Textbook Of Gynecology. Dc Dutta’s

Chapter 21. Endometriosis and Adenomyosis

ENDOMETRIOSIS

DEFINITION

Presence of functioning endometrium (glands and stroma) in sites other than uterine mucosa is called endometriosis. It is not a neoplastic condition, although malignant transformation is possible.

These ectopic endometrial tissues may be found in the myometrium when it is called endometriosis interna or adenomyosis. More commonly, however, these tissues are found at sites other than uterus and are called endometriosis externa or generally referred to as endometriosis.

Endometriosis is a disease of contrast. It is a benign but it is locally invasive, disseminates widely. Cyclic hormones stimulate growth but continuous hormones suppress it.

PREVALENCE

During the last couple of decades, the prevalence of endometriosis has been increasing both in terms of real and apparent. The real one is due to delayed marriage, postponement of first conception and adoption of small family norm. The apparent one is due to increased use of diagnostic laparoscopy as well as hightened awareness of this disease complex amongst the gynecologists.

The prevalence is about 10 percent. However, prevalence is high amongst the infertile women (30-40%) as based on diagnostic laparoscopy and laparotomy.

Fig. 21.1 : Common sites of endometriosis

This theory can explain endometriosis of the abdominal viscera, the rectovaginal septum and the umbilicus.

SITES (Table 21.1)

♦ Abdominal ♦ Extra-abdominal ♦ Remote Abdominal: It can occur at any site but is usually confined to the abdominal structures below the level of umbilicus.

Extra-abdominal: The common sites are abdominal scar of hysterotomy, cesarean section, tubectomy and myomectomy, umbilicus, episiotomy scar, vagina and cervix.

TABLE 21.1 I SITES OF ENDOMETRIOSIS

Common sites

Rare and remote sites

♦ Ovaries

♦ Pelvic peritoneum

♦ Pouch of Douglas

♦ Uterosacral ligaments

♦ Rectovaginal septum

♦ Sigmoid colon

♦ Appendix

♦ Pelvic lymph nodes

♦ Fallopian tubes

• Umbilicus

• Abdominal scar

• Episiotomy scar

• Lungs

• Pleura

• Ureter

• Kidney

• Arms • Legs

• Nasal mucosa

PATHOGENESIS still remains unclear and is full of theories. The principal ones are:

Retrograde Menstruation (Sampson's theory)

There is retrograde flow of menstrual blood through the uterine tubes during menstruation. The endometrial fragments get implanted in the peritoneal surface of the pelvic organs (dependent sites, e.g. ovaries, uterosacral ligaments). Subsequently, cyclic growth and shedding of the endometrium at the ectopic sites occur under the influence of the endogenous ovarian hormones. Retrograde menstruation per se is unlikely to produce endometriosis. Probably, a genetic factor or favorable hormonal milieu is necessary for successful implantation and growth of the fragments of endometrium. While this theory can explain pelvic endometriosis, it fails to explain the endometriosis at distant sites.

Coelomic metaplasia (Meyer and Ivanoff)

Chronic irritation of the pelvic peritoneum by the menstrual blood may cause coelomic metaplasia which results in endometriosis. Alternatively, the mullerian tissue remnants may be trapped within the peritoneum. They could undergo metaplasia and be transformed into endometrium.

TABLE 21.2 THEORIES TO EXPLAIN ENDOMETRIOSIS AT DIFFERENT SITES

Sites

Theory

• Pelvic endometriosis

• Pelvic peritoneum

♦ Retrograde menstruation

♦ Coelomic metaplasia

• Abdominal viscera

• Rectovaginal septum

• Umbilicus

♦ Coelomic metaplasia

• Abdominal scar

• Episiotomy scar

• Vagina, cervix

• Lymph nodes

• Distant sites (Lungs, pleura, skin, lymph nodes, nerves)

♦ Direct implantation

♦ Lymphatic spread

♦ Vascular spread

♦ Genetic

♦ Immunologic

Direct Implantation

According to the theory, the endometrial or decidual tissues start to grow in susceptible individual when implanted in the new sites. Such sites are abdominal scar following hysterotomy, caesarean section, tubectomy and myomectomy. Endometriosis at the episiotomy scar, vaginal or cervical site can also be explained with this theory.

This theory however, fails to clarify endometriosis at sites other than mentioned.

Lymphatic Theory (Halban): It may be possible for the normal endometrium to metastasize the pelvic lymph nodes through the draining lymphatic channels of the uterus. This could explain the lymph node involvement.

Vascular Theory: This is sound at least to explain endometriosis at distant sites such as lungs, arms or thighs.

Genetic and Immunological Factors

Genetic basis of endometriosis probably accounts for less than 10 percent of the patients. There is 6-7 times increased incidence in first degree relatives. Multifactorial inheritance is thought of. However, a defect of local cellular immunity may be responsible for the ectopic tissue to grow in abnormal sites only in susceptible women.

Peritoneal macrophages normally remove the menstrual debris by phagocytosis. Pelvic endometriosis is associated with a subclinical peritoneal inflammation resulting in increase in peritoneal fluid. In patients with endometriosis, the activated macrophages secrete several factors like cytokines, interleukin-1, a TNT, integrins and angiogenic factors. These factors promote the growth of endometrial cells over the ectopic sites. Ectopic endometrium is more resistant to apoptosis. Furthermore activated macrophages reduce sperm motility, increase sperm phagocytosis and interfere with fertilization.

