22 November 2021

Oophorectomy has cognitive consequences

Cancer Clinical Women

Removing ovaries before menopause can more than double the risk of cognitive impairment down the track, according to new research .

A study published in the journal Neurology has shown that women who had a bilateral oophorectomy before the age of 46 and before menopause had more than twice the risk of being clinically diagnosed with mild cognitive impairment decades later. 

Three decades after the procedure, they performed worse on a battery of cognitive tests than those who did not have their ovaries removed. But there was no association with impairment if the oophorectomy occurred after the age of 46 for premenopausal women, or at any age after menopause. 

The association with impairment was also linked with the reason for the bilateral oophorectomy. The increased risk occurred when ovaries were removed for a benign ovarian condition (such as endometriosis), but did not exist when the ovaries were removed because of cancer. 

Consequent oestrogen replacement therapy did not appear to influence cognitive outcomes.

“These findings … may help women at mean risk levels of ovarian cancer to better evaluate their risk-to-benefit ratio of undergoing bilateral oophorectomy prior to spontaneous menopause for the prevent of ovarian cancer,” the authors said.

The link between brain ageing and early removal of ovaries has been known for some time, but the authors said it was still not included in mainstream literature on dementia risk factors.

“The major reasons for this lack of recognition are the association of age at which oophorectomy is performed … and controversial data about the association of [oestrogen therapy] after oophorectomy, with cognitive decline or dementia,” they explained. 

To fill in the knowledge gaps, researchers analysed data from two previous studies. 

One study followed more than 2700 women, 625 of whom had had a bilateral oophorectomy for more than 15 years. The other examined a cohort of women with mild cognitive impairment and compared them with a healthy cohort matched for age, sex and other variables. In this second study, researchers found more than twice the odds of impairment for those who had both ovaries removed before the age of 46 and before natural menopause than for those who still had their ovaries.

The odds of impairment were even higher for women who had the procedure for a benign ovarian condition, before the age of 50 and before menopause. 

Whether the association between cognitive impairment and bilateral oophorectomy is causal or not is still unclear. There could be genetic or other risk factors shared across the two groups, suggested the authors. Or it may be causal and related to sudden and long-term lower levels of circulating oestrogen, or progesterone and testosterone, or increased gonadotropins released by the pituitary gland, or complicated combinations of all those as well as other factors such as smoking or obesity. 

And perhaps it’s not the same for everyone.

Dr Rod Baber, professor of obstetrics and gynaecology at the University of Sydney and past president of the International Menopause Society, said the study “re-emphasised how important it is that surgeons don’t remove a woman’s ovaries without a very good reason”.

Fortunately, surgical practice in Australia has changed a great deal over the past decade, according to Professor Baber. 

“It used to be that you were 45 or 48 and people would say, ‘Oh look, we’ll take your ovaries out because that will reduce your risk of ovarian cancer, and we’ll just give you hormones and you’ll be fine’. And they weren’t,” he recalled.

“Now we would say the only indication to remove ovaries early would be for a malignant condition and for people who carry the genetic mutations that increase their risk of a malignant condition,” he said. “So BRCA1, we would say ovaries removed about the age of 40, or when your family is complete if you want to have one, and for BRCA2 probably about 45.

“The evidence there is pretty clear that if you do that, you should give those women hormone replacement until about the normal age of the menopause, and ensure that if you do, it doesn’t increase their risk of suffering from the cancers that you’ve removed the ovaries to prevent.”

The study found that the association between early removal of ovaries and cognitive decline was not affected by whether the women were given oestrogen therapy.

But Dr Baber cautioned that, as noted by the authors, there were several unknowns.

“What we don’t know from this paper is what type of hormone replacement therapy was used, what dose, what delivery system, if there was a delay before they started it, or indeed for how long the women took it,” he pointed out.

“We should not remove a woman’s ovaries prematurely without having a very good reason to do so. But whenever we do, we must replace their missing sex hormones with appropriate body-identical hormone therapy to improve their quality of life, to protect their cardiovascular health, and to protect their bones, even if there is in fact no net benefit or harm with regard to their cognitive health,” he said.

Neurology 2021, online 11 November

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