William H. Parker, MD

What Are the Treatment Options for         Fibroids?

If you need treatment for fibroids, there are a number of         options available to you. Your choices should be guided by the medical         problems the fibroids are causing, your desire to have children, and         your feelings and thoughts about surgery or other options. I think it is         important for you to know all the options available. Even if some         treatments do not apply at the current time, your condition or symptoms         may change. If you understand the potential for future symptoms and         problems, as well as the alternative means of treatment available, much         of the mystery of fibroids will disappear.  
 

Although most women will have fibroids during their lifetime,         only a small number of them will ever need treatment. The vast majority         of women with fibroids are unaware of them until their doctor feels them         at the time of a routine exam. Some women have very minor symptoms,         which are not bothersome at all. If that is the case for you, then no         treatment is necessary. I consider careful observation to be the primary         treatment option.  

The cause of the growth of fibroids is not well understood, and the         rate of growth is unpredictable. Most fibroids never grow; others grow         gradually over the course of many years; and some seem to go through         growth spurts and then may stop growing entirely. The only way to know         what is happening is to have a pelvic examination on a regular basis. I         usually examine women with fibroids every three to six months. If the         fibroid grows during that time period, the growth will be discovered         early, and a number of options, short of hysterectomy, should still be         available. If the fibroid seems to be growing, I usually do exams more         frequently, generally every month, until the growth stops.         Ultrasonography, a simple test that uses sound waves to make a picture,         may also be used to determine the size of the fibroids.

On the other hand, fibroids may sometimes grow large enough to cause         constant discomfort, pressure, and even pain. And, while not dangerous,         the discomfort may lead you to choose surgery as treatment for fibroids.         One added note: very large fibroids may partially block blood flowing         from the legs back to the heart. This can lead to swelling of the legs         and some discomfort. Very rarely, it can also lead to formation of blood         clots in the legs that can be dangerous. If you have very large         fibroids, it is important that you not sit for prolonged periods of time         so that clots have less chance to form.

Doctors have been taught that if a woman has fibroids the size         of a large grapefruit (or a twelve-week pregnant uterus) or larger, she         would be at risk for other health problems. This reason-the future         possibility of problems-simply does not make sense to me. If you have a         large fibroid and you are feeling fine, I can't see the need for you to         undergo surgery. It is actually likely that your large fibroid will         never go on to cause you any bothersome symptoms.  

Doctors also feel that large fibroids make it very difficult to         perform a thorough pelvic examination and fear that a less than optimum         pelvic examination can result in missing an early diagnosis of ovarian         cancer. Unfortunately, ovarian cancer is extremely difficult to diagnose         in the early stages, with or without fibroids, even with the most         sophisticated and expensive testing (see 

This is a frustrating and difficult reality for us all. Usually, by         the time a gynecologist can feel an abnormality of the ovary during the         pelvic exam, the disease has already spread. It is also common for         gynecologists to not be able to feel every patient's ovaries because of         the size of the ovaries, the position of the ovaries, or the weight of         the patient. It would make no sense to recommend a hysterectomy to every         woman whose ovaries were unable to be felt by her gynecologist. And no         study has ever shown that removal of a uterus enlarged with fibroids         will make any difference in the early detection of ovarian cancer.

Another argument for aggressive surgery relates to the belief that         the risks and complications of surgery are greater if the surgery is         delayed and the uterus grows larger. As shown in a recent study by Dr.         Robert Reiter of the University of Iowa College of Medicine, the         complication rate for women who have hysterectomies for large fibroids         is no different from that for women with small fibroids. A myomectomy         may be safely performed on a woman with large fibroids.

Dr Stanley West, Dr. Reginald Ruiz and I just submitted an article         for publication reviewing the results of 91 women with uterine fibroids         larger than a four month sized pregnant uterus operated on by Dr. West         between 3/1/98 and 2/28/03 . The results compare very favourably to         other studies of women who had a hysterectomy for large fibroids.

Therefore, surgery is only reasonable if you have symptoms that truly         warrant the risk, time, stress, and money that an operation entails.         Many patients with uterine fibroids need no treatment.

Unfortunately, there are no medications currently available         that are able to prevent the formation of fibroids or permanently shrink         them once they are present. Medicines are often used to buy time or         reduce symptoms. For some women, a reduction in discomfort is enough to         indefinitely postpone surgery. For others, medication allows a more         relaxed time period to prepare emotionally and physically for an         inevitable surgery. Medications may also temporarily reduce the size of         the fibroids enough to allow for a less invasive surgery with a quicker         recovery. For some women who are approaching menopause, the "bought         time" may lead them right into menopause, when the natural loss of         estrogen and progesterone

Lupron and Synarel are two of the medications that work by temporarily         shutting off the ovaries' ability to make estrogen and progesterone, and         menstrual periods temporarily cease. Since estrogen and progesterone are         necessary for fibroids to grow, the lack of hormones causes fibroids to         shrink. Because these medications are destroyed by digestive fluids in         the stomach, they must be given in a non-pill form. Lupron is given by         injection, and Synarel is administered by nasal spray.  