Environment theory suggests somatic mutations of cells due to environmental factors (pollutants, dioxins). Ovarian and deep infiltrating endometriotic lesions are explained with this theory.

Thus, it is certain that, not all cases of endometriosis at different sites can be explained by a single theory.

PATHOLOGY—General Considerations

♦ The endometrium (glands and stroma) in the ectopic sites has got the potentiality to undergo changes under the action of ovarian hormones

♦ While proliferative changes are constantly evidenced, the secretory changes are conspicuously absent in many; may be due to deficiency of steroid receptors in the ectopic endometrium

♦ Cyclic growth and shedding continue till menopause. The periodically shed blood may remain encysted or else, the cyst becomes tense and ruptures

♦ As the blood is irritant, there is dense tissue reaction surrounding the lesion with fibrosis. If it happens to occur on the pelvic peritoneum, it produces adhesions and puckering of the peritoneum

♦ If encysted, the cyst enlarges with cyclic bleeding. The serum gets absorbed in between the periods and the content inside becomes chocolate colored. Hence, the cyst is called chocolate cyst which is commonly located in the ovary. Chocolate cyst may also be due to hemorrhagic follicular or corpus luteum cyst or bleeding into a cystadenoma. For this reason, the term endometrial cyst or endometrioma is preferred to chocolate cyst

♦ In spite of dense adhesions amongst the pelvic structures, the fallopian tubes remain patent.

Naked Eye Appearance: The appearance of the lesion depends to a great extent on the organ(s) involved, extent of the lesion and reaction of the surrounding tissues.

Pelvic endometriosis: Typically, there are small black dots, the so called ‘powder burns" seen on the uterosacral ligaments and pouch of Douglas (Fig. 21.2). Fibrosis and scarring in the peritoneum surrounding the implants is also a typical finding. Other subtle appearances are: red flame shaped areas, red polypoid areas, yellow brown patches, white peritoneal areas, circular peritoneal defects or subovarian adhesions. These lesions are thought to be more active than the “powder burn” areas.

Fig. 21.2 : The appearance of pelvic endometriosis. Note the black dots and puckered peritoneum. Sites of involvement are: ovaries, uterosacral ligaments and pelvic peritoneum

The ovaries are frequently involved usually bilaterally. The endometriomas (chocolate cysts) are of varying sizes and are visible as bluish colorations. The ovaries get adherent to the pelvic structures including rectum and sigmoid colon.

Microscopic Appearance: There is presence of endometrial tissue—both glands and stroma. Due to pressure effect, the lining epithelium of the cyst may be absent or flattened (cuboidal) or replaced by granulation tissue. Adjacent to the lining epithelium, there may be presence of large polyhedral phagocytic cells, laden with blood pigmenthemosiderin (pseudoxanthoma cells). The cyst wall is composed of fibrous tissue and compressed ovarian cortex.

CLINICAL FEATURES OF PELVIC ENDOMETRIOSIS

Patient Profile

The age is between 30-45. The patients are mostly nulliparous or have had one or two children long years prior to appearance of symptoms. Infertility, voluntary postponement of first conception until at a late age and higher social status are often related. Thus, it is more common in private than hospital patients. There is often family history of endometriosis. Outflow tract obstruction is an important cause when it is seen in teenagers (10%).

Symptoms

♦ About 25 percent of patients with endometriosis have no symptom, being accidentally discovered either during laparoscopy or laparotomy.

♦ Symptoms are not related with extent of lesion. Even when the endometriosis is widespread, there may not be any symptom; conversely, there may be intense symptoms with minimal endometriosis.

♦ Depth of penetration is more related to symptoms rather than the spread. Lesions penetrating more than 5 mm are responsible for pain, dysmenorrhea and dyspareunia.

♦ Non-pigmented endometriotic lesions compared to the classic pigmented “powder burns” lesions produce more prostaglandin F (PGF) and hence are more painful.

♦ The symptoms are mostly related to the site of lesion and its ability to respond to hormones. Midline lesions are more symptom producing. Degree of pain is not related to the severity of endometriosis.

Dysmenorrhea (70%)

There is progressively increasing secondary dysmenorrhea. The pain starts a few days prior to menstruation; gets worsened during menstruation and takes time, even after cessation of period, to get relief of pain, (co-menstrual dysmenorrhea). Pain usually begins after few years pain-free menses. The site of pain is usually deep seated and on the back or rectum.

Increased secretion of PGF 2a, thromboxane Pfrom endometriotic tissue is the cause of pain.

Abnormal menstruation (20%o): Menorrhagia is the predominant abnormality. If the ovaries are also involved, polymenorrhea or epimenorrhagia may be pronounced. There may be premenstrual spotting.

Infertility (40-60%): Whether endometriosis causes infertility or infertility produces endometriosis is not clear. Endometriosis is found in 20-40 percent of infertile women, where as in about 40-50 percent patients with endometriosis suffer from infertility. The multiple factors involved in producing infertility have been depicted in p. 231 (Table 16.2).

