause that likely can be related to both these brain neuronal changes and life stresses. Short-term memory also can be affected by both.
Many women consider estrogen supplementation in perimenopause, not just for hot flashes and sleep disorders but also to feel better. Most current animal and human studies now are focusing on the role of estrogen replacement beginning in the perimenopausal period. Why? Initiated at this time of dramatic hormonal change in which estradiol is rapidly withdrawing and key inflammatory proteins are increasing, the benefits of estradiol protection for bone, brain, skin, and heart are more likely than if initiated late in menopause when inflammation-induced damage already has occurred.
The Women’s Health Initiative Memory Study (WHIMS), one arm of the WHI, confirmed that hormone supplementation started some years after menopause did not protect against early dementia or cognitive decline. However, many believe that this study chose the wrong hormone preparations (premarin made of over 12 estrogens but very little estradiol and medroxyprogesterone, a synthetic chemical version of progesterone) and the wrong age group of women (mean age of 62 years). Had they used pure estradiol with micronized progesterone, and had they studied perimenopausal women, the results would likely have been different.
Bottom Line: Many perimenopausal women report a greater sense of well-being and mood on hormone replacement therapy.
By James Woods, M.D.
Dr. Woods treats patients for menopause at the Hess/Woods Gynecology Practice.
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James Woods | 4/16/2015
