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News Review From Harvard Medical School

Keep Ovaries, Researchers Say

Removing the ovaries as well as the uterus during a hysterectomy does not help most women and might do harm, concluded a study published August 1 in the journal Obstetrics & Gynecology. Many women now have their ovaries removed at the same time as a hysterectomy to prevent ovarian cancer, but the ovaries do have a function after menopause since they produce hormones, the Associated Press (AP) reported. Using a mathematical model based on previous studies, researchers concluded that ovary removal may increase the risk of death from heart disease for women under 65, AP reported.

By Howard LeWine, M.D.
Harvard Medical School

What Is the Doctor's Reaction?

Of the thousands of medical studies reported each year, only a handful have an immediate and very significant impact on the daily practice of medicine and surgery.

One such study has just been published in the August issue of the medical journal Obstetrics and Gynecology. The study examined the overall benefit of routine removal of the ovaries when a woman has a hysterectomy (surgical removal of the uterus) for a disease other than cancer, such as prolapse of the uterus, fibroids or endometriosis.

Until now, the official position regarding surgical removal of the ovaries (called oophorectomy) at the time of hysterectomy is to individualize the decision, assuming the woman is at the usual low risk of ovarian cancer. However, the most common practice is to perform oophorectomy routinely for women who have completed menopause.

In women younger than 40, the general recommendation is not to remove the ovaries. For women between 40 and 54, gynecologists vary in how strongly they will recommend routine oophorectomy.

Although not everyone has agreed, the general dogma has been that once a woman reaches menopause, ovarian production of hormones falls to such a low level that the ovaries offer little if any health benefits. Removing them almost completely eliminates cancer and other diseases of the ovary. Complication rates from hysterectomy with and without oophorectomy are nearly equal.

Now we have new compelling data that refutes the dogma. According to the results in this study, women under the age of 65 actually have better outcomes by not having oophorectomy at the time of hysterectomy, when the procedure is performed for diseases other than cancer. Women in the 65 and older group did not show a survival advantage either with or without routine oophorectomy.

What Changes Can I Make Now?

If you have a family history of ovarian cancer or a genetic predisposition to ovarian cancer-related syndromes (such as multiple family members with breast cancer or known positive BRCA genes), the results of this study are not relevant to you. Women with these characteristics were excluded from the study.

For the vast majority of women, this new information is very helpful. Even after menopause, the ovaries make small amounts of estrogen, and often make relatively significant quantities of certain male-type hormones that may have important health benefits. Interestingly, women who had routine oophorectomy under age 65 had higher death rates from heart disease than women who kept their ovaries.

Ovaries that continue to produce even small amounts of female and male hormones will help to maintain bone strength, preventing osteoporosis and fractures, a major cause of disability and death in older women.

Despite the apparent advantages of ovary conservation, it is quite reasonable for a woman to make the choice to have oophorectomy so she will not worry about developing ovarian cancer.

What Can I Expect Looking to the Future?

Like all studies, this study has potential pitfalls that the researchers recognize and state. Other questions about the methods used and conclusions drawn probably will arise. However, the results of this study will change how gynecologists present the pros and cons of routine oophorectomy with hysterectomy for benign disease. The decisions by patients and their doctors can now be based upon better facts rather than just "what is done."

 

EDITORIAL ACCOMPANYING THE STUDY

DOGMA, SKEPSIS, AND THE ANALYTIC METHOD: THE ROLE OF PROPHYLACTIC OOPHORECTOMY AT THE TIME OF HYSTERECTOMY

David L. Olive, M.D.
Professor of Obstetrics and Gynecology
University of Wisconsin School of Medicine

Dogma is a well entrenched concept in the medical world, playing a critical role in both education and everyday clinical practice. Not one of us has progressed through our training and careers immune to the dogmatic hand-me-downs of an earlier, more experienced generation. Walking alongside tradition, dogma is an important foundation upon which much of allopathic medicine is constructed.

