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Endometriosis is characterized by the presence of ectopic endometrium (i.e., endometrial issue outside the uterine cavity) and is found in approximately 20% of patients who undergo pelvic laparotomy. It was first recognized as a distinct clinical entity by Sampson in 1921. Endometriosis has been estimated to be the primary causative factor in about 25% of infertile couples. This disease, therefore, deserves recognition as an important health problem of women.
In 1927 Sampson proposed that endometriosis might occur because of implantation and growth of viable endometrial fragments deposited in the peritoneal cavity by way of retrograde menstruation. This hypothesis was vigorously debated, the major opponent being Emil Novak, the premier gynecologic pathologist of the era. Novak proposed instead that the disease might originate from metaplasia of coelomic epithelium, "the primitive peritoneum." He suggested that retrograde menstruation, if it occurred at all, was quite rare, and that the shed endometrium was necrotic and incapable of implantation and growth. It remained for Ridley to demonstrate the viability of shed endometrial tissue by collecting menstrual debris and implanting it in the anterior abdominal wall of women. Subsequent excision of the area showed grossly and microscopically typical endometriosis in several, but not all, patients. Interestingly, the author suggested, among other possibilities, that "an unknown factor of host acceptance or rejection of transplanted endometrial tissue" might be present. The concept of retrograde menstruation, much debated in the early years, has steadily acquired increased validity with time. Blumenkrantz and associates observed bloody peritoneal fluid during menses in nine of 11 patients undergoing peritoneal dialysis. Subsequently Halme and colleagues noted bloody peritoneal fluid in 90% of 84 menstruating women with patent tubes who underwent laparoscopy; blood was seldom present in women with occluded tubes. Thus two requisites for acceptance of Sampson's concept, retrograde menstruation and the viability of shed endometrium, are established, and most authorities now accept the theory of implantation of fragments of shed endometrium. This theory, however, cannot explain the occasional observation of endometrial implants in sites distant from the pelvis. Endometrium has been identified in various distant sites, including the brain, thorax, and extremities. One is left with no rational explanation of these distal lesions other than transport by blood or lymph.
Considerable evidence suggests a heredity tendency to acquire endometriosis. The prevalence of endometriosis in the population at large is estimated at 1%. First-degree relatives of patients have been reported by several authors to have a prevalence rate of 5% to 6%. The familial distribution of affected people is most consistent with polygenic-multifactorial inheritance. It is of interest that patients with familial endometriosis have a significantly higher probability to have severe disease.
Some investigators have suggested that immunologic rejection inhibits growth of shed endometrium, and that a deficiency in cell-mediated immunity may be a characteristic of women who develop the disease. At least one group of investigators found a high incidence of autoimmunity in women with endometriosis, suggesting that endometriosis may be an autoimmune disease. Indeed, they state that it meets all the classic criteria for autoimmune dis-ease-polyclonal B cell activation, tissue damage, multiorgan involvement, female preponderance, familial occurrence, and increased concurrence with other autoimmune diseases. It is conceivable that some as yet poorly denned immunologic deficiency may be inherited as a polygenic-multifactorial trait and secondarily allow development of endometriosis from tubal regurgitation of shed endometrium.
The ovary is the most common site of endometriosis: the cul-de-sac and uterosacral ligaments are the next most frequent. The characteristic pathology of endometriosis is the so-designated chocolate cyst of the ovary. Typically, the ovary containing the cyst is adherent to the pelvic side wall and posterior broad ligament. When opened, it discharges a thick fluid resembling chocolate syrup that is composed of old blood and menstrual debris. Less extensive endometriosis is often identified in practices that specialize in infertility since diagnostic laparoscopy is likely to be done earlier and in patients without palpable disease. The lesions may range from a few pigmented "powder burns" in the cul-de-sac and along the uterosacral ligaments to large cystic lesions associated with massive pelvic adhesions. Nodules of endometriosis ranging from 1 cm to 2 cm in diameter along the uterosacral ligaments and even extension into the rectovaginal septum may occur. Extensive fibrosis is characteristically present at the site of lesions. Although the large and small bowel are commonly involved, intestinal obstruction secondary to endometriosis is uncommon. Endometriosis implants, while usually pigmented, may consist only of white opacified areas of pelvic peritoneum; such lesions should be recognized despite the absence of pigmentation. The American Fertility Society has devised a staging system that allows specific definitions of the extent of the disease process. Such a classification is useful in determination of proper therapy and prognosis.