Dyspareunia (20-40%)

The dyspareunia is usually deep. It may be due to stretching of the structures of the pouch of Douglas or direct contact tenderness. As such, it is mostly found in endometriosis of the rectovaginal septum or pouch of Douglas and with fixed retroverted uterus.

Chronic Pelvic Pain

The pain varies from pelvic discomfort, lower abdominal pain or backache. The cause may be multifactorial. These include—(i) Inflammation in the peritoneal implants and release of PGF, and also due to adhesions and ovarian cysts. (ii) Action of inflammatory cytokines released by the macrophages.

(iii) Invasion of nerves or involvement of bladder and bowel. The pain aggravates during period.

Abdominal Pain

There may be variable degrees of abdominal pain around the periods. Sometimes, the pain may be acute due to rupture of chocolate cyst.

Other Symptoms

The symptoms are related to the organ involved.

♦ Urinary—frequency, dysuria, back pain or even hematuria

♦ Sigmoid colon and rectum—painful defecation (dyschezia), diarrhea, constipation, rectal bleeding or even melena

♦ Chronic fatigue, perimenstrual symptoms (bowel, bladder)

♦ Hemoptysis (rarely), catamenial chest pain

♦ Surgical scars—cyclical pain and bleeding (see Fig. 21.5).

Abdominal ExaminationAbdominal palpation may not reveal any abnormality. A mass may be felt in the lower abdomen arising from the pelvis— enlarged chocolate cyst or tubo-ovarian mass due to endometriotic adhesions. The mass is tender with restricted mobility.

Pelvic Examination

Bimanual examination may not reveal any pathology. The expected positive findings are—pelvic tenderness, nodules in the pouch of Douglas, nodular feel of the uterosacral ligaments, fixed retroverted uterus or unilateral or bilateral adnexal mass of varying sizes (Fig. 21.3).

Speculum examination may reveal bluish spots in the posterior fornix.

Rectal or rectovaginal examination is often helpful to confirm the findings.

DIAGNOSIS

Clinical diagnosis is by the classic symptoms of progressively increasing secondary dysmenorrhea, dyspareunia and infertility. This is corroborated by the pelvic findings of nodules in the pouch of Douglas, nodular feel of the uterosacral ligaments, fixed retroverted uterus and unilateral or bilateral adnexal mass. However, physical examination has poor sensitivity and specificity. Many patients have no abnormal findings on examination.

Serum marker CA 125—A moderate elevation of serum CA 125 is noticed in patients with severe endometriosis. It is not specific for endometriosis, as it is significantly raised in epithelial ovarian carcinoma (see p. 377, 522, 653). However, it is helpful to assess the therapeutic response and in follow up of cases and to detect any recurrence after therapy. Monocyte Chemotactic Protein (MCP-1) level is increased in the peritoneal fluid of women with endometriosis.

IMAGING

Ultrasonography is not much helpful to the diagnosis. TVS can detect ovarian endometriomas. Transvaginal (TVS) and Endorectal ultrasound are found better for rectosigmoid endometriosis.

Magnetic Resonance Imaging (MRI) is a diagnostic tool. There is a characteristic hyperintensity on T1 weighted images and a hypointensity on T2 weighted images.

CT is better compared to ultrasonography in the diagnosis. MRI is useful for deep infiltrating endometriosis.

Colonoscopy, rectosigmoidoscopy and cystoscopy are done when respective organs are involved.

Laparoscopy is the gold standard. Confirmation is done by double puncture laparoscopy or by laparotomy.

Other benefits are: ♦ Confirmation of the lesion with site, size and extent. ♦ Biopsy can be taken at the same time. ♦ Staging (p. 309) can be done. ♦ Extent of adhesions could be recorded. ♦ Opportunity to do laparoscopic surgery if needed (p. 306) .

The classic lesion of pelvic endometriosis is described as ‘powder burns ’ or ‘match stick ’ spots on the peritoneum of the pouch of Douglas (see p. 309). Findings may be recorded on video or DVD (RCOG- 2006) Microscopically some of these lesions contain endometrial glands, stroma and hemosiderin-laden macrophages.

Biopsy confirmation of excised lesion is ideal but negative histology does not exclude it. None of the imaging techniques including ultrasound, can diagnose specifically the peritoneal endometriosis. Emperic medical treatment is usually not recommended except for pain relief and to reduce menstrual flow.

DIFFERENTIAL DIAGNOSIS

Chronic pelvic infection is most often confused with symptomatic endometriosis. The clinical presentation is almost similar. Laparoscopy is helpful in actual diagnosis.

Ovarian endometrioma (chocolate cyst): Ovary is the most common site for endometriosis. It starts with a superficial endometriotic implant over the ovarian surface. The endometriotic tissue gradually invades the ovarian stroma. Cyst formation is due to periodic shedding and bleeding from the implant.

Leakage of this altered blood along with inflammation, leads to adhesion formation with the adjacent structures. Fallopian tubes may be affected. Epithelial lining of the cyst contain endometrial glands and stroma. Due to pressure effect the lining epithelium may be flattened. When the cyst ruptures the characteristic thick, tarry fluid (chocolate material) escapes.

If asymptomatic, may be confused with benign ovarian tumor and in symptomatic one, with malignant ovarian. Presence of nodules in the pouch of Douglas further confuses the diagnosis. Ultrasonography showing homogeneous internal echoes may be helpful (see Fig. 21.4). Laparoscopy differentiates one from the other. Too often, the diagnosis is made only during laparotomy.

