Adenomyosis: Difficult to Diagnose, and Difficult to Treatdownloads.hindawi.com/journals/dte/2001/340321.pdf · 90 C. WOOD women having MRI and uterine histology have adenomyosis[12]

Diagnostic and Therapeutic Endoscopy, Vol. 7, pp. 89-95Reprints available directly from the publisherPhotocopying permitted by license only

(C) 2001 OPA (Overseas Publishers Association) N.V.Published by license under

the Harwood Academic Publishers imprint,part of Gordon and Breach Publishing,member of the Taylor & Francis Group.

Short Communication

Adenomyosis: Difficult to Diagnose, andDifficult to Treat

C. WOOD*

Endometriosis Care Centre of Australia, Monash IVF, Monash University, Melbourne, Victoria, Australia

(Received 16 June 2000," Revised 14 August 2000; In finalform 4 September 2000)

Drug therapy may be effective in controlling symptoms but the frequent coexistence ofendometriosis and the lack of controlled studies make their efficacy difficult to quantify.Danazol IUD has been shown to reduce symptoms. Conservative surgery involving endo-myometrial ablation, laparoscopic myometrial electrocoagulation or excision has proven tobe effective in more than 50% of patients, although follow up has been restricted to threeyears. Arterial uterine artery embolization is a new technique which may be tried before con-sidering hysterectomy. Hysterectomy may still be necessary in severe cases of adenomyosis.

Keywords: Adenomyosis, Treatment

INTRODUCTION

The treatment of adenomyosis has been limited bythe difficulty and delay associated with the dia-gnosis, often not until after hysterectomy. Magneticresonance imaging, high resolution vaginal ultra-sound and uterine biopsy has improved earlydetection of adenomyosis [1].

Diagnosis of the extent and localization of thedisease is difficult, even with magnetic resonanceimaging (MRI), colour doppler vaginal ultrasoundand uterine biopsy techniques [2-9]. MRI is the

most sensitive test for detection of adenomyosisbut it is also the most expensive, limiting accessto affluent health care systems [8]. Uncertainty indefining the site and more particularly the extentof adenomyosis make it difficult to determine thefeasibility and accuracy of complete excision whenconserving the uterus. This is one reason why hyster-ectomy has remained the most popular operationfor adenomyosis.CA125 may be useful in diagnosisor determining the extent of the disease [10,11].

In subfertile women, under the age of 30 years,with dysmenorrhoea and menorrhagia, 28 of 56

* Tel.: +61 3 9415 7722. Fax: +61 3 9415 8461.

89

90 C. WOOD

women having MRI and uterine histology haveadenomyosis [12].One of the difficulties assessing results of

therapy is the lack of certainty of diagnosis, even

with histology, because of false negatives, anduncertainty of the MRI criteria for diagnosis.The specificity of the diagnosis by MRI, hasbeen determined by a junctional zone thicker than5mm. Thickness greater than 5mm has beenfound in 40% of normal subjects having serialMRI measurements which also showed thicken-ing up to 12mm and focal myometrial bulgingwhich may result from uterine contractions [13].Myometrial changes in thickness, nodularity andasymmetry, and increased vascularization may beseen at MRI and sensitive vaginal ultrasound.Drug therapy may be effective in controlling

symptoms but the frequent coexistence ofendomet-riosis and the lack of controlled studies make theirefficacy difficult to quantify. Danazol IUD hasbeen shown to reduce symptoms.

SPECIFIC ENDOSCOPIC SURGICALTECHNIQUES

The choice of a suitable surgical proceduredepends upon the site and extent of disease, theage of the patient, the desire for future pregnancy,the patient’s desire for certain cure or not, and thesurgical skill of the gynaecologist.

Endo-myometrial Ablation/Resection

Endo-myometrial resection is most suited topatients with disease limited to the endo-myomet-

rial junction as menstrual symptoms may bereduced and the pathology may be removed. Itmay also be useful when adenomyosis is presentin the outer myometrium as laparoscopic myomet-rial excision alone may not cure menstrualsymptoms, either because excision may be incom-plete or the menstrual symptoms are not caused bythe outer myometrial adenomyosis. Desire for afuture pregnancy contraindicates endo-myometrialresection.

Technique

The technique of endometrial ablation has beenwell described. If MRI or ultrasound shows theextent and site of endo-myometrial distortionthe procedure can be modified to include 2-3 mmof myometrium in the affected areas. The whole ofthe endometrium should be removed as menorr-

hagia may be due to factors other than the adeno-myosis. Deeper myometrial removal or ablationcarries the risk of causing increased bleeding assignificant arteries are situated about 5 mm deepto the myometrial surface. Histology of the excisedmyometrial fragments may help to confirm orrefute the diagnosis.When endo-myometrial resection has been per-

formed as a single operative procedure, menstrualsymptoms have been controlled in 55% of womenfor at least 2 years (Table I).

