Death rates rise when women under 45 years old undergo bilateral ovariectomy -- surgical removal of both ovaries -- and do not receive proper hormone replacement therapy, according to a new Mayo Clinic study to be published in the October 1 issue of The Lancet Oncology. Mortality from all causes increased 1.7 times for women in this age category, and was particularly increased for estrogen-related cancers and diseases of the brain and cardiovascular system. The increased risk was mainly restricted to those women who were not given estrogen after the surgery until at least age 45 (within five years of the approximate age of normal menopause). Also, the increased risk became evident only 10 or more years after the ovariectomy.
Walter Rocca, M.D., Mayo Clinic neurologist, epidemiologist and lead study investigator, made these discoveries serendipitously while investigating links between ovary removal and brain diseases such as Parkinson's disease and dementia.
"These findings reopen the debate about preventive removal of the ovaries for younger women," says Bobbie Gostout, M.D., Mayo Clinic gynecologic surgeon who is not a study author but consulted with Dr. Rocca. "We don't see a dramatic increase in risk for early death from any one condition, but Dr. Rocca's study did show some increase in risk of death from breast and uterine cancers, and neurologic and vascular conditions. Collectively, this information tells us that a procedure that previously looked advantageous in protecting women's health may actually have disadvantages. We need to be very thoughtful about ovariectomy, as it may put younger women at risk for an earlier death."
Dr. Rocca says that if a woman under 45 has ovarian cancer or a benign disease in the ovaries that requires removal, however, compelling reason remains to remove the ovaries. Removal may also be considered in older women and in women with a very high risk of ovarian cancer, he says.
Dr. Gostout indicates that these findings will change her surgical practice for women under age 45.
"For me this changes the nature of the discussion," she says. "Women in whom we've discovered ovarian cancer or benign disease of the ovary will still be counseled to have it treated, including ovariectomy. We will use the findings from the Mayo Clinic study to guide the discussion on estrogen replacement therapy and will encourage most young women to take estrogen until age 50. But, for women with average risk for breast and ovarian cancer where we might have considered preventive ovariectomy, the discussion will have more of an emphasis on conserving the ovaries for protecting the health of the woman."
Continuing preventive ovariectomies in average-risk younger women and emphasizing estrogen replacement therapy thereafter may not be an adequate solution to diminish the risk, however, as compliance is poor for taking estrogen replacement therapy, says Dr. Gostout. Dr. Rocca adds that the protective effect from endogenous estrogen -- estrogen coming naturally from one's own ovaries with daily and monthly cyclic variations -- may not be the same as the effect of estrogen replacement therapy.
The study's investigators propose several theories to explain the finding of increased early deaths for younger women who have preventive ovariectomy without adequate estrogen replacement:
* Premature estrogen deficiency following the surgery increased the risk for various diseases that in turn reduced survival
* The surgery revealed an underlying pre-existing condition in these women that caused early death following surgery
* These women may have a genetic predisposition to uterine diseases or other symptoms that prompted hysterectomy, which then prompted preventive ovariectomy, while the same predisposition also increased the risk of cancer or other causes of death following the surgery
The study findings also have general research implications for the role of estrogen, according to Dr. Rocca. "Our results confirm that estrogen is probably protective of the brain and cardiovascular system," he says. "They also further establish that the effects of estrogen are age-dependent: estrogen may be clearly useful and protective at younger ages, but it may become less important after menopause and then may have no effect or may be disadvantageous if given as treatment in later years."
To conduct this study, Dr. Rocca and colleagues followed women who had undergone unilateral or bilateral ovariectomy between 1950 and 1987 while residing in Olmsted County, Minn., home of Mayo Clinic. All of these women had the surgery prior to menopause and for reasons other than cancer. The study evaluated 1,293 women with unilateral ovariectomy, 1,097 women with bilateral ovariectomy and, for comparison, 2,390 women who had not undergone ovariectomy. All women were followed until their deaths or until the end of the study, which was staggered between 2001 and 2006, via a combination of interviews with the women or a surviving relative, medical records and death certificates. A unique strength of this study, according to the investigators, was a 25- to 30-year median follow-up time. A total of 1,292 women died during the follow-up; 33 of them died after undergoing bilateral ovariectomy for cancer prevention before age 45. Only a long-term study such as this can reveal these changes in death rates, says Dr. Rocca.
In the United States, 1.2 million ovariectomies are performed annually. Half are unilateral, in which one ovary is removed, and in the other half both ovaries (bilateral) are removed. Half of bilateral ovariectomies are prophylactic -- done to prevent the possibility of future ovarian cancer (approximately 300,000 women per year). The American Cancer Society has estimated approximately 20,000 new cases of ovarian cancer will occur in 2006, and approximately 15,000 women will die from the disease this year.
Study authors also include Brandon Grossardt; Mariza de Andrade, Ph.D.; George Malkasian, M.D.; and Joseph Melton III, M.D. Dr. Gostout consulted with Dr. Rocca about how these findings may affect ovariectomy practice at Mayo Clinic.
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