These medications take about two weeks to begin shrinking the         fibroids, and the full effect is seen after three months. At that time,         most fibroids will decrease in size by about 50 percent of their volume.         The shrinking effect is maintained for as long as you use the         medication, but there is rarely any further shrinkage after the third         month of treatment. If the medication is stopped, the ovaries begin to         produce hormones again and the fibroids return to their original size         within three months. Therefore, the medication has no permanent effect         and is primarily used to reduce symptoms and allow time to correct         anemia and plan surgery. In addition, long-term use of these medications         is limited by their side effects and the risk of osteoporosis.

Two medications used to treat uterine fibroids are now in clinical         trials. Both drugs act by blocking the growth-promoting action of         progesterone on fibroids. The first drug is RU-486, also known as the         abortion pill. This medication is being studied in Rochester , NY and         the researchers have found about a 50% reduction in fibroid size after         taking this oral medication. Because the drug blocks progesterone but         not estrogen, the estrogen from the ovaries can stimulate the lining         cells of the uterus without any counter action by the progesterone.         After a year of treatment, about 5% of women had overgrowth of these         lining cells, although no one developed pre-cancer or cancer. There is         some concern that continued use of this medication might eventually lead         to pre-cancer or cancer, but again, this has not been found so far.         Other side-effects include hot flashes

Low-dose mifepristone for uterine leiomyomata.
 Authors: Eisinger SH, Meldrum S, Fiscella K, le Roux HD, Guzick                 DS.


 
 OBJECTIVE: To compare the effect of 5 and 10 mg of mifepristone                 on uterine leiomyoma size and symptoms, and to measure side                 effects.

METHODS: Forty premenopausal women with large,                 symptomatic leiomyomata were randomized to receive either 5 or                 10 mg of mifepristone daily for 6 months in an open-label study.                 Uterine volume was measured at bimonthly intervals by sonography.                 Serum concentrations of hemoglobin levels, follicle-stimulating                 hormone, and liver enzymes were obtained, and endometrial                 samples, symptoms, and menstrual bleeding were also assessed.

RESULTS: Nineteen of 20 subjects taking 5 mg and all 20                 subjects taking 10 mg completed all 6 months of the study. Mean                 uterine volume shrank by 48% (P <.001) in the 5-mg group and                 49% (P <.001) in the 10-mg group, a nonsignificant                 difference. Leiomyoma-related symptoms were comparably reduced                 in both groups. Amenorrhea occurred in 60-65% of both groups.                 Hemoglobin levels increased by 2.5 g/dL in anemic subjects. The                 incidence of hot flashes increased significantly over baseline                 in the 10-mg group but not in the 5-mg group. Simple endometrial                 hyperplasia occurred in 28% of all subjects, with no difference                 between groups. No atypical hyperplasia was noted.

CONCLUSION: Mifepristone in doses of 5 mg or 10 mg                 results in comparable leiomyoma regression, improvement in                 symptoms, and few side effects. Further study is needed to                 assess the long-term safety and efficacy of low-dose                 mifepristone.

The other progesterone blocking drug is Asoprisnil. Early results         also show about a 50% shrinkage in fibroid size.

I am including the only published abstract so far (funded by TAP the         company that makes the drug):

Asoprisnil (J867): a selective progesterone receptor                 modulator for gynecological therapy.
             
             Authors: DeManno D, Elger W, Garg R, Lee R, Schneider B, Hess-Stumpp                 H, Schubert G, Chwalisz K.

Steroids. 2003 Nov;68(10-13):1019-32.
             
             TAP Pharmaceutical Products Inc., 675 N. Field Drive , 600452,                 Lake Forest , IL , USA
             
             Asoprisnil is a novel selective steroid receptor modulator that                 shows unique pharmacodynamic effects in animal models and                 humans. Asoprisnil, its major metabolite J912, and structurally                 related compounds represent a new class of progesterone receptor                 (PR) ligands that exhibit partial agonist and antagonist                 activities in vivo. Asoprisnil demonstrates a high degree of                 receptor and tissue selectivity, with high-binding affinity for                 PR, moderate affinity for glucocorticoid receptor (GR), low                 affinity for androgen receptor (AR), and no binding affinity for                 estrogen or mineralocorticoid receptors. In the rabbit                 endometrium, both asoprisnil and J912 induce partial agonist and                 antagonist effects. Asoprisnil induces mucification of the                 guinea pig vagina and has pronounced anti-uterotrophic effects                 in normal and ovariectomized guinea pigs. Unlike antiprogestins,                 asoprisnil shows only marginal labor-inducing activity during                 mid-pregnancy and is completely ineffective in inducing preterm                 parturition in the guinea pig. Asoprisnil exhibits only marginal                 antiglucocorticoid activity in transactivation in vitro assays                 and animal models. In male rats, asoprisnil showed weak                 androgenic and anti-androgenic properties. In toxicological                 studies in female cynomolgus monkeys, asoprisnil treatment                 abolished menstrual cyclicity and endometrial atrophy. Early                 clinical studies of asoprisnil in normal volunteers demonstrated                 a dose-dependent suppression of menstruation irrespective of the                 effects on ovulation, with no change in basal estrogen                 concentrations and no antiglucocorticoid effects. Unlike                 progestins, asoprisnil does not induce breakthrough bleeding.                 With favorable safety and tolerability profiles thus far,                 asoprisnil appears promising as a novel treatment of                 gynecological disorders, such as uterine fibroids and                 endometriosis.

Can Lupron Be Used for Women Approaching         Menopause?

