• Hormones like estrogen play a critical role in health, and research is ongoing about how estrogen levels impact the risk of developing certain conditions.
  • A recent study found that women who had their first period at age 12 or younger had a decreased risk for dementia.
  • The researchers suggest that estrogen exposure at a later age may also have a reduced risk for dementia.

Dementia is a growing concern as people are living longer.

Because there is no current cure for dementia, experts are continuing to explore dementia risk factors and protective factors. One area of interest is how the hormone estrogen and its levels may influence dementia risk for women.

A new study published in The American Journal of Geriatric Psychiatry looked at specific reproductive characteristics and their relationship to dementia risk.

The researchers found that participants with more prolonged exposure to estrogen were at a decreased risk for dementia. Estrogen exposure could be described as the number of years between starting menstruation and undergoing menopause or receiving a hysterectomy or oophorectomy.

In contrast, those with less time of estrogen exposure were at an increased risk for dementia. This also included participants who began menstruation at a later age.

The study authors concluded that estrogen may act as a protective factor against dementia, but more research in this area is needed.

Study author Dr. Hee Kyung Park, PhD, of the Division of Psychiatry at University College London, told Medical News Today:

“Although this study showed the protective effects of longer lifetime estrogen exposure, there are inconsistencies in the results in human studies. Future diverse cohort studies should determine the effects of estrogens on the risk of dementia.”

Estrogen is a hormone that plays a vital role in the female reproductive system. It influences breast development, the changes in the lining of the uterus, and helps prevent vaginal dryness. However, estrogen impacts other elements of the body’s functions as well.

“Estrogen has an impact on multiple systems within the body — skin, heart, vasculature, hair, pelvic musculature, brain, mucus membranes, and the urinary system,” non-study author Dr. Kecia Gaither, double board certified OB-GYN and maternal-fetal medicine specialist and director of Perinatal Services at NYC Health + Hospitals/Lincoln in New York City, told MNT.

Estrogen levels are lower after menopause, which is when menstruation has stopped for a year. After menopause, there may be an increased risk for health conditions like osteoporosis and heart disease.

Non-study author Dr. Michael Krychman, board certified OB-GYN and medical director of Women’s Health Services at MemorialCare Saddleback Medical Center in Laguna Hills, CA, explained to MNT:

“When a woman goes through menopause, and her estradiol and testosterone levels plummet, this may lead to a constellation of symptoms including but not limited to hot flashes, vaginal dryness, painful intercourse, [and] loss of libido. With loss of estrogen, a woman will experience accelerated bone loss, which can lead to osteopenia or osteoporosis. Other common symptoms a woman may experience with fluctuations in hormones may include weight gain, mood changes, and fatigue. It is not uncommon for appetite, sleep, and growth to be affected too.”

Women are often at a higher risk for dementia.

Researchers of the present study wanted to understand how estrogen impacted dementia risk and whether or not the length of estrogen exposure played a role in that risk.

Researchers analyzed data from 273,260 participants in the UK Biobank, only including individuals who self-identified as women. They excluded participants who already had dementia.

Participants provided data on several factors, including age at menarche, history of reproductive surgeries, age at menopause, and childbearing history.

Researchers defined the age of last estrogen exposure as the age of natural menopause, the age of undergoing a bilateral oophorectomy, or the age of undergoing a hysterectomy.

If participants didn’t report these ages, they defined last estrogen exposure as “age at data collection minus 1 year since the absence of menstruation defines menopause for at least 12 months.”

If participants didn’t report natural menopause or surgery, researchers assumed that they had ongoing estrogen exposure. Participants also reported whether or not they had ever received hormone replacement therapy.

Researchers further collected data on confounders, including family history of dementia, education level, body mass index (BMI), smoking, diabetes, and high blood pressure. Throughout the study, 3,694 participants developed dementia.

Overall, researchers found that a prolonged time of estrogen exposure was associated with a decreased risk for dementia. Based on their analysis, they discovered that participants with a later age of last estrogen exposure had a 24% decreased risk for dementia.

Participants who reported menarche at age 15 or older had a 12% increased risk for dementia, and participants with a surgical history had an overall 8% increased risk for dementia.

Researchers did not find an association between hormone replacement therapy (HRT) and dementia risk. The results point to the potential protection estrogen may provide against dementia.

Dr. Krychman shared his thoughts on the findings:

“The role of estrogens and cognitive decline is a complicated and complex phenomenon, and the protective effect of estrogen in the development of dementia remains unclear. This study showed that prolonged exposure to estrogen might play a protective role in the development of dementia, but as the authors do mention, there are many confounders in the study.”

This research does have certain limitations. The researchers used data from the U.K. Biobank, which doesn’t necessarily reflect all populations or allow for accurate generalizations of the results. There’s also a risk that reports from participants had some inaccuracies. Researchers did not include the oldest age bracket, which could have influenced the results.

Additionally, some data for reproductive variables was missing. Researchers also note that the number of women who experienced natural menopause was much higher than the women with a history of surgeries, so this may have impacted the results. They also did not have details about the use of hormone replacement therapy.

Dr. Park noted another potential area for further study: “The effects of estrogen could be investigated in people with early-onset dementia and late-onset dementia,” she said.

“If the protective effects of estrogen may persist for at least 10 to 15 years after menopause, the effects of estrogen might be different in late life. The interaction between APOE genotype and estrogen should be investigated in the future.”

Despite these limitations, the study points to the potentially protective effects of estrogen when it comes to dementia risk. More research is needed before any major updates are made to clinical practice.

Dr. Krychman noted the following:

“There is no easy, simplistic answer. [The] window phase hypothesis demonstrated that estrogen may have an effect [on] dementia prevention if therapy is started early (within the first 5 years of menopause. Whereas other studies like the Woman’s Health Initiative Memory Study (WHIMS) showed deleterious effects due to estrogen action on the brain. Results should be interpreted with cautious optimism, and all women who are concerned about dementia should seek medical care and a proper assessment and evaluation.”

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