The sources of dogma may be multiple and varied. Clinical and basic research, clinical experience, logic, opinion, and critical debate all contribute to the development of our dogmatic precepts. The common interpretation of dogma is the uncritical assertion of a belief, but in fact dogmatism is a form of explicit expression of the sum total of past data, leaving little room for ambiguity of stance.

The new evidence-based approach to medical thinking brings with it an inherent attack upon the dogmas of the past, a skeptic's approach to analysis of the available data. Such skepsis is in fact an important co-conspirator with dogma to produce optimization of patient care, for it serves to periodically challenge and either ultimately support or refute the prevailing wisdom. As suggested by Edmond Murphy, "its relationship to dogma is like that of a grindstone to a blade: for the grindstone may destroy the blade of poor metal, but is what turns a lump of chilled steel into a sword" (1).

The role of prophylactic oophorectomy at the time of hysterectomy has long been a controversial issue. Proponents have argued that the procedure is justified due to the elimination of future ovarian cancer risk, as well as the decrease in future surgery or treatment of symptomatology related to retained ovaries. They suggest that the role of the ovary is for reproduction and hormone production, and when each of these functions cease (or are expected to terminate soon) the ovary serves no purpose other than generating mischief (2). Critics of this view point out that even post-menopausal ovaries are hormonally active, albeit not principally for the production of estrogen, and the importance of ovarian androgen production in later life has not been entirely delineated (3). Moreover, the psychological impact of castration can be profound in some individuals (4).

The result has been an uneasy dogma. Despite the official position by the American College of Obstetricians and Gynecologists that the decision should be individualized (5), the predominant teaching is that prophylactic oophorectomy in the low-risk patient should be avoided under the age of 40, should be routinely performed over age 55, and should be considered and discussed in the interval between. Most of us practice according to this dogma, and many utilize the cutoff of age 45 as a practical delineator for when to strongly advise the procedure.

In this issue of Obstetrics and Gynecology, Parker and colleagues perform decision analysis in an attempt to evaluate whether prophylactic oophorectomy at the time of hysterectomy for benign disease, in the woman with no apparent risk factors for ovarian malignancy, is in fact advantageous (6). Their calculations draw upon the best available evidence regarding mortality risks for a variety of disorders that have been linked to the presence or absence of ovaries. These data are then subjected to Markov modeling to estimate age-specific mortality for four situations: ovarian conservation with and without subsequent estrogen therapy, and oophorectomy with and without subsequent estrogen therapy. Their findings suggest that women undergoing oophorectomy are at greater mortality risk when the surgery is performed prior to the age of 65; furthermore, removal of the ovaries could not be shown to produce a survival benefit at any age.

To be sure, there are several shortcomings in this study. A decision analysis model is only as good as the data placed into it. In this case, while several elements of the input are drawn from high-quality data sources, a number of probability estimates are from trohoc studies with substantial potential bias. Still other data are derived from calculation, and some pieces of the puzzle are missing entirely resulting in assumptions of unknown validity.

More importantly, the calculated increase in mortality associated with oophorectomy (in the absence of estrogen therapy) derives almost entirely from enhancement of coronary heart disease risk. The magnitude of this risk derives from the Nurses' Health Study, a prospective cohort investigation (7). Given the design, the study is certainly subject to allocation and ascertainment bias, and other findings from the study have proven not to be congruent with randomized data from the Women's Health Initiative (8). Thus, the validity of the findings can easily be questioned.

Nevertheless, the authors have demonstrated via sensitivity analysis that even if no coronary heart disease increase is seen with oophorectomy, there remains no demonstrable advantage to the procedure in terms of longevity! This finding raises a multitude of follow-up questions worthy of investigation. Can these findings be supported as higher quality data are accumulated for inclusion into the model? If the results of the study are supported, can we define subgroups at low risk for ovarian cancer that may still benefit from oophorectomy? Can we utilize other outcome measures (quality of life, cost) to help weigh the relative value of this procedure? These are important considerations for future researchers.