Laparoscopic Myometrial Electrocoagulation

Electrocoagulation has the capability of shrinkingadenomyosis by causing necrosis. The techniquehas been applied to localized or extensive disease

TABLE Results of conservative surgery, 1991-97

Symptom free

N 6 mths 24 mths

Hospital stay

(days)

Complications

Endo-myometrial resection 18Myometrial electrocoagulation 11Myometrial excision 25Subsequent hysterectomy

12 10(55%)7 6(55%)

20 16 (64%)10/54(18.5%)

1-21-3

003*

* 3 patients had a temperature of > 37.5 for more than 2 days.

DIFFICULTY IN DIAGNOSING ENDOMETRIOSIS 91

[1]. The adenomyosis can be detected by MRI,vaginal ultrasound, inspection of the uterus atlaparoscopy, myometrial needling, or manualpalpation during gasless laparoscopy to detectdifferences in consistency between normal andabnormal tissue. Electrocoagulation may beless accurate than surgical excision as electricalconduction in the abnormal tissue may be incom-plete and this cannot be checked at the time ofsurgery, It may also reduce the strength of themyometrium by replacing abnormal myometriumwith scar tissue. The width of the scar maybe more extensive than after surgical excisionwhen close apposition of normal myometrium isachieved.

Extensive myometrial electrocoagulation hasbeen performed in two women aged 42 and 46years with extensive adenomyosis on the anteriorand posterior uterine walls; drug therapy hadfailed, excision was not feasible, and hysterectomywas not wanted. Two years later both are freeof severe menstrual pain and bleeding. Diffusemultifocal electrocoagulation of the myometriumcontaining adenomyosis may be sufficient tocontrol symptoms. The risk of uterine rupturefollowing extensive electrocoagulation is demon-strated by the following experience. One patienthad two laparoscopic procedures involvingmyometrial electrocoagulation, one of whichwas also associated with excision of an elevatedadenomyotic area. The patient was aware ofthe risk of uterine rupture, she had not res-ponded to GnRH analogue therapy, was notsuitable for extensive myometrial excision andhad refused hysterectomy as she wished to

attempt conception even if this failed. A sub-sequent pregnancy resulted in uterine rupture at12 weeks.Electrocoagulation is best suited to women

over 40 years of age, who do not wish to conceive,and who wish to avoid more extensive surgerysuch as excision or hysterectomy. Even if recur-

rence occurs the procedure may be repeateduntil the onset of the menopause when symptomscease.

Technique

Uterine manipulation with a Valtchev manipulatorimproves access to the diseased areas by facilitat-ing antero-posterior and lateral movement of theuterus.

Vasoconstricting agents such as adrenaline andvasopressin are not used routinely as excessivebleeding has not been experienced and the blanch-ing of the myometrium after vasoconstrictionmakes it difficult to determine the devascularizingeffect of electrocoagulation or uterine vesselclosure.

Closure of the ascending uterine artery may beperformed if technically feasible, future pregnancyis not wanted, and the site of the adenomyosis is inthe upper uterine body. Bipolar forceps, clips or

suture ligation may be used to close the uterinevessels.

Electrocoagulation of the adenomyosis may becarried out with unipolar or bipolar needles, using50 watts coagulation current. Bipolar needles havea theoretical advantage of concentrating currentbetween the two needles, but their effectiveness isdiminished by the tendency of the two needles tomove close together as they penetrate the myomet-rium. Additionally, the area of coagulation mayspread outwards from each needle, simulating theeffect of monopolar electrocoagulation.The extent of coagulation can be controlled by

reducing the current strength and changing thetime the needle(s) are held in position. In order toreduce the possibility of severe surface necrosisand carbonization, either of which may encouragefuture adhesion formation, the insulated part ofthe needle is buried a few millimetres below theuterine surface before electrocoagulation is com-menced. The insulation on the bipolar needle canbe extended so that the active part of the electrodeis shortened in order to avoid surface coagulationand necrosis. Needle punctures are made at 1-2 cmintervals, depending on the spread of the coagu-lative effect. The depth of needle puncture mayvary, depending on the thickness of the adeno-myotic myometrium determined preoperatively

92 C. WOOD

by ultrasound or MRI. If hysteroscopic endo-myometrial ablation has also been carried out, thedepth of laparoscopic needle electrocoagulationmay be reduced.

