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Ovary Removal May Up Chronic Kidney Disease Risk

— Researchers suggest increased risk due to estrogen deprivation

Last Updated September 21, 2018
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Ovary removal increased a woman's risk for chronic kidney disease (CKD), according to a new study.

Premenopausal women who underwent a bilateral oophorectomy had a 42% higher risk for developing CKD compared with premenopausal women with intact ovaries (adjusted HR 1.42, 95% CI 1.14-1.77), reported Walter Rocca, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.

Twenty years after the time of oophorectomy, the absolute risk for incident CKD was 20.2% (95% CI 17.3%-23.5%) compared with a risk of only 13.6% for women with intact ovaries (95% CI 11.2%-16.4%) -- raising the absolute risk by 6.6%.

This associated risk only increased with a younger age of ovary removal. Women who underwent oophorectomy at age 45 or younger had a 59% increased risk for developing CKD (aHR 1.59, 95% CI 1.15-2.19; absolute risk increase 7.5%), the group reported in the .

"This is the first study that has shown an important link between estrogen deprivation in younger women and kidney damage. Women who have their ovaries surgically removed have an increased long-term risk of chronic kidney disease," Rocca explained in a statement.

His recommendation, therefore, he said, was that women who do not have an increased genetic risk for breast cancer and ovarian cancer should avoid surgical removal of the ovaries as a preventive measure due to these heightened risks.

For the analysis, the researchers looked at data from 1,653 women who underwent bilateral oophorectomy prior to menopause onset and the age of 50. Compared with the 1,653 matched controls of women with intact ovaries, women who underwent oophorectomy were more likely to have a higher body mass index and a prior diagnosis of hypertension, diabetes, chronic obstructive pulmonary disease, asthma, heart arrhythmias, and psychological disorders.

During the median 14-year follow-up period, 211 women in the oophorectomy group developed incident CKD -- defined as an estimated glomerular filtration rate less than 60 mL/min per 1.73 m2 measured on two occasions over 90 days apart -- compared with only 131 women in the reference group.

Estrogen therapy seemed to mediate this elevated risk somewhat in women who underwent oophorectomy. Incident CKD risk was higher for women who did not receive any estrogen therapy prior to age 46 (aHR 2.07, 95% CI 0.72-5.92; ARI, 11.9%) compared with women who did receive estrogen therapy (aHR 1.52, 95% CI 1.05-2.20, ARI 12.5%), although this difference was not statistically significant.

The findings weren't necessarily surprising, the researchers said, since animal models have suggested that estrogen deprivation may be harmful to both kidney structure and function. "Mesangial cells that are critical to the pathogenesis of glomerulosclerosis express both estrogen receptor subtypes (a and b) in mice and humans," the team wrote. "Estrogen has been found to prevent the accumulation of extracellular matrix and decrease the synthesis of type 1 and type 4 collagen."

Other observational studies in humans have also suggested a link between estrogen therapy and a lowered risk for albuminuria, Rocca and co-authors said.

They stated that based on this evidence, it may be that loss of estrogen following a bilateral oophorectomy is the underlying mechanism for this increased risk for CKD. However, there is conflicting evidence in humans on the effects of estrogen therapy on the kidney. Future research, therefore, should be aimed specifically to look at "the effects of hormone therapy on kidney function and be guided by the timing hypothesis -- i.e., that the effects of estrogen vary with the age of the woman."

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    Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The study used the resources of the Rochester Epidemiology Project, which is supported by awards from the National Institute on Aging and National Institutes of Health. The study was also supported by funds from the Mayo Clinic Research Committee.

Rocca and co-authors reported having no conflicts of interest.

Primary Source

Clinical Journal of the American Society of Nephrology.

Rocca W, et al “CKD in patients with bilateral oophorectomy” Clin J Am Soc Nephrol 2018; DOI: 10.2215/CJN.03990318.