A woman with fibroids who is approaching menopause can use         Lupron or Synarel until menopause begins. Then the natural supply of         estrogen will cease, and the fibroids will remain small without any         medication. However, because the exact age of natural menopause is         unpredictable, this can turn into an expensive proposition-$2,000 per         year-and is usually not covered by medical insurance. But, for some         women, this treatment plan may be useful.  

Are There Any Other Promising         Medications on the Horizon?

Pirfenidone is a new, not yet available, medication that blocks         the growth of existing fibroids and may stop the formation of new         fibroids. Although the exact mechanism of action is not known,         pirfenidone affects the production of collagen, a major component of         fibroids. Other effects of pirfenidone on cell growth factors may also         be important. Studies are now under way to evaluate how fibroids respond         to this new drug and to evaluate its side effects. In the future, women         with small fibroids may be able to take pirfenidone, or a medication         like it, to prevent fibroid growth and avoid any other need for         treatment.

Can Focused Ultrasound Be Used to Treat         Fibroids?

Ultrasound is a form of energy, and when used at high intensity         and focused on an object, the energy can be used to destroy that object.         This principle has recently been used in experiments for the treatment         of fibroids. The ultrasound energy is generated outside the body but         focused on a fibroid in the uterus. The procedure presently takes a few         hours to treat each fibroid. The size of the fibroid that can be         successfully treated is limited to about a two-inch (5cm) diameter. This         procedure is in its early development. We hope these techniques can be         refined so that the procedure time will be shorter, and the size of the         treated fibroid can be larger.

Articles

If you need treatment for fibroids, there are a number of options available to you. Your choices should be guided by the medical problems the fibroids are causing, your desire to have children, and your feelings and thoughts about surgery or other options. I think it is important for you to know all the options available.

Conservative Treatment for Fibroids

Throughout history, menstruation has been associated with myth and         superstition. Menstrual blood was felt to cure leprosy, warts,         birthmarks, gout, worms and epilepsy. It has been used to ward off         demons and evil spirits. Menstruating women have been separated from         their tribes in order to prevent a bad influence on the crops or the         hunt. As recently as 1930, the cause of abnormal menstrual bleeding was         felt to be an undue exposure to cold or wet just prior to the beginning         of the period.  

In modern times we have learned that menstruation is the end of the         monthly cycle a woman's body goes through if conception has not occured,         allowing the uterine lining to start over again for the next cycle. We         have made quantum leaps towards understanding the role menstruation         plays in preparing a woman's body for reproduction. And we have learned         a great deal about the treatment of many of the problems of abnormal         periods. Science has thankfully dispelled the myths and superstitions         that surrounded menstruation and sexuality, but the mystery and wonder         of these processes stays with us still. 

Since the days that I studied the female hormone system in medical         school, new research has revealed an astonishingly complex system of         hormones and nerve transmitter proteins that interplay to regulate the         monthly menstrual cycle

. The system is balanced, but in certain         situations - such as times of stress, when body weight changes, when         taking medications - it is easily upset. Once the balance is upset,         bleeding can occur that is outside of the normal pattern. Also, cells         that form abnormal growths within the uterine lining - polyps,         hyperplasia, cancer- can cause bleeding as they develop. In the first         part of this chapter, we will deal with the circumstances and solutions         for problems with your periods. The second part of the chapter will deal         with painful periods and the new ideas and treatments for this common,         bothersome and, sometimes, incapacitating problem. 


 The onset of menstrual periods occurs between the ages of 9-17 with the         average age being 13. Adolescents tend to have periods that are far         apart and then establish more regularity over the subsequent few years.         Most adult women will have a menstrual cycle, measured from the first         day of any bleeding to the next episode of bleeding, about every 21-35         days. Although women expect to bleed every 28 days, only 15% of women         actually have cycles that length. Bleeding usually lasts 4-6 days with         some women bleeding a few days longer or shorter. Most women lose about         6 teaspoons of blood each month. Interestingly, the number of days         between periods changes over time, with periods becoming further apart         as women reach their forties. 

Abnormal bleeding is said to occur if you have a period more often         than every 21 days, less often than every 35 days, or if you have         bleeding or spotting in between periods. Very heavy bleeding, saturating         a pad or tampon every hour or two for more than a few hours, is also         abnormal. There are a number of causes of abnormal bleeding, and the         good news is that almost all of them are benign and easily treatable.         The most common causes are hormonal changes, ovarian cysts, uterine or         cervical polyps, overgrowth of the uterine lining cells (hyperplasia),         fibroids, and, rarely, precancer or cancer of the uterus. The following         sections will explain each of these problems in detail. 

WHAT SHOULD BE DONE IF YOU HAVE ABNORMAL BLEEDING DURING         PERIMENOPAUSE OR AFTER MENOPAUSE?
 

As menopause approaches, most women will experience lighter and less         frequent periods. However, the likelihood of bleeding from other causes         such as hyperplasia (lining overgrowth), polyps, or precancer or cancer         of the uterus increases at this time of your life. Bleeding that is         irregular, very heavy (need to change a pad every hour or two) or         prolonged (more than seven days) is abnormal and it is important to         establish the cause. The best way to accomplish this is with a sampling         of the cells from the uterine lining. The diagnostic methods available         include hysteroscopy, endometrial biopsy, and D&C. These methods are         fully described in this chapter.

