Why is estrogen related to the risk of dementia in women

The dementia epidemic that exists in the world today exposes everyone to face a major challenge, with a major impact on individuals, caregivers, families and health systems. Fifty million people live with dementia worldwide, and this number is projected to triple by 2050, according to figures from the World Health Organization (WHO).

To date, there is no effective treatment that modifies the course of dementia; mitigation and modification of risk factors therefore present opportunities to reduce the burden associated with dementia in the population. Age-standardized global prevalence and dementia mortality rates were estimated to be higher in women than in men.

While the risk of developing dementia increases with age, the measure that the female predominance of patients that exists is simply due to women's longer life expectancy remains far from conclusive, and female-specific reproductive factors may explain these sexual disparities.

A recent analysis conducted by a group of professionals from the University of New South Wales in Australia and published in Plos Medicine, found that some reproductive events, as a start early or late menstruation, early menopause and hysterectomy, were linked to an increased risk of dementia during pregnancy or abortion, and late menopause was linked to a lower risk. But having children was not one of them, with a similar relationship observed between the number of children and the risk of dementia in men and women.

The lead author, Jessica Gong, of the George Institute for Global Health at the University of New Wales, suggested that although it appeared that reproductive events related to changes in hormone levels in women might be involved in the risk of dementia, the exact relationship was still unknown.

“While the risk of developing dementia increases with age, we still don't know whether the higher rates seen in women are simply because they live longer,” Gong explained. But it's possible that female-specific reproductive factors may explain some of the sexual differences.” Estradiol is the most predominant form of estrogen during reproductive life (from the beginning of menstruation to menopause) and estriol is the main estrogen during pregnancy. The use of hormones that originate outside the body, such as oral contraceptives during the reproductive years, and hormone replacement therapy (HRT) in old age 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 some parameters that were associated with an increased risk of dementia, such as early and late first menstruation, first birth at a younger age, and hysterectomy, specifically hysterectomy without surgical removal of one or both ovaries, or if hysterectomy was performed after removal of the ovary.

On the contrary, factors associated with a decreased risk were having been pregnant once, having had an abortion once, a longer reproductive life, and a late menopause. “With regard to external hormones, the use of oral contraceptive pills was associated with a lower risk of dementia, but the findings of our study did not support an association between HRT and the risk of dementia,” Gong said.

The authors proposed that risk variation in women may not be associated with motherhood because a similar pattern was observed between the number of children begotten and the risk of dementia among a similar number of men in the same study. “We found that the higher risk of dementia associated with 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 dementia on the rise and in the absence of significant progress in treatment, the focus has been on reducing the risk of developing the disease. “More research is needed to understand whether these differences are associated with lifelong exposure to the body's own estrogen and whether the use of external hormones could influence the risk of developing dementia,” Gong added. Our findings may be useful in identifying high-risk women to participate in future clinical trials to evaluate possible preventive measures and treatments,” the specialist concluded.

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