Preventive Ovary Removal Linked To Early Death In Younger Women

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.


Mayo Clinic


200 First St. SW

Rochester, MN 55902

United States


Mayo Clinic

Tufts Researchers Discover New Neuron Development In Brains Of Nulliparous Mothers

Maternal behavior itself can trigger the development of new neurons in the maternal brain independent of whether the female was pregnant or has nursed, according to a study released by researchers at Tufts University's Cummings School of Veterinary Medicine. These findings performed in adult, virgin rats were published in Brain Research Bulletin and are available online at dx.doi/10.1016/j.brainresbull.2009.08.011.



In the study, virgin, or nulliparous, rats were exposed to foster pups each day until they began to exhibit maternal behavior, including crouching over the young, grouping them, or retrieving them back to the nest. Data from the study showed that the nulliparous rats exposed to pups have increased numbers of new neurons.



The research was undertaken by Cummings School Department of Biomedical Sciences researchers Miyako Furuta and Robert Bridges, who is the head of the Cummings School's reproduction and neurobiology section.



Previous research has found that exposure to young can stimulate maternal behavior not only in rats, but also mice, hamsters, monkeys, and even humans. Increased creation of new neurons, or neurogenesis, has also been shown during pregnancy and lactation in rodents and associated with maternal behavior, but studies analyzing neurogenesis in nulliparous animals exhibiting maternal behavior had not been done. The area of the brain that was the focus of the present study was the subventricular region - a region involved in the production of cells that affect odor recognition and possibly recognition of young. Bridges and Furuta found increased numbers of new neurons in the subventricular zone in adult, nulliparous rats that behaved maternally compared with numbers in subjects that either were not exposed to young or exposed to young, but did not behave maternally.



What stimulates increased new neuron production in the nulliparous mothers is not known. One possibility is that the hormone prolactin, which stimulates both the onset of maternal behavior as well as production of neurons during pregnancy, may play a role in the production of new neurons in nulliparous females exhibiting maternal behavior. However, this possibility remains to be investigated. A second possibility is that stimulation received from the young themselves may, in fact, play a crucial role in stimulating maternal neuron production.



"As with all scientific studies, these findings trigger more questions than answers," said Dr. Robert Bridges, section head of reproduction and neurobiology at Tufts University's Cummings School of Veterinary Medicine. "Next, we hope to determine what role this neurogenesis plays in terms of the female's behavior and physiological processes. Where do these new cells migrate to within the brain and what do they do? For example, do they affect how a female subsequently perceives her young through recognition of baby odors? These are the questions we hope to answer."



The study was funded by a National Institutes of Health grant.



In addition to clinical research, the Cummings School of Veterinary Medicine at Tufts University receives National Institutes of Health funding for basic science research in four major areas: Bridges' reproduction and neurobiology section, infectious diseases, pulmonology, and liver/gastrointestinal function.



Source: Tom Keppeler


Tufts University, Health Sciences

Cedars-Sinai's Women's Cancer Research Institute Recognized As One Of The Nation's Top Centers For Gynecologic Oncology

Cedars-Sinai Medical Center's Gynecologic Oncology Division was named among the nation's top 10 programs by Contemporary OB/GYN, a leading publication read by the nation's obstetricians and gynecologists.


The award recognizes institutions for overall expertise as well as for leadership in research, patient care and community outreach. Cedars-Sinai's Women's Cancer Research Institute was the only center in the Los Angeles area to receive the award.


"We're pleased to be included in this list of Centers of Excellence for gynecologic cancers," said Beth Karlan, M.D., director of Cedars-Sinai's Women's Cancer Research Institute at the Samuel Oschin Comprehensive Institute and an internationally recognized cancer surgeon and research scientist. "The innovative research as well as the level of care and support we offer our patients at Cedars-Sinai truly merits this recognition."



The award was determined by information provided by key opinion leaders in the field, self-reported data and other information, and included criteria such as number of research protocols, patient satisfaction, level of technological equipment onsite, outcome data and national awards and recognition.


Other Centers of Excellence recognized included M.D. Anderson Cancer Center, Yale Cancer Center and Duke University Medical Center.


According to Contemporary OB/GYN, the purpose of the list was to provide physicians with information on top-notch treatment centers so that they could refer their patients with gynecologic cancers to some of the best centers in the United States.



Source
Cedars-Sinai's Women's Cancer Research Institute

Nomination Of Sebelius For HHS Secretary Consistent With Obama's 'Pro-Choice Agenda,' Washington Post Columnist Says

"It is probably not a coincidence" that President Obama has nominated a Roman Catholic -- Kansas Gov. Kathleen Sebelius (D) -- to serve as HHS secretary and "implement" many policies in his "pro-choice agenda," Michael Gerson writes in a Washington Post opinion piece. According to Gerson, the "coercion of those who disagree" with this agenda is "a common thread" for Obama. Although the president "has every right to a pro-choice Cabinet," the nomination of Sebelius "seems designed to provide religious cover" and "also smacks of religious humiliation -- like asking a rabbi to serve the pork roast or an atheist to bless the meal," Gerson says. He continues, "Sebelius, though strongly pro-choice, was capable of occasional compromise. But she consistently fought against the serious enforcement of Kansas' late-term abortion restrictions." Sebelius is in the group of "Catholics who assert the sanctity of life while defending legal abortion," he writes.

According to Gerson, Catholics who support abortion rights have various explanations for their stance. He says, "Some say they will not impose their private religious views on others. But moral beliefs about human dignity are not religious dogmas such as transubstantiation or the Trinity." He asks, "Couldn't a Catholic politician support women in crisis and effective protection for viable children?" Catholic abortion-rights supporters say that "legal remedies on abortion have been exhausted, so we might as well focus on the common-ground issue of abortion reduction -- a cause that does deserve support," Gerson says. However, he also contends that "legal remedies have not been exhausted; they have been preempted by the courts." He continues, "The exercise of democracy on abortion would probably lead to broader protections for viable children. And it is difficult to imagine how anyone committed to the principle that 'all life is sacred' could oppose such a democratic outcome." Gerson adds that "if a politician believes life is sacred, the destruction of more than a million lives a year cannot be merely one issue among many." He concludes that Sebelius and other Catholic politicians who support abortion rights "are disagreeing with their church on a fundamental issue of justice -- which is their right;" however, "It is also the right of their church to point out their incoherence" (Gerson, Washington Post, 3/11).


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