This test allows the doctor to look inside the uterus by placing the         hysteroscope, a small telescope, through the vagina and into the opening         in the cervix. Once inside the uterus, the lining cells can be         inspected. Polyps, fibroids, hyperplasia and cancer can all be seen with         the hysteroscope. The procedure, called hysteroscopy, can be done in the         office in about 5 minutes and usually does not require any anesthesia.         The information the doctor can get from this procedure is invaluable.         Because many problems can be clearly seen, the diagnosis is often         certain. A number of studies have shown that the diagnosis made by         hysteroscopy followed by scraping the visualized abnormal area of lining         cells is more accurate than when a D&C is performed blindly without         the hysteroscope. 


 Endometrial ablation is an outpatient surgical procedure used to stop or         decrease bleeding from the uterus. The traditional method of performing         endometrial ablation uses electrical energy passed into the uterus at         the end of a telescope in order to burn and destroy the lining of the         uterus The uterus is filled with fluid and the doctor is able to look         through the telescope and watch to make sure the entire lining is         destroyed. This technique is very effective, but does require special         training and skill on the part of the doctor. As a result, many doctors         never learned how to perform endometrial ablation and do not offer the         procedure to their patients as an alternative to hysterectomy. 

Newer methods of ablation have recently been developed that should         allow most gynecologists to perform the procedure without involved         special training. Some of these devices may even be able to be used in a         doctor?s office, avoiding anesthesia and the added costs of a hospital.         In addition, neither of the new methods uses fluid to hold the uterus         open during surgery and thus avoids the extremely rare chance that extra         fluid might get absorbed into the bloodstream and cause complications.         One of these methods uses an expandable metal device that is inserted         into the uterus like an IUD, Once the device is expanded inside the         uterus, a gentle suction pulls the uterine lining close to the         instrument and an electrical current burns the lining cells. This         procedure only takes 90 seconds and the results have been excellent.         Another device circulates hot water inside the uterus to burn the lining         cells. This device has been specially engineered to keep the water at a         low pressure so that it cannot escape through the tubes. If the device         senses a leak it automatically shuts off. Because the water circulates         freely throughout the entire uterine cavity, the shape of the cavity         will not affect the results. As a result, the device is very effective         for women with fibroids, enlarged or abnormally shaped uterine cavities.         This procedure takes about 10 minutes and results have been comparable         to the other methods. Other devices are in development and, hopefully,         endometrial ablation will become more available to women as an         alternative to hysterectomy for heavy bleeding.
 
 

HOW WELL DOES ENDOMETRIAL ABLATION WORK? 


 After endometrial ablation, the ovaries continue to make normal amounts         of hormone, but without lining cells, bleeding cannot occur. In 50%         percent of patients, all the lining cells have been destroyed, and these         women never have another menstrual period again. In an additional 40%         percent of women, a few lining cells have been left behind, and these         women will experience a light flow for a few days each month. For 10% of         women, no improvement is noted. Still, 90% of the women who have this         procedure are extremely happy not to have to tolerate the severe and         debilitating monthly bleeding they had previously had. Women who have         had an endometrial ablation are among the most satisfied patients in my         practice. After surgery, they are able to return to normal activity and         life unencumbered by the fatigue and inconvenience associated with heavy         bleeding. 

Endometrial ablation may only be performed on women who do not wish         to have any, or any more, children. Once the lining cells of the uterus         are destroyed by the procedure, there is no place for a developing fetus         to attach within the uterus. Despite this, it is best to use some form         of contraception after the procedure. If some cells remain following         endometrial ablation, there exists the rare possibility of pregnancy. In         the few cases where pregnancy has occurred, termination of the pregnancy         has been recommended. Doctors have been concerned that without adequate         cells lining the inside of the uterus, the placenta would grow         abnormally, directly into the muscle wall of the uterus and take hold         like the roots of a tree. As a result, the placenta would not be able to         separate at the time of delivery, and hemorrhage could occur. 

WHAT ARE THE CAUSES OF PAINFUL PERIODS (DYSMENORRHEA)?
 

Dysmenorrhea refers to the pain accompanying a period. Most         menstruating women have uterine contractions of moderate strength that         each last for less than thirty seconds and occur about every 3 to 5         minutes. However, women who experience severe dysmenorrhea have cramps         that last up to 90 seconds with only a few seconds of rest in between.         And, the strength of the contraction may be up to 5 times greater than         normal. 

We now know that dysmenorrhea results from the release of a chemical         substance, called prostaglandin, from the lining cells of the uterus at         the time of the menstrual period. The prostaglandin causes contractions         of the muscle wall of the uterus, "menstrual cramps". In fact,         if you give prostaglandin to a woman by injection, severe menstrual         cramps result. Along the same lines, prostaglandin is now used to help         start the contractions of labor in women who, for medical reasons, need         to deliver their babies promptly. 

Women who have dysmenorrhea have been found to produce more         prostaglandin in the lining cells of the uterus than woman who do not         have cramps. And, when the increased amount of prostaglandin is released         at the time of the period, stronger uterine contractions are the result.         As we will discuss, new medications are now available that prevent the         formation of prostaglandins in the uterus and thus can prevent or         decrease menstrual cramps. 

The following questions and answers can be found in         our 

ARE ADOLESCENTS PRONE TO ABNORMAL             BLEEDING? 