While this study is certainly not definitive regarding the issue of prophylactic oophorectomy, it is sure to provide significant impact upon clinical practice. It is likely that the discussion regarding oophorectomy in the post-menopausal woman undergoing hysterectomy was brief and pointed; this is no longer likely to be the case. In the already complex discussion regarding oophorectomy among peri-menopausal women, the issue of potential effect upon mortality must now be brought to the table. The very topic of life expectancy as a result of a surgical procedure is probably one that is too infrequently broached. The result is likely to be a more lively, informative, and considered discussion with many women. Such enhanced complexity of interaction, while time-consuming to many and annoying to some, will almost certainly add to the quality of information utilized by the consenting patient.

As we tear down old dogmas with skepsis and subsequent analysis, we will inevitably create newer, shinier, fancier ones. It is important that we realize such pronouncements are rarely definitive or unassailable; that shortcomings virtually always exist in any collected packet of evidence, no matter how scrupulous the designers. It is our responsibility as physicians and patient advocates to continuously challenge these new truths with a critical eye, a reasoned perspective, and whenever possible a smattering of imagination.

References

  1. Murphy EA. Skepsis, Dogma, and Belief. Uses and Abuses in Medicine. Jo hns Hopkins University Press, Baltimore, 1981, p. 17.
  2. Mattingly RF. TeLinde's Operative Gynecology. Fifth edition. J. B. Lippincott Co., Philadelphia , 1977, pp. 198-199.
  3. Guzick DS, Hoeger K. Sex, hormones, and hysterectomies. New Engl J Med 2000;343:730-731.
  4. Taylor M. Psychological consequences of surgical menopause. J Reprod Med 2001;46:317-324.
  5. ACOG Practice Bulletin. Prophylactic Oophorectomy. 1999.
  6. Parker WH, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS. Ovarian conservation at the time of hysterectomy for benign disease. Obstet Gynecol 2005; in press.
  7. Colditz G, Willett W, Stampfer M, Rosner B, Speizer F, Hennekens C. Menopause and the risk of coronary heart disease in women. N Engl J Med 1987;316:1105-1110.
  8. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321.

 

Keeping Ovaries After Hysterectomy Boosts Survival

By Kathleen Doheny
HealthDay Reporter

MONDAY, Aug. 1 (HealthDay News) -- Removing the ovaries along with the uterus during a hysterectomy done for noncancerous conditions is common in women over the age of 45, but a new study suggests it may not be the wisest course for long-term survival.

Keeping the ovaries is clearly best for women up to age 65 who are at average risk of getting ovarian cancer and get a hysterectomy for noncancerous conditions, said study author Dr. William Parker, a staff gynecologist at Santa Monica-UCLA Medical Center in Los Angeles. His finding appears in the August issue of Obstetrics & Gynecology .

In his review of 20 years of published data from various sources, Parker and his team found that preserving the ovaries in this group of women reduces their risk for heart disease and hip fractures.

"Twenty-five times more women die from heart disease every year than from ovarian cancer," Parker said.

For many years, the prevailing medical wisdom has been to remove the ovaries when the uterus is removed if women are past childbearing age to prevent ovarian cancer, Parker said. About half of women have their ovaries removed during hysterectomy.

However, the ovaries keep making small amounts of estrogen for years after natural menopause. Ovarian testosterone and androstenedione, two hormones, have been documented in some women in their 80s. Muscle and fat cells turn testosterone into circulating estrogen, in turn protecting against heart disease and osteoporosis.

Each year in the United States , more than 600,000 hysterectomies are performed. Ninety percent are performed for benign diseases, Parker said, such as uterine fibroids or endometriosis, in which the lining of the uterus begins to grow on the outside of the uterus and on nearby organs.

Parker's team tried to find out the age-specific risks for five conditions linked to the presence or absence of ovaries, including ovarian cancer, breast cancer, heart disease, hip fractures and stroke. They compared four strategies for hypothetical groups of women aged 40 to 80 who had a hysterectomy: ovary conservation with or without estrogen therapy later, and ovary removal with or without estrogen therapy later.

