Q. What is endometriosis?
A. Endometriosis is a disease characterized by the presence of tissue which is histologically identical to endometrium (the inner lining of the uterine wall) outside the uterine cavity. Usually, endometriosis is confined to the pelvic and lower abdominal cavity; however, it has occasionally been reported to be in other areas, as well.
Endometriosis is one of the most common problems that gynecologists currently face. It is one of the most complex and least understood diseases in our field and, despite many theories, we still do not have a clear understanding of the cause or of its relationship to infertility. Since this disorder is primarily a human disease and rare in other animal species, accumulation of the facts has been slow.
Although endometriosis has been considered a pathological or separate disease entity, it may not be a disease at all. It may actually be the clinical manifestation of a more basic underlying disorder, such as a basic chemical or physiological abnormality that affects the tubal motility or immune system which could be responsible for the initiation or progression of endometriosis in patients with retrograde menstrual flow. By the same token, endometriosis may not be the cause of infertility, but the result of it. Historically, it has been shown that sometimes our understanding of a disease has awaited the technology to explain it. This may very well be the case with endometriosis, especially in regard to its immunological aspects. Further technological developments may be necessary in order for us to fully understand this problem.

Q. How common is endometriosis?
A. In literature, the prevalence of this disease in the general population has been reported to be about five percent of the female population of reproductive age. However, in women with severe menstrual cramps, the incidence of endometriosis has been reported to be between 25 and 35 percent.

Q. Is there any age group which is more prone to endometriosis?
A. Endometriosis has been reported only in the reproductive ages, which means right after the start of the menstrual cycle until menopause or immediate post-menopausal years.
We believe that ovarian function is necessary for the development and maintenance of these endometrial implants. The disease is normally not seen before age 15 or after menopause. In recent years, we have seen more patients with endometriosis below the age of 20. This is due to the use of laparoscopy in evaluating women with symptoms suggestive of endometriosis.
In a recent study of 140 patients aged 10.5 years to 19 years who were complaining of severe pelvic pain, 47 percent had documented endometriosis at laparoscopy as the sole reason for their pelvic pain.

Q. Is endometriosis based on a genetic or familial factor?
A. Several studies have shown that the incidence of endometriosis is much higher in women having a sister or mother who has already had endometriosis. There was a study conducted involving more than 150 women with endometriosis; of these, 18 (12 percent) were found to have a mother or sister with endometriosis. However, in the same group of women, only two (1.5 percent) showed that they had a mother-in-law or sister-in-law who had endometriosis. This clearly shows that there is a familial tendency with endometriosis. As one can see from these figures, there is almost an eight-fold increase in the risk of endometriosis in women whose mother or sister has been diagnosed as having the disease.
Equally important was the finding that endometriosis on a familial basis tended to be at a more advanced stage when diagnosed and also that it acts more aggressively. It has been suggested that endometriosis might result from an inheritable immunodeficiency state.

Q. Is it true that women who have their tubes tied are protected against endometriosis?
A. Theoretically, blockage of the tubes by tubal ligation or by any other cause (for instance, pelvic inflammatory disease) should protect against the further production of endometriosis. However, a recent investigation of women requesting tubal ligation reversal has not supported this concept. The prevalence rates for endometriosis were found to range from 2 percent through 12 percent in two studies. When an infertile population is studied, these rates range from 5 percent through 35 percent.

Q. Is it true that intercourse during the menstrual cycle increases the risk of endometriosis?
A. This has not been proved. It has been suggested that intercourse during menses might increase tubal activity and increase the backflow of the menstrual cycle through the tubes and thus increase the risk of endometriosis. However, there are no statistics to bear this out.

Q. At the time of my laparoscopy, my doctor was not able to get a biopsy. Is the physical appearance of endometriosis adequate for diagnosis?
A. A biopsy of the lesion does document the presence of endometrial tissue. I believe that the gross appearance of endometriosis and visual inspection of the pelvis is adequate and accurate for diagnosis of endometriosis. However, before any treatment starts, the diagnosis should be confirmed by visual inspection. In a recent study in 86 patients with a visual diagnosis via laparoscopy, diagnosis was confirmed in 93 percent by biopsy. However, in those cases that were believed not to have endometriosis by visual inspection, only 6 percent had a tissue diagnosis of endometriosis confirmed.
It is also important that the surgeon you select is well educated in the appearance of endometrial lesions. Today, many surgeons will videotape the laparoscopy and this can be reviewed at a later date if there are any questions.

Q. Why does endometriosis seem to be discussed more in recent years?
A. Endometriosis is one of the most common gynecological diseases and is responsible for a significant portion of gynecological surgeries each year. Almost as important as the numbers is the fact that young women with endometriosis are often faced with difficult decisions regarding their future reproduction. One of the main symptoms or consequences of endometriosis is infertility, and since there has been a renewed interest in the United States in fertility, there has also been a renewed interest in this disease. The introduction of the laparoscope for more accurate diagnosis of endometriosis has also helped us to diagnose more cases in earlier stages in younger women.
The result of this increased attention is that more and more women are now forewarned about the symptoms of the disease.

Q. Is it true that endometriosis is more common in some races?
A. There seems to be some evidence among researchers that Caucasian women are at greater risk than blacks. Two studies have found the prevalence of endometriosis in blacks to be half that of whites. However, the notion that black women rarely suffer from endometriosis is incorrect. Some data shows that the risk of disease among Asian women is even higher than in Caucasians. There are also several studies which suggest that this disease is more common among higher socio-economic groups of women.

Q. Is there a characteristic menstrual cycle of the woman who has endometriosis?
A. Yes. Many studies have shown that women with endometriosis begin their menstrual cycle at a significantly younger age than women without the condition. Endometriosis is more prevalent in women who have a regular cycle than in women who have an irregular cycle. Another interesting characteristic is that patients with endometriosis have a shorter interval between their periods (less than 27 days). Severe menstrual cramps are also seen much more frequently in endometriosis.
It has been shown that the chance of having endometriosis is four times greater in patients with severe menstrual cramps as compared to women with mild menstrual cramps. Another point is that patients with a prolonged menstrual flow are apt to have endometriosis. It has also been found that if the menstrual flow is longer than a week, the risk of developing endometriosis is 2.5 times greater than in women who have a menstrual flow lasting less than a week.
It has been suggested that the total bulk of endometrial cells cast into the peritoneal cavity may be a factor. Women with a greater number of menstrual days (a factor of days of flow and cycle interval) had twice the risk of developing endometriosis.

Q. Is there a relationship between endometriosis and the use of tampons?
A. This is unlikely. Scientifically, there has not been any basis to conclude that the use of tampons increases the risk of developing endometriosis. Also, with regard to other hygienic practices (such as douching after the menstrual period), it has not been shown that this increases the risk of endometriosis.

Q. Do women with more menstrual cramps have a greater tendency to acquire endometriosis?
A. Although one of the most common characteristics of women with endometriosis is severe menstrual cramps, this appears to be the result of the disease rather than a precursor to it.

Q. If I put off having children until my 30s or later, do I have a greater chance of getting endometriosis? Also, is there any truth to the belief that delayed childbirth can lead to endometriosis?
A. This theory first surfaced in the early 1950s along with the idea that early childbearing offered protection against endometriosis. Although the incidence of endometriosis is higher in women who delay having their first child, this may be because of the fact that endometriosis causes infertility. It is therefore difficult to distinguish whether the infertility preceded or followed the endometriosis. We do believe, however, that pregnancy does have a protective effect on women with endometriosis.

Q. I have heard that career women have a higher chance or risk of developing endometriosis. Is there any truth to this?
A. At the present time there is no scientific justification that supports this theory, and it is more of a myth than a fact that endometriosis is primarily a disease of thin, Caucasian, career women with compulsive personalities.
Although there are studies that show women who exercise regularly had a lower risk of developing endometriosis than women who did not, the protective effect appeared to be confined to women who had begun their activity at an early age and who exercise more than two hours weekly. The types of activity most likely associated with decreased risk were conditioning exercises such as jogging. It is presumed that exercise may influence the risk of this disease through its effect on the level of hormones, such as estrogen, in the women's bodies.

Q. My mother used DES while she was pregnant with me. Does this use of DES in utero increase the risk of endometriosis?
A. At the present time, there is no clear study which can relate an increase in endometriosis incidence with DES exposure.

Q. Are you seeing more endometriosis in younger women today?
A. We are diagnosing this disease right now in a younger age group of women. Twenty-five years ago, our diagnosis was mainly based on severe symptoms and palpable masses in the pelvic area, and was confirmed by laparotomy. Patients were typically in their mid or late 30s. However, with the use of laparoscopy, the typical age at which the diagnosis is being made has dropped significantly. Currently, it is somewhere in the mid to late 20s. We are expecting a further decline in the average age of diagnosis because of the added knowledge of the disease in younger women and also the availability and increased use of laparoscopy in confirming diagnosis.