Endometriosis is generally limited to women of reproductive age, but it may occur in adolescents and postmenopausal women. The most characteristic symptom is pelvic pain. Pain usually occurs only with menses, but in some women it is present throughout the cycle. Sometimes the pain is sufficiently severe to require narcotics and bed rest. Dyspareunia is frequently present.
An interesting variation of pain in endometriosis occurs when the sciatic nerve is involved. The pain is cyclic and often radiates down the leg; in advanced cases numbness, and weakness of the leg with foot drop may occur.
Infertility is a frequent complaint in women with endometriosis, and the disease has been estimated to account for about 25% of primary infertility. The mechanism responsible for infertility with mild disease and no adhesion formation is unknown. One investigator postulated that the increased number of peritoneal fluid macrophages present in patients with endometriosis may enter the fallopian tubes and phagocytize sperm before fertilization. In support of this concept, Halme showed that women with endometriosis had increased cyclic activation of peritoneal macrophages.
Other postulated mechanisms include increased prostaglandin synthesis, ovulatory dysfunction, and autoimmune disorders. None of these hypotheses has proved to be of importance.
Pelvic examination in women with mild endometriosis is normal. With more advanced disease tender nodularity along the course of the uterosacral ligaments is often present, and is best appreciated on rectal examination. There may be palpable disease in the rectovaginal septum, and ovarian endome-triomas of varying sizes may be present. The ovaries are often fixed to the posterior uterus, broad ligament, or pelvic side wall, and this may be appreciated on rectal or vaginal examination.
The presence of endometriosis may be suspected in patients whose symptoms and physical findings are consistent with such a diagnosis. However, diagnosis can be made only by direct visualization. This is usually carried out by laparoscopy, but occasionally the diagnosis is proved at laparotomy for acute symptoms. Because treatment of endometriosis either is surgical or involves prolonged and expensive therapy, it should not be initiated without a certain diagnosis.
The treatment method used is predicated on the patient's specific complaints and physical findings and is greatly affected by the patient's wishes regarding future childbearing.
Surgical treatment of endometriosis is undertaken because of severe cyclic pain, often associated with infertility and with the presence of an adnexal mass with or without infertility. Surgical management of the woman who has completed her childbearing and who has symptomatic endometriosis is not complicated by the necessity to preserve the uterus and ovaries. Most authorities agree that hysterectomy and resection or fulguration of visible implants are required. The disposition of the ovaries, however, remains somewhat debatable. Some physicians report a high incidence of recurrent symptomatic disease when the ovaries are retained, and recommend that patients who have completed childbearing have abdominal hysterectomy and bilateral salpingoophorectomy. Williams and Pratt report that one-third of patients who have conservative operation require subsequent operation for endometriosis. Replacement therapy with exogenous estrogens is simple and appears to prevent the complications associated with hypoestrogenism.
More conservative operation often is required in women who desire immediate childbearing or who want to preserve reproductive function for the future. Because of the paucity of controlled studies of subsequent attainment of pregnancy in surgically treated patients, evaluation of surgical outcome is difficult. The evaluation of surgical results is more difficult because staging of the disease was not recorded in many of the older references.
The lack of any controlled prospective studies designed to evaluate the efficacy of either laparoscopic fulguration or laser vaporation of endometrial implants currently precludes evaluation of the results of such treatment. Schenkin and Malinak reported that 75% of untreated patients with mild endometriosis conceived within one year. In a carefully designed prospective study Seibel and co-workers reported a 60% pregnancy rate in the six-month period after diagnosis of mild endometriosis. Reports of laparoscopic fulguration or vaporization of implants do not indicate pregnancy rates superior to those in untreated patients, although sufficient data is not available to rule out a beneficial effect. When laser vaporization or cautery of implants can be done safely at the time of diagnostic laparoscopy, it is probably advisable to do so for whatever benefits it may confer.
