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Ovary Removal Raises Young Women's Death Risk
by: Leslie Sabbagh
Younger women who have had their ovaries removed should consider estrogen therapy if they are under the age of 45, a new study suggests.
Mayo Clinic researchers found that those who said no to hormone therapy faced a higher death risk than those who said yes.
Many women with high-risk family histories have their ovaries removed, a procedure known as an oophorectomy, to help them avoid cancer or other diseases. However, experts said this new data should give them pause when deciding whether to use hormone replacement therapy afterwards.
According to one specialist, the study suggests that estrogen may have different risks and benefits, depending on a woman's age: protecting health at a younger age, seemingly neutral at menopause, but harmful at an older age.
"The study tells us that estrogen for women under 45 is very important to maintain health. Estrogen is a complex hormone in its interactions in the body, and has importance far beyond the reproductive tract," said Dr. Bobbie Gostout, a Mayo Clinic gynecologic surgeon who was not involved in the research.
The findings are published in the Oct. 1 issue of Lancet Oncology.
In their study, the researchers developed a statistical model of death due to ovarian cancer, breast cancer, coronary heart disease, hip fracture and stroke. Risks for all of these illnesses have been tied to estrogen levels.
"We aimed to investigate survival patterns in a population-based sample of women who had received an oophorectomy, and compare these with women who had not received an oophorectomy," the researchers wrote.
Women who had oophorectomies for reasons other than cancer before menopause were compared with age-matched women in the same population who did not have oophorectomies.
There were nearly 1,300 women with unilateral oophorectomy (one ovary removed), nearly 1,100 with bilateral oophorectomy (both ovaries removed), and close to 2,400 controls in the study.
The team found that certain younger women who have prophylactic bilateral oophorectomy -- surgical removal of both ovaries -- were at an increased risk of death from all causes.
Overall, mortality was not increased in women who had both ovaries removed, but that changed when the researchers broke down the findings by age.
For example, mortality was significantly higher in women who had both ovaries removed before the age of 45 years than women with intact ovaries. Furthermore, this increased mortality was seen mainly in women who had not received estrogen supplementation to the age of 45 years.
Although having both ovaries removed before age 45 years is associated with increased death risk, it is uncertain whether it helps cause death, or is merely a marker of some other underlying risk, the authors wrote.
No increased mortality was recorded in women who had just one ovary removed, regardless of their age, the study found.
In the United States, prophylactic oophorectomy prevents about 1,000 cases of ovarian cancer each year. Over the last three decades doctors have been gradually increasing their recommendations that women have ovaries removed at time of hysterectomy to avoid the risk of cancer, "but that wonderful prevention has been at the cost of removing ovaries in 300,000 women per year," Gostout said.
"This 25-year study showed a decreased incidence in ovarian cancer, however that was countered by adverse health impact in other areas," said Gostout. The increased death risk did not show up for at least a decade, and was 1.7 times greater than normal, the study found.
The work is exciting because it fills in part of the information deficit for women in this age bracket, she added.
Before this study, people were applying lessons from Women's Health Initiative -- a study that focused on women 60 years and older -- to much younger women, recommending that estrogen not be used any longer than five years.
"This study shows that could be an error -- that women under the age of 50 face a different risk/benefit scenario than older women," Gostout said.
But whether all women who've had bilateral oophorectomy should receive estrogen therapy isn't yet proven, another expert said.
The researchers looked at associations in this study, "but don't prove cause and effect," noted Dr. Andrew Berchuck, director of gynecologic oncology at Duke University, and president-elect of the Society of Gynecologic Oncologists. Estrogen replacement after menopause is a "patient-by-patient decision, and physicians and patients must look at individual risk factors and symptoms," he said.
There's a long-running debate about what age to remove ovaries, "but there's very little science because these studies require long-term follow-up, and that's hard to do," Berchuck said. "This study adds some ammunition to the argument that says 'leave the ovaries in closer to the natural age of menopause' -- about 50 years -- but it's by no means conclusive," he said.
Gostout agreed these decisions are tough, and best left to an individual woman and her doctor. "If a woman is considering hysterectomy, she will probably be invited to make a decision about her ovaries. That decision should be highly individualized," Gostout cautioned. "No woman should be told that because she's having a hysterectomy her ovaries must removed as well." Rather, the decision is based on age and family risk for breast and ovarian cancer, she said.
If a woman needs her ovaries removed because of disease or elects to have them removed, estrogen replacement is recommended until the average age of menopause, age 50, Gostout said.
"Don't be scared away from estrogen-replacement therapy in the premenopausal age because there are some concerns in the postmenopausal age," Berchuck added.
In the meantime, women who have had their ovaries removed in the past should not be "alarmed or frightened," Gostout said, since "the increased risk [of illness] for any single woman is very tiny." She said it might also be reasonable for these women to ask their physicians about "estrogen-replacement therapy if they're not already taking it and they're less than 50 years of age."
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