Q. Do you see endometriosis after menopause?
A. Normally, no. This is because the growth of endometrial implants are dependent upon the female hormone. After menopause, the ovaries cease to produce the hormones that promote the growth of endometriosis and we usually do not see many cases. However, after menopause, there are two factors which may promote or maintain endometriosis. One is the use of estrogen replacement therapy and the other is the presence of high endogenous estrogen in obese patients.

Q. Is endometriosis a disease of modern times?
A. The presence of endometrial tissue outside the uterus was first reported about 300 years ago in 1696 by Sabiard. However, since the turn of the century, and especially in the 1920s, it has been known that endometrial tissue outside of the uterus is responsible for painful menstruation, pelvic pain, pain with intercourse and infertility. The fact that we have been hearing more about endometriosis in the past two or three decades is, I think, due to more awareness by the public and physicians about the condition.
Today, physicians are looking more for this condition in patients who have pelvic pain, pain with menstruation and infertility. Also, there are better tools for diagnosing endometriosis, especially in the early stages. The primary tool was once only the pelvic examination, or at the time of surgery. However, with the use of laparoscopy, we are diagnosing this disease in women in earlier stages who have the above-mentioned symptoms.

Q. What does endometriosis look like?
A. The presence of endometriosis is characterized by blue-gray lesions on the peritoneal surface, over the pelvic peritoneum or pelvic structures. This distinct appearance can be attributed to the encapsulated menstrual blood and menstrual debris. However, the appearance is critically dependent upon the longevity of the tissue implanted. The initial appearance may be just an irregularity or discoloration of the peritoneal surface. Initially, these lesions may appear tan or hemorrhagic in color. After establishment of viable endometrial transplant and menstrual shedding, the presence of entrapped menstrual debris gives the tissue the typical blue-gray and powder burn appearance.
Many times the lesion of endometriosis may not have any color at all. These lesions are called nonpigmented endometriosis. Many experts believe that a young patient or a patient in the reproductive ages (15 to 50) who has an area on the peritoneal surface that does not look normal, and who is having symptoms of endometriosis (i.e., pelvic pain, pain with periods or intercourse, and infertility), should be considered as having endometriosis until it is proven otherwise.
Clinically, these early lesions, although less impressive than pigmented ones when viewed laparoscopically, are just as important in producing pain and infertility.

Q. What are the most common symptoms of endometriosis?
A. The symptoms of endometriosis may be highly variable from one patient to another. The magnitude of the symptoms may not correlate with the extent of the disease, either. For example, a patient with severe disease may have very little pain. However, the likelihood of infertility does increase as the severity of the disease increases. The clinical presentation and symptoms of the disease are also frequently related to the anatomical site of the disease.
The most common sites of the disease are the ovaries, the pelvic peritoneum, the cul-de-sac behind the uterus, the uterosacral ligament, and also the posterior surface of the uterus. The most common symptom is pelvic pain, which can be spontaneous, pain with menstruation or pain with intercourse. Other common symptoms are abnormal uterine bleeding, spotting prior to periods, and infertility.

Q. Do these endometrial implants or endometriosis act like normal endometrium inside the uterus?
A. Not always. Endometrial implants can undergo cyclic histological changes similar to those found in normal endometrium. This shows that in most cases, ectopic endometrium is responding to hormonal changes that occur in the female every month. The endometrial tissue in endometriosis also undergoes atrophy after menopause, or after prescription of the medication that stops ovarian function.
However, the response is not similar in all cases. One reason for this discrepancy is the finding that estrogen receptors have been identified in a minority of endometriotic tissues. Another possible answer to the discordancy between normal endometrium and endometriosis and the apparent failure of drug therapy in some women is the lack of enzymes in endometriotic tissue for hormonal actions.

Q. Why are ovaries the most common site of endometriosis?
A. If we accept the theory that retrograde menstruation is in large part responsible for the initiation of endometriosis in those women susceptible to the implantation of the endometrial cells, then the number one reason is the position of the ovary. The ovaries are adjacent to the opening of the tube in the pelvic area and that location alone will make the ovaries more prone to be contaminated with the regurgitated menstrual flow.
The other reason is that the ovaries have the highest level of steroid hormone compared to any other organ and hence they represent an ideal environment for implantation and growth of the endometrial tissue. In different studies, the involvement of the ovaries (either unilaterally or bilaterally) has been reported up to 75 percent of the time.

Q. What is a chocolate cyst?
A. Ovarian endometriosis probably starts as a surface lesion. The process becomes invasive and the endometriotic lesion internalizes into the ovarian tissue. Once the menstrual flow and debris collect at the site of endometriosis in the ovaries, endometrial cysts form that are filled with chocolate-colored liquid. These are commonly called chocolate cysts, or endometriomA. These are nothing more than cysts which represent debris from prolonged cyclic menstruation in an enclosed areA. These cysts may sometimes attain impressive size, with some documented as large as a baseball or grapefruit that completely obliterate the normal ovary. However, usually there is a well-demarcated separation between the cyst wall and the normal adjacent ovarian tissue.

Q. I was told that the changes in the peritoneal fluid due to endometriosis is one of the causes of my infertility. What does this mean?
A. Peritoneal fluid is the fluid which every person has in their abdominal cavity and which functions as a lubricant for the abdominal and pelvic organs. It has become apparent in the past decade or so that the presence of endometriosis is associated with changes in this peritoneal fluid, its volume, its cellular population and its biochemistry. Generally, it has been shown that the volume of the fluid is increased in women with endometriosis. The leukocytes have also been shown to be increased in number in the fluid of patients with endometriosis.
Also, the prostaglandin hormone concentration has been reported to be elevated in peritoneal fluid as well as the level of proteolytic enzymes which are all consistent with the localized inflammatory reaction around the endometriotic implants. Since these hormones could each alter the environment of the peritoneal fluid, which is in very close proximity to the ovaries and tubes, it can potentially alter their function. In recent studies, it has been shown that the peritoneal fluid in patients with endometriosis can act as a toxin to an embryo and may even stop the growth of the embryo in its early stages.

Q. What are the most common sites of endometriosis in the pelvic area?
A. If we accept the theory of retrograde menstruation as the main cause for the initiation of endometriosis, the ovaries are the most frequently involved organ (in 75 percent of cases) because of the unique characteristics of their site. The next most common areas are the posterior cul-de-sac (70 percent of cases), the area between the uterus and the bowel, and the anterior fold of the uterus between the uterus and the bladder (35 percent of cases). Presumably, this is due to the effects of gravity. The next most common area is the posterior aspect of the pelvic wall and the uterosacral ligaments (35 percent) which are attached behind the uterus. The ureters are the most commonly affected pelvic organs also due to their site, which is again sitting close to the ovarian bed or opening of the tube to the pelvis. The next most common sites are the uterus (10 percent), the tubes, the sigmoid colon and the appendix. Due to high motility and active peristalsis, the small bowel is the least frequent organ involved in endometriosis (less than one percent).

Q. What are the other common areas outside of the pelvis where we find endometriosis?
A. Endometriosis has been found in the appendix (2 - 5 percent of cases), large bowel (3 to 4 percent of cases) and the small bowel (less than one percent of cases). Much less frequently, we find endometriosis in the gall bladder, stomach, spleen and liver.

Q. I was told that I have endometriosis on my incision where I had a Cesarean section. How is this possible?
A. At the time of a C-section, pieces of the uterine lining could be transplanted in the incision and start growing. In a recent study of 56 cases of endometriosis in surgical sites, almost half of the cases followed a C-section. These lesions cause local cyclical pain and, on occasion, even cyclical bleeding. Treatment is obviously surgical removal of the involved area.

Q. What are pelvic adhesions? Why do people with endometriosis have adhesions?
A. Scarring of the peritoneum around endometriosis is a typical and very common finding. The explanation for this is that the bleeding that occurs around each menstrual cycle gets collected, and since there is no escape for this blood, it will start irritating the adjacent peritoneal surface, then start producing irritation and inflammation and eventually, scarring. These adhesions are most common in the immobile pelvic structures, and are most commonly found in the pelvic sidewalls, behind the uterus, between the sigmoid bowel or colon, and on the posterior aspect of the uterus and cervix.

Q. If the retrograde flow of menstrual bleeding through the fallopian tube is a major mechanism for endometriosis, why don't all women have endometriosis?
A. Although some degree of menstrual backflow occurs almost universally, only those women who are predisposed to having endometriosis will allow the cells to implant in the pelvic areA. Patients who have some deficiency in their immunological system, women who have more frequent periods (shorter than 27 days), or women who have longer days of bleeding with their period (more than 7 days) are more prone to develop endometriosis.

