Does hormone therapy during menopause boost or reduce the risk of dementia? Here’s the science

By 2050 approximately 135 million people around the world will suffer from dementia. The most common cause of dementia is Alzheimer’s disease. Women are at greater risk of Alzheimer’s disease than men, even after accounting for women’s longer lifespans.

Symptoms of Alzheimer’s disease most often appear after the age of 65. However, changes in the brain begin decades before symptoms appear. For women, this usually coincides with the transition to menopause.

Menopause results from a reduction in the body’s production of two hormones produced by the ovaries: estrogen and progesterone. These hormonal changes are associated with a wide range of symptoms, including scorching flashes, night sweats, difficulty sleeping, decreased libido, mood changes, and brain fog.

For decades, menopausal hormone therapy (also called hormone replacement therapy or HRT), which includes estrogen alone or estrogen in combination with progesterone, has been prescribed to relieve the symptoms of menopause.

But how does menopausal hormone therapy affect the risk of dementia? And why do some studies say therapy increases risk and others say it reduces it?

Hormones and the brain

Much of the preclinical (animal) research shows that estrogen helps protect the brain. It reduces any damage to nerve cells and supports overall brain health.

Estrogen-responsive receptors are found in areas of the brain associated with reproductive functions. But they come in too areas of the brain essential for learning, memory, and higher-order cognitive abilities such as planning, organization, and decision-making.

The loss of the “neuroprotective” effect of estrogen after menopause is thought to contribute to more cases of Alzheimer’s disease in women than in men.

Clinical trials also showed that women who underwent medical or surgical menopause before the age of natural menopause had an increased risk of dementia and cognitive impairment throughout their lives.

It’s a risk appears to be reduced in women who take estrogen therapy after surgery.

This led researchers to hypothesize that adding estrogen back – through hormone therapy during menopause – could protect and maintain women’s cognitive health.

However, the research results were not consistent.

Can hormone therapy during menopause affect the risk of dementia?

Concerns about the risk of dementia and hormone therapy during menopause stem in part from the unexpected results of a landmark study conducted more than two decades ago.

The findings showed The employ of hormone therapy in postmenopausal women aged 65 years and older has been associated with an increased risk of dementia.

However, these studies have some key limitations:

1) most women were over the age of 65 and more than ten years postmenopausal

2) the type of estrogen and progestin (a synthetic form of progesterone) used may have less impact on brain health.

Recently published systematic review and meta-analysis The scientific data linking hormone therapy to the risk of Alzheimer’s disease included findings from 51 different reports published through 2023.

The results showed that if hormone therapy was started in midlife, or more generally within ten years of the last menstrual period, the risk of developing Alzheimer’s disease later in life was reduced compared with women not using any hormone therapy.

The greatest risk reductions were associated with estrogen-only hormone therapy.

However, when hormone therapy was considered tardy in life or more than ten years after menopause, estrogen-only therapy had a neutral effect on the risk of Alzheimer’s disease.

However, estrogen-progestogen therapy was associated with an increased risk.

Just one clinical trial has been published since this meta-analysis. This study examined the long-term effects of menopausal hormone therapy initiated early in menopause.

At the time of joining the study, the women were on average 52.8 years venerable and 1.5 years postmenopausal. They were randomly assigned to receive estrogen (with or without progestin) or placebo for four years.

Ten years later, researchers followed 275 women. They found no cognitive effects (no harm or any benefit) based on whether women were exposed to 48 months of hormone therapy or a placebo.

What influences your risk?

The effect of postmenopausal hormone therapy on the risk of dementia appears to depend on several factors. These include the date you start taking the medication, how long you are taking it, the type of hormones you are using, and the person’s genetic and health conditions.

1. When does therapy begin: the critical window hypothesis

One of the key factors determining the impact of menopausal hormone therapy on cognitive function and the risk of dementia appears to be the timing of therapy initiation in relation to menopause. This is called the “critical window hypothesis.”

According to this hypothesis, estrogen can only facilitate protect neurons in the brain if it is started early in menopause, especially in the few years after menopause, when the brain may still be more responsive to hormones.

2. Type of menopausal hormone therapy and the role of progesterone

The type of hormones included in hormone therapy may vary significantly in their molecular structure, as well as in their physiological effects.

Different types of estrogen (such as estradiol or conjugated estrogen) and the inclusion of progestin (required in women who have not had a hysterectomy) may have different effects on brain health and dementia risk.

Some research suggest that adding a progestin to estrogen therapy could counteract some of the cognitive benefits of estrogen itself, possibly by blocking estrogen receptors in the brain.

3. The role of vasomotor symptoms

Vasomotor symptoms such as scorching flashes and night sweats are a sign of menopause. There were more vasomotor symptoms associated with poorer memory but also increase in biological markers associated with the risk of dementia.

Therefore, one possible pathway through which menopausal hormone therapy may reduce the risk of Alzheimer’s disease is through its effect on reducing vasomotor symptoms.

4. A person’s genetics and health

The greatest genetic risk factor for older-onset Alzheimer’s disease is having one or more copies of a specific version of the APOE gene, called APOE e4.

Is emerging hypothesis that women at genetic risk of Alzheimer’s disease may benefit most from hormone therapy.

What does this mean for you?

The clinical and scientific community continues to debate whether hormone therapy during menopause may play a role in the risk of Alzheimer’s disease.

In general, the decision to employ hormone therapy should be made individually, taking into account age and timing of menopause, health status, and specific menopausal symptoms.

We need more research before we can make firm decisions about the role of hormone therapy and the risk of dementia, but based on current evidence, hormone therapy may be beneficial if started early in menopause, especially for women at genetic risk for Alzheimer’s disease.