Rupture of the chocolate cyst: During operation, while separating the adhesions, the cyst invariably ruptures with escape of chocolate colored blood. The rupture of the cyst can occur spontaneously causing acute abdomen with clinical features suggestive of acute ectopic. Acute abdomen is confused with torsion or rupture of the ovarian tumour, disturbed ectopic pregnancy, appendicitis or diverticulitis.

COMPLICATIONS OF ENDOMETRIOSIS

■ Endocrinopathy—This may be mostly responsible for infertility (Table 21.3)

■ Rupture of chocolate cyst

■ Infection of chocolate cyst

■ Obstructive features:

- Intestinal obstruction

- Ureteral obstruction → hydroureter → hydronephrosis → renal infection

■ Malignancy is rare, the commonest one being adenoacanthoma.

Staging

The diagnosed endometriosis should be appropriately staged based on laparoscopic findings.

♦ To predict prognosis

♦ To choose therapy

♦ To evaluate the treatment protocol.

The scoring is (revised) by the American Fertility Society and is presented in Table21.4. The stage is determined by adding specific points given to each.

Limitations of AFS staging

• Laparoscopy or laparotomy has to be done.

• Interobserver and intraobserver variation.

• No correlation between the extent of disease and the degree of symptoms.

• Staging has not been correlated with fertility outcome.

• Staging has not been correlated with optimum mode of therapy.

TREATMENT OF ENDOMETRIOSIS

Endometriosis needs to be treated as it is a progressive disease (30-60%).

♦ Preventive ♦ Curative

Preventive

The following guidelines may be prescribed to prevent or minimize endometriosis:

• To avoid tubal patency test immediately after curettage or around the time of menstruation

• Forcible pelvic examination should not be done during or shortly after menstruation.

• Married women with family history of endometriosis are encouraged not to delay the first conception but to complete the family.

Curative: The objectives are:

• To abolish or minimize the symptoms—pelvic pain and dyspareunia

• To improve the fertility

• To prevent recurrence.

But, it is difficult to achieve the objectives because of obscure etiology and unpredictable life history. The results of treatment are difficult to evaluate because of lack of uniform staging or grading. The following facts are to be borne in mind.

• Asymptomatic in good number of cases.

• Subjective symptoms are not proportionate to objective signs.

• Frequent association with infertility.

• Remission during pregnancy and menopause.

Prerequisites prior to therapy are accurate diagnosis with the help of laparoscopy along with staging and pictorial documentation.

Treatment options for Pelvic Endometriosis :

► Expectant Management (observation only)

► Medical Therapy• Hormones • Others

► Surgery• Conservative • Definitive

► Combined Therapy• Medical and Surgical

Determinants of Treatment Options

• Age of the patient.

• Size and extent of lesions.

• Severity of symptoms.

• Location of disease.

• Desire for fertility.

• Results of previous therapy.

Expectant Treatment

Endometriosis is a progressive disease in about 30-60 percent of women. It is not possible to predict in which woman it will progress. Some form of treatment is often needed regardless of the clinical profile and to arrest the progress of the disease. However, in women with minimal to mild endometriosis role of any treatment is controversial. Cumulative pregnancy rate is similar when expectant treatment is compared with conservative surgery. Case selection is important (see Table 21.5).

Protocols for Expectant Management

Observation with administration of non-steroidal anti-inflammatory drugs or prostaglandin synthetase inhibiting drugs are used to relieve pain. Ibuprofen 800-1200 mg or mefenamic acid 150-600 mg a day is quite effective.

The married women are encouraged to have conception. Pregnancy usually cures the condition. This is due to absence of shedding and decidual changes in the ectopic endometrium causing its necrosis and absorption.

Hormonal Treatment

The aim of the hormonal treatment is to induce atrophy of the endometriotic implants. It should be considered suppressive rather than curative because of high recurrence rate.

The mechanism of endometrial atrophy is either by producing ‘pseudopregnancy ’ (combined oral pills) or by ‘pseudomenopause’ (Danazol) or by ‘medical oophorectomy’ (GnRH agonists). The hormonal use is gratifying in superficial peritoneal implants and endometriomas of less than 1 cm.

The drugs used are combined estrogen and progestogen (oral pill), progestogens, danazol and GnRH analogues. All the drugs are used continuously to produce amenorrhea and as such individualization of the dose is required.

Combined estrogen and progestogen

The low dose contraceptive pills may be prescribed either in a cyclic or continuous fashion with advantages in young patients with mild disease who want to defer pregnancy. It causes endometrial decidualization and atrophy (see p. 191). It may induce amenorrhea. It relieves dysmenorrhea. Anastrozole an aromatase inhibitor is found to reduce the growth and pain of endometriosis (p. 534).

Progestogens: It causes decidualization of endometrium and atrophy (see p. 191). High doses may suppress ovulation and induce amenorrhea.

Oral route is commonly used. Injectable preparations as depot form should be withheld in patients wishing to conceive. Ovulation may remain suspended for several months following withdrawal of the therapy. The side effects (see p. 537) are well- tolerated. The drug is comparatively cheaper than danazol. Progesterone Antagonists (Mifepristone 50-100 mg/day) has also been found effective.