Q. Is there any evidence that viable cells are in the menstrual flow?
A. Yes. The presence of viable endometrial cells in the menstrual flow has been demonstrated by culturing the menstrual flow and obtaining tissue cultures. Other evidence has been the presence of viable endometrial cells in the fallopian tube. Endometrial cells which have been obtained from the menstrual flow have been demonstrated to be plantable to other areas of the abdomen (i.e., the abdominal wall).
Other evidence supporting this theory is that endometriosis is extremely common at the site of the menstrual blood flow through the tube into the peritoneal cavity; for example, the pelvic sidewall next to or adjacent to the tube and the ovarian surface. Another interesting point is that the mobile pelvic structures, such as the bowel or fallopian tubes themselves, are less likely to allow attachment of transplanted endometrial cells, whereas fixed structures are anticipated and also have been shown to have a higher frequency of having these implants on them.
After reviewing all of these reasons, it becomes obvious that the preponderance of evidence suggests that endometriosis is a consequence of implantation of viable endometrial cells through the fallopian tubes at the time of menses.

Q. Are there any other theories as to how endometriosis is developed besides this backflow theory?
A. Other theories for how endometriosis comes about include the following:
1. Spread of endometrial cells to other areas of the pelvis or other organs through the lymphatic channels.
2. Spread of endometrial cells through the blood vessels. The presence of many cases of endometriosis which have been reported in the lung, skin, thigh and extremities can be explained by this mode of transport.
3. Spread of endometrial cells through surgery. For example, at the time of cesarean section, some of the endometrial tissue can be spread or trapped in the abdominal wall and produce endometriosis in the future.

Q. Are there any women who are more prone to have endometriosis?
A. Yes. Women in the reproductive age group are more prone to have endometriosis.
Endometriosis is also common in women who have had uninterrupted cyclic menstruation for periods of more than five years. By this, I mean a woman who has had a period every month for five years which has not been interrupted by pregnancy. Endometriosis is less commonly seen in women with irregular cycles who are not ovulatory (not producing an egg), and in women who have stopped their regular cyclic period by any means such as pregnancy and lack of ovulation. Giving medication to produce pseudo-pregnancy or pseudo-menopause can stop the growth of endometriosis and give clinical improvement to the patient. Frequent pregnancies, especially those initiated early in the menstrual life (during the teen years), seem to insulate women against endometriosis, at least temporarily. Also, we have seen that endometriosis occurs more frequently in some families than in others.

Q. How old is the disease?
A. Theoretically, endometriosis should have existed since the beginning of time. However, the first description was about 300 years ago and the first detailed description was in 1860 by a physician named Von Rokitansky.
Our modern-day understanding of endometriosis began with the pioneering efforts of a private physician named Sampson in Albany, New York, in the 1920s. Dr. Sampson proposed that the menstrual backflow through the tubes contained viable endometrial cells which could be transplanted to ectopic sites.

Q. Is endometriosis confined to women?
A. While this has been reported almost exclusively in women, there have been several case reports of histological endometriosis in men. These have occurred all in men with cancer of the prostate who were undergoing high-dose estrogen therapy. In these men, endometriosis was found in the prostate.

Q. I have been hearing a lot about ovarian involvement in endometriosis. What about the tubes?
A. The fallopian tubes, particularly in the early stages of endometriosis, are rarely involved anatomically in the process of endometriosis. However, with the progression of the disease, the distal portion of the tube can become adhered to the ovaries and result in diminished mobility and also, presumably, inadequate ovum pickup, and again, decreased fertility in the patient with endometriosis. There is a common understanding among experts in the field of endometriosis that if you see pelvic adhesions, especially around the ovaries and in a patient with no history of pelvic infection whose tubes are open, then this patient has endometriosis. That again goes along with the theory that the tubes are one of the last organs to become anatomically affected by endometriosis. The reason for this could be the mobility of the tube.

Q. Why does the presence of endometriosis cause pelvic pain?
A. In the early stages of endometriosis, small areas of surface endometriosis tend to rupture, which could produce pelvic irritation and pelvic pain. Another reason for the pain can be the presence of adhesions in the pelvic area which make the pelvic organs rather fixed. Any motion of these organs (e.g., during intercourse), could produce pelvic pain. One other theory for pelvic pain during the menstrual cycle in patients with endometriosis has been the chemical changes that occur in the peritoneal fluid. The sudden onset of severe generalized abdominal pain is highly suggestive of leakage or rupture from an endometrioma into the abdominal cavity.

Q. What are the symptoms and characteristics of endometriosis?
A. The most common symptoms include the following:
1. Progressive pelvic pain associated with or occurring just prior to menstruation (75 percent of patients). The localization of the pelvic pain is often related to the site involved in the endometriotic lesion. Usually, the pain is most marked just prior to the start of the menstrual flow and extends into the first few days of the menstrual cycle. Some patients may have pain prior or during ovulation due to the involvement of the ovaries. In some of these women, the pain may persist to the end of their menstrual cycle. Pain during menses (dysmenorrhea), one of the cardinal symptoms of endometriosis, often becomes more severe as the disease progresses.
2. Painful intercourse (32 percent of patients). Painful intercourse (dysparunia) is very common when endometriosis involves the tissues behind the uterus and pelvic walls and the pelvic floor surfaces and the ligaments in this area (the so-called uterosacral ligaments). The pain could be more pronounced and excruciating with deep penetration.
3. Painful bowel movements. Endometrial implants on the colon or the bladder in more advanced stages may cause pain with bowel movements or urination.
4. Premenstrual straining and abnormal uterine bleeding. Disorders of the menstrual cycle, such as premenstrual spotting, abnormal uterine bleeding, lack of ovulation or irregular or inadequate ovulation are common in endometriosis although such disorders are not at all specific to this disease. In some even extensive and advanced stages of endometriosis, the ovarian function has been found to be quite normal.
5. Pain in the suprapubic and bladder area.
6. Painful urination and occasional blood in the urine.
7. Infertility. As far as infertility and endometriosis, it has been shown that the prevalence of endometriosis is three times higher in infertile women when compared to the general population.

Q. Can I have endometriosis without having any symptoms?
A. This does occur in some patients. The symptoms of endometriosis are highly variable. For instance, a patient with very extensive endometriosis may be incapacitated with pain or have very few symptoms. The same variability can be seen in mild endometriosis. Therefore, if the classic symptoms and signs and the physical findings of endometriosis are present in a patient, the diagnosis obviously could be straightforward. However, the absence of symptoms or physical findings does not mean that endometriosis is not present. Infertility is, at times, the only symptom, which is why we like to work up cases of unexplained infertility with diagnostic laparoscopy which will reveal any endometriosis.

Q. What are the characteristics of the pain associated with endometriosis?
A. Pelvic pain and painful periods in particular are the cardinal symptoms of endometriosis. In the most classic type of endometriosis, the pain usually starts shortly after menarche, which is the first few months right after the start of the period as a teenager. Most patients will attest that they always had pain with their period which eventually got worse as the years went by and increased in intensity and severity. The pain is usually on the sides and often is described by patients to be "a pain deep inside me."
The pain is produced by bleeding and a so-called "miniature period" at the site of endometriosis, which causes swelling of the peritoneum around it, which, in turn, causes pain. Another possible mechanism for the pain could be the chemical changes in the peritoneal fluid (i.e., changes in the prostaglandins which have been postulated to sensitize nerve endings to pain stimuli). However, why some women have painful periods with even a very mild degree of endometriosis cannot be fully understood, especially in view of the fact that other patients with much more extensive disease have much less pain and, in some cases, no pain at all. One other explanation for patients with pain in endometriosis is the involvement of other organs, such as the rectum or colon. Bleeding of the endometriosis around or in the muscle wall of the colon and rectum again causes expansion of this area and associated pain. This causes pressure and some sense of urgency for bowel movements during the menstrual period in some patients, especially if the disease is more extensive and is getting into the lumen of the bowel. It can also cause bloody stools during or prior to menstruation.

Q. Is painful intercourse a symptom of endometriosis?
A. Painful intercourse (dysparunia) is one of the most common symptoms of endometriosis, especially in the more advanced or severe stages. The pain is described by patients as occurring during deep penetration and also as being deep in the pelvis. Although in its early stages this pain is at the lateral side of the pelvis, soon after it could be anywhere or all over the pelvic area, and can make intercourse unpleasant and miserable for the patient. This may also play a role in subsequent infertility.

Q. Is it true that some patients with endometriosis have bloody stools, bloody urine, painful urination and painful bowel movements?
A. If the endometriosis has invaded to the rectum or bladder's innermost lining, the mucosa, the patient may have bloody stools or urine during the menstrual cycle when the bleeding occurs in these areas. We must emphasize that these are not very common symptoms of endometriosis. Involvement of these areas is usually seen in extensive or advanced stages of endometriosis, and not many patients progress to these stages today. This is mainly due to our knowledge of endometriosis in recent years and the more liberal use of diagnostic tools, mainly laparoscopy, in the early detection of endometriosis.

