532

ENDOMETRIOSISBy R. M. FEROZE, M.D., F.R.C.S., M.R.C.O.G.

Obstetric and Gynaccological Surgeon, King's College Hospital; Surgeon, Chelsea Hospital for Women.

Endometriosis is disease in which tissueresembling more or less perfectly the endometriumis found in ectopic sites; these sites are usually con-fined to the pelvis, but extra-pelvic lesions are alsoencountered. The condition is common in womenwho are infertile or relatively infertile. It usuallybegins to cause symptoms around the age of thirtyyears, and the disease is then progressive in mostcases until ovarian function ceases. In thosewomen who have borne children, and they seldomhave had more than one, the symptoms follow somenine to ten years after the last confinement.Meigs (I949) is of the opinion that self-imposedinfertility is conducive to the development ofendometriosis, but there is no doubt that thedisease, once present, is itself a serious obstructionto conception. The nature of the condition remainssomewhat of a mystery, for whilst it is capable offorming tumours of a kind, these do not behavelike either true benign or malignant tumours and,unless stromatous endometriosis be included, theynever directly cause the death of the patient.PathologyThe sites of the lesions can be grouped as

follows :A. Pelvic,

(a) Genital Tract:I. Uterine:

(i) Diffuse.(ii) Localized.

2. Extra-uterine:(b) Extragenital.

B. Extra-pelvic.On microscopical examination the essential

feature is the appearance of the endometrial-liketissue, consisting of both glandular structures andstroma, in the various sites. The resultant picturevaries considerably according to the tissue invol-ved; for example, in the uterus there may be anaccurate reproduction of normal endometrium,whereas in the ovary it may sometimes be imposs-ible to find microscopical evidence of any recogniz-able endometrial tissue. The ectopic endometriumis usually responsive to the influence of the ovarian

hormones, and all variations may be seen rangingfrom the decidual reaction of pregnancy to theabnormal picture associated with cystic glandularhyperplasia. In other cases, there is no'physio-logical response and the endometrium remains inthe proliferative phase.

In the uterus itself the process may be eitherdiffuse, when it is called adenomyosis, or morelocalized to form an adenomyoma. Adenomyosisoften attacks one wall of the organ to a muchgreater extent than the other, giving rise to aslightly asymmetrical enlargement. The adenomy-oma bears a superficial resemblance to the fibromy-oma, but it has no capsule, its whorled andtrabeculated cut surface does not show the circum-scribed nodular arrangement of the fibromyoma,and it is frequently revealed by the tell-talehaemorrhagic or 'chocolate' spots, which are theendometrial islands scattered amongst the musclefibres.

In the last thirty years or so a number of authorshave described a rare condition known as stroma-tous endometriosis, in which there is invasion of theuterus, or occasionally of the ovary, by cells indis-tinguishable from the normal stroma of theendometrium; glandular structures are not foundamongst these stroma cells. Apart from themicroscopical appearance of the cells there seemsto be little reason to consider this condition as alliedto endometriosis. Although it has been describedin younger women, many cases have occurred inpatients over forty years of age and even in somewomen past the menopause. Indeed the onset ofthe menopause, either natural or induced, does notalways cause regression of the condition. Cyclicalbleeding into the abnormal cell masses does notoccur, and menorrhagia rather than dysmenorrhoeais the main symptom. There is a tendency to formpolypoidal masses which project into the cavity ofthe uterus. Spread to, and invasion of, tissues andstructures in contiguity with the uterus may occur.Finally, local recurrence, sometimes after a longpatent period, is not unknown and has in somecases resulted in the death of the patient. Park(I949) in an interesting paper on the subject sug-gests the use of some non-committal term like

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$34 POSTGRADUATE MEDICAL JOURNAL November -I956

