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Premenopausal oophorectomy tied to increased risk of cognitive impairment

JAMA Network Open
Reuters Health - 16/11/2021  - Women who underwent premenopausal bilateral oophorectomy were at greater risk of mild cognitive impairment (MCI) and worse performance on cognitive tests 30 years later in case-control and cross-sectional studies.

"The evidence is adequate to guide practice," Dr. Walter Rocca of Mayo Clinic in Rochester, Minnesota told Reuters Health by email. "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 MCI and dementia."

"The decision has to be individualized," he said. "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 should be discouraged."

"Even women who have ovarian or uterine cancer should be informed of the increased risk," he added. "A more difficult decision has to be made by women who carry a high-risk genetic variant such as a BRCA1 or BRCA2 high-risk variant. These women need to trade a set of future risks (cancer) for another set of future risks (non-cancer morbidity and mortality)."

As reported in JAMA Network Open, Dr. Rocca and colleagues conducted case-control and cross-sectional studies by combining data from the Mayo Clinic Study of Aging (MCSA) and the Rochester Epidemiology Project medical record-linkage system.

Odds of MCI and global or domain-specific z scores on cognitive tests were measured at the first MCSA visit. The median lag time between premenopausal bilateral oophorectomy and cognitive evaluation was 30 years.

Among 2,732 women (median age at evaluation, 74) who participated in the MCSA, the case-control study included 283 with MCI (10.4%) and 2,449 without.

Overall, bilateral oophorectomy before menopause and before age 46 was associated with MCI (adjusted odds ratio, 2.21) compared with no bilateral oophorectomy.

The association with MCI varied by surgical indication - e.g., for a benign ovarian condition, the aOR was 2.43 - but not for cancer or no ovarian condition. The presence of an association did not vary by use of estrogen therapy after the procedure, with aORs of 2.56 with estrogen and 2.05 without.

The cross-sectional study included 625 women (median age, 75) with a history of bilateral oophorectomy and 2,107 women (median age, 73) without. Premenopausal bilateral oophorectomy before age 46, performed in 161 women, was associated with decreased global cognition z score (beta, −0.17), attention and executive domain z score (beta, −0.21), and Short Test of Mental Status score (beta, −0.51), compared with no bilateral oophorectomy.

Dr. Marios Georgakis of Massachusetts General Hospital in Boston, coauthor of a related editorial, told Reuters Health by email, "It is a controversial topic, especially if we think that for the majority of cases, removal of the ovaries is not necessary."

"The argument for doing the procedure alongside hysterectomy in women with benign uterus problems is related to the prevention of ovarian cancer," he said. "Under no side effects, this sounds like a reasonable approach. But in view of the potentially increased long-term risk of aging disorders, we need to carefully re-evaluate the risk-benefit ratio in a personalized manner."

"This study has a retrospective design and therefore does not allow an accurate quantification of the different long-term risks and benefits associated with oophorectomy in premenopausal women," he noted. "Studies that prospectively follow up women could give more reliable estimates and thus inform decision-making."

"Still though," he added, "I would argue that young women who have not yet reached menopause and who are about to undergo oophorectomy should be informed about these potential long-term risks."

SOURCE: https://bit.ly/3oyU5mQ and https://bit.ly/3otxLeo JAMA Network Open, online November 11, 2021

By Marilynn Larkin

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