ENDOMETRIOSIS

Endometriosis denotes presence of functioning endometrial tissue in an abnormal location, in other words, outside the uterus (Box 35.1). The locations and the approximate chance of the lesion affecting the organ or structure are shown in Figure 35.1.

Diagnosis Can only be diagnosed at laparoscopy and confirmed by biopsy Symptoms Frequently symptomless, the main reasons for investigation being menstrual irregularities, premenstrual ‘dysmenorrhoea’ pain, non-cyclical pelvic pain, dyspareunia and infertility Management Outcome

Aetiology

How the endometrium reaches the ectopic locations is not entirely understood. The explanation to account for most of the endometrial lesions is retrograde passage of endometrial tissue along the Fallopian tubes during menstruation. This is supported by the observation that endometriosis only occurs in primates that menstruate and that explains the majority of sites where it is found: on the ovaries, the uterosacral ligament, or in the cul-de-sac (pouch of Douglas). It is believed that retrograde menstruation occurs in most women, but the development of other than temporary endometrial nodules (blisters) only occurs in some women. To explain the rare deposits of endometriosis in distant sites, for example the umbilicus, the lung and eye, lymphatic or haematogenous spread has been suggested. Metaplasia of mesothelial coelomic cells into endometrial cells has also been suggested.

Once viable endometriotic tissue has reached and adhered to the ectopic location, it still has to be explained why it survives and grows, instead of being eliminated by macrophages. A current theory is that there may be a defect in cell-mediated immunity which permits the endometrial tissue to survive. In order to grow in these ectopic sites, the endometrial tissue has to respond to cyclical oestrogen and, to a lesser extent, progesterone. If a constant oestrogen milieu occurs, as in pregnancy, the lesions tend to be attacked by macrophages and become fibrotic.

Why endometriosis spontaneously regresses or fails to progress in half of the cases is also not fully understood.

Pathology

Whatever the location, the ectopic endometrium, surrounded by stroma, implants and forms a miniature cyst, which responds to the cyclic secretion of oestrogen and progesterone, just as the uterine endometrium does. During menstruation, bleeding occurs in the cyst, and the blood, endometrial tissue and tissue fluid are trapped. Over the next cycle, the tissue fluid and the blood plasma are absorbed, leaving dark, thickened blood. The cycle recurs each month and slowly the cyst enlarges, containing increased amounts of tarry, chocolate-coloured inspissated blood. The maximal size of the cyst depends on its location. Small cysts may remain small, or be attacked by macrophages and become small fibrotic lesions. Ovarian cysts (endometriomata) tend to be larger than other cysts, but do not usually become larger than a medium-sized orange. As the cyst grows, internal pressure may destroy the active endometrial lining, making the cyst non-functional.

Rupture or leakage of material from even small cysts is not uncommon. The released inspissated blood is very irritating, with the result that multiple adhesions surround the cysts. The ectopic endometrium and stromal cells also tend to infiltrate adjacent tissues, leading to more pelvic adhesions and fixation (Fig. 35.2). If an ovarian cyst is found which looks like an endometrioma, but there are no adhesions, the diagnosis is unlikely to be endometriosis.

Endometriotic tissue, compared with endometrium, has increased levels of oestrogen, prostaglandins and acute inflammatory cytokines such as interleukin-1β, interleukin-6 and tumour necrosis factor. These inflammatory cytokines in company with increased proteolytic metalloproteins may promote implantation of the endometrial fragments. The prostaglandin release is enhanced by increased cyclooxygenase (COX) expression and is mediated by increased oestradiol, including endometriotic oestradiol, and vascular endothelial growth factor (VEGF) levels. The increased prostaglandin production directly induces pain (PGE₂), vasoconstriction and uterine contractions (PGF_2α) and inflammatory and immune responses. Progesterone does not appear to have a major role in the pathogenesis and endometriotic tissue has very low levels of progesterone receptors.

As mentioned, the ovary is most often involved, and ovarian endometriosis may present as small superficial implants (red or black spots) or a larger endometrial cyst. Lesions on the surface of the broad ligament occur either directly from implanting endometrial tissue or as a secondary spread from the ovarian deposit. In these locations the endometrial deposits cause puckering of the peritoneum and adhesions to the posterior surface of the uterus, often fixing it in retroversion. Lesions in the cul-de-sac are of interest, as they may not be palpable or visualized by a laparoscope unless the laparoscopy is made during menstruation.

Clinical features

The clinical features of endometriosis are often non-specific. In at least a quarter of women who have the disease it is symptomless. The symptoms may be bizarre because of the varying locations of the disease and, in many cases, the lack of correlation with the extent of the lesions. They include pain, menstrual irregularities, dyspareunia and infertility.

Clinical examination

Abdominal and pelvic examination may show no abnormality if the lesions are small. It has been suggested that the pelvic examination should be made during menstruation, or soon after, to detect lesions in the pouch of Douglas that may not be apparent at other times of the menstrual cycle. Larger cysts cause fixed, tender nodular swellings and may be easily palpable.

Diagnosis

It is often difficult clinically to distinguish endometriosis from pelvic inflammatory disease or an ovarian cyst. Because of this, it is necessary to visualize the lesions through a laparoscope and to biopsy them to confirm the diagnosis. At laparoscopy the extent of the disease should be determined, as this will influence the treatment (Table 35.1).

Management of endometriosis

The management of endometriosis depends on the extent of the disease (see Table 35.1), on the severity of the symptoms, and on the desire of the woman to retain her fecundity. In primary care the combined oral contraceptive and non-steroidal anti-inflammatory drugs should be included. Figure 35.3 is an algorithm showing the management of this disease, details of which will now be discussed.

Psychological aspects of endometriosis

The knowledge that she has endometriosis can cause considerable distress to a woman. In part, this is because of the poor correlation between the size and number of the lesions and the symptomatology, and in part it is due to the publicity that endometriosis receives in the popular press.

The doctor should explain what endometriosis is and what it is not. The differentiation between endometriosis and the premenstrual syndrome needs to be discussed because some symptoms are similar. The relationship between endometriosis and infertility needs to be discussed and treatment strategies outlined. The woman should be made aware of the choices of hormonal treatment and surgery (or a combination of the two), and of their relative merits in her case. The fact that endometriosis may recur following either treatment needs to be brought to her attention. However, the doctor should offer qualified optimism about the outcome, and should stress the importance of adequate follow-up.

ADENOMYOSIS

Adenomyosis is the presence of functioning endometrial tissue which has penetrated the myometrium by direct spread from the uterine lining (Box 35.2).