Endometriosis

A benign disease in which functioning endometrial tissue is present in sites outside the uterine cavity.

Endometriosis is usually confined to the peritoneal or serosal surfaces of intra-abdominal organs, commonly the ovaries, posterior broad ligament, posterior cul-de-sac, and the uterosacral ligaments.

Less common sites include the serosal surfaces of the small and large bowel, ureters, bladder, vagina, surgical scars, and pleural cavity.

Etiology and Epidemiology

The most widely accepted hypothesis is that endometrial cells are transported from the uterine cavity to implant at ectopic sites.

Retrograde flow of menstrual tissue through the fallopian tubes could cause intra-abdominal endometriosis, while the lymphatic or circulatory systems could spread endometriosis to distant sites (eg, the pleural cavity).

Another possible explanation is the transformation of coelomic epithelium into endometrium-like glands (ie, coelomic metaplasia).

There is evidence of a familial inheritance pattern, with the occurrence of endometriosis increased by 6% in first-degree relatives of women with endometriosis. Additional factors associated with an increased incidence include delay in childbearing, Oriental race, and mlullerian duct anomalies.

Although the reported incidence varies, endometriosis is commonly found in 10 to 15% of women between the ages of 25 and 44 yr who are actively menstruating. Increased use of diagnostic laparoscopy has also detected endometriosis in teenagers. It has been estimated that 25 to 50% of infertile women have endometriosis. In patients with severe endometriosis and distortion of normal pelvic anatomy, the incidence of infertility is high because of impaired ovum pickup and tubal transport mechanisms. However, some patients with minimal endometriosis and normal pelvic anatomy are also infertile and may have an increased incidence of luteal phase dysfunction, luteinized unruptured ovarian follicle syndrome (“trapped oocyte”), increased peritoneal prostaglandin production, and/or increased peritoneal macrophage activity to account for their decreased fertility.

Symptoms and Signs

The clinical manifestations are pelvic pain, pelvic mass, alterations of menses, and infertility. Some women with severe endometriosis may be asymptomatic, while others with minimal disease may have incapacitating pain.

Dyspareunia and midline pelvic pain pre- or perimenstrually, particularly beginning after several years of pain-free menses, may occur. Such dysmenorrhea is an important diagnostic clue. Lesions on the large bowel or bladder may cause pain with defecation, abdominal bloating, rectal bleeding with menses, or suprapubic pain during urination. Endometriotic implants on the ovary or adnexal structures can form an endometrioma (ie, a cystic mass of endometriosis localized to an ovary) or adnexal adhesions, giving rise to a pelvic mass. Occasionally, rupture or leakage from an endometrioma may be associated with acute abdominal pain.

Diagnosis

The diagnosis is suspected on the basis of the symptoms described above and/or physical findings.

Pelvic Examination may be normal or may reveal visible lesions on the vulva or cervix, in the vagina, the umbilicus, and in surgical scars. There may be a retroverted and fixed uterus, enlarged ovaries, or uterosacral nodularity.

The diagnosis can be established only by visualizing lesions, usually by endoscopy of the pelvis. In the absence of visible lesions on physical examination, the primary diagnostic modality is direct visualization and/or biopsy of lesions by laparoscopy.

Diagnosis could also be made during laparotomy or on sigmoidoscopy or cystoscopy. Microscopically, endometriotic implants consist of endometrial glands and stroma, structurally identical to endometrium (most implants can bleed during menstruation). By definition, both glands and stroma must be present to diagnose endometriosis. These tissues contain estrogen and progesterone receptors that allow for growth and differentiation in response to the sequential changes in ovarian steroids during the menstrual cycle. Thus, the macroscopic appearance (clear, red, brown, black) and size of these implants vary. When confined to the peritoneal cavity, bleeding from these lesions is thought to initiate an inflammatory process followed by fibrin deposition and adhesion formation, which eventually leads to distortion of peritoneal surfaces and of normal pelvic anatomy.

Other diagnostic procedures (eg, ultrasonography, barium enema, IV urogram,) may be useful for demonstrating the extent of disease and following its course but are not specific or adequate for diagnosis. Investigational serum markers for endometriosis (eg, CA-125 and antiendometrial antibody levels) may help monitor the disease but will require further refinement. Infertility studies may be indicated.

Staging the disease as minimal, mild, moderate, or severe is important to formulate a treatment strategy and evaluate response to therapy. The revised staging criteria of the American Fertility Society are based on the location of implants, presence of superficial or deep endometriosis, and presence of filmy or dense adhesions. This classification scheme divides the degree of endometriosis into minimal, mild, moderate, or severe categories. Shown in Figure 172.1 is an example of stage III (moderate) endometriosis.

Treatment

Treatment must be individualized to the patient's age, symptoms, desire for pregnancy, and extent of disease. In general, treatment modalities include medically suppressing ovarian function to arrest the growth and activity of the endometrial implants, conservative surgical resection of as much of the endometriosis as possible, a combination of the 2 therapies, and extirpative surgery (total abdominal hysterectomy with or without unilateral or bilateral salpingo-oophorectomy).

Various drugs are available that suppress ovarian function and/or growth of the endometrial tissue. These are listed in Table 172.1 with examples of dosages and side effects.

Continuous oral contraceptives are less commonly used because other agents, such as danazol (an antigonadotropin that blocks ovulation) and gonadotropin-releasing hormone (GnRH) agonists (which produce a state of relative and reversible hypoestrogenemia), have become available. Pregnancy rates with medical therapy range from 40 to 60%. It is not clear that fertility rates are improved by treatment of mild or minimal endometriosis.

It must be emphasized that suppressive medical therapy or conservative surgery does not effectively cure endometriosis, and recurrence is observed in most patients. Only total ablation of ovarian function will prevent recurrence of endometriosis.

Cyclic oral contraceptives given following medical therapy and/or conservative surgery may slow progression of the disease and are warranted in women wishing to delay childbearing.

Moderate to severe cases are treated most effectively by excision of as many implants as possible, while preserving reproductive potential. Indications for surgery include the presence of endometriomas (> 2 to 3 cm), significant pelvic adhesions, fallopian tube obstruction, and intractable and incapacitating pelvic pain not responsive to medical therapy.

Care must be taken to prevent adhesion formation during surgery by using microsurgical techniques. With the newer operative laparoscopic approach, it is possible in some cases to electrocauterize peritoneal or ovarian lesions or to vaporize or excise them with a CO2, argon, or neodymium:yttrium-aluminum-garnet (Nd:YAG) laser.

Pregnancy rates following this conservative surgical approach are about proportional to the severity of the endometriosis and range from 40 to 70%.

In patients with midline pelvic pain, laparoscopic resection of the uterosacral ligaments with electrocautery or laser therapy may reduce the degree of suppressive medical treatment may enhance fertility rates.

Extirpative (radical) surgery should be reserved for patients with intractable pelvic pain who have completed childbearing.

Following removal of the uterus and ovaries, replacement estrogen therapy can be started postoperatively or may be delayed for 4 to 6 mo if significant disease is left in situ.

Adjunctive suppressive medical therapy may be necessary in this interval. In the younger patient, one should consider preserving ovarian function, although recurrence rates of 3.5 to 85% have been reported.