Early Menopause, Delayed Hormone Therapy May Be Risk Factors For Alzheimer's Disease: Study

Not only does hormone therapy help improve severe symptoms related to menopause, but is also hypothesised to prevent cognitive impairment. 

Women who underwent hormone therapy around the age of menopause onset did not show increased risk of Alzheimer's disease, a brain disorder that slowly destroys memory and thinking cells, and subsequently, the ability to carry out the simplest tasks. 

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Early menopause and delayed hormone therapy can increase the risk of developing Alzheimer's disease, a new study suggests. However, women who underwent hormone therapy around the age of menopause onset did not show increased risk of Alzheimer's disease, a brain disorder that slowly destroys memory and thinking cells, and subsequently, the ability to carry out the simplest tasks. 

A set of symptoms that includes memory loss and difficulties with thinking, problem-solving or language is called dementia, and can occur when the brain is damaged by diseases such as Alzheimer's disease. 

The study describing the findings was recently published in the journal JAMA Neurology. 

Women can take care of themselves during menopausal transition by considering hormone therapy.

All about menopause

Menopause is the time that marks the end of a woman's menstrual cycle, and is diagnosed after she has gone 12 months without a menstrual period. In the years leading up to menopause, women may have changes in their menstrual cycle, and experience symptoms such as hot flashes. This phase is called menopausal transition or perimenopause.

Perimenopause mostly begins in women between ages 45 and 55, and while it usually lasts about seven years, it can be as long as 14 years, according to the United States National Institutes of Health (NIH). The levels of oestrogen and progesterone dramatically fluctuate during perimenopause. 

Lifestyle factors such as smoking, diet consumption, exercise, weight, age, race and ethnicity can affect the duration of perimenopause. 

During perimenopause, a woman's body begins to use energy differently, her fat cells change, and she may gain more weight easily. Women may also experience changes in their bone or heart health, their body shape and composition, and physical function. 

Other symptoms which women can experience in the months or years leading up to menopause include irregular periods, hot flashes, night sweats, mood changes, thinning of hair, dry skin, vaginal dryness, chills, sleep problems, weight gain, slowed metabolism, and loss of breast fullness, among others, according to Mayo Clinic. 

In order to be sure if these symptoms are a result of menopausal transition, women should undergo tests to detect the levels of the follicle-stimulating hormone and estradiol (E2), which is the form of oestrogen mainly made by the ovaries. 

What is hormone therapy?

The two basic types of hormone replacement therapy are systemic hormone therapy, which administers systemic oestrogen in the form of pills, skin patches, rings, gel, cream or spray, and contains a higher dose of the female sex hormone;  and low dose-vaginal products, which come in the form of cream, tablet or ring, and are used to treat the vaginal and urinary symptoms of menopause. Meanwhile, systemic hormone therapy can treat all menopausal symptoms.

What is premature menopause?

Menopause that occurs spontaneously before the age of 40 or due to surgical intervention before the age of 45 is called premature menopause. This has been associated with increased risk of Alzheimer's disease dementia. Not only does hormone therapy help improve severe symptoms related to menopause, but is also hypothesised to prevent cognitive impairment. 

Findings of the Women’s Health Initiative study that began two decades back

The NIH's Women's Health Initiative (WHI) study, which began in 1991, found that the use of hormone therapy was linked with an almost two-fold greater incidence of dementia compared to a placebo among women aged 65 years and older. This was possibly because hormone therapy was initiated in these women many years after the onset of menopause. 

What did brain scans of women reveal?

In order to better understand these findings, Rachel Buckley from the Massachusetts General Hospital, and corresponding author on the paper, along with her colleagues used positron emission tomography (PET) neuroimaging to study certain mechanisms. 

A PET scan is an imaging technique that uses a radioactive drug, or tracer, to observe the metabolic or biochemical functions of one's tissues and organs. Using PET neuroimaging, a technique to study the structure and function of the central nervous system, the researchers tried to figure out the link between the presence of two proteins involved in Alzheimer's disease dementia and the age of menopause and use of hormone therapy. The two proteins are beta amyloid and tau.

In a statement released by Mass General Brigham, a Boston-based hospital network, JoAnn Manson, one of the co-authors on the paper, said the team's previous findings from the WHI suggested that starting hormone therapy early in menopause, rather than late initiation, provides better outcomes for heart disease, cognitive functions and all-cause mortality. The current study suggests that the same is true for tau deposition. This means that starting hormone therapy early in menopause decreases the deposition of tau proteins, which are involved in Alzheimer's disease dementia.

Delayed hormone therapy led to elevated levels of tau protein

The highest levels of tau were only observed in hormone therapy users who reported a long delay between age at menopause onset and their initiation of hormone therapy, according to Buckley. 

The fact that delayed hormone therapy and tau deposition could be linked with each other is a new finding, the authors said.

As part of the study, the researchers analysed PET scans from 292 cognitively unimpaired adults to determine the levels of amyloid and tau in seven regions of the brain.

On comparing the brain scans of women and men of the same age, the authors found that women had more tau deposits, especially in the cases where they also had increased levels of beta amyloid. 

The association between abnormal levels of beta amyloid and tau was much stronger in women who had earlier menopause onset, according to the study. 

Elevated tau levels were observed in some regions of the brain close to the memory centre, and which are known to be involved in the progression of Alzheimer's disease dementia. 

When women underwent hormone therapy five years or more after menopause, the levels of tau and amyloid in their brains increased.

Gillian Coughlan, the first author on the paper, said up to 10 per cent of women experience premature menopause, and that hormone therapy can have negative effects on cognition, only if initiated several years after the onset of menopause. 

Therefore, women should consider hormone therapy close to the onset of menopause. A diet rich in fruits and legumes can help delay menopause.