Danazol (Danocrine), an isoxazole derivative of 17?-ethinyltestosterone, was first marketed as a specific antigonadotropin. Subsequent studies have not confirmed a direct antigonadotropic effect in women. Danazol does not suppress the basal level of gonadotropin in intact women, but does consistently suppress the ovulatory midcycle gonadotropin peak. It binds to androgen, progesterone, and glucocorticoid receptors, and appears to have both mild androgenic and progestational effects. It binds to sex hormone-binding globulin, displacing testosterone and increasing circulating free testosterone. It inhibits several enzymes involved in ovarian steroidogenesis, including cholesterol side-chain cleavage enzyme, 30-hydroxysteroid dehydrogenase, lyase, and 21-hydroxylase. It does not inhibit aromatase. When given in doses of 400 mg to 800 mg daily, danazol has caused marked regression of implants and relief of symptoms of endometriosis. Therapy needs to be continued for four to 12 months. Unfortunately there is a high rate of recurrence of symptoms and physical evidence of disease, making danazol impractical for treatment of women who have no further desire for childbearing. The efficacy of danazol for treatment of infertility is still being debated, but most evidence suggests that it does not improve conception rates. No randomized trials of danazol in patients with moderate or severe disease have been published. However, Seibel and associates' well-designed prospective study showed no improvement in pregnancy rates in mild disease, and a prospective multi-institutional study derived pregnancy rate figures no better than those reported with no therapy. Olive and Haney have reviewed the available data, which strongly suggest no increment of pregnancy rates after danazol treatment. In addition to its probable ineffectiveness for enhancement of conception rates, danazol produces significant side effects. The most commonly encountered are weight gain, muscle cramps, decreased breast size, flushing, mood changes, acne, edema, and, occasionally, hirsutism. Because an occasional woman will observe deepening of the voice, it should be used with caution in singers. Thus the role of danazol in the management of endometriosis, even after 20 years, is still incompletely defined. In our opinion it may be useful to stabilize the disease until a decision for childbearing is finalized.
The use of progestational agents for treatment of endometriosis was predicated on the observation that pregnancy seemed to cause regression of endometriosis. Before the introduction of danazol, progestagen-estrogen combinations, usually administered in very high doses, were the primary agents used for endometriosis. These agents undoubtedly cause a clinical regression of implants, probably brought about by decidual transformation followed by necrosis and absorption. Using pseudopregnancy alone, The side effects of treatment with the high doses of progestin-estrogen combination are severe and include weight gain, hypertension, thromboembolism, and depression. Because of severe side effects, some of which may be fatal, this treatment regimen should be abandoned.
The observation that continuous administration of gonadotropin releasing hormone (GnRH) causes suppression of gonadotropin release from the pituitary led to trials of long-acting synthetic agonists for treatment of endometriosis. Several clinical trials have shown regression of endometrial implants after four to six months of treatment of GnRH agonists. However, ovarian endometriomas rarely show regression, and in areas in which endometriosis was identified before treatment, disease was present on biopsy in one study even if not visible at laparoscopy. Additionally, there is a high incidence of recurrent symptoms after stopping treatment. Side effects include hot flashes, vaginal dryness, emotional symptoms, and, perhaps most significant, an increased rate of bone loss evidenced by elevated urine calcium levels and increased hydroxyproline excretion. More time is required to evaluate the role of agonist therapy in this disease. No data has been published regarding fertility after treatment.
A variety of other hormonal treatments, including diethylstilbestrol and methyltestosterone, have been suggested for treatment of endometriosis and now are of historical interest only.
Sixty-five years after its recognition as a distinct disease entity, endometriosis remains an enigma. Although retrograde menstruation probably accounts for most cases of the disease, the factors that determine which women will develop implants are largely unknown. The mechanisms that cause infertility in stage I and stage II disease are still unknown, but adhesive disease and ovulatory dysfunction account for infertility in more advanced cases.
Treatment remains unsettled and varies widely among different investigators. The following treatment plan, however, seems reasonable.
The patient with significant symptoms of pain and dyspareunia who does not desire further childbearing is best treated with abdominal hysterectomy and bilateral salpingo-oophorectomy followed by estrogen replacement therapy
No effective treatment for infertility has been described for the patient with stage I or II disease, and conception rates are identical with or without treatment. Therefore, if implants can be safely coagulated or vaporized at the time of diagnostic laparoscopy, it is probably in order to do so for whatever advantage this may confer. If conception does not occur after 12 to 24 months of observation, such patients may respond to ovarian hyperstimulation and intrauterine insemination, gamete intrafallopian tube transfer (GIFT), or in vitro fertilization (IVF). More advanced disease probably is best treated surgically, since adhesive disease and endometriomas do not appear to respond to medical treatment. Conservative surgery with adhesiolysis and resection or fulguration of visible endometriosis yields an ultimate pregnancy rate of 40% to 50%. In patients who do not conceive after 12 to 24 months, GIFT and IVF are viable options.
|Ministry of public health of ukraine bukovinian state medical university|