CAN STRESS INTERFERE WITH YOUR             PERIODS? 

CAN CHANGES IN THE AMOUNT OF             EXERCISE YOU DO CAUSE ABNORMAL BLEEDING? 

CAN ANOREXIA NERVOSA INTERFERE WITH             YOUR PERIODS? 

CAN ANY MEDICATIONS INTERFERE WITH             THE MENSTRUAL CYCLE? 

CAN DRUG OR NARCOTIC USE CAUSE             ABNORMAL PERIODS? 

CAN PROBLEMS WITH YOUR THYROID GLAND             INTERFERE WITH YOUR PERIODS? 

CAN OTHER HORMONAL PROBLEMS             INTERFERE WITH YOUR PERIODS? 

CAN OVARIAN CYSTS CAUSE IRREGULAR             PERIODS? 

CAN MISSING PERIODS LEAD TO ANY             OTHER PROBLEMS?

WHAT IS THE TREATMENT FOR ABNORMAL             PERIODS?

WHAT IS THE TREATMENT IF IRREGULAR             BLEEDING IS DUE TO MISSED OVULATION?

WHEN IS A D&C NECCESARY FOR             ABNORMAL HORMONAL BLEEDING?

ARE THERE HOMEOPATHIC REMEDIES FOR             ABNORMAL BLEEDING DUE TO HORMONAL CAUSES?

WHAT IS POLYCYSTIC OVARIAN DISEASE (PCO)?

WHAT KIND OF BLEEDING PROBLEMS MAY             DEVELOP IN MENOPAUSE?

WHAT SHOULD BE DONE IF YOU HAVE             ABNORMAL BLEEDING DURING PERIMENOPAUSE OR AFTER MENOPAUSE?

WHAT IF YOU ARE BLEEDING WHILE YOU             ARE ON HORMONE REPLACEMENT THERAPY FOR MENOPAUSE?

POLYPS, FIBROIDS, HYPERPLASIA AND           CANCER

WHAT KIND OF BLEEDING PROBLEMS CAN             FIBROIDS CAUSE? 

WHAT IS THE BEST TREATMENT IF THE             CAUSE OF BLEEDING IS FIBROIDS?

Throughout history, menstruation has been associated with myth and superstition. Menstrual blood was felt to cure leprosy, warts, birthmarks, gout, worms and epilepsy. It has been used to ward off demons and evil spirits. Menstruating women have been separated from their tribes in order to prevent a bad influence on the crops or the hunt. As recently as 1930, the cause of abnormal menstrual bleeding was felt to be an undue exposure to cold or wet just prior to the beginning of the period.

Problems with your Periods

Of the 600,000 hysterectomies performed yearly in the U.S., approximately  300,000 are accompanied by prophylactic bilateral oophorectomy, traditionally  suggested as the best strategy to decrease the rate of ovarian cancer. However,  excluding women from high-risk families, ovarian cancer is a relatively uncommon  malignancy. At age 50, only about one in 1,500 women will be diagnosed with  ovarian cancer and at age 70, the age of peak incidence, only 1 in 400 will be  found to have ovarian cancer. In fact, while 16,000 women die of ovarian cancer  every year, 70,000 die of lung cancer, 28,000 die of colon cancer and 40,000 die  of breast cancer. Notably, 490,000 women die of heart disease every year and  about 48,000 women die within one year following hip fracture. 
 
 


 Premenopausal oophorectomy causes an immediate loss of all ovarian hormones.  Following menopause, the ovary continues to produce androstenedione and  testosterone in significant amounts until age 80 and these androgens are  converted in fat, muscle and skin into estrone. Following oophorectomy,  menopausal women have significantly lower levels of androstenedione and  testosterone than naturally menopausal women. 
 
 Oophorectomy has been shown to increase the risk of cardiovascular disease, the  major cause of death for women. Oophorectomy after age 50 increases the risk of  developing a first MI by 40% (RR 1.4, CI 1.0-2.0). Both estrogens and androgens  inhibit bone resorption, and androgens increase bone formation. One study found  that after 16 years of follow-up, women who were postmenopausal at the time of  oophorectomy had 54% more osteoporotic fractures than women with intact ovaries.  And, women older than 60 have a twofold increase in mortality (OR 2.18, CI  2.03-2.32) within a year following a hip fracture. 
 
 

 
 The ideal way to study risks and benefits of oophorectomy would be with a  prospective, randomized trial. However, that study would require 8,000 women to  be randomized to oophorectomy or ovarian conservation and then followed for 40  years to ascertain causes of mortality. It is unlikely that this kind of study  will ever be performed.
 
 Therefore, in order to study the risks and benefits of prophylactic oophorectomy,  we used a Markov computer model that can help to make complex medical decisions.  We reviewed the literature for studies that examine the incidence of disease and  mortality from 5 conditions that appear to be related to ovarian hormones:  coronary heart disease (CHD), ovarian cancer, breast cancer, stroke and hip  fracture, as well as data for death from all other causes. We then found data  for the relative risk of developing these five conditions for women having  either oophorectomy or ovarian conservation between the ages of 40 and 75. Next,  we calculated risk estimates for these conditions for every 5-year interval  until women in our model either died or reached the age of 80. We deliberately  chose to measure mortality because good data for quantifying morbidity or  quality of life is not available. 
 