For women at average risk of ovarian cancer, heart disease, osteoporosis, breast cancer and stroke, the probability of survival to age 80 after hysterectomy at ages 50 to 54 ranged from 62 percent for those who kept their ovaries but didn't take estrogen, to 53 percent for those who had their ovaries removed but didn't take estrogen.

Keeping the ovaries without estrogen therapy reduced the percent of women dying by age 80 of heart disease from 15 percent to 7 percent, and those dying of hip fractures from nearly 5 percent to 3 percent.

The reductions in those two diseases, Parker said, far outweigh the increase in ovarian cancer deaths by age 80.

"If you take out the ovaries, the risk of ovarian cancer goes to zero," Parker said, "but you lose the protection against heart disease and the prevention of osteoporosis."

Was he surprised? "Yes. I really did think that taking out the ovaries wasn't beneficial for [overall] mortality," Parker said. "But I didn't suspect that leaving them in would be so clearly beneficial."

Another expert familiar with the new study, Dr. Richard Paulson, a professor of reproductive medicine at the University of Southern California, Los Angeles, praised the work. "It's wonderful," he said. "When I first read it, my first thought was, why has this not been done before?"

"What has been lacking up to this point was a good analysis for the data. You've got the cancer doctors saying, 'You can't leave them behind, the patient is going to get cancer [of the ovaries] and die.' On the other hand, you have the hormone doctors, the endocrinologists who are saying that the postmenopausal ovaries make important hormones, and we should leave them intact. What was needed was for someone to crunch the numbers and come up with relative risks."

Neither Paulson nor Parker think practice will change overnight. But the new study is food for thought, and women aged 45 and above who are facing a hysterectomy for noncancerous conditions should be aware of the new analysis, they said.

 

Conserving Ovaries at Hysterectomy May Boost Long-Term Survival

Rueters

By Megan Rauscher

NEW YORK (Reuters Health) Aug 03 - The results of a Markov decision analytic model indicate that leaving both ovaries intact in women 65 years old or younger has long-term survival benefits in patients at average risk for ovarian cancer who undergo hysterectomy for benign disease.

"Prophylactic oophorectomy is often recommended concurrent with hysterectomy for benign disease," Dr. William H. Parker from the University of California , Los Angeles , and colleagues note in the August issue of Obstetrics and Gynecology.

The model they developed, however, shows that women who undergo oophorectomy before age 55 have 8.58% excess mortality by age 80. Those who undergo oophorectomy before age 59 have 3.92% excess mortality.

There is "sustained, but decreasing," benefit of ovarian conservation until the age of 75, "when excess mortality for oophorectomy is less than 1%," the authors report. "These results were unchanged following multiple sensitivity analyses and were most sensitive to the risk of coronary artery disease," according to the team.

"The important point," Dr. Parker said, "is that gynecologists who have been looking at the issue of oophorectomy have focused on one thing -- ovarian cancer. Women are living longer and the major killer of women is heart disease, taking 25 times more women's lives than ovarian cancer."

"The ovaries produce testosterone and androstenedione for 30 years after menopause," he continued, "and these hormones are converted into estrogen, continuing the protection of the heart and bones. So, I think we need to look at the bigger picture, including the long-term implications of oophorectomy."

"Our study does shows that oophorectomy may be harmful if performed before age 65 and may be of no benefit at any age," Dr. Parker told Reuters Health. "These results, of course, do not apply to women at high risk of ovarian cancer," he emphasized.

Obstet Gynecol 2005;106:219-226.

 

Removal of Ovaries Increases Heart Disease Risk

The common practice of removing the ovaries during hysterectomy should be discouraged, new research sustains. Oophorectomy, the removal of ovaries, seems to harm rather than help, and may actually shorten the lives of the female patients undergoing it.

Hysterectomy implies the removal of the uterus and sometimes the cervix (total hysterectomy) and is performed particularly when cancer threatens, but also, more recently, for reasons that are not life-threatening - fibroid tumors, excessive menstrual bleeding, although there are more options for these disorders then hysterectomies. 90% of the 615,000 hysterectomies performed each year are for non-cancerous reasons.

