Preventive Bilateral Oophorectomy Ups CV Mortality

Lisa Nainggolan

January 13, 2009

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January 13, 2008 (Rochester, Minnesota) — A new study has found that women who underwent preventive bilateral oophorectomy--removal of both ovaries--before the age of 45 were at increased risk of cardiovascular death some 20 to 30 years later [1]. But the results also show that this increased mortality can be attenuated by estrogen treatment, say Dr Cathleen M Rivera (Mayo Clinic, Rochester, MN) and colleagues in their paper in the January 2009 issue of Menopause.

Senior author Dr Walter A Rocca (Mayo Clinic) told heartwire that this paper provides new data to help guide the individualized assessment of the risks and benefits of prophylactic bilateral oophorectomy in young women. "People like myself and many others are contributing pieces of evidence that will be useful to a woman and the treating physician to make a decision. Each woman is different, and I don't want to say, 'do it, or don't do it,' because there is sometimes a reason that you still want to proceed and do the surgery. If we give this blank statement that something is good or bad, we damage women more than helping them."

However, he does believe that his and other research warrants a reconsideration of the guidelines regarding preventive bilateral oophorectomy. Thankfully, he notes that the American College of Obstetricians and Gynecologists (ACOG) has already issued a statement to this effect in January 2008.

Rocca stresses that he is a neurologist who got sidetracked into this research, but "I believe that any informed gynecologist in the UK, US, or Europe facing a case of very early preventive bilateral oophorectomy would definitely be aware of what has been in the literature in the past few years and would sit down with his or her patient and discuss the pros and cons of this surgery."

Bilateral Oophorectomy Patients Had 50% Higher CV Mortality

"Any informed gynecologist in the UK, US, or Europe facing a case of very early preventive bilateral oophorectomy would . . . sit down with his or her patient and discuss the pros and cons of this surgery."

Rivera and colleagues explain that every year, around 300 000 women in the US decide to undergo bilateral oophorectomy for the prevention of ovarian cancer and, for women who don't carry genetic variants that increase the risk of ovarian cancer, the risk/benefit balance of this preventive surgery "remains uncertain and controversial." In addition, a further 300 000 women undergo bilateral oophorectomy for a benign condition every year. For all of these women, it also remains uncertain whether estrogen treatment should be started after surgery and for how many years it should continue, they note.

To address the long-term health consequences of unilateral or bilateral oophorectomy and subsequent estrogen treatment in young women, they studied all cardiovascular conditions reported anywhere on the death certificates for women included in the Mayo Clinic Cohort Study of Oophorectomy and Aging who had undergone oophorectomy before menopause between 1950 and 1987.

The mortality associated with cardiovascular disease was studied in a total of 1274 women who had undergone unilateral oophorectomy (removal of one ovary) and 1091 women who had bilateral oophorectomy; these were matched with the same outcomes for 2383 referent women from the same population who had not undergone oophorectomy.

Those who underwent unilateral oophorectomy experienced a reduced mortality associated with cardiovascular disease compared with referent women (hazard ratio 0.82; p=0.04). In contrast, those who had bilateral oophorectomy before age 45 years experienced an almost 50% increased mortality associated with cardiovascular disease, compared with the referent population (HR 1.44; p=0.04).

And in the women who underwent bilateral oophorectomy, the hazard ratio for mortality was increased further if they were not treated with estrogen through age 45 years (HR 1.84; p=0.001). However, in those who were treated with estrogen through age 45, the therapy appeared to offset the negative effects of bilateral oophorectomy (HR 0.65; p=0.28; test of interaction, p=0.01).

Estrogen Treatment Through Age 45 Alleviates CV Mortality Risk

"The most important finding is that women who undergo bilateral oophorectomy early in life (under age 45) do have an increased risk of cardiovascular mortality," Rocca told heartwire . "This has been suggested before by others and by us, but this is a full report in which the women were followed for a long time."

He concedes, however, that the methodology used in this study--in which CV mortality was defined as cardiovascular diseases mentioned anywhere on the death certificate--"is not as good as studying the incidence of cardiovascular disease, because, of course, many cardiovascular diseases are not causes of death. But at least it captures those instances of CVD that were severe enough to warrant mention on the death certificate. It's a broader net, but it's not a perfect net. However, it's a good approximation."

The second important finding of the study relates to the data on estrogen given after surgery, he says. "One big question has always been if a woman needs to have her ovaries removed--because in the balance of bad and good, the decision is still for removal--to what extent will estrogen treatment eliminate or offset the negative effects of these hormonal changes?

"In our study, we divided the women with [bilateral] oophorectomy into two groups: those who received treatment at least through the age of 45; and those who either got no treatment or got it for such a short period of time that it was not through age 45. We found that if women underwent the surgery and received estrogen at least through age 45, their risk [of cardiovascular death] went away or did not show, while if they did not receive that treatment--which we consider a kind of minimum--well, those are the ones, in a nutshell, who were driving the negative effect.

"If a [bilateral] oophorectomy has to be done before the age of 45, then the woman has to be made aware of this increased risk of cardiovascular problems and . . . considered for adequate estrogen-replacement therapy.

"So we conclude that if a [bilateral] oophorectomy has to be done before the age of 45, the woman has to be made aware of this increased risk of cardiovascular problems, and this would be one good reason to be considered for adequate estrogen-replacement therapy, at least to age 45 or maybe to age 50, which is the age of natural menopause."

  1. Rivera CM, Grossardt BR, Rhodes DJ, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 2009; 16:15-23. Abstract

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