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ASRM Review: Aging and the Brain: Restoring Neurologic Functioning Through Hormone Replacement Therapy

Aging and the Brain: Restoring Neurologic Functioning Through Hormone Replacement Therapy

Presented by Robert A. Greene, MD, FACOG
North State Women's Center
Redding Medical Center

Summary written by Christine Schroeder, Ph.D.

Many changes that occur with age are written off as inevitable consequences of the getting older. Indeed, these effects are often the subject of humorous comments, even amongst affected individuals. In recent years, however, increasing research in a wide variety of fields has drawn these assumptions of inevitability into question.

The incidence of neurodegenerative diseases, such as Parkinson's and Alzheimer's disease (AD) has increased dramatically in recent years. Much of this increase is due to the ever-higher life expectancy of the American population. In addition to this general increase in risk, however, research shows that women are at far greater risk of these disorders than are their age-matched male peers.

The emerging data suggest that the hypoestrogenism associated with menopause may be the root cause of this elevated risk for women. Estrogen supplementation, for example, has been shown to slow the development of both AD and Parkinson's. The exact mechanisms by which the benefit of estrogen occurs has not been pinned down as of yet; however, it is thought to be a combination of some or all of the following:

Increased cerebral blood flow 
Increased pre- and post-synaptic production of neurotransmitters 
A decrease in oxidative damage 
Increases in dendrite branching 
Increased growth factor production 
Inhibition of adhesions and cytokines associated with AD 
 

Developments in advanced imaging have allowed the study of blood flow in the brain. These images demonstrate that cerebral blood flow is dramatically reduced during a hot flash. Thus, hypoestrogenism contributes to decreased blood flow, and hot flash episodes exacerbate this pattern even further. Most strikingly, the pattern of cerebral blood flow during a hot flash is highly similar to the patterns characteristic of AD. It is unlikely that normal levels of hot flashes immediately cause AD; rather, hot flashes year after year may be an additive stressor that adds to other deleterious side effects of hypoestrogenism.

Many of the disorders that ERT helps to treat are associated with diminished cerebral blood flow, which is thought to be a prime contributor to dementia. These include arteriosclerosis and peripheral vascular diseases. The effects of estrogen replacement therapy (ERT) on these neurodegenerative disorders can be dramatic. Research has shown that:

Symptoms of AD and Parkinson's can be mitigated or reversed after as few as six weeks of ERT

AD can be delayed by 50% with ERT 
AD patients who are on ERT generally go into full time nursing care 6 to 12 months later than AD patients who are not on ERT

In addition to the human misfortune that well-applied ERT may alleviate, the monetary costs would be substantial as well. Estimates are that, if all AD patients entered full nursing care just one month later, it would mean an annual saving of $1.2 billion in the United States alone. In view of the fact that ERT can delay entry by six to twelve months, the potential benefit is remarkable.

The National Institutes of Health is currently sponsoring the Women's Health Initiative Memory Study; the goal of this long-term research project is to define more precisely the relationships between ERT and neurological disorders. Nevertheless, the evidence to date strongly indicates that estrogen is neuroprotective, and these effects should be considered when decisions are made about long-term estrogen replacement therapy