Q. I was told that I have uterine fibroids and endometriosis. Does this happen frequently?
A. Endometriosis can often co-exist with other gynecological problems. These problems could also be a contributing factor in some of the patient's symptomatology (i.e., prolonged and abnormal periods, pelvic pain, pelvic pressure and even infertility). Almost 15 percent of patients with endometriosis have other pelvic pathology, such as uterine fibroids, unrelated to endometriosis.

Q. How often does endometriosis lead to cancer?
A. The risk of endometriosis developing into a cancerous lesion is very low. Various studies have shown that one to two and half percent of the patients with endometriosis may develop cancerous lesions at the site of endometriosis. However, if we look at the normal endometrium and ovaries, the same risk exists.

Q. I have pain all the time and since the pain of endometriosis is usually just prior and during the menstrual cycle, is it possible that I have endometriosis?
A. Usually, the pain associated with endometriosis is right before or during the menstrual period in the initial stages; however, as the disease progresses, it may occur throughout the cycle. The pain may be acute or chronic. In about half of the patients with severe or extensive endometriosis, the pain is chronic all through the cycle which gets worse right before and during menstruation, and during or shortly after intercourse.
In the past, some clinicians have used pain medications which have been known to be anti-prostaglandin as a test by giving it to the patient and assuming that if they have relief, they have endometriosis. However, this does not appear to be the most valid way of diagnosing endometriosis. In my assessment, the patient with pelvic pain, painful periods, painful intercourse and infertility has endometriosis unless it is proven otherwise. Again, in my assessment, the best available way at the present time to diagnose endometriosis is a laparoscopy and direct visualization of the lesion.

Q. I have had two spontaneous miscarriages and later on, when I was diagnosed as having endometriosis, I was told that these events could be related. Is this true?
A. The relationship between spontaneous miscarriages and endometriosis has been a matter of controversy for quite a while. However, many investigators have shown that the rate of miscarriage is higher in patients with endometriosis and shows a marked decline after treatment. It is believed that the biochemistry of the hormones in these patients can explain this phenomenon; for example, decreased serum progesterone in some of the patients and an increased serum prolactin in others. Also, the basic autoimmune problem in these patients can also be a cause.

Q. On pelvic examination, I had a retroplaced uterus and my doctor said I had endometriosis. How common is this?
A. A uterus tilted backward is not a specific sign of endometriosis; however, when a patient has endometriosis behind the uterus during the years of menstruation, endometrial implants eventually will form and attach adhesions to the uterus and the pelvic wall, which can displace the uterus. A retroverted uterus has been found in 47 percent of patients with documented endometriosis, but in only 17 percent of women without endometriosis. Whether this is a cause or an effect is unknown. However, the experts in the field agree that the presence of a retroplaced, fixed uterus and pelvic pain along with other symptoms of endometriosis definitely deserves further investigation.

Q. I had a hysterectomy and removal of my tubes and ovaries. However, two years later, I had a very painful area in my pelvis and was told that I had endometriosis. Is this possible?
A. Yes. Sometimes when a total abdominal hysterectomy with removal of both tubes and ovaries is performed, the surgeon cannot remove all of the implants in the pelvic areA. When both ovaries are removed, the patient needs replacement of an exogenous hormone, namely estrogen or estrogen and progesterone. These exogenous hormones can stimulate the remaining endometrial implants and cause persistent cyclic bleeding and eventually produce painful nodules of endometriosis in the pelvic areA. This is found most commonly in the top of the vaginal area where the uterus has been removed. This can also happen in patients who have a hysterectomy without removal of the ovaries.
To prevent this from happening in patients with any possibility of presence of residual endometriosis following total abdominal hysterectomy and removal of the ovaries, estrogen replacement therapy should not be started immediately. Instead, in these cases, a 12-month treatment with progestins (i.e., 200 mg. medroxy progesterone acetate injections every three months) should be instituted before estrogen therapy starts.

Q. What is the significance of CA-125?
A. There has been extensive investigation of a membrane antigen called CA-125 in women with endometriosis. Several reports have suggested that levels of CA-125 are elevated in women with endometriosis, particularly those in the advanced stages of the disease. A recent study of this antigen level showed it to be high in 90 percent of women with pelvic pain who had endometriosis while it was only elevated in 10 percent of another group of women with pelvic pain without endometriosis. It has been suggested on the basis of these studies that this test could discriminate as a possible diagnostic blood test procedure for the diagnosis of endometriosis in patients with pelvic pain.

Q. Are there any diseases that can be misdiagnosed as endometriosis or vice versa?
A. Endometriosis presents many of the same symptoms as other gynecological diseases. The pain and infertility associated with endometriosis can be seen in other conditions. The most common pelvic disease that could be misdiagnosed as endometriosis is pelvic inflammatory disease, which causes pain, pain with intercourse, and infertility. The other condition is benign or malignant ovarian tumors and other pelvic tumors. Even pathological conditions of the bowel, rectum, bladder, ureter or other urinary organs could simulate endometriosis and be misdiagnosed as endometriosis. This is why we strongly believe that for confirmation and accurate diagnosis of endometriosis, one should do a laparoscopy and biopsy, if needed. Most definitely, no patient should be treated for endometriosis without the diagnosis being confirmed by laparoscopy.
Pelvic congestion syndrome with large pelvic verocosities which may get worse premenstrually could also be misdiagnosed as endometriosis. Diagnostic laparoscopy could be very helpful in confirming the diagnosis. Many cases of endometriosis involving the bladder wall are misdiagnosed as chronic urinary tract infection with essentially negative urine cultures. In these cases, cystoscopy (looking into the bladder) and laparoscopy could be very helpful.

Q. After I had a hysterectomy, I was told that I had adenomyosis. Is that different from endometriosis?
A. Yes. Endometriosis is a condition which is characterized by the presence of endometrium, or tissue which is histologically identical to endometrium, outside the uterine cavity, the pelvic walls or other areas of the pelvis. Adenomyosis is the presence or invasion of the endometrium into the uterine wall, not outside of the uterus. That is why it has also been called internal endometriosis, although it usually has a much different clinical presentation than that of endometriosis.
However, some of the symptoms could be quite similar. Pelvic pain, heavy and abnormal uterine bleeding and staining and spotting between two periods are the most common symptoms of adenomyosis, and these are also very common in patients with endometriosis. Another feature which makes adenomyosis different than endometriosis is that it occurs in an older age group of patients than endometriosis. Again, endometriosis starts right after menarche, it can be seen in teenage patients, and it is very common in the mid-20s and mid-30s. However, the average age of patients with adenomyosis is 40. Most of these people do not have a problem of infertility, and indeed one of the characteristics of the patients with adenomyosis is that they have already had the number of children that they desired. In this condition, the ovaries are rarely involved in the process and since the invasion of the endometrium is just to the wall of the uterus, the uterus in these patients is usually enlarged symmetrically.
The diagnosis can really only be made after removal of the uterus by looking at the uterine wall under the microscope. The only treatment at the present time for adenomyosis is hysterectomy. Most of the time, this is not a source of major concern to the patient since most of these patients have already had their children and are at the end of the spectrum of the childbearing age.

Q. Before I had my laparoscopy, I was told I might have endometriosis or a chronic case of pelvic inflammatory disease. How are these different?
A. Chronic pelvic inflammatory disease (PID) has most of the symptoms and physical findings of pelvic endometriosis. Most of the patients with PID have bilateral pelvic adhesions, adhesions around the tubes and ovaries, and they might have a mass in the pelvic areA. since it happens also in younger age groups, these two conditions could be misdiagnosed or could simulate each other very much. These two conditions may also have some similarity in their ultrasound examinations (i.e., a cyst in the ovary as a result of endometriosis could resemble a chronic ovarian abscess). However, if one goes back to the history of these patients with PID, it will usually be found that there is a history of acute pelvic infection, and a history of fever and pain which subsided with antibiotic therapy. Again, for confirming the diagnosis of either of these and differentiating them from each other, diagnostic laparoscopy is necessary and recommended.

Q. What is hydrosalpinx?
A. This is a collection of fluid in the tube which has been blocked at the fimbriated end of the tube. Hydro means fluid and salpinx means tube. A hydrosalpinx occurs in this manner: the tube produces tubal fluid all of the time and the fluid escapes from the tube via the tubal opening. If there is a blockage in the distal portion of the tube, the so-called fimbriated end, the tubal fluid cannot escape and will collect in this area, thus producing what is called a hydrosalpinx. Q. What is hematosalpinx?
A. Hematosalpinx appears in patients who have endometriosis in their tubal lumen. eHHemato means blood and salpinx means tube. During the time of menstruation and the bleeding of endometriosis, blood can get collected inside the tubal lumen, especially if the other side of the tube is also blocked. The collection of the blood in the tube then produces a condition which is called hematosalpinx. This condition has a very similar appearance to a tubal pregnancy; however, it is a chronic condition.

