Premenopausal ovaries removal and subsequent cognitive performance


A study in JAMA Network Open has concluded that women who undergo bilateral oophorectomy before menopause are significantly more likely to develop mild cognitive impairment and poorer performance on cognitive tests about 30 years later compared to women who do not have the procedure.

“Our previous studies indicated an association between bilateral oophorectomy and later development of dementia,” said first author Walter Rocca, MD, MPH, professor of epidemiology and neurology at the Mayo Clinic, in Rochester, Minnesota. “The current study complements those original studies.”

The study combined data from the Mayo Clinic Study of Aging (MCSA) and the Rochester Epidemiology Projectmedical records-linkage system, a unique research infrastructure based on medical record information for a complete population.

The MCSA study comprised a population-based sample in Olmsted County, Minnesota, consisting of 2,732 women, aged 50 to 89 years, who participated from 2004 to 2019 and underwent a clinical evaluation and comprehensive cognitive testing.

The study compared 283 women who had mild cognitive impairment to 2,449 women who were cognitively unimpaired at their first research visit. Women with mild cognitive impairment were more likely to have undergone bilateral oophorectomy before age 46 years in their history.The risk measured as an odds ratio was increased 2.21 times.

The association of ovaries removal with mild cognitive impairment varied by surgical indication and was higher for women who underwent the oophorectomy for a benign ovarian condition, but not for those who had a cancer indication or no ovarian condition.

Estrogen therapy or no estrogen therapy after bilateral oophorectomy did not vary the risk of mild cognitive impairment: 2.56 and 2.05 more likely, respectively.

The median lag time between bilateral oophorectomy before menopause and prior to age 50 years and cognitive evaluation was 30 years (range 22 to 38 years).

A comparison of 625 women with a history of bilateral oophorectomy and 2,107 women without a history of bilateral oophorectomy showed that premenopausal ovaries removal was significantly associated with a decreased performance on a global cognitive test, an attention and executive domain test, and a Short Test of Mental Status, as opposed to no bilateral oophorectomy.

“Based on our previous work and on our interpretation of the literature so far, we were expecting the findings,” Rocca told Contemporary OB/GYN®. “This study is important, though, because it is the first one focusing on mild cognitive impairment. In addition, the link between premenopausal bilateral oophorectomy and cognitive decline or dementia has not yet become mainstream accepted knowledge. This new piece of evidence is an important step forward.”

The evidence is adequate to guide practice decision-making, according to Rocca. “Gynecologists and women’s health clinicians should explain to women considering bilateral oophorectomy before spontaneous menopause that there is a risk-to-benefit balance between prevention of ovarian cancer and risk of chronic diseases, including mild cognitive impairment and dementia,” he said. “The decision needs to be individualized; however, for most women at average risk of ovarian cancer who have no ovarian conditions or a benign ovarian condition, removal of the ovaries before spontaneous menopause as a prevention strategy should be discouraged.”

Furthermore, the general recommendation is that women who have a justified indication for a premenopausal bilateral oophorectomy because they are at high risk of ovarian cancer should receive estrogen treatment after the oophorectomy and through the age of spontaneous menopause, which occurs at approximately age 50 years.

“Unfortunately, our study did not show a significant attenuation of the risk by estrogen treatment,” said Rocca.

Rocca and his colleagues are now conducting a series of studies to reveal the mechanisms linking bilateral oophorectomy, hormonal deprivation, and brain degeneration. “These studies involve measuring changes in the blood via blood biomarkers and in the brain using imaging techniques,” Rocca said. “We are also studying the harmful effects of bilateral oophorectomy in premenopausal women on other organs and tissues, such as the kidney, lung, and liver.”


1. Rocca WA, Lohse CM, Smith CY, et al. Association of premenopausal bilateral oophorectomy with cognitive performance and risk of mild cognitive impairment. JAMA Netw Open. 2021;4(11):e2131448. doi:10.1001/jamanetworkopen.2021.31448

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