 


 For women who have a hysterectomy with ovarian conservation at ages 50-54 and  who are not at high risk of ovarian cancer, coronary heart disease,  osteoporosis, breast cancer, or stroke, the probability of surviving to age 80  was 62.46%, compared to 53.88% if oophorectomy was performed. This 8.58%  difference in survival is primarily due to fewer women dying of CHD and hip  fracture, far outweighing the 0.47% mortality rate from ovarian cancer. If  surgery occurs at ages 55-59, the survival advantage is 3.92%, but after age 64  there was no significant difference in survival. (see graph)
 
 For a hypothetical group of 4,000 women ages 50 to 54 undergoing hysterectomy  with oophorectomy, our analysis predicts 343 excess deaths (mostly from CHD).  For the risk of ovarian cancer to outweigh the risks of CHD and hip fracture  following oophorectomy, CHD deaths would need to be 95% lower than what the  rates among women are currently.
 
 Although quality of life issues are of great importance to women, data were not  available to include these in our model. Premenopausal, and for some  post-menopausal women, oophorectomy may lead to the onset of hot flushes and  mood disturbances, a decline in a sense of well-being, a decline in cognitive  functioning, poor sleep quality, depression and a decline in sexual desire and  frequency. While estrogen therapy may reduce both these symptoms, only 17% of  women have continued hormone therapy after the WHI and fewer now start hormones  at the time of menopause. Also, the number of patients still taking either  statins or Bisphosphanates after 1 year is less than 20%. Therefore, any  assumption that medical treatment can decrease risks following oophorectomy is  questionable. 
 
 The results of our model suggest that the decision to perform prophylactic  oophorectomy should be approached with great caution for the majority of women  who are at average risk of developing ovarian cancer and who are under the age  of 65. The American College of Obstetricians and Gynecologists recommends that  “the decision to perform prophylactic oophorectomy should be based not only on  the patient’s age but also on other factors that weigh individual risk for  developing ovarian cancer against loss of ovarian function”. Hopefully, our  results will encourage a dialogue between doctors and women who are considering  ovarian conservation or oophorectomy.
 
 

Ovarian Conservation at the Time of Hysterectomy for Benign Disease


 
 William H. Parker, MD, Michael S. Broder, MD MPH, Zhimei Liu, PhD, Donna Shoupe,  MD, Cindy Farquhar, MD, Jonathan S. Berek, MD, MMSc. 
 
 

Obstetrics and Gynecology 2005;106:219-26.

 Prophylactic oophorectomy is often recommended concurrent with  hysterectomy for benign disease. The optimal age for this recommendation in  women not at high risk for ovarian cancer has not been determined.
 
 

 Using published age-specific data for absolute and relative  risk, both with and without oophorectomy, for ovarian cancer, coronary heart  disease (CHD), hip fracture, breast cancer, and stroke, a Markov decision  analysis model was used to determine the optimal strategy to maximize survival  for women not at high risk of ovarian cancer. For each 5-year age group from  40-80, four strategies were compared: ovarian conservation or oophorectomy; and  use of ERT or non-use. Outcomes as proportion of women alive at age 80 were  measured. Sensitivity analyses were performed varying both relative and absolute  risk estimates across the range of reported values. 
 
 

 Ovarian conservation until age 65 benefits long-term survival  for women undergoing hysterectomy for benign disease; women with oophorectomy  before age 55 have 8.38% excess mortality by age 80 and before age 59 have 3.92%  excess mortality. There is sustained, but decreasing, benefit until the age of  75, when excess mortality for oophorectomy is less than 1%. These results were  unchanged following multiple sensitivity analyses and were most sensitive to the  risk of coronary heart disease.
 
 

 Ovarian conservation until at least age 65 benefits long-term  survival for women not at high risk of ovarian cancer when undergoing  hysterectomy for benign disease.

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    3. 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;316:1105-10.

    4. Melton J, Khosla S, Malkasian G, Achenbach S, Oberg A, Riggs L. Fracture risk after bilateral oophorectomy in elderly women. J Bone Miner Res. 2003;18:900-05.

    5. Keene G, Parker M, Pryor G. Mortality and morbidity after hip fractures. BMJ. 1993:13:1248-50.

    6. Sherwin BB. Hormones, mood, and cognitive functioning in postmenopausal women. Obstet Gynecol. 1996 87:20S-26S.

    7. Buist D, Newton K, Miglioretti D, Beverly K, Connelly M, Andrade S, et al. Hormone therapy prescribing patterns in the United States. Obstet Gynecol 2004;104:1042-50.

Of the 600,000 hysterectomies performed yearly in the U.S., approximately 300,000 are accompanied by prophylactic bilateral oophorectomy, traditionally suggested as the best strategy to decrease the rate of ovarian cancer.

Benefits of Ovarian Conservation at the Time of Hysterectomy for Benign Disease


Susan is a 58-year-old woman who saw her family physician                   after a few weeks of mild abdominal pain and bloating. The                   examination of her abdomen was normal, as was a pelvic and                   rectal exam. Blood tests for infection, liver and gall bladder                   problems were also normal. Susan and her doctor were both                   reassured by all this, and she was given a medication to                   reduce any spasm in the intestines. When the pain and bloating                   persisted despite the medication, her doctor ordered some                   X-rays of her intestines and a sonogram of her gall bladder                   and pelvis. All of these tests were also normal, with the                   exception of a 2-inch fluid filled cyst seen in her left                   ovary. 