' stromatoid neoplasm of the myometrium.' Butthis is unlikely to compete with the more conciseappellation at present used. Novak (I953), how-ever, considers the condition to be a variety ofadenomyosis, with the exception of the apparentlymalignant types, which he classifies as uterinesarcomata. Goodall (I944) also classified the con-dition as a type of endometriosis.The extra-uterine sites in the genital tract in-

clude the ovaries, Fallopian tubes, uterine liga-ments, peritoneum covering the tract, cervix,vagina and recto-vaginal septum. In the ovariesthe chocolate cyst is the most notorious lesion.Chocolate cysts vary in size, but are seldom largerthan 4 in. in diameter; they may be quite small andmultiple; frequently they are bilateral. Becausethese cysts tend to perforate so that their contentsleak outside the ovary, adhesions form around thesites of perforation and spread to contiguous struc-tures follows. The appearances at laparotomy arefairly typical, in that the cystic ovaries are adherentto the posterior leaf of the broad ligament, withcharacteristic puckering of their surface, andthere is an escape of tarry fluid as an attempt ismade to free them. However, it is well to remem-ber that not all chocolate cysts are due to endo-metriosis; haemorrhage can occur into any cyst ofthe ovary.

Peritoneal involvement is most commonly seenin the pouch of Douglas, when the uterus isfound to be retroverted and fixed by dense ad-hesions to the rectum, which is drawn up, thusobliterating the pouch. Characteristic' blueberry'spots, or tiny endometrial cysts, may be seen alongthe line of contact between the viscera. Elsewherethe lesions are seen as small endometrial cysts,either alone or in association with foci of nodularity,puckering and adhesions. In the uterosacral liga-ments such nodular thickening is common andmay be the first detectable physical sign of thedisease. When the round ligament is involved aswelling may rarely appear in the groin. Theseligamentous lesions are true adenomyomata andbecome: swollen and painful during menstruation.The rectovaginal septum is usually involved in

association with extensive genital tract involvementelsewhere, but on occasion it is the main site.The lesion presents a fairly characteristic nodular,infiltratFve thickening, which might, however, bemistaken for malignant disease of the rectum. Thefact that endometriosis seldom erodes the mucosaof the bowel should help to distinguish betweenthe two conditions, but it should be rememberedthat on rare occasions malignant change can super-vene on the lesions of endometriosis.The extragenital sites in the pelvis include

peritoneum, bowel, in particular the sigmoid colon,gnd the bladder and ureters. In the bowel the

lesions may cause stricture formation and mimicmalignant disease, but search should be made forsigns of endometriosis elsewhere, for the tell-tale' blueberry' spots and for the absence of involve-ment of lymph nodes, or of erosion of the mucosa.Cystoscopy will only be of value in endometriosisof the bladder late in the course of the disease,when grape-like cysts and ' blue folds of oedema '(Phillips, I934) will be seen.

Extrapelvic sites include the umbilicus, lapar-otomy scars, hernial sacs, the bowel, the perineumand the vulva. More bizarre situations, such asthe back of the thigh, the upper arm and the pleurahave been authentically described, but they areexceedingly rare. The more superficial lesionspresent the characteristic tender swelling, whichenlarges and becomes more painful during themenstrual period.SymptomsDue to the diversity of lesions, the symptomat-

ology is equally diverse, but the most outstandingfeature is pain. By far the commonest complaintis of severe, acquired and progressively increasingdysmenorrhoea: this dysmenorrhoea may have apremenstrual congestive phase, but the most severepain occurs during menstruation and has a ten-dency to persist throughout the period. Kelly andSchlademan (I949), who drew attention to thissymptom, found acquired dysmenorrhoea in about48 per cent. of 179 cases and progressive dys-menorrhoea in about 33 per cent. It is assumedthat the pain is due to distension caused by men-struation of the enclosed ectopic endometrium.However, as has been noted above, the aberrantendometrium does not always respond to theovarian hormones and yet these lesions may still beassociated with considerable pain. Sometimeswidespread pelvic endometriosis is found un-expectedly during laparotomies for other con-ditions, such as uterine fibr9myomata, when nosymptoms referable to endometriosis have beenpresent; and, conversely, patients with little morethan slight nodularity of the uterosacral ligamentsand a little puckering of one ovary may havemarked symptoms. This discrepancy between theextent of the involvement and the severity of thesymptoms makes a rational explanation of thecause of the pain difficult. Other types of pain metwith are constant backache, situated low down inthe spine, pain around the rectum, both worseduring menstruation, and deep dyspareunia. Thesesymptoms are common with the classical lesionsinvolving the ovaries, the pouch of Douglas andthe uterosacral ligaments.

