Prophylactic Bilateral Oophorectomy: Mortality Risk in Women Under 45

ROCHESTER, Minn., Sept. 14 -- Prophylactic bilateral oophorectomy before women are 45 results in an increased risk of all-cause mortality, especially if they are not given replacement estrogen, found researchers here.

Overall, for women of any age, a prophylactic bilateral oophorectomy appeared to make little difference in the risk of death, according to Walter Rocca, M.D., of the Mayo Clinic College of Medicine.

But removing the ovaries before the age of 45 resulted in a 67% increase in the risk of death from any cause, compared with a population-based group, with much of the increase coming among women who were not given replacement estrogen, Dr. Rocca and colleagues reported in the Sept. 14 online issue of Lancet Oncology.

The finding was based on a cohort study involving 2,365 women who underwent either a unilateral or bilateral oophorectomy in Olmstead County, Minn., from 1950 through 1987. Olmstead County is home to the Mayo Clinic.

Each woman in the treated cohort was age-matched to a woman in the same population who had not had her ovaries removed. The study covered a period prior to the discovery of mutations in BRCA susceptibility genes, which led to an increase in prophylactic bilateral oophorectomy.

The researchers found that having a unilateral oophorectomy as a result of endometriosis significantly decreased the risk of death. The hazard ratio was 0.70 with a 95% confidence interval from 0.49 to 0.99.

On the other hand, a bilateral oophorectomy for either a benign tumor or inflammation significantly increased the risk of death regardless of the age of the patient. The hazard ratios were 1.50 and 1.44 with 95% confidence intervals from 1.08 to 2.09 and 1.01 to 2.07, respectively.

Overall, though, no increased mortality risk was seen for either unilateral or bilateral oophorectomy, Dr. Rocca and colleagues noted.

But when the analysis was restricted to women under the age of 45 having a bilateral oophorectomy, the researchers found a significantly increased risk of all-cause mortality. The hazard ratio was 1.67, with a 95% confidence interval from 1.16 to 2.40, which was significant at P=0.006.

If the women were also estrogen deficient, Dr. Rocca and colleagues found, the risk of death was nearly double that among the women in the population group. The hazard ratio was 1.96, with a 95% confidence interval from 1.28 to 3.01, which was significant at P=0.002.

The risk for women with early bilateral oophorectomy who were given estrogen did not differ significantly from the population group.

While all-cause mortality was higher for women under 45 who had a bilateral oophorectomy than for women in the population group, the researchers also analyzed specific causes of death and found some significant differences:

• Estrogen-related cancer deaths were more than three times higher than among referent women (P=0.009).
• Non-cancer deaths were almost twice as high (P=0.009).
• Among non-cancer deaths, mortality related to neurological or mental disease was more than six times higher (P=0.003).

While it's not clear why the procedure increases the risk of death in some women, Dr. Rocca and colleagues suggested several theories:

• The premature estrogen deficiency after oophorectomy might increase the risk for other diseases.
• The oophorectomy might reveal a pre-existing condition in these women that caused early death.
• Some women might have a genetic predisposition to diseases or symptoms that prompt hysterectomy including prophylactic oophorectomy, and the same predisposition might increase the risk of cancer or other causes of death.

"For me this changes the nature of the discussion," said Mayo Clinic surgeon Bobbie Gostout, M.D., who was not a member of the study team.

"Women in whom we've discovered ovarian cancer or benign disease of the ovary will still be counseled to have it treated, including ovariectomy," Dr. Gostout said. "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."

The authors suggest that on the basis of these data, women who receive prophylactic ovariectomy should receive estrogen until age 50.

The study has some limitations, Dr, Rocca and colleagues noted, including the time when the surgeries took place. Between 1950 and 1987, they said, "surgical practice and estrogen use may have differed from current standards."

Also, some of the cause-of-death results were based on small numbers, which might have inflated their significance, the researchers said.