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A Healthier Respect for Ovaries
David J. Waters, DVM, PhD, Diplomate ACVS

A recent study by my research group appearing next month in Aging Cell reveals shortened longevity as a possible complication associated with ovary removal in dogs (1). This work represents the first investigation testing the strength of association between lifetime duration of ovary exposure and exceptional longevity in mammals. To accomplish this, we constructed lifetime medical histories for two cohorts of Rottweiler dogs living in 29 states and Canada: Exceptional Longevity Cohort = a group of exceptionally long-lived dogs that lived at least 13 years; and Usual Longevity Cohort = a comparison group of dogs that lived 8.0 to 10.8 years (average age at death for Rottweilers is 9.4 years). A female survival advantage in humans is well-documented; women are 4 times more likely than men to live to 100. We found that, like women, female Rottweilers were more likely than males to achieve exceptional longevity (Odds Ratio, 95% confidence interval = 2.0, 1.2 - 3.3; p = .006). However, removal of ovaries during the first 4 years of life erased the female survival advantage. In females, this strong positive association between ovaries and longevity persisted in multivariate analysis that considered other factors, such as height, adult body weight, and mother with exceptional longevity.

In summary, we found female Rottweilers who kept their ovaries for at least 6 years were 4.6 times more likely to reach exceptional longevity (i.e. live >30 % longer than average) than females with the shortest ovary exposure. Our results support the notion that how long females keep their ovaries determines how long they live.

In the pages that follow, I have attempted to frame these new findings in a way that will encourage veterinarians to venture beyond the peer-reviewed scientific text and data-filled tables of Aging Cell to consider the pragmatic, yet sometimes emotionally charged implications of this work. Call it a primer for the dynamic discussions that will undoubtedly take place, not only between practitioners and pet owners, but also within the veterinary profession. Call it a wake-up call for how little veterinarians have been schooled in the mechanistic nuts and bolts underlying the aging process. Call it an ovary story.

Do ovaries really promote longevity? Observed associations between exposures and outcomes may not necessarily be causal, so we explored alternative, non-causal explanations for the association between ovaries and exceptional longevity in our study. But we found no evidence that factors which may influence a pet owner's decision on age at ovary removal - for example, earlier ovariectomy in dogs with substandard conformation or delayed ovariectomy to obtain more offspring in daughters of long-lived mothers - could adequately account for the strong association.

There is another aspect of our data pattern that gives us further confidence that ovaries really do matter when it comes to successful aging. A simple explanation for the observation that ovaries promote longevity would be that taking away ovaries increases the risk for a major lethal disease. In Rottweilers, cancer is the major killer. We found, however, that by conducting a subgroup analysis that excluded all dogs that died of cancer, the strong association between intact ovaries and exceptional longevity persisted. After excluding all cancer deaths, females that kept their ovaries the longest were 9 times more likely to reach exceptional longevity than females with shortest ovary exposure. Thus, we observed a robust ovarian association with longevity that was independent of cause of death, suggesting that a network of processes regulating the intrinsic rate of aging is under ovarian control. This work positions pet dogs, with their broad range of lifetime ovary exposure, to become biogerontology' s new workhorse for identifying ovary-sensitive physiological processes that promote healthy longevity.

Interestingly, our findings in dogs surface just as data from women are calling into question whether those who undergo hysterectomy should have ovary removal or ovary sparing. In fact, our results mirror the findings from more than 29,000 women in the Nurses' Health Study who underwent hysterectomy for benign uterine disease (2). In that study, the upside of ovariectomy - protection against ovarian, uterine, and breast cancer - was outweighed by increased mortality from other causes. As a result, longevity was cut short in women who lost their ovaries before the age of 50 compared with those who kept their ovaries for at least 50 years. Taken together, the emerging message for dogs and women seems to be that when it comes to longevity, it pays to keep your ovaries.

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