Susan came to the office worried that this test indicated                   ovarian cancer. On examination, I couldn't feel anything                   abnormal. In addition, there was no tenderness on examination                   of her uterus, tubes or ovaries and it seemed unlikely that                   her original complaints of pain and bloating were at all                   related to a gynecologic problem. But when I reviewed the                   sonogram, it was clear that a cystic mass was, in fact,                   present. We performed a CA-125 test which was thankfully                   normal. At this point, the suspicion of ovarian cancer was                   extremely low but because a mass was present, I recommended                   surgery to remove it. We performed a laparoscopy the next                   week. During surgery, it was immediately clear that the mass                   was not her ovary, but rather her fallopian tube that was                   filled with fluid. This probably resulted from a previous                   infection that had occurred many years before and had never                   caused any symptoms or problems. In fact, had the sonogram not                   been performed, no one would have ever known about the                   "cyst," and she never would have had surgery. We did                   remove the tube through the laparoscope in order to prevent                   similar confusion in the future. The pathologist confirmed                   that this was an old infection that had been cured by the                   body's defenses long ago. I think Susan's case illustrates                   that medical tests are not foolproof and sometimes can lead to                   other unnecessary tests or procedures. 

If cancer is one of the most dreaded word in the English language,         then for most women, "ovarian" is the worst adjective to place         before "cancer". In all the bad news we sometimes deal with in         gynecology, this is the most frightening. Since the death of Gilda         Radner, a comedienne who made so many of us laugh, people seem to be         much more aware of ovarian cancer. This increase in interest has led to         enhanced medical research regarding ovarian cancer. Studies are being         done on the cause or causes, the treatment, and importantly, a means of         early detection. For the 5% of ovarian cancer patients for whom the         cancer may be hereditary, genetic research is evolving to help determine         who actually is at risk. While we still feel as if we are groping in the         dark with this disease, when I think back to five years ago, I know that         we are making strides. The following chapter deals with what we now know         about the detection, treatment and prevention of ovarian cancer. If you         are anxious and concerned about this disease, I hope that this         information allays many of your fears. 


While extremely frightening, ovarian cancer is a rare disease. Only one         out of every 15,000 women at the age of thirty will be found to have the         disease. At 40, about the age that Gilda Radner was discovered to have         ovarian cancer, only one of every 10,000 women have this disease. At the         age of 60, the average age at which women get ovarian cancer, only one         of every 1500 women will be found to have it. In your entire lifetime,         if you live to be 90 years old, you have a 1 in 70 chance of developing         ovarian cancer. While concerning, compare this with the 1 in 3 chance a         women has of dying of a heart attack by the time she is 90 - or the fact         that you are more likely to die from an auto accident and twice as         likely to die from colon cancer than you are from ovarian cancer. This         is not to diminish the human toll from this terrible disease. However,         all of the interest and media coverage surrounding ovarian cancer has         given the impression that the disease is now more common, that there is         an epidemic. In fact, the incidence of ovarian cancer is no greater now         than it was 25 years ago. 


No. In fact, for a premenopausal woman found to have a growth on her         ovary, there is over a 90% chance that this growth is benign. Even for a         postmenopausal woman, an ovarian growth has a 70% chance of being         benign. Therefore, if a growth is found on your ovary, do not panic. It         will most likely not be a cancer. Chapter 4 is devoted to the types of         benign ovarian cysts most commonly seen. 

IS SONOGRAPHY A GOOD SCREENING TEST FOR OVARIAN CANCER?


Unfortunately, the answer is no. Sonography is a medical test that uses         sound waves bounced off the ovaries to form a picture on a screen, much         like the technology used for ship's sonar. This technique was felt to be         a promising method to detect growth in the ovaries that might be the         beginning of a cancer. The hope was that this test would detect ovarian         cancer before it had a chance to spread. Unfortunately, the test has a         hard time distinguishing ovarian cancer from other cysts on the ovaries         which are benign. These benign cysts are much more common than ovarian         cancer, and most of them do not need to be treated at all. 

A study that illustrates this problem was conducted in England where         an ad was placed in the paper for free ovarian cancer screening. Within         a short period of time, 5700 women readily agreed to get this free         testing. Of the 5700 women who had a sonogram of their ovaries         performed, 361 of them had abnormal appearing ovaries. All 361 of these         women then underwent major abdominal surgery. Three of these women were         found to have widely spread ovarian cancer that would have been easily         detected by a pelvic exam. And only three women with early ovarian         cancer were found and cured. This is wonderful for the three women whose         lives were saved by the sonogram. However, 355 women had a major surgery         that they did not need. They were subjected to the risks of anesthesia,         bleeding, need for transfusion, infection, and injury, in addition to         the discomfort of surgery and the time needed for recovery. At this         point, for the general population the risk that an abnormal screening         sonogram may lead to unnecessary surgery seems to outweigh the benefit. 