Levonorgestrel-releasing-IUCD when used, is found to reduce dysmenorrhea, pelvic pain, dyspareunia and menorrhagia significantly. It is specially useful for rectovaginal endometriosis.

Danazol (p. 530)

Danazol therapy is to be started from the day 5 of the menstrual cycle. The dose (600-800 mg daily) is variable and depends upon the extent of the lesions but should be adequate enough to produce amenorrhea. The patient should use barrier methods of contraception to avoid virilization of a female fetus in accidental pregnancy. Resolution of endometriotic lesions has been seen in about 80% of cases but the recurrence rate is high (40%). The side effects are at times intense and intolerable to the extent of discontinuation of the therapy. A few often persist even after the therapy. The drug is costlier than progestogen. Gestrinone (p. 531) has got the same mechanism of action like that of danazol. The side effects are less than danazol. Administration is simple, twice a week (see Table 21.6).

GnRH analogues (p. 525) —When used continuously act as medical oophorectomy, a state of hypoestrinism and amenorrhea. The goal is to maintain a reduced level of serum estrogen (30-45 pg/mL) so that growth of endometriosis is suppressed. The side effects are more tolerable than danazol. The drugs have got limited availability and costliest of all the drugs used. Long-term therapy (more than 6 months) should be avoided (see add-back therapy p. 527, 528).

Results: The efficacy of the hormone therapy is judged by relief of symptoms, reduction of the volume of the lesions as revealed by second look laparoscopy, improvement of fertility and prevention of recurrence. For quick relief of symptoms and reduction of the volume of the lesion, GnRH analogues are the best. Progestogens take some time to achieve these objectives. Danazol is placed midway between the two.

TABLE 21.6 HORMONES USED IN ENDOMETRIOSIS

Drugs

Dose

Mechanism

Side effects

Combined estrogen progestogen (oral pill)

1-2 tablets

6-9 months

Pseudopregnancy

Tolerated (see ch. 29)

Progestogens (p. 534)

Oral

• Medroxyprogesterone acetate

• Dydrogesterone

• Norethisterone

IM

• Medroxyprogesterone

IUCD

• Levonorgestrel-releasing-IUCD (p. 459)

10 mg thrice daily x 6-9 months 10-20 mg daily x 6-9 months 10-30 mg daily x 6-9 months

150 mg 3 months interval x 2

Pseudopregnancy

Tolerated (see p. 537)

Danazol (p. 530)

400-800 mg orally in 4 divided doses x 6-9 months

Pseudomenopause

Less tolerated (see p. 531)

Gestrinone (p. 530)

1.25 or 2.5 mg twice a week x 6-9 months

Pseudomenopause

Well tolerated (see p. 531)

GnRH analogues (p. 525)

• Leuprolide 3.75 mg IM monthly x 6 months

• Naferelin 200 pg intranasally daily x 6 months

• Goserelin 3.6 mg depot IM monthly x 6 months

Medical oophorectomy

Well tolerated (see p. 526)

Taking every aspect together (pain relief, pregnancy rates, recurrence rates, costs and side effects), no single medical treatment is superior to others.

Following medical suppression or other conservative surgery, residual endometriotic lesions may regenerate once the ovarian function is reestablished. Overall recurrence rate is about 40 percent after 5 years.

SURGICAL MANAGEMENT OF ENDOMETRIOSIS

Indications

♦ Endometriosis with severe symptoms unresponsive to hormone therapy.

♦ Severe and deeply infiltrating endometriosis to correct the distortion of pelvic anatomy.

♦ Endometriomas of more than 1 cm.

Surgery may be conservative or definitive.

CONSERVATIVE SURGERY

Conservative surgery is planned to destroy the endometriotic lesions in an attempt to improve the symptoms (pain, subfertility) and at the same time to preserve the reproductive function.

Laparoscopy is commonly done to destroy endometriotic lesions by excision or ablation by electrodiatherapy or by laser vaporization. Conservative surgical treatment in minimal to mild endometriosis (ablation plus adhesiolysis) improves the fertility outcomeLaparoscopic uterosacral nerve ablation (LUNA) is done when pain is very severe. The advantage of laser is to cut the tissues precisely with least chance of damage to the underlying vital structures. Great deal of technical expertise is essential to avoid injury to the ureters.

Surgical treatment improves fertility and symptoms in women with moderate and severe endometriosis.

OVARIAN ENDOMETRIOMAS (see Fig. 21.4)

♦ Small endometrioma (< 3 cm) is aspirated laparoscopically. The cyst cavity is irrigated with normal saline. Cyst wall epithelium is destroyed by laser vaporization.

♦ Large endometrioma (> 4 cm) is often associated with extensive adhesion to other pelvic structures. Laparoscopy is necessary for ovarian cystectomy and adhesiolysis.

Results: Laparoscopic cystectomy is effective in relieving pain in about 74% cases of mild to moderate disease. Pregnancy rate is observed in about 60% cases with moderate and 35% cases with severe disease. Restoration of normal pelvic anatomy improves fertility in cases with severe endometriosis. High pregnancy rate is observed within first 6 months of conservative surgery.