Q. I had blocked tubes near the uterus and I was told it was due to endometriosis. How often does this happen?
A. Endometriosis can be one of the causes of tubal blockage right at the junction of the tube and uterus. Since the junction of the tube and uterus is very fine an produces a condery narrow, the presence of a small amount of endometriosis in this site could indeed block the tube. In one study of patients with tubal blockage at the junction of the tube and the uterus, it was shown that over 60 percent of these patients had tubal blockage due to endometriosis.

Q. How can you differentiate between endometriosis, which causes bleeding in the rectum and bladder, and other diseases of these two organs?
A. One manner of differentiation is by history. Usually, endometriosis in these two organs will cause bleeding during or right after the menstrual period. These patients will have cyclic bleeding with their bowel movements or with urination as opposed to bleeding caused by other diseases of the rectum or bladder. However, to confirm and verify the diagnosis, one should have a sigmoidoscopy or flexible colonscopy (the better choice), or cystoscopy and also a biopsy, if needed.

Q. What is the best way to diagnose endometriosis?
A. Direct visualization of the endometrial lesion is currently the best method for definitive diagnosis. This is done by laparoscopy. As we have mentioned again and again, the patient's history will suggest that she might have endometriosis. Pelvic examination will corroborate this diagnosis. However, it is the direct visualization that confirms or verifies the presence of endometriosis. The diagnosis was once done mainly through, or at the time of, laparotomy or major surgery. Today, laparoscopy has replaced other modalities of verifying the diagnosis of endometriosis.

Q. What is laparoscopy?
A. Laparoscopy is a procedure in which the physician can look directly inside the abdomen and pelvic area and observe the anatomy of the abdominal and pelvic cavity and detect any pathological findings. In performing a laparoscopy, after induction of anesthesia, a very small incision is made, usually about 1/4 inch, right underneath or inside the folds of the navel. A telescope-like instrument is then inserted which is usually as thin as, and slightly longer than, a pencil. This instrument is attached to a light source which illuminates the pelvic and abdominal cavity. The physician can then look directly inside the cavity and observe the uterus, tubes, ovaries and other pelvic structures. He can then observe any pathological findings, such as pelvic adhesions, ovarian cysts, pelvic endometriosis or any other abnormal conditions.
The diagnosis of endometriosis is not the only use for laparoscopy. It has also been used in the diagnosis of infertile women, especially if the infertility has been longer than two years, or if the infertility screening studies have been normal, or in any patient with so-called unexplained infertility. Another use or indication for laparoscopy has been in other types of pelvic inflammatory disease or patients with pelvic adhesions. Laparoscopy has also been used extensively in the past decade as a tool for the treatment of many pelvic conditions.

Q. Can somebody undergo laparoscopy and still have the diagnosis of endometriosis missed?
A. If the laparoscopy is done in a classic and orderly manner, the diagnosis will almost always be made at the time of laparoscopy. By this, I mean a systematic evaluation of the pelvic organs should occur. For example, the physician should look underneath the uterus, the anterior and posterior side of the uterus, the bladder fold, the pelvic sidewall, the ovaries and the tubes. He should then proceed to look behind the ovaries and specifically in the space between the ovaries and the pelvic sidewall.
Not performing a thorough laparoscopy can be one of the reasons that endometriosis is missed at the time of laparoscopy. There is also a technique called second puncture laparoscopy, which mans making another small incision about 1/4 inch around the pubic area and sending a manipulator into the pelvic area and, with the use of this along with the upper laparoscope, to observe the pelvic organs. This is used to manipulate, grasp and move the pelvic organs, especially the ovaries, and to look behind the surface of the ovaries and make sure that no endometriosis in that site is missed as this is one of the most common sites of endometriosis. Findings at the time of laparoscopy should be clearly written, noted and dictated in the patient's operative note (including negative findings).

Q. Do you recommend laparoscopy in patients with suspected endometriosis even if they are not interested in their future fertility?
A. Yes, particularly if the patient is suffering from pelvic pain and we are planning to start treatment for endometriosis. If the patient's history and pelvic examination are suggestive and indicative that the patient might have endometriosis, then the definitive diagnosis can only be made with diagnostic laparoscopy or direct visualization of the pelvic organs at the time of laparotomy, or open abdomen surgery. We strongly believe that no one should be started on treatment for endometriosis without a verification and a diagnosis by laparoscopy or laparotomy and, in some cases, even with a tissue biopsy and a pathological diagnosis.

Q. What is a "second look" laparoscopy?
A. A group of experts in the field of endometriosis have suggested doing another laparoscopy at the end of the treatment period to evaluate the effectiveness of treatment. Because this is the second laparoscopy, it is called a "second look" laparoscopy. In fact, this procedure is becoming much more popular today as compared to 10 or 15 years ago, even for patients who have had major surgery for infertility. For example, more and more infertility experts are going in two to four weeks following a tuboplasty to do another laparoscopy for lysis of adhesions after the major surgery.

Q. I was told that I have pelvic defects. Can you explain this?
A. The pelvic wall is covered by a thin layer called the peritoneal layer. Occasionally there are some defects in this lining which resemble small tears or holes. In several recently published studies, it has been shown at about 1/2 to 2/3 (and in one study, up to 80 percent) of those patients with pelvic defects have endometriosis. For this reason, evaluation and close inspection of the periphery, walls and floors of these defects is highly recommended.

Q. How helpful is a pelvic sonogram (ultrasound) in diagnosis of endometriosis?
A. In cases where endometriosis has produced ovarian endometrioma (chocolate cysts), this test could be helpful to confirm the presence of the cystic mass in the ovaries. Most endometriomas have a specific image of "ground glass" on sonograms as a consequence of collecting old blood and cellular debris. However, this sign is not only seen in endometriosis; the only definite diagnosis of endometriosis is made through laparoscopy. In the past few years, we have been using vaginal ultrasound that yield better images and does not require a full bladder (a very uncomfortable waiting period).

Q. I had a hysterosalpingogram. Could this have shown my endometriosis?
A. This test is designed for exploration of the cavity inside the uterus and to evaluate the patency of the fallopian tubes; in some patients with endometriosis, there is a specific pattern in the tubes, for example, a looser muscle in the wall of the tube, or elevation of the proximal part of the tube (the part near the uterus). However, since endometriosis is a disease basically outside the uterus, this test cannot function properly for the diagnosis of endometriosis.

Q. Is there an optimum time during the menstrual cycle for performing the diagnostic laparoscopy?
A. Choosing a day during the menstrual cycle to perform a laparoscopy depends on several factors. First, what is the purpose of the laparoscopy? Is it for the diagnosis of endometriosis, for evaluation of infertility, or are we looking for other pathological problems? For patients in whom we do a laparoscopy for evaluation of infertility and tubal patency, the best time is right after finishing a period and right before ovulation. This is so we can be sure that the patient is not pregnant and also so that the lining inside the uterus does not cause any problem for evaluating tubal pregnancy. However, if the purpose of laparoscopy is to evaluate ovulation, the best time is seven days or so after the presumed ovulation. Laparoscopy for diagnosis of endometriosis in patients suffering from pelvic pain can be done at any time during the cycle.

Q. What are the pitfalls in the diagnosis and management of endometriosis?
A. If one bases the diagnosis of endometriosis just on history or pelvic examination, misdiagnosis of other conditions as endometriosis or endometriosis as some other condition can occur. The other significant pitfall is to have preconceived notions about the typical or so-called prototype of patients with endometriosis. For example, although it has been proposed that there is a "prototype" of a patient who has endometriosis (Caucasian, slim, possibly over-anxious, one who has postponed her fertility), endometriosis can indeed be found in any woman and should be highly suspected in patients with pelvic pain, specifically pain with their periods, and infertility. Indeed, there is a saying in which I strongly believe: "this is a disease of equal opportunity."
Endometriosis can also be missed in patients with infertility who have a normal infertility workup. In infertile patients, if every other test in the workup, including a hysterosalpingogram, is normal, the patient still could have endometriosis and indeed, the suspicion should be higher. Another pitfall in the diagnosis of endometriosis is a shallow or superficial look at the time of the laparoscopy into just a few areas of the pelvis and concluding that the patient does not have endometriosis. Laparoscopy should be thorough and systematic and all of the possible areas that could be affected by endometriosis must be examined. Another problem can be the physician's expectation of a typical type of "powder burn" pattern of endometriosis. Endometriosis can present itself in many different ways. It may be seen as just pelvic adhesions or with very minimal visual evidence of endometriosis. It can be seen as a peritoneal defect. It can be seen as other atypical endometriotic lesions, such as petechial areas, ecchymotic areas, or areas with yellowish or brownish discoloration, or even with no color (the so-called "nonpigmented" endometriosis).

