For decades, bilateral oophorectomy has been a common practice to eliminate the possible risk of developing ovarian cancer. However, the new study shows that while women receiving bilateral oophorectomy do have a decreased risk of contracting ovarian cancer and breast cancer, they face a higher risk of death overall, a higher risk of fatal and nonfatal coronary heart disease, and a higher risk of lung cancer. In addition, removing the ovaries does not appear to provide any overall increased survival benefit.
The investigation, titled "Ovarian Conservation at the Time of Hysterectomy and Long-Term Health Outcomes in the Nurses' Health Study," pulled together an international team under the direction of William H. Parker, M.D. of John Wayne Cancer Institute and researchers from Harvard Medical School. In 2004, Dr. Parker, a practicing gynecological surgeon and researcher, began to question the value of removing a woman's ovaries for prophylactic reasons, since the average risk of ovarian cancer is relatively low. Ovarian cancer accounts for about 3% of all cancers in women, and is responsible for less than 1% of all causes of death in women.
Dr. Parker turned to the Nurses' Health Study, one of several large-scale studies that provide researchers with decades of reliable health data on older women. Started in the mid-1970s, the first Nurses' Health study has continuously tracked 121,700 female registered nurses to assess risk factors for cancer and cardiovascular disease.
The team focused on a set of 29,380 women from the study: 16,345 had hysterectomy with bilateral oophorectomy, and 13,035 had hysterectomy with ovarian conservation. They evaluated incident events and death from coronary heart disease (CHD), stroke, breast cancer, ovarian cancer, lung cancer, colorectal cancer, total cancers, hip fracture, pulmonary embolus, and death from all causes. Women were divided into age groups to reflect pre- and post-menopausal status at the time of hysterectomy, as well as whether or not they had received estrogen replacement therapy.
After adjusting for multiple independent risk factors, the researchers found several striking trends: Removing both ovaries was indeed associated with a markedly lower risk of ovarian cancer, as well as a reduced risk of breast cancer and cancer overall. However, women with oophorectomy had a significantly higher risk of CHD, stroke and lung cancer.
Looking at survival rates, women with oophorectomy had a higher risk of death from CHD, lung cancer and all cancers. The risk of death from all causes was significantly greater for women who were younger than age 50 at the time of surgery. The study concluded that for every 24 women having bilateral oophorectomy, at least one woman will die prematurely from any cause as a result of the procedure.
While the risk of dying from ovarian cancer did decrease dramatically after oophorectomy, the risk to women whose ovaries had been conserved was also extremely low (34 deaths out of 13,305 women, or 0.26%).
Importantly, no analysis or age group showed an increased survival associated with oophorectomy.
"For the last 35 years, most doctors have been routinely advising women undergoing hysterectomy to have their ovaries removed to prevent ovarian cancer," said Dr. Parker. "We believe that such an automatic recommendation is no longer warranted."
Dr. Parker asserted that women who are at high risk of ovarian cancer should indeed consider oophorectomy as part of hysterectomy: this includes women with a family history of ovarian cancer, and women who carry BRCA1 or BRCA2 gene mutations that increase the risk of ovarian cancer.
"Certainly, some women do have a high risk of ovarian cancer, but this is relatively rare in the general population," Dr. Parker explained. "For the majority of women, the risk of ovarian cancer is very low. While taking out the ovaries will effectively prevent ovarian cancer, this study shows that it significantly increases the risk of other diseases that are much more likely to kill you, such as heart disease, stroke and lung cancer, which are far more common causes of death."
The study report notes that ovarian cancer kills 14,700 women in the U.S. each year, while CHD accounts for 326,000 deaths, and stroke accounts for approximately 86,900 deaths annually.
"We believe these results highlight the need for a new conversation between the patient and doctor, framed by the patient's specific risk factors and personal concerns," Dr. Parker said.
"Before menopause, the ovaries make a lot of estrogen, plus androgens including testosterone and androstenedione. These hormones keep the heart, bones and blood vessels healthy," Dr. Parker explained. "After menopause, the ovaries make less estrogen, but continue to produce androstenedione and testosterone, which are converted by fat and muscle cells into estrogen. So there is a continued source of estrogen from these hormones that continues to protect the blood vessels. If you remove the ovaries, you lose the estrogen and the androgens, and the benefits to the blood vessels."
Interestingly, although the protective effects of estrogen have been known for decades, no researchers had investigated the oophorectomy connection until now.
"Nobody to date had thought to look at the big picture," Dr. Parker said. "That is, how does the survival data actually inform the decision about whether to take out the ovaries or not?"
Reflecting on his motivation to develop the study, Dr. Parker explained, "I have been in private practice for many years, and this is something my patients and I have to deal with on a regular basis. After a while, the common knowledge appeared to be wrong. It didn't make sense to me to advise women to have their healthy ovaries removed when there might be benefits that we hadn't accounted for."
"We need to tell our patients that they should consider the benefits of keeping their ovaries over the long term," Dr. Parker concluded. "And in my experience, most women intuitively think this is the right answer."
"Ovarian Conservation at the Time of Hysterectomy and Long-Term Health Outcomes in the Nurses' Health Study." William H. Parker, Michael S. Broder, Eunice Chang, Diane Feskanich, Cindy Farquhar, Zhimae Liu, Donna Shoupe, Jonathan S. Berek, Susan Hankinson, JoAnn E. Manson.
Obstetrics & Gynecology, Vol. 113, No. 5, May 2009
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