Whilst sterility, or relative infertility, is acommon finding, it is seldom the main symptom.Infertility clinics do not seem to discover the early

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November 1956 FEROZE: Endometriosis 535

stages of the disease amongst their clientele. Men-strual disorder is fairly common in endometriosisand is due either to pelvic congestion or, morelikely, to a common underlying endocrine disorder.The more obvious methods of presentation in thesuperficial lesions have been mentioned. The mostdramatic symptoms, such as cyclical haematuria orintestinal obstruction, occurring in conjunctionwith menstruation are rarely met. When thebladder is involved it is the base and trigonal regionwhich is most often affected and increased fre-quency of micturition, dysuria and suprapubicpain are the usual symptoms. Whilst small bowellesions may cause some degree of stricture forma-tion, this seldom occurs in the more commonlyaffected sigmoid colon, and here the lesion is mostoften discovered at laparotomy for involvement ofthe genital tract.

DiagnosisDespite the unusual nature of endometriosis,

the correct pre-operative diagnosis is often over-looked. In Kelly and Schlademan's series only14 per cent. of cases were correctly diagnosed.Whilst this difficulty is in part due to the fact thatthe condition may be relatively or completelysymptomless, or be masked by coincidental disease,such as fibromyomata, it is often due to ignoringthe possibility of its presence. It is a disease likepelvic tuberculosis, which needs to be borne inmind in the gynaecological clinic if it is to becorrectly diagnosed more often. Acquired andprogressive dysmenorrhoea in a sterile or relativelyinfertile woman about 30 years old should arousesuspicion. The presence of a fixed retroversion,or tender nodularity in the pouch of Douglas, isalso suggestive of endometriosis. The final diag-nosis can only be made, however, by surgicalexploration backed up in most cases by histology.But there are times when the diagnosis has to bemade solely on the macroscopical appearances atlaparotomy, for microscopical evidence may belacking, as is not infrequent in chocolate cysts ofthe ovary.Treatment

Treatment presents many difficulties becausethe disease tends to be progressive until ovarianfunction ceases. Whilst this makes it relativelyeasy to cure older women and those not quite soold, who have yet managed to satisfy their repro-ductive ambitions, in the younger women, who,unfortunately, present the larger group, it meansthat permanent cure is unlikely at the first attempt.In the former group complete extirpation of ovariantissue is all that is essential; this is, of course,usually combined with excision of the affectedtissues. When bowel, bladder or rectovaginal sep-

tum are involved such surgical castration is suf-ficient to cause regression of the lesion and, pro-vided malignancy has been excluded, resection isonly necessary where stricture formation is presentor imminent. In the younger age group conserva-tive measures must be practised and reproductivefunction retained for as long as is reasonable.Whilst analgesics may suffice in the early stages,something more drastic is required before long.Surgical intervention in these circumstances is atbest a piece-meal affair. Resection of diseasedtissues must be undertaken with conservation ofovarian function; division of adhesions bindingdown the uterus, tubes and ovaries may aid con-ception;. ventro-suspension will help to preventfurther adhesions forming; presacral neurectomyis of value to relieve pain only for lesions whichinvolve the uterus and uterosacral ligaments, butis valueless when the ovary is involved; finally,diathermy coagulation is some help for the discretesmall foci scattered about the pelvis. Recurrencein these young women is to be expected, unlesspregnancy follows. Although infertility is commonin endometriosis, pregnancy does occur in a smallnumber of cases, as Gainey et al. (I952) showed.Whilst it is true that many of these cases were onlydiagnosed presumptively, others were confirmedby operation and microscopical examination. Theseworkers state that several of their cases showedmarked subjective and objective improvementduring pregnancy and that this improvement wassustained subsequent to confinement for periodsranging up to four years. A few patients success-fully undertook further pregnancies. Kelly andSchlademan (I949) also report pregnancy follow-ing conservative operations for endometriosis in23 per cent. of women who might reasonably havebeen expected to conceive. This possibility ofconception, and the hope of the beneficial action ofpregnancy, is the basis for conservative treatmentand has led to the idea of inducing a pseudo-pregnant state by oestrogen therapy. Karnaky(1954), wJo has been advocating this method oftreatment for some years, endeavours to keep hispatients in a state of amenorrhoea for periods upto nine months. He uses micronized stilboestrol,starting with a dosage of i mg. per day andgradually increasing up to 100 mg. per day. Somepatients require even larger doses to avoid bleeding.Karnaky claims striking results in that extensivelesions have disappeared and pain has been relieved.Haskins and Woolf (1955) also report good resultsin i5 cases treated along these lines and claimfreedom from symptoms for periods. up to twoyears following treatment. There still remains,however, widespread reluctance to use such largedoses of oestrogens in this country and also insome quarters of the United States (Novak, 1956).