Q. I was diagnosed as having Stage III endometriosis at the time of laparoscopy. What does this mean?
A. The American Fertility Society has established a classification for the different stages of endometriosis. This classification is aimed at not only labeling the severity of the disease, but also to be helpful in providing a prognosis for future treatment and the future fertility of the patient. In the past 25 years, efforts have been made to classify endometriosis based on the extent of the spread of the lesions, the involvement of pelvic structures in the disease, and the extent of pelvic adhesions and blockage of the tubes. The latest revised classification, reported in 1985 by the American Fertility Society, uses the point system for stages of endometriosis and divides endometriosis into four stages: Stage I is minimal; Stage II is mild; Stage III is moderate; Stage IV is severe.

Q. What percentage of patients with endometriosis are infertile?
A. This question is difficult to answer since we do not really have exact data on the subject. However, different studies have shown that between 30 and 50 percent of patients who suffer from endometriosis have some degree of reproductive failure. This figure is almost three times higher than the number of women in the general population who have difficulty getting pregnant. In terms of what percent of infertile patients have been found to have endometriosis, again, different studies have shown different figures, but the general consensus is around 15 to 20 percent of infertile patients are suffering to some degree from endometriosis.

Q. In infertile patients with endometriosis, what is causing the infertility? A. At the present time, there is not one single factor that can explain the cause of infertility in all patients with endometriosis. Obviously, the cause of infertility in women with severe endometriosis is much easier to understand. In these patients, the extent of the pelvic adhesions, the distortion of the tubes and ovaries, and occasionally because of the destruction of the ovarian tissue, the infertility can be easily explained due to the anatomical distortions that affect the pickup of the egg by the tube and the effect of severe endometriosis of the ovary and ovulation.
However, the cause or relationship of endometriosis in the minimal stage on infertility is not as clear, and what makes matters more fascinating is that we see many women with endometriosis who have normal fertility. However, the fact that 60 to 70 percent of these patients with minimal to mild endometriosis who also have infertility will conceive after treatment, and the fact that the majority of them will conceive within the first year after treatment, is convincing evidence that the presence of endometriosis can interfere with fertility.
In a study which was done in a group of patients who received donor semen insemination as a treatment for infertility, it was found that the presence of mild endometriosis decreased their chance of pregnancy. So there is evidence that even minimal endometriosis can interfere with fertility.
The mechanism by which endometriosis could interfere with reproduction has been suggested to be:
1. interference with normal ovulation by interfering with development of follicular growth and function;
2. interference with sperm mobility;
3. interference with the release of eggs, thereby causing inadequate or even no ovulation;
4. changes in the peritoneal fluid, thereby producing a hostile environment for sperm and ovum.

Q. Can you explain why patients with endometriosis have adhesions?
A. Although the exact cause is still a mystery, it is the general consensus that adhesions result from irritation in the pelvic areas, and possibly from a secondary inflammation due to a miniature menstruation within the implants in the pelvic area.

Q. I read that endometriosis can cause infertility through a substance called prostaglandin. What is this and is it true?
A. Prostaglandin is a chemical substance which has multiple functions. It was first discovered in the seminal fluid, but later on, it was found in many other fluids in the pelvic and abdominal cavity. Some studies have indicated that the level of prostaglandin in this fluid is increased in patients with endometriosis. This increment has been postulated to be the cause of some ovarian dysfunction in patients with endometriosis, and some of the problems that these patients have with tubal function could also be attributed to prostaglandin. Prostaglandins have also been accused of interfering with sperm-ovum interaction, embryo growth, interfering with sperm motility, and interfering with the function of some central nervous system areas that are responsible for control of reproduction. One recent finding shows increased production of prostaglandin in minimal and fresh endometrial lesions. This can explain why some patients with minimal endometriosis can have significant symptoms (i.e., pain and infertility) despite their minimal stage of endometriosis.

Q. After I was diagnosed as having endometriosis, I was told that I have inadequate ovulation. How common is this?
A. Abnormalities of ovarian function are a common finding in patients with endometriosis. Several theories have been proposed to explain inadequate ovulation and in some patients even lack of ovulation. The fascinating point is that endometriosis is a disease of women with ovulation (by this I mean the patient has to have ovulatory cycles in order to develop endometriosis). However, after the development of endometriosis, the presence of endometrial tissue in the pelvic and peritoneal cavities will cause some degree of abnormality or inadequacy of ovulation. Some studies say that up to 50 percent of patients with endometriosis have some degree of ovulatory dysfunction and this should certainly be taken into account in the treatment of patients with endometriosis and infertility.

Q. I was told that I have luteal phase defect. What is this and how common is it?
A. The luteal phase is the second half of the menstrual cycle. The menstrual cycle traditionally has been divided into two parts. The first two weeks have been called the proliferative phase. This is the time that the ovarian follicle is being developed. The lining inside the uterus is proliferating and getting ready for ovulation and possible implantation.
The second half of the menstrual cycle, or the last two weeks, is characterized by a dramatic increase in the hormone progesterone, which is produced by the part of the ovary which is called the corpus luteum. The presence of progesterone is very critical for proper implantation of the fertilized egg and adequate amounts of this hormone are necessary for implantation. In patients with endometriosis, several studies have indicated that there is a higher incidence of this luteal phase deficiency or luteal phase defect. Another problem which has recently been described in patients with endometriosis is the so-called luteinized unruptured follicle syndrome. In this case, the patient will ovulate but the egg does not come out of the ovary and it becomes entrapped in the ovary, which can obviously account for infertility in some of the patients with endometriosis.

Q. What are my options for relieving my pain?
A. Since the pain in women with endometriosis has been attributed to the presence of inflammatory process as a result of the high levels of prostonoids in the endometrial implants, the use of nonsteroidal anti-inflammatory drug (NSAID) that interferes with the production of these chemicals makes quiescence in the patient. Studies have shown that the use of medication such as naproxen sodium (Anaprox-Syntex) can cause substantial pain relief (in over 80 percent of cases) in patients with laparoscopic documented endometriosis. The same results have also been achieved with ibuprofen. I should mention that these medications seem to be more effective when initiated at the first signs of discomfort rather than waiting for severe pain to develop.
The use of codeine-based pain medications, so long as there is close supervision and limited course (a few days each month) has little addiction possibilities and, in many patients, could be extremely helpful in pain relief.

Q. Do you recommend hormonal treatment for controlling pain?
A. During the 1960s and 1970s, oral contraceptives were used with reported 80 percent efficacy. However, because of annoying side effects, this is no longer an acceptable option. During the 1980s, danazol was a popular and excellent choice for prolonged relief of pain; relief even continued in two-thirds of patients after finishing the treatment course. However, this medication was not free of unwanted side effects either; these included weight gain, swelling, decreased breast size, acne, increased hair growth and deepening of the voice.
In the past decade and with the approval of the FDA in the past five years, a hormone which is produced by the brain has been used for this purpose, GnRh-agonist.

Q. I was told that I had a slight decrease in my bone density while on GnRh-A. Can you explain this?
A. Studies have shown that there could be a three to six percent decrease in bone density after six months of therapy. However, the follow-up at one year shows that in 75 percent of patients, normal bone density was present. The physiological reason for this bone loss is very clear and is due to the decrease of estrogen, the same mechanism that works with women in their post-menopausal years. Clinical research studies have been done and are on the way to find a method of supplementation with low dose estrogen and/or progestin to allow stabilization of bone without reduction of the therapeutic effect. Calcium supplementation has also been recommended during medical therapy. It should be emphasized that routine bone density studies prior to or during the medical therapy are neither recommended nor cost effective.

Q. I took medication for six months, and despite this, my symptoms continued. How can this be explained?
A. With any form of medical therapy, up to one-third of the patients will not respond and obviously will not experience any improvement in their pain or other symptoms. This may be due to the loss or alteration of estrogen receptors and/or enzymatic systems which are necessary for the metabolizing the hormones, or simply inadequate levels of drug delivery to the endometriotic area due to extensive scarring or lack of blood supply.

Q. When do you recommend medical therapy in patients who want to get pregnant?
A. As has been stated many times over, no medical treatment for endometriosis should be initiated before a confirmed diagnosis by laparoscopy. My personal philosophy is that any lesion that can be treated at the time of laparoscopy (by any means, laser, cauthery, surgical removal) must be treated. In cases where I feel I removed all visible lesions, I encourage the patient to try for pregnancy for six to nine months; if pregnancy does not occur, medical therapy might be initiated. However, in cases where, at the time of surgery, we are not able to remove the major bulk of the lesions, medical therapy can be initiated immediately following the surgery. In cases where there is extensive endometriosis and large endometrioma (especially those confirmed by a previous laparoscopy), a pre-operative, three to six month medical therapy can be helpful and may increase the chance of more complete removal during conservative surgery.

