Ovary removal before menopause linked to cognitive decline

Human brains consist of two types of brain tissue: gray and white matter. According to the National Library of Medicine, gray matter controls movement, memory, and emotions.

White matter plays a different role in the brain. White matter consists of nerve fibers or axons which allow the brain to process information and send signals to other parts of the brain and the 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 females because PBOs can 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. Females may also opt to have their ovaries removed if genetic testing indicates a mutation in their BRCA gene, which puts them at a higher risk for both breast and ovarian cancer.

According to the study, having both ovaries removed before menopause can cause “abrupt endocrine dysfunction. as a result of removing the ovaries. The endocrine system is responsible for producing and releasing hormones, and the ovaries play a direct role in the production of estrogen, progesterone, and testosterone hormones.

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

The study included 1,011 female participants who had MRIs 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 between ages 40 to 45 (43 participants)
• PBO between ages 46 to 49 (39 participants)

The reference group was substantially larger, with 907 participants who did not have a history of having a PBO before turning 50. After sorting out the participants into groups, Mielke compared the white matter integrity of each group.

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

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

Some regions of the brain that females who had PBOs before 40 saw changes in include:

• anterior corona radiata
• genu of the corpus callosum
• inferior fronto-occipital fasciculus
• superior occipital

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

Females in the age 40–44 group did not show any differences in white matter integrity compared to the reference group, but females in the age 45–49 group did experience reductions in white matter volume.

Mielke took estrogen replacement therapy into consideration and noted that 80% of females in all age groups that had PBOs took hormones, so she was unsure if it had any effect on the white matter findings.

More research is necessary, but the study findings do show that females who have a PBO procedure before going through menopause may be at a higher risk for white matter decrease later in life. These initial findings may factor into someone’s decision to consider PBO for a non-life-threatening condition.

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

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

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

— Verna Porter, MD, neurologist

Porter explained why ovary removal could potentially contribute to cognitive impairment.

When the ovaries are removed, the body’s source of the hormones estrogen and testosterone are 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 findings are concerning for females who have PBO procedures before menopause, Porter noted that hormone replacement therapy (HRT) could help reduce the risk of cognitive issues.

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

However, not all females who undergo PBO are candidates for estrogen therapy afterward.

“Other strategies include lifestyle interventions such as regular physical exercise, cognitive training, a balanced diet rich in antioxidants and omega-3 fatty acids, and managing 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 females who had 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 it’s possible these findings could influence future guidelines.

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

— Jonathan Rasouli, MD, neurosurgeon