Hysteroscopic endo-myometrial ablation maybe performed in association with myometrial elec-trocoagulation as menorrhagia and dysmenor-rhoea may not be related to the presence of outermyometrial adenomyosis.

Sterilization should be offered to all womenhaving myometrial electrocoagulation because ofthe possible future risk of uterine rupture in preg-nancy.

Bleeding is rare during electrocoagulation andcan be controlled by using a vasopressor or myo-tonic drugs such as adrenaline, oxytoxin or vaso-pressin, or by bipolar electrocoagulation or sutureligation.

Patients are usually in hospital for 8-24 hours.No complications have been observed includingpost-operative infection, bleeding or subsequentadhesion formation.The result of the surgery may be assessed by

symptom relief and MRI or vaginal ultrasound.Loss of features of adenomyosis including reduc-tion of myometrial thickness, reduced vascularityand normal myometrial appearance have all beenobserved. Symptom relief may occur and persistfor several years in the presence of reduced ultra-sound evidence of adenomyosis.

Myometrial Excision

Adenomyosis may be excised if it does notinvolve the major portion of the uterus, and itsextent can be defined as previously described. Thetechnique is also suitable for adenomyomaswhere the margins of the pathology are moreeasily defined. It may be useful in women wishingto become pregnant, providing sufficient myo-metrium remains to allow uterine expansion andterm pregnancy and the scar formed afterexcision is not wide or shallow. MRI or colourdoppler ultrasound after surgery should be usedto check both for cure, the width and depth of

scar, and the possible association of residualadenomyosis close to the scar, before attemptsat conception are advised.

Technique

Preoperative GnRH analogues or Danazol mayreduce uterine vascularity, correct anaemia if thepatient has severe menorrhagia, and reduce oper-ative bleeding which facilitates surgery by laparo-scopy rather than laparotomy. Vasoconstrictordrugs may also reduce bleeding at the time ofsurgery.

Prior to myometrial excision, as with electrosur-gical coagulation, the uterine blood supply may bereduced by suture or clip ligation or bipolar dia-thermy of the ascending uterine vessels in womennot concerned with fertility. Apart from reducingbleeding during surgery the reduction in bloodflow may reduce future growth or developmentof adenomyosis.Two associated surgical procedures may be

offered, sterilization to prevent conception andhysteroscopic endomyometrial ablation if menor-rhagia is present, and fertility is not required.

Minilaparotomy may be required to facilitatemyometrial excision. Laparotomy instrumentscan gain entry to the abdomen through a 2-4 cmincision which may be sufficient to remove andrepair areas of myometrium up to 6 8 cm.A Valtchev uterine manipulator is used to posi-

tion the adenomyotic areas as close as possible to alaparoscopic or minilaparotomy incision. Some-times a myoma screw may stabilize the diseasedarea and aid excision. A diathermy spoon using100 watts monopolar current, or scalpel, are suit-able for excision. The spoon has the advantage ofcutting effectively with the sharp end close to thetissue, and coagulating vessels when the convexcurve of the spoon compresses the vessel. Whenthe tissue is very firm the scalpel may be prefer-able, providing more effective and rapid excision.The margin of the adenomyosis may be deter-mined by change in appearance, vascularity or

consistency; finger palpation may be an advantage.


Closure of incisions longer than 5-6cm mayrequire laparotomy instruments as excision of asignificant volume of myometrium increases thetension at the myometrial edges which may haveto be stretched to close the defect. If the uterinewound is brought into a minilaparotomy incision,the defect can be closed more easily and quickly.Absorbable sutures (No. 1) are used in one ormore layers. If there is a large defect a single layerthrough and through suture may best approximatethe wound, acting as a tension suture, and becauseof the increased thickness of the whole myomet-rium, it is less likely to tear as tension is increasedto attain closure.

Anti-adhesives such as Interceed(R) and Goretex(R)

membrane may be used. The frequency ofadhesions after excision of adenomyosis has notbeen reported. Interceed may be used if perfecthaemostasis is obtained. Application of Surgicel(R)

prior to Interceed may improve haemostasis andallow the use of Interceed. If bleeding persistsGoretex can be stapled over the wound. This neednot be removed unless pregnancy is planned. Uter-ine enlargement may displace the membrane fromthe uterus which may attach to other organs.Hysterectomy may still be necessary in severe

cases of adenomyosis. Severity of adenomyosis isrelated to late diagnosis. Early diagnosis mayimprove treatment and investigations are indicatedin women with menstrual pain or menorrhagia notresponding to drug therapy.

Results of Conservative Surgery

Conservative surgery in a personal series of 62women with adenomyosis and diagnosed by vagi-nal