Q. I continued to have menstrual bleeding while on medical therapy. Does this mean that the medication was not working?
A. Although it is expected that medical therapy should somehow affect the normal menstrual cycle, not all patients will stop menstruating and many continue cyclic bleeding. In some reports, spotting during therapy has been reported in up to 60 percent of the patients. It is believed that the bleeding is not always a good indicator of sufficient levels of medication.

Q. How do you monitor the medical treatment efficacy?
A. The best way to monitor therapy is through measuring the serum estrogen, which in most patients will drop adequately within one to two weeks. In cases with large endometriosis, a pelvic sonogram every three months can show the decrease in size. Pelvic examination is another suggested testing method; however, serum CA-125 measurements have not been found to be helpful.

Q. How do you evaluate the results of therapy after treatment for endometriosis?
A. Most of us use the patient's symptom relief and improvement in pelvic examination for monitoring the effects of medical therapy. In our experience, the decrease in pelvic pain with menstruation and intercourse as well as the softening of the nodules on the uterosacral ligament and decrease in thickness, hardness induration in the space behind the uterus, in the cul-de-sac correlates with the laparoscopic findings of improvement of endometriosis.
However, the most direct and reliable way to evaluate the effect of treatment is by comparing the laparoscopic findings before treatment with laparoscopic findings after treatment. Obviously, if the aim of treatment is pregnancy, the achievement of pregnancy is undoubtedly a very remarkable way to evaluate the effectiveness of the treatment.

Q. How long do you use danazol?
A. Although the initial clinical investigations were based on six months of danazol therapy, the duration of the treatment should be individualized to the specific needs of the patient. For example, the course of treatment could vary from three months, in the case of conservative therapy, to many years. Certainly it has been used in many studies up to two or three years in patients who are suffering from severe pelvic pain or in patients who do not want any kind of surgical therapy. For achieving pregnancy, usually six to nine months of a high dose (800 mg daily) of danazol has proven sufficient to give adequate results.

Q. Can you get pregnant while taking danazol? If so, does it have any ill effects on the fetus?
A. In high doses (800 mg daily), danazol is a very strong and effective contraceptive. The incidence of ovulation has been estimated to be less than one percent with this dose. However, in lower doses (less than 400 mg daily), the incidence of ovulation is quite substantial; this is why we recommend a barrier contraceptive (such as a diaphragm or condom) to be used by patients taking this dosage. Another factor that increases the risk of pregnancy in patients who are taking danazol is the patient's own neglect in taking medication regularly. It has been reported that patients who take the medication intermittently have a high incidence of pregnancy.
In answer to the second part of the question, the answer is yes. Danazol has some weak androgenic (male hormone) effect, which can produce female pseudohermaphroditism in the female fetus of these mothers taking danazol. Again, this is why we recommend that patients who are using danazol (especially in dosage of less than 400 mg daily) use a barrier contraceptive, and we recommend that they do sporadic pregnancy tests to ensure that they are not pregnant.

Q. How effective is danazol?
A. The effectiveness of danazol depends on the patient's symptomatology and also on the stage of the endometriosis. For relieving pain, the overall literature reports somewhere between 70 and 90 percent of patients with endometriosis will have some relief of pain after danazol therapy. The post-danazol pregnancy rate again depends on the stage of endometriosis. However, the overall pregnancy rate in a group of patients with all stages of endometriosis has been around 40 percent, which is not much higher than in patients without danazol therapy. That is why we believe the laparoscopic laser treatment for mild to moderate forms of endometriosis at the time of initial laparoscopic evaluation is currently the most effective single type of treatment.
Another area in which danazol has been helpful is in the treatment of endometriosis outside of the pelvis; for example, in the lung, bowel and other areas where surgery cannot always be done safely. However, it should be noted that although the symptoms will regress during the course of treatment, regrettably, the symptoms will recur after discontinuation of treatment. This recurrence is one of the major problems we have had in treating endometriosis with danazol, even with pelvic endometriosis. That is why, after danazol treatment in patients with large ovarian endometrioma, if the cyst still persists and the patient is interested in her future fertility, ovarian cystectomy or removal and excision of endometriosis via CO2 laser, laparoscopy or laparotomy is indicated.
At any rate, it has been shown that even after a complete and aggressive course of treatment for endometriosis, at least 25 percent of patients will have a rapid recurrence after discontinuation of the medication.

Q. I have noticed some deepening and changing of my voice while I was taking Danocrine. Is this a common side effect?
A. Yes, indeed. It has been reported that up to 80 percent of patients taking Danocrine will show some side effects due to its androgenic nature. These changes include increased hair growth, the presence of acne, the presence of oily skin and, as you noticed, deepening of the voice. Unfortunately, some of these could persist even after the patient discontinues the medication.
Another side effect of Danocrine is the changes it can produce in the liver enzymes and the serum level of lipoproteins, the so-called LDL and HDL, which are low density lipoprotein cholesterol and high density lipoprotein cholesterol. Therefore, there is some concern about arteriosclerosis in patients who are taking Danocrine.

Q. Lately, I have been hearing more and more about GnRh agonist and I was told that this may be a promising treatment for endometriosis. Is this true?
A. The growth of endometriosis is dependent upon the level of estrogen in the blood (the major hormone produced by the ovarian follicle). The production of this hormone is stimulated by two hormones from the pituitary gland, namely FSH (follicle stimulating hormone) and LH (luteinizing hormone). FSH and LH are called gonadotropins. The production of these hormones is also controlled by another hormone that is produced in the brain: GnRH, which is the gonadotropin releasing hormone.
It has been shown that the presence of GnRH in blood stimulates the production of LH and FSH. Also, the administration of these hormones exogenously in one pulse (one dose) per hour is associated with the secretion of LH and FSH. However, the administration of GnRH in a rate of more than three pulses per hour, or in a continuous fashion, produces an initial increase in LH and FSH which is followed by a drastic decrease in LH and FSH. Therefore, on the basis of this finding, the continuous administration of GnRH agonists has been used for the treatment of endometriosis in the past several years.
Initial investigation has shown that they are effective in relieving symptoms of endometriosis within a month of administration. Studies which were conducted after diagnostic laparoscopic confirmation of endometriosis, and after treatment, showed that besides the regression of symptoms, the GnRH showed significant reduction in the size of endometrial implants after therapy.
Lupron (luproid acetate) and Synarel (nafarelin acetate) are the two agonists approved by the FDA for treatment of endometriosis. Lupron is administered in monthly injections (3.75 mg intramuscular) and causes profound pseudo-menopausal status in most, but not all, patients. Synarel is administered as an intranasal spray employing a metered nasal spray system (each spray contains 200 micrograms).
The side effects of GnRH are basically that of low estrogen, and the most common complaints have been hot flashes and other symptoms of menopause, including lack of sleep, mild and transient depression and, in some patients, breast tenderness and decreased sex drive.

Q. I have a friend who was treated in France with a medication named Gestrinone. Is this available in the United States, and how does this work on endometriosis?
A. Although the use of this medication is rather new for treatment of endometriosis, it has been known to us since the 1970s as a once-a-week contraceptive. Gestrinone works by increasing the male hormones (androgens) in the body. Increasing the androgens produces a hostile environment for the ovarian follicle to grow. Therefore, patients who have been taking Gestrinone have blocked follicular production and diminished production of estrogen, which is necessary for the growth and development of the endometrium in endometriosis. The second mechanism by which Gestrinone can affect endometriosis is a decrease in the secretion of the central hormones for stimulation of the ovaries, i.e., LH and FSH.
There are several advantages to this medication. First, it can be used two or three times per week rather than daily, and the side effects are rather less than Danocrine, although some patients have shown signs of acne, headaches, spotting and abnormal uterine bleeding, some mild weight gain and increased hair growth. However, this medication apparently does not alter the blood cholesterol or triglyceride levels. Several studies in Europe and other parts of the world have shown that this medication could result in about 90 percent relief in the symptoms of endometriosis about two months or so after the initiation of treatment. The pregnancy rate in these patients has been shown to be similar to that of Danocrine.

Q. My older sister was treated with testosterone for her endometriosis. Isn't this a potent male hormone and are they still using it for the treatment of endometriosis?
A. Yes, testosterone is actually a male hormone. It was first used about 30 years ago for treatment of endometriosis through a direct androgenic effect. Although testosterone supplies effective relief against the symptoms of endometriosis, its fertility rate has not been as good as other treatment modalities, e.g., danazol. However, we have been reluctant to use testosterone for treatment of endometriosis due to its potent androgenic action and its side effects, which are very potent. Another danger of using testosterone is that patients can get pregnant while being treated with it and could inadvertently continue to use it during pregnancy with some significant side effects to the fetus.

