How does menopause affect the central nervous system?

Updated: Jun 06, 2018
  • Author: PonJola Coney, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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The association between estrogen and memory function is an intriguing area of research. Normal aging itself induces a decline in certain cognitive capabilities, and a lack of estrogen may contribute to this process. If this is the case, postmenopausal estrogen therapy may be able to preserve this function and slow or even prevent decline in certain cognitive functions.

An inherent difficulty in this area involves the limitations of objective cognitive testing for functions such as memory. Postmenopausal women receiving estrogen therapy have shown better performance on memory testing than postmenopausal control subjects not receiving estrogen therapy. [74, 75] The effect of estrogen is to slow the decline of preserved memory function. Women’s Health Initiative (WHI) data do not show improved cognitive function in women taking either hormone therapy or estrogen therapy. [39, 40]

Current data suggest that Alzheimer disease (AD) is more common in women than in men, even when the longer average lifespan of women is taken into account, because AD is primarily an age-related condition. [76] In earlier studies, estrogen therapy appeared to reduce the relative risk of AD or to delay its onset. [77, 78] Estrogen therapy has not been shown to improve cognitive function in patients with AD; it cannot reverse previous cognitive decline and therefore has no role as a sole treatment modality in AD. WHI data support this view.

The menopausal transition (MT) is frequently a time of depressive symptoms arising from direct hormonal effects and changes in life circumstances and occurring secondary to effects such as estrogen-related sleep disturbance and vasomotor symptoms. However, major depression is associated with the female sex at all ages. Objective demonstration of a cluster of cases around menopause has been difficult, though there is some anecdotal evidence for such clustering.

Regardless of whether the criteria for a definitive diagnosis of major depression are met, depressive symptoms should always be considered in the context of level of functioning; any functional impairment warrants consideration of intervention.

In all but a very few cases, symptoms caused by menopause may not be distinguishable from symptoms caused by primary depression. Treatment of depressive symptoms with estrogen in perimenopause, the postpartum period, [79] and premenstrual syndrome is common, with observed resultant improvement in functioning and mood, both subjective and objective, in many clinical instances.

Clinical depression, however, warrants treatment with antidepressants, with estrogen showing benefit as adjuvant therapy in this scenario. Short-term use of estrogen during times of estrogen fluctuation seems to be of some benefit. [80]

The microcellular effects of estrogen in the central nervous system (CNS) have yet to be clearly outlined, but further research may reveal intricate processes by which estrogen exerts a direct effect on CNS function. One of these processes may turn out to be a reduction in free radical damage by estrogen therapy.

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