Infertility associated with endometriosis: When there is no improvement of infertility due to endometriosis with the usual treatment, couple should be counseled for ART (p.251). Controlled ovarian hyperstimulation with IUI, IVF, GIFT and ICSI are the different methods (see p. 250). Definitive surgery: It is indicated in women with advanced stage endometriosis where there is: (i) No prospect for fertility improvement. (ii) Other forms of treatment have failed. (iii) Women with completed family.

Definitive surgery means hysterectomy with bilateral savlpingo-oophorectomy along with resection of the endometrial tissues as complete as possible.

Combined Medical and Surgical

Preoperative hormonal therapy aims at reduction of the size and vascularity of the lesion which facilitate surgery. The idea of postoperative hormonal therapy is to destroy the residual lesions left behind after surgery and to control the pain. But it does not improve fertility. It is generally avoided.

Duration of therapy is usually 3-6 months preoperatively and 3-6 months postoperatively. The cumulative probability of pregnancy at 3 years following laparoscopic surgery was 47% (51% for stage I, 45% of stage II, 46% of stage III and 44% for stage IV). Overall risk of recurrence is 40% by 5 years time.

Emperical treatment of pelvic pain with the presumptive diagnosis of pelvic endometriosis may be given with combined oral contraceptives.

ENDOMETRIOSIS AT SPECIAL SITES

♦ Abdominal scar ♦ Umbilicus

♦ Bladder and ureter ♦ Gut

♦ Cervix and vagina ♦ Lung

Scar (Fig. 21.5): It usually manifests following abdominal hysterotomy, cesarean section, myomectomy or even tubectomy. Implantation theory can explain its entity.

The patient complains of painful nodular swelling over or adjacent to the scar which increases in size and often bleeds during periods. The size is variable, nodular feel, tender with restricted mobility.

Fig. 21.5: Bleeding from a scar endometriosis. The patient was examined during her menstruation

Associated pelvic endometriosis is usually absent.

The same type of nodular swelling can be found over episiotomy scar. Treatment is by excision. Hormone therapy is ineffective.

Umbilicus: There is nodular painful swelling which increases in size and becomes tender during period. At times, bleeding may also occur. Coelomic metaplasia theory can explain its origin.

Treatment is by excision.

Bladder: The patient complains of dysuria, frequency, hematuria and lower abdominal pain specially during periods. Cystoscopic examination reveals blue area of the mucosa. IVP may reveal ureteric stricture and hydroureteric or even hydronephrotic changes on the affected side.

Treatment is not much effective with hormones. Local excision of the bladder wall and repair should be done. In ureteric involvements, the segment of the ureter is to be excised followed by implantation of the ureter to the bladder.

Gut: The rectum, sigmoid colon or even the small intestine are the common sites. Coelomic metaplasia theory can explain the endometriosis at these sites. The mucosa is not involved, a differentiating feature from malignancy.

The patient complains of periodic colicky pain on defecation or at times bleeding per rectum specially during periods. Associated pelvic endometriosis is a constant feature. There may be even features of subacute intestinal obstruction.

Rectal examination and investigations like sigmoidoscopy and barium enema confirm the diagnosis.

Lungpleura, and brain are the rare sites. This may cause catamenial pneumothorax or seizures during mens.

Treatment: Hormone treatment may be effective. If it fails, surgery may have to be done. In young patients, resection anastomosis and in patients above 40, removal of the ovaries may help regression of the lesions.

Cervix and vagina: The lesions are usually due to implantation of the endometrium over the trauma inflicted at operation or following delivery. The only complaint may be dyspareunia. The lesion is revealed by speculum examination. Confusion may arise with carcinoma cervix. There is, bleeding on touch in carcinoma. Confirmation is done by biopsy. Treatment by hormone is ineffective. Surgical excision may be required.

ADENOMYOSIS

DEFINITION: Adenomyosis is a condition where there is ingrowth of the endometrium, both the glandular and stromal components, directly into the myometrium.

CAUSES: The cause of such ingrowth is not known. It may be related to repeated childbirths, vigorous curettage or excess of estrogen effect. Pelvic endometriosis co-exists in about 40 percent.

PATHOGENESIS: Histologically, it is characterized by the extension of endometrial glands and stroma beneath the endometrial—myometrial interface (EMI). As the submucosa is absent, endometrial glands lie in direct contact with the underlying myometrium. It forms nests, deep within myometrium. Subsequently, threre is myometrial hyperplasia around the endometriotic foci. Myometrial zone anatomy was observed by MRI. A junctional zone (with low signal intensity on T2 weighted images) is defined at the innermost layer of myometrium. It is thought that the disturbance of normal junctional zone (JZ) predisposes to secondary infiltration of endometrial glands and stroma to inner myometrial zone. The disturbance ofjunctional zone (JZ) may be due to the endometrial factors, genetic predisposition or altered immune response. Trauma to the deeper endometrium (repeated curettage), causing breakdown of EMI is also taken as an important etiologic factor.

PATHOLOGY: The growth and tissue reaction in the endometrium depend on the response of the ectopic endometrial tissues to the ovarian steroids. If the basal layer is only present, the tissue reaction is much less, as it is unresponsive to hormones. But, if the functional zone is present which is responsive to hormones, the tissue reaction surrounding the endometrium is marked. There is hyperplasia of the myometrium producing diffuse enlargement of the uterus, sometimes symmetrically but at times, more on the posterior wall. The growth may be localized or may invade a polyp (adenomyomatous).