As for the removal of ovaries when hysterectomy is performed, federal data from the late 1990s show that 78 percent of women between ages 45 and 64 who underwent a hysterectomy had their ovaries taken out as well , though most were not at particular risk for ovarian cancer. Medical attitude is generally to take them out as a protective measure, even in women who are not at particular risk of ovarian cancer. Reasons in support of this were that childbearing was over and menopause imminent, as well as ovarian cancer particularly deadly. There is no evidence, however, that oophorectomy is beneficial for these women, this current study confirms. The ovaries can be left intact in women who have a normal risk of cancer.

The lead researcher of the study, Dr. William H. Parker, clinical professor at the University of California, Los Angeles School of Medicine, used data from other studies about women's mortality risks and from studies tracking heart attacks and bone-thinning osteoporosis in oophorectomy patients; he created a model of how women with different characteristics would fare with ovary removal at different ages.

The models suggest that, for women whose ovaries were removed before the age of 65, there was an increased risk of death from heart disease.

As many as 18,000 women a year may die prematurely because of ovarian surgery

Dr. William H. Parker

Dr. Parker found that 9% fewer women who had an oophorectomy between ages 50 and 54 reached the age of 80 than women who had a hysterectomy, but kept their ovaries. He also reached the conclusion that the older a woman was when she had her ovaries removed, the smaller was the impact on her chances of reaching 80 and the younger a woman is when she has an oophorectomy, the longer the absence of ovaries will have an impact on her health.

Surprisingly enough, women who kept their ovaries also reduced their chances of developing ovarian cancer by 40 percent, as compared with women who did not have hysterectomies at all.

Dr. Parker is hoping that doctors will now consider both the advantages and disadvantages of this practice and present both to their patients before advising them to have their ovaries removed. The findings were published in yesterday's issue of the journal "Obstetrics & Gynecology".

 

Study on ovaries sparks debate

Tuesday, August 02, 2005

By PATRICIA NORRIS
pnorris@repub.com

SPRINGFIELD - Local doctors urged the public to use common sense when digesting a new study that found thousands of women may die prematurely after their ovaries are removed.

"I would encourage women to be reluctant to give up any of their organs until someone can prove to them it is in their health's interest," said Dr. Reed Shnider, director of preventive cardiology and wellness at Baystate Medical Center .

It has been customary for surgeons to remove the ovaries of women who have a hysterectomy, particularly if they are over 45, to eliminate the risk of ovarian cancer. Ovarian cancer is uncommon but frequently deadly, because it has vague initial symptoms and often goes undiagnosed until cancer has spread throughout the body.

The study, published in the journal of Obstetrics and Gynecology, suggests patients need to be aware that ovaries provide benefits long after menopause. The ovaries apparently release small amounts of hormones that reduce heart disease and keep bones healthy, allowing women to live longer.

"The article caught my attention," said Dr. Michel Prefontaine, chief of the division of gynecological oncology at Baystate. "I treat mostly cancer so I have a jaundiced view of the subject. What I do see often enough is women who have had hysterectomies at 49 and then at 59 have ovarian cancer. I feel bad that this was a missed opportunity to prevent disease. But I don't see all of the other women who keep their ovaries and do well."

Prefontaine suggests women should know their family histories for breast and ovarian cancer. It may come down to how a patient interprets her own risk, he said.

"I had a woman today who was reading the article and she was saying, 'I don't care about the risk of heart attack. Ovarian cancer is much worse.' You may live longer but the suffering with ovarian cancer is not negligible," he said.

At the very least, the study should hammer home to doctors and patients that ovary removal should not be automatic.

"It's not going to be a one-minute discussion," Prefontaine said.

Shnider said the study also points out that ovaries know what the cardiologists don't - how to provide women with the right dose and mixture of hormones to keep their hearts healthy. Synthetic hormone replacements have been problematic, Shnider said.

"It appears the ovaries have natural wisdom that we don't have. So it is worthwhile to hold on to every organ you can within reason in order to get the benefits," he said.

 

 

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