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536 POSTGRADUATE MEDICAL JOURNAL November I956

Testosterone is a more popular form of therapy inGreat Britain, but in the main it can be onlypalliative in its action, for size and duration of dosemust be limited by fear of unwanted side effects.It.is noteworthy, however, that Macafee (I954)has caused complete resolution of a lesion in theperineum with testosterone. X-ray induction ofthe.menopause is of value only when surgery hasalready been undertaken, as the diagnosis must ofnecessity remain presumptive until the abdomenhas been explored. There are two types of casewhere such treatment is indicated, first in theolder woman in whom complete extirpation ofovarian tissue has been impossible due to technicaldifficulties, and secondly in the younger womanwho has a recurrence of symptoms following con-servative surgical intervention, and for whom radio-therapy is preferred to a further difficult surgicalventure.The aetiology of the condition has been dis-

cussed at length by many authors and so will bementioned but briefly here. The main theoriesare:

i. Cullen's direct invasion theory, which mostauthors agree accounts for many cases of adeno-myosis uteri, although there are some who believethe myometrium capable of forming both glandularand stromal cells.

2. Sampson's implantation spill theory, which,after a period of rejection, is now again being morewidely accepted, particularly in view of the experi-mental evidence furnished by Scott and Te Lindeto show that in monkeys menstrual endometriumcan implant in the abdomen and give rise toendometriosis.

3. Iwanoff's serosal metaplasia theory has manysupporters and ingenious explanations are offeredto explain all the reported lesions by this onetheory. However, there seems to be no convincingexplanation why there is never any transitionalform seen and why the metaplasia should be sofocal in nature and not more generalized.

4. Halban's lymphatic theory has few adherents;although lymph nodes have been found with endo-metrial structures in them, they are not common.

Whilst endometriosis is not a true neoplasm, itbears many close resemblances to one and thereforeit might not be unreasonable to suppose that thespread of viable endometrial cells to ectopic situa-tions could occur in a number of different waysand that, in differing circumstances, any one ormore of the above theories might account for thevarious lesions of endometriosis.

I wish to thank Mr. A. J. Bailey for preparingthe photomicrographs from material belonging tothe Department of Pathology, Chelsea Hospitalfor Women.

BIBLIOGRAPHYGAINEY, H. L., KEELER, J. E., and NICOLAY, K. S. (1952),

Amer. J. Obstet. Gynec., 63, 511.GOODALL, J. R. (I944), ' A Study of Endometriosis,' 2nd edition,

Lipincott, Philadelphia.HASKINS, A. L., and WOOLF, R. B. (I955), Amer. J. Obstet

Gynec., 5, I13.KARNAKY, K. J. (1954), Mississippi Valley med. J., 76, I87.KELLY. F. J., and SCHLADEMAN, K. R. (I949), Surg. Givnec.

Obstet., 88, 230.MACAFEE, C. H. G. (1954), J. Obstet. Gynaec. Brit. Emp., 6I, 349.MEIGS, J. V. (I949), Surg. Gynec. Obstet., 89, 3I7.NOVAK, E. (X953), ' Gynecologic and Obstetric Pathology,' 3rd

edition, Saunders, Philadelphia, p. 222.NOVAK, E. (1956), Obstet. Gynec. Survey, IX, I22.PARK, W. W. (1949), J. Obstet. Gynaec. Brit. Emp., 46, 759.PHILLIPS, R. B. (I934), Ibid., 4I, I65.

RUTHIN CASTLE, NORTH WALESA Clinic for the diagnosis and treatment of Internal Diseases (except Mental or Infectious Diseases). The

Clinic is provided with a staff of doctors, technicians and nurses.The surroundings are beautiful. The climate is mild. There is central heating throughout. The annual

rainfall is 30.5 inches, that is, less than the average for England.The Fees are inclusive and vary according to the room occupied.

For particulars apply to THE SECRETARY, Ruthin Castle, North Wales.Teaegrams: Catle, Ruthin. Telephone: Ruthin 66

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