Naked eye appearance: There is diffuse symmetrical enlargement of the uterus; the posterior wall is often more thickened than the anterior one. The size usually does not increase more than a large orange (12-14 weeks pregnant uterus). On cut section, there is thickening of the uterine wall. The cut surface presents characteristic trabeculated appearances. Unlike fibroid, there is no capsule surrounding the growth. There may be visible blood spots at places (Figs 21.6 and 21.7).

Histological examination: Histological examination reveals glandular tissue like that of endometrium surrounded by stromal cells in the myometrium. The response of the ectopic endometrial tissue to ovarian hormones is minimal as the invasion is predominantly in the basal layer (Fig. 21.8).

CLINICAL FEATURES

In about one-third, it remains asymptomatic being discovered on histological examination.

Fig. 21.6: Specimen of adenomyosis with characteristics features as described in Fig. 21.7

Fig. 21.7: Adenomyosis. Note the absence of capsule and presence of dark blood spots

Fig. 21.8: Histologic picture of adenomyosis

Patient profile: The patients are usually parous with age usually above 40.

Symptoms: Menorrhagia (70%)—The excessive bleeding is due to increased uterine cavity, associated endometrial hyperplasia and inadequate uterine contraction. During normal menstruation, there are antegrade propagation of subendometrial contractions from the fundus to the cervix. In adenomyosis with distorsion of junctional zone myometrial contractions are abnormal and inadequate (see below).

Dysmenorrhea (30%)—Progressively increased colicky pain during period is due to retrograde pattern of uterine contractions. It also depends on the number and depth of adenomyotic foci in the myometrium. When the depth of penetration is > 80% of the myometrium, the pain is severe. Other causes of pain are—local tissue edema and prostaglandins.

Dyspareunia or frequency of urination—are due to enlarged and tender uterus.

Infertility: Women with adenomyosis have a higher incidence of infertility and miscarriage. The reasons are: (a) abnormal function of the subendometrial myometrium, (b) retrograde myometrial contractions, (c) interference in sperm transport and blastocyst implantation and (d) abnormal endomerial immune respose and nitric oxide level.

Signs: Abdominal examination may reveal a hypogastric mass arising out of the pelvis and occupying the midline. The size usually does not exceed 14 weeks pregnant uterus.

Pelvic examination—reveals uniform enlargement of the uterus.

The findings, however, may be altered due to associated fibroid or pelvic endometriosis.

Ultrasound and Color Doppler (TVS) characteristics are: Myometrium normally has three distinct zones of different echogenecity. The inner layer is hypoechoic relative to the middle and outer layer. This subendometrial halo is characteristic in adenomyosis. Other features are: (i) heterogenous echogenecity, (ii) hypoecoic myometrium with multiple small cysts in the myometrium (honeycomb appearance), (iii) increased vascularity within the myometrium (see Fig. 21.9).

Magnetic Resonance Imaging (MRI): It is more specific to the diagnosis. Low signal intensity JZ < 8 mm excludes the disease. Whereas JZ thickness > 12 mm is suggestive of adenomyosis.

TREATMENT: The treatment is surgical. There is little place of hormone therapy. Treatment with progestins or cyclic estrogen and progestin have got little benefit. Levonorgestrel-releasing-IUS (p. 479) is found to improve the menorrhagia and dysmenorrhea. Danazol—loaded (300-400 mg) intrauterine device (IUD) is also found to improve the symptoms of menorrhagia and dysmenorrhea. Serum danozol levels were not detectable and the side effects were minimal.

Surgical management: (A) Conservative surgery: • Adenomyomectomy • Uterine mass reduction (Laparotomy or laparoscopy). (B) Hysterectomy (parous and aged women).

STROMAL ENDOMETRIOSIS

This is a rare condition where the endometrial stromal cells, without glandular components, are present in places other than uterine mucosa.

PATHOGENESIS: The stromal cells extend into the myometrium or even broad ligament along the course of the lymphatics and muscle bundles. As there is a chance of recurrence, it is considered as locally malignant. The uterus is uniformly enlarged as in adenomyosis. Microscopic examination reveals round and oval cells of endometrial stroma.

Clinical features are similar to a case of adenomyosis.

TREATMENT: Hysterectomy with bilateral salpingo-oophorectomy is the effective surgery. In younger patients, the ovaries may be preserved. Radiotherapy may be needed in proved cases following its recurrence or incomplete surgery.

KEY POINTS

The presence of functioning endometrium (stroma and glands) in sites other than uterine mucosa is called endometriosis. Endometriosis is a disease seen in the reproductive years of a woman as its growth depends on estrogen. The incidence is about 10 percent but incidence is high (30-40%) amongst infertile women as based on diagnostic laparoscopy and laparotomy. The commonest abdominal site is ovary followed by pouch of Douglas and uterosacral ligaments (organs on the dependent part of the pelvis).

Endometriosis is a disease of contrast. It is a benign disease but it is locally invasive, disseminates widely and proliferates in the lymph nodes. Minimal disease may have severe pain whereas large endometriosis may remain asymptomatic. Cyclic hormones stimulates growth whereas continuous hormones suppress it.