In addition, it has been calculated that if all 43 million American         woman over the age of 50 had a pelvic sonogram every year, we might         expect 2.5 million women to have an abnormality found. Thirty-seven         thousand of these women would be found to have ovarian cancer that would         otherwise have not been detected so early. But, 2,463,000 women would         have had unnecessary surgery. Of those women, 2,500 might be expected to         die from the procedure, and 112,500 would have a serious complication.         In addition, the cost of the sonograms would be $11.8 billion per year.         The cost of the unnecessary surgeries would be about $ 37.5 billion per         year. So for all these reasons, a sonogram is not recommended as a         routine screening test for ovarian cancer.

SHOULD YOU GET GENETIC TESTING FOR OVARIAN CANCER? 


Some women with a strong family history for ovarian cancer have been         found to have a mutation in a gene called BRCA, which stands for BReast         CAncer gene. In addition to inheriting a higher risk of getting breast         cancer, women with this mutation have a higher risk of developing         ovarian cancer. In the general population this mutation occurs in about         1 out of 1,000 women. However, in women of eastern European Jewish         descent the mutated gene occurs in 20 out of 1,000 women. Women who have         a BRCA mutation have a 25-50% chance of developing ovarian cancer in         their lifetimes, compared to the 1% risk for women who do not have the         mutation. Interestingly, women who have this gene mutation and develop         ovarian cancer develop a less aggressive cancer and survive longer than         women who do not have this mutation. As is true for the non-genetic form         of ovarian cancer, taking birth control pills substantially reduces the         risk of inherited ovarian cancer. 

Testing for this gene is now available for women who suspect they are         at high risk because of a family history of ovarian cancer. Deciding         whether to be tested is often a difficult decision. There are a number         of reasons you might consider getting the test. If it is negative, then         neither you nor your daughters need to be concerned about an increased         risk of this disease. This often lifts an enormous burden of worry. If         the test is positive, then you will have some decisions to consider.         With an increased risk of ovarian cancer (and an increased risk of         breast cancer), the available options to decrease this risk are drastic;         removal of your ovaries and/or breasts (mastectomy). Removal of your         ovaries will eliminate your risk of ovarian cancer but does involve a         surgical procedure. 

Removal of ovaries can now be performed with laparoscopic surgery as         an outpatient, but general anesthesia is necessary and, as is true with         all surgery, includes some risk. In addition, removal of the ovaries         will not prevent a very rare form of inherited cancer that affects the         inside lining of your abdomen called the peritoneum. In that this gene         mutation also increases your risk of breast cancer you will need to         address the issue of removal of your breasts, mastectomy, for         preventative reasons. Your age, childbearing issues, your feelings about         the possibility of cancer, and your feelings about surgery and removal         of feminine parts of your body are all important issues. These are         extremely difficult decisions and are best made with the counseling and         advice of a trained genetic counselor. It is important to see the         genetic counselor before you get tested, so that these issues can be         discussed in advance of the results. Ask your doctor to recommend         someone to you or call a nearby medical center for a referral.

The following questions and answers can be found in our book

What Causes Fibroids? 
 	Do Birth Control Pills Cause Fibroids? 
 	What Are the Different Types of Fibroids? 
 	Can Fibroids Cause Bleeding Problems? 
 	Can Fibroids Cause Pain or Pressure? 
 	Can Fibroids Cause Sudden Pain? 
 	Can Fibroids Cause Urinary Problems? 
 	Can Fibroids Cause Infertility? 
 	Can Fibroids Cause Miscarriage? 
 	Can Fibroids Cause Problems During Pregnancy? 
 	Do Fibroids Mean A Cesarean Section? 
 	Do Growing Fibroids Mean Cancer? 
 	What If You Have Large Fibroids? 
 	Can My Fibroids Just Be Watched? 

What Are the Treatment Options for Fibroids? 
 	Can You Take Medication for Fibroids? 
 	Are There Any New Medicines for Fibroids? 
 	What Are the Side Effects of Lupron and Synarel? 
 	When Should Lupron or Synarel Be Used? 
 	What About Danacrine? 
 	Can Progesterone Be Used To Treat Fibroids? 
 	Are Holistic Remedies Effective for Treating Fibroids? 
 	Do You Need Surgery for Fibroids? 
 	What If You Have Uncontrollable Bleeding? 
 	What If You Are at Risk for Kidney Damage? 
 	What If There Is Concern That The Fibroids Might Be Cancer? 

What Is a Myomectomy? 
 	What is an Abdominal Myomectomy? 
 	What is a Laparoscopic Myomectomy? 
 	Can Lasers Be used for Myomectomy? 
 	Can Myomectomy Lead to Scar Tissue ? 
 	What is a Vaginal Myomectomy? 
 	What is Myoma Coagulation (Myolysis)? 
 	What is Resectoscope Myomectomy? 
 	What is Endometrial Ablation? 
 	Do I Need a Hysterectomy for Fibroids? 

What is Adenomyosis? 
 	What Are the Symptoms of Adenomyosis? 
 	How Is the Diagnosis of Adenomyosis Made? 
 	What Is the Treatment for Adenomyosis?

Susan is a 58-year-old woman who saw her family physician after a few weeks of mild abdominal pain and bloating. The examination of her abdomen was normal, as was a pelvic and rectal exam. Blood tests for infection, liver and gall bladder problems were also normal.

William H. Parker, MD

Articles

Conservative Treatment for Fibroids

Problems with your Periods

Benefits of Ovarian Conservation at the Time of Hysterectomy for Benign Disease

Ovarian Cancer And The Search For Early Detection