Dementia: Ovary removal before menopause linked to cognitive decline

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A new study shows that removing the ovaries before menopause is associated with less white matter in the brain later in life. Andreas Selter/Getty Images
  • A new study examined the brains of women who had their ovaries removed before menopause.
  • Sometimes, women need to undergo this type of procedure to treat conditions such as ovarian cancer or endometriosis.
  • The study’s findings show that women who undergo oophorectomy before menopause have a decline in white matter in their brains later in life.
  • A decrease in white matter is associated with cognitive impairment.

A new study examined the cognitive effects of having the ovaries removed in women.

A researcher at Wake Forest University used data from the Mayo Clinic Study of Aging to study women who had their ovaries surgically removed before menopause—a procedure called bilateral premenopausal oophorectomy (PBO).

When a woman undergoes a PBO, it affects the body’s hormones, which can lead to cognitive impairment such as dementia. The researcher, Professor Michelle Mielke, wanted to see if there was a physiological reason for this to happen.

By studying magnetic resonance imaging (MRI) results from more than 1,000 women, Michelle Marie Mielke, PhD, a professor of epidemiology and prevention at WFU, learned that women who underwent PBOs experienced reductions in white matter in many of their brains.

The findings appear in Alzheimer & Dementia: Journal of the Alzheimer’s Association.

The human brain consists of two types of brain tissue: gray matter and white matter. According to National Library of Medicinegray matter controls movement, memory and emotions.

White matter plays a different role in the brain. White matter is made up of nerve fibers or axons that run through the brain process information and send signals in other parts of the brain and central nervous system.

Both forms of brain matter decrease with age, which can contribute to cognitive dysfunction.

In the current study, Mielke examined white matter in the brains of women because PBOs may be associated with cognitive impairment.

Sometimes, having a PBO is medically indicated when a woman has ovarian cancer, a history of ovarian cysts, endometriosis, or ovarian torsion. Women can also choose to have their ovaries removed if genetic testing shows a mutation in their BRCA genewhich puts them at a higher risk for breast and ovarian cancer.

According to the study, removing both ovaries before menopause can cause “sudden endocrine dysfunction. as a result of the removal of the ovaries. of endocrine system is responsible for the production and release of hormones, and the ovaries play a direct role in the production of the hormones estrogen, progesterone and testosterone.

With that in mind, Mielke wanted to see if the endocrine dysfunction caused by PBOs contributes to any physiological changes within the brain that might explain the cognitive dysfunction.

The study included 1,011 female participants who had MRI and diffusion tensor imaging (DTI) on file. DTI measures white matter in the brain.

Mielke divided the participants who had a PBO into the following groups:

  • PBO before age 40 (22 participants)
  • PBO aged 40 to 45 (43 participants)
  • PBO aged 46 to 49 (39 participants)

The reference group was significantly larger, with 907 participants who did not have a history of PBO before the age of 50. After dividing the participants into groups, Mielke compared the integrity of each group’s white matter.

The study found that women who underwent a PBO procedure before turning 40 had lower white matter integrity in their brains later in life compared to the reference group.

“Women who had bilateral premenopausal oophorectomy before age 40 had significantly reduced white matter integrity in multiple brain regions,” Mielke said in a news release.

Some brain regions in which women who had PBO before their 40s saw changes include:

  • anterior corona radiata
  • genus of the corpus callosum
  • inferior fronto-occipital fasciculus
  • upper occipital

While the study states that these brain regions are not typically associated with cognitive decline or Alzheimer’s disease, it does note that there was a change in the superior temporal white matter, which is associated with Alzheimer’s pathology.

Women in the 40-44 age group showed no difference in white matter integrity compared to the reference group, but women in the 45-49 age group experienced reductions in white matter volume.

Mielke considered estrogen replacement therapy and noted that 80% of women in all age groups who had PBO received hormones, so she wasn’t sure if it had any effect on the white matter findings.

More research is needed, but the study’s findings suggest that women who have a PBO procedure before they go through menopause may be at a higher risk for decreased white matter later in life. These initial findings may influence one’s decision to consider PBO for a non-life-threatening condition.

Verna Porter, MD, a board-certified neurologist and director of Dementia, Alzheimer’s Disease and Neurocognitive Disorders at the Pacific Neuroscience Institute in Santa Monica, CA, spoke to Medical News Today regarding the study findings.

“The findings are very interesting as they highlight a potential long-term consequence of bilateral premenopausal oophorectomy (PBO),” said Porter.

“Women who had their ovaries removed before age 40 showed reduced white matter integrity, suggesting an increased risk for cognitive impairment and dementia. This highlights the critical role of ovarian hormone regulation in maintaining brain structure/function, particularly in maintaining white matter integrity.

– Verna Porter, MD, neurologist

Porter explained why having an ovary removed could potentially contribute to cognitive impairment.

When the ovaries are removed, the body’s source of the hormones estrogen and testosterone is also removed. Both hormones have “neuroprotective properties” that contribute to brain health.

“Both hormones contribute to overall brain health, influencing mood, cognition and neuroprotection,” Porter said.

While the study’s findings are concerning for women who have PBO procedures before menopause, Porter noted that hormone replacement therapy (HRT) may help reduce the risk of cognitive issues.

“Estrogen therapy, especially when started soon after oophorectomy and within several therapeutic windows, can help preserve white matter integrity and cognitive function,” Porter said.

However, not all women who undergo PBO are candidates for estrogen therapy afterwards.

“Other strategies include lifestyle interventions such as regular physical exercise, cognitive training, a balanced diet rich in antioxidants and omega-3 fatty acids, and management of cardiovascular risk factors,” Ported added.

Jonathan Rasouli, MD, a neurosurgeon with the Department of Neurological Surgery at Staten Island University Hospital in New York, also spoke with MNT about the study.

“The study’s findings are important because they show that women who have their ovaries removed before age 40 have reduced white matter integrity later in life,” Rasouli said.

“This suggests a potential long-term impact on cognitive health and highlights the importance of hormonal balance in brain maintenance.

While this area needs more research, Rasouli noted that it’s possible these findings could influence future guidelines.

“These results may influence future guidelines by emphasizing the importance of maintaining hormonal balance in women considering oophorectomy at an earlier age. They may lead to recommendations for cognitive health monitoring and consideration of HRT to mitigate risks. The findings advocate a more nuanced approach to women’s health, particularly regarding surgical decisions and hormone therapies.

– Jonathan Rasouli, MD, neurosurgeon

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