Abdominal scar is the commonest site of endometriosis following hysterectomy, hysterotomy, cesarean section, tubectomy or myomectomy (Fig. 21.5).

The disease is full of theories and no one single theory can explain endometriosis at all sites. Genetic basis and defect of local cellular immunity may be implicated (Table 21.2). In spite of dense adhesions amongst the pelvic structures, the fallopian tubes are usually patent. In pelvic endometriosis, typically there are small black dots—‘powder burns' or "gunshot" seen on uterosacral ligaments and pouch of Douglas. Other lesions are flame-shaped polypoidal, hemorrhagic and white patches.

About 25 percent have got no symptom. Symptoms are not related to the extent of lesion. Severity of endometriosis and the degree of pelvic pain are not always proportional. Unlike primary dysmenorrhea, the pain lasts for many days before and after the menstruation.

Dysmenorrhea is associated in 50 percent, menorrhagia in 60 percent and infertility in 40-60 percent. Endometriosis is found in 30-40 percent of infertile women.

Clinical diagnosis is by the classic symptoms of progressively increasing dysmenorrhea, dyspareunia, infertility and feel of nodules in the pouch of Douglas. Confirmation is by laparoscopy or laparotomy.

Histologic diagnosis of endometriosis is ideal. Microscopic diagnostic features are: presence of endometrial glands, stroma and hemosiderin-laden macrophages.

Double puncture laparoscopy is considered the ‘gold standard' for the diagnosis.

The natural course of the disease is ill understood. It is progressive in about 30-60 percent patients and for the remainder it is either static or resolve spontaneously. Unfortunately, it is impossible to predict in which patient it will progress. Red blood filled lesions are the most active phase of endometriosis. Serum marker CA 125 is helpful in follow up cases of proved endometriosis.

Endometriosis is often associated with tubal and ovarian damage (see Table 21.4). These combined factors along with endocrinopathy (Table 21.3) may be responsible for infertility. However, the association of minimal to mild endometriosis and infertility is controversial.

The complications include endocrinopathy (LPD, anovulation, LUF or elevated prolactin level) rupture chocolate cyst, infection of the cyst or obstructive features (intestinal or ureteric).

Other complications of endometriosis are: Acute abdomen due to rupture of chocolate cyst, infection of the cyst, colorectal obstruction and ureteral obstruction.

The short-term goals of treatment for endometriosis are : (i) relief of pain and (ii) improvement of fertility. The long-term goal is to prevent progression or recurrence of the disease.

Expectant treatment is extended to unmarried or young married with no abnormal pelvic findings. Endometriosis causes pelvic inflammation. So the drugs used are non-steroidal, anti-inflammatory drugs (NSAIDs) or prostaglandin synthetase inhibitors.

The hormonal treatment should be considered suppressive rather than curative. The mechanism of atrophy can be explained by pseudopregnancy or by pseudomenopause or by medical hypophysectomy (see p. 311). The commonly used hormones are given in the Table 21.6.

The objective of medical therapy is to create amenorrhea (hypoestrogenic state). Aromatase inhibitors (letrozol 2.5 mg daily) are used to inhibit aromatase which converts androgens to estrogens. Estrogen promotes its growth (p. 310, 531). The overall fertility rate and the recurrence rate is about 40 percent.

The effect of danazol is by its 'pseudomenopause' response. The side effects are due to its androgenic and anabolic properties (see p. 530). GnRH agonists produce 'Medical oophorectomy' and the side effects are due to the estrogen deprivation (see p. 525). 'Add back' therapy is suggested with chronic use of GnRH agonists.

Conservative surgery in endometriosis includes removal of all macroscopic endometriosis, lysis of adhesions and restoration of normal pelvic anatomy. The surgery is preferably done by laparoscopy (diathermy, laser vaporization). Endoscopic laser surgery is the best in selected cases for the treatment of pain and to prevent the disease progress.

Ovarian endometriosis (< 3 cm) is treated by laparoscopic cyst aspiration. The cyst wall is vaporized to destroy the mucosal lining. Large ovarian endometrioma (> 3 cm) is treated by laparoscopic ovarian cystectomy. Laparoscopic adhesiolysis should be done at the same time. Laparoscopic ovarian cystectomy improves fertility.

Preoperative medical treatment with GnRH analogue may reduce the vascularity and the extent of the disease. Postoperative medical treatment should not prevent pregnancy as the chance of pregnancy is highest during the first 6-12 months after the conservative surgery.

Definitive surgery includes total hysterectomy with bilateral salpingo-oophorectomy. Laparotomy is done for advanced stage disease or in women who has completed her family.

Postoperative estrogen replacement therapy after total hysterectomy and bilateral oophorectomy may be given 3 months after surgery. The risk of recurrence is very low.

Adenomyosis primarily occurs in parous women over the age of 35. Adenomyosis is associated with pelvic endometriosis in 40 percent. Menorrhagia (70%) and dysmenorrhea are the chief complaints. Uterus is diffusely enlarged (2-3 times). Uterine size > 14 weeks gestation is rare.

Hormone treatment is often ineffective. Levonorgestrel-releasing IUS (p. 484) is found to improve menorrhagia and dysmenorrhea. Hysterectomy is the effective treatment in a parous and aged women.



If you find an error or have any questions, please email us at admin@doctorlib.info. Thank you!