Ovary Removal Linked to Potential Cognitive Decline: New Research

For women not at increased risk of ovarian cancer, the procedure may be unnecessary and can harm brain white matter.

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Women considering ovary removal to prevent cancer face a trade-off. Early removal of both ovaries may damage white matter in the brain, potentially increasing the risk of cognitive decline. However, the exact reasons behind this are still unclear.

This may soon change, however.

In a study published in Alzheimer’s & Dementia, researchers have uncovered new insights into how the sudden loss of sex hormones following premenopausal ovary removal—known as premenopausal bilateral oophorectomy (PBO)—can harm brain structure and potentially lead to cognitive decline.

Neuroimaging Sheds Light on Brain Changes

“We know that having both ovaries removed before natural menopause causes abrupt endocrine dysfunction, which increases the risk of cognitive impairment and dementia,” Michelle Mielke, lead author of the study and a professor and chair of epidemiology and prevention at the Wake Forest University School of Medicine, said in a statement. “But few neuroimaging studies have been conducted to better understand the underlying mechanisms.”

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The research team analyzed data from the Mayo Clinic Study of Aging, a long-term research initiative that began in 2004. They identified just more than 1,000 women who had undergone diffusion tensor imaging, an MRI technique that assesses brain white matter integrity. Of them, 907 had not undergone premenopausal bilateral oophorectomy (PBO). The study participants were grouped as follows:

• 22 women who underwent premenopausal bilateral oophorectomy (PBO) before age 40
• 43 women who underwent PBO at ages 40 to 45
• 39 women who underwent PBO at ages 46 to 49
• 907 women who did not undergo PBO before age 50

Researchers found reduced white matter integrity in multiple brain regions among women who had the surgical procedure before age 40. Similar trends were observed in women who underwent PBO at ages 46 to 49. There were no differences in brain pathways for women who had PBO at ages 40 to 44 compared with women who didn’t have the procedure.

As many as 80 percent of participants who had their ovaries removed also had a history of estrogen replacement therapy (ERT). However, despite the use of ERT by these women, their white matter integrity remained diminished.

This suggests that the loss of testosterone, rather than estrogen, plays a critical role in brain health, according to researchers.

Testosterone is a hormone primarily associated with male characteristics, but it’s also present in women in smaller amounts. In women, it’s produced by the ovaries and adrenal glands. Thus, according to the study, removing both ovaries leads to a sudden drop in testosterone production.

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“Given the effects of testosterone on brain white matter, and the result in our study that most women who underwent PBO used ERT but still have reduced white matter integrity, it may be hypothesized that the explanation for our results is in part due to loss of testosterone,” the authors wrote. They emphasized the need for additional research to further understand how white matter changes relate to cognitive impairment.

Hormonal Influence on Brain Structure

The ovaries produce hormones both before and after menopause. Before menopause, they primarily produce estrogen, progesterone, and testosterone. After menopause, they mainly produce testosterone and androstenedione.

“Having both ovaries removed results in an abrupt decrease in both estrogen and testosterone in women,” according to Ms. Mielke.

Throughout life, significant differences in white matter volume and integrity exist between men and women, primarily because of the influence of sex hormones. Men typically have larger white matter volumes than women, a difference that persists both before and after menopause.

Recent research involving transgender people and those with androgen insensitivity syndrome, a genetic disorder in men that does not allow them to produce male sex hormones, further demonstrates testosterone’s possible role in preserving white matter health.

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The new study noted that female-to-male transgender people receiving testosterone therapy show increased white matter integrity.

“While these findings are important for women to consider before having premenopausal bilateral oophorectomy for non-cancerous conditions,” Ms. Mielke said in the statement, “we need a larger and more diverse cohort of women to validate these results.”

Reasons for Hysterectomy and Ovary Removal

About 500,000 hysterectomies are performed annually in the United States, making it the second most common surgical procedure for women after cesarean delivery, according to Johns Hopkins Medicine. Most hysterectomies occur between the ages of 40 and 50.

An estimated 23 percent of women ages 40 to 44 and 45 percent of women ages 45 to 49 undergo bilateral oophorectomy for ovarian cancer prevention, including among those at average risk. Outside of cancer prevention, a woman may choose to have both ovaries removed if she has:

• A tubo-ovarian abscess: A pus-filled pocket involving a fallopian tube and ovary
• Endometriosis: Growth of uterine-like tissue outside the uterus, often forming cysts (endometriomas) on the ovaries
• Noncancerous ovarian tumors or cysts: Removal can prevent cysts from bursting and causing complications
• Ovarian cancer: Oophorectomy is a treatment option
• Ovarian torsion: Twisting of an ovary

Among women who have undergone hysterectomy, about one-quarter of those ages 40 to 44 and nearly half of those ages 45 to 59 have also had their ovaries removed, according to a 2023 study published in Menopause.

Decision-Making for Ovarian Cancer Risk

For women at high risk of ovarian cancer, deciding to remove the ovaries before menopause as a preventive measure requires careful consideration of both benefits and risks. Genetic testing is recommended to identify high-risk mutations, such as BRCA (breast cancer gene), to help guide decisions about preventive surgery.

Women with BRCA1 mutations face a significantly higher risk of ovarian cancer compared with the general population, according to Columbia University Irvine Medical Center.

While the lifetime risk for the general population is about 1 percent, 35 percent to 45 percent of women with BRCA1 mutations may develop ovarian cancer.