Life events that influence estrogen levels may be linked to a woman’s risk of dementia later in life

Life events that influence levels of estrogen, a female hormone, may be linked to a woman’s risk of developing dementia later in life, according to new research.

The analysis found that certain reproductive events – such as early or late onset of menstruation, early menopause and hysterectomy – were linked to a higher risk of dementia while having ever been pregnant or having had an abortion and menopause more late were associated with a lower risk.

But motherhood was not one of them, with a similar relationship observed between the number of children and the risk of dementia in both men and women.

Lead author Jessica Gong of the George Institute for Global Health said that while it appears reproductive events linked to changes in hormone levels in women may be involved in dementia risk, the exact relationship was still unknown.

“While the risk of developing dementia increases with age, we don’t yet know if the higher rates seen in women are simply due to them living longer,” Ms Gong said. “But it’s possible that female-specific reproductive factors could account for some of the sex differences.”

Dementia is rapidly becoming a global epidemic, currently affecting approximately 50 million people worldwide. This figure is expected to triple by 2050, mainly due to the aging of the population. Rates of dementia and associated death are both known to be higher in women than in men.

Estradiol is the most predominant form of estrogen during reproductive life (from onset of menstruation to menopause) and estriol is the major estrogen during pregnancy. The use of hormones from outside the body, such as birth control pills during childbearing years, and hormone replacement therapy (HRT) later in life can also influence estrogen levels.

To examine these relationships in more detail, researchers at the George Institute analyzed data from a total of 273,240 women without dementia who were registered with the UK Biobank, a large-scale biomedical database. After adjusting for other factors that might have influenced the results, they found that the following were associated with an increased risk of dementia:

  • Early and late onset of menstruation, younger age at first birth, and hysterectomy – especially hysterectomy without surgical removal of one or both ovaries, or if the hysterectomy took place after the ovaries were removed.

Conversely, the factors associated with a reduced risk were the fact of having already been pregnant, having had an abortion, a longer reproductive lifespan and a later menopause.

“With regard to external hormones, the use of oral contraceptive pills was associated with a lower risk of dementia, but the results of our study did not support an association between HRT and the risk of dementia,” said said Ms. Gong.

The authors proposed that the variation in risk among women may not be associated with childbearing, as a similar pattern was observed between the number of children fathered and the risk of dementia in a similar number of men in the same study.

“We found that the higher risk of dementia related to early menopause (natural and artificial) was more pronounced in women of lower socioeconomic status,” she added.

“Social deprivation is likely to be an important determinant of dementia risk as well as other aspects of women’s health.”

With the increase in dementia and in the absence of significant therapeutic breakthroughs, the focus has been on reducing the risk of developing the disease.

“Further research is needed to understand whether these differences are associated with the body’s lifetime exposure to estrogen and whether the use of external hormones might influence the risk of developing dementia,” Ms Gong added.

“Our results may be useful in identifying women at high risk to participate in future clinical trials to assess preventive measures and potential treatments.”


George Institute for Global Health

Journal reference:

Gong, J. et al. (2022) Reproductive factors and risk of incident dementia: a cohort study of UK Biobank participants. OLP Medicine.

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