Q. What is the role of oral contraceptives in the treatment of endometriosis?
A. Oral contraceptives were one of the first medical treatments for endometriosis. Indeed, the first report for the use of these medications came out about 35 years ago and the scientific basis for that was the production of so-called pseudo-pregnancy due to these hormone combinations. Birth control pills are a combination of estrogen and progesterone, and they function by producing anovulation, or stopping ovulation in the patient. The biggest problem here is that since there is estrogen in these pills, it makes sense that the estrogen may have the reverse effect on endometriosis and actually stimulate activity in the endometriotic lesion. That is why contraceptive agents that have been recommended for the treatment of endometriosis are the ones with low estrogen and high progesterone. Studies which have compared the effects of oral contraceptives with danazol treatment for endometriosis have shown that it is half as effective as danazol in relieving the symptoms, and the major side effects are much like other oral contraceptives (consisting of breakthrough bleeding, nausea and vomiting).

Q. My mother was given a medication named progestin. What is this and how effective is it in the treatment of endometriosis?
A. Progestin is synthetic progesterone and in fact was one of the very early hormonal treatments for endometriosis. In general, it works on FSH and LH by inhibiting their production and secretion, and causing an acyclic low estrogen environment. Obviously, this would affect the growth of the endometrium and endometrial implants. In addition, since all of these agents contain some weak androgenic activity, they also have been shown to have some direct effect on the tissue.
One reason these medications did not really achieve popularity and are not being used at the present time as a first line agent for the treatment of endometriosis is that there are severe side effects, such as bloating, weight gain, depression and irregular bleeding. They also require large doses to be effective, and these large doses occasionally produce a rather prolonged effect on the ovarian production of estrogen. After treatment, some patients have a prolonged history of amenorrhea (not having periods).

Q. What do you think about the no treatment option?
A. In the past, and prior to the use of laser treatment, the expectant therapy or no therapy was an option in some patients with mild or minimal endometriosis. Since up to 60 percent of these patients were getting pregnant within two years of follow-up, this method was an accepted way of follow-up and treatment. However, we believe that since diagnosis of endometriosis is usually made at the time of laparoscopy, lasers should be used to treat any endometriosis that is found and, if pregnancy does not occur in nine to twelve months, other treatment modalities can be applied.

Q. Can endometriosis be decisively diagnosed by pelvic exam?
A. As with symptoms, the clinical signs of endometriosis during a pelvic exam may be nonexistent, minimal, or marked as a function of location and total mass of the disease. However, there are clinical signs that can increase the index of suspicion in patients with symptoms of endometriosis: thickness and feeling of nodularity in the posterior pelvic area; pain and tenderness during pelvic examination; fixation or relative decreased mobility in the tubes or the ovaries due to the presence of pelvic adhesions; presence of a uterus tilted backward and, in more advanced cases, due to the presence of endometrioma, feeling of pelvic mass. However, none of these clinical signs are a decisive sign of endometriosis, and final diagnosis can only be confirmed by laparoscopy.

Q. Who is a candidate for conservative surgical treatment?
A. In the past 20 years, and particularly in the past 10 years, conservative laparoscopic surgery has become the treatment of choice for most cases of endometriosis (more than 90 percent). It has repeatedly been reported that results of laparoscopic surgery are at least as good, if not better, than the results of laparotomy. This is in regard to economic considerations (decreased hospital time), cosmetic considerations (lack of a long scar), and the convenience of a quicker recovery. Because of this, patients have themselves made this method the preferred first line of treatment. We think that very few patients with endometriosis may not be manageable via laparoscope.
Key to the success of this therapy method:
1. Any and all visible lesions that can be removed safely must be removed, including nonpigmented and the so-called atypical endometriosis. 2. Any suspicious lesions, particularly on the ovaries, should be biopsied.
3. In cases where all the lesions cannot be removed, efforts should be made to remove as much disease as possible (so-called debulking) to give a better chance for post-operative medical therapy.
4. Although it has been reported that the success rate (relief of pain and/or pregnancy) following laser surgery is not any greater than other types of treatment (i.e., electrocautery, blunt dissection or sharp dissection), I personally prefer the use of laser therapy because we can safely destroy the endometriotic lesions next to or even on sensitive pelvic structures, such as the bladder, bowel and ureter, without damaging the normal tissue.

Q. How successful is laparoscopic surgery? A. The results obviously depend on the patient's initial complaints and also on the type of the procedure that is performed. The reports available in clinical studies in the past two decades indicate that removal of endometriosis and ablation, along with lysis of adhesion, can give relief of the pain to 70 to 90 percent of the patients, with a 10 to 20 percent rate of recurrence within three years of the treatment.
However, when the patient's main concern has been fertility, studies of more than 1000 patients have found a greater than 65 percent pregnancy rate in mild endometriosis, 50 percent in moderate, and 40 percent in severe cases of the disease. An interesting observation is that approximately 75 percent of patients who conceive after a conservative surgery do so within the first 12 months of the surgery. Since the outcome of the surgery and the pregnancy rate are inversely related to the stage of the endometriosis, early detection and treatment is the key to higher success.
It has also been reported that post-operative medical therapy in all subjects gives a superior pregnancy rate. Also, in our experience (in more than 1000 cases of endometriosis), the CO2 laser has been a superior laser for treatment for pain relief and for restoration of fertility.

Q. Do you have any recommendations for increasing the pregnancy success rate after conservative surgical treatment? A. One should make sure that there are not any other factors besides endometriosis which were contributing to the couple's infertility. Such factors might include cervical factors, sperm disorders, or luteal phase defect, among others. If such factors are present, they should be corrected.
It has also been suggested and reported that post-operative medical therapy could result in a superior pregnancy rate. However, our philosophy has been that since the first nine to twelve months after a complete removal and vaporization of the endometriosis is the most critical and productive time (75 percent of the patients who get pregnant following surgery do so during this time), medical treatment can be initiated after this period. In cases where a complete removal was not possible during the surgical procedure, immediate post-operative medical therapy can result in far superior success rates.

Q. What is the role of assisted reproductive techniques such as in vitro fertilization (IVF) and gamele intra fallopian transfer (GIFT) in the treatment of infertility of patients with endometriosis?
A. In the past 10 years, and more specifically in the past five years, IVF and GIFT have been documented to be of great benefit in patients with long-term infertility and endometriosis that has failed surgical and medical therapy. IVF and GIFT have shown, overall, a 25 and 30 percent pregnancy rate, respectively. In other words, there is no difference in pregnancy rates for endometriotic patients when compared with other groups of patients using these techniques.

Q. How often does endometriosis recur following treatment?
A. In different reports, the recurrence rate of endometriosis following surgical and/or medical therapy is 10 to 20 percent. However, there are a few points which should be kept in mind when considering these figures:
1. Pregnancy following any treatment will decrease the risk of recurrence dramatically. In one study, the rate of reoperation was four percent in patients who conceived after treatment, and 40 percent in those who did not.
2. Although the rate of pain relief is more than 60 percent after a second operation, the pregnancy rate after the second procedure is approximately 25 percent. 3. The more advanced the stage of endometriosis at the time of the initial surgery, the higher the rate of recurrence.
4. Although the mean time of reoperation is about three years after the initial surgery, new studies and "second look" laparoscopies have confirmed the recurrence of active endometriosis after only a few months following therapy in some patients.
5. Not all patients who have recurrence of pain and other symptoms were found to have endometriosis in the "second look" laparoscopy. Interestingly enough, only 30 percent had documented endometriosis, and the majority were found to have pelvic adhesions or other causes of pelvic pain.
6. In infertile patients with recurrence of endometriosis, particularly in patients over 35 with a long history of infertility and more advanced stages of endometriosis, IVF could be a better substitute to a second surgery if the initial surgery or medical treatment fails.

References

Babaknia, A. Laparascopic CO₂ laser treatment of infertile patients with endometriosis who failed to respond to initial medical or surgical therapy. Proceedings of the 38th Annual Meeting of the Pacific Coast Fertility Society, p. 27, 1988.
Corson, S. L., M.D. Endometriosis: The Enigmatic Disease. Canada: Essential Medical Information System, 1992.
Is mild endometriosis a disease? (Debate). Human Reproduction, 9:2202-2211, 1994.
Martin, D. C., et al. Laparascopic appearance of peritoneal endometriosis. Fertil. Steril., 51:63-67, 1989.
O'Connor, D. T. Endometriosis. New York : Churchill Livingstone, 1987.
Shaw, R. W., ed. Endometriosis. Park Ridge, N.J.: Parthenon Pub. Group, 1990.
Wilson, E. A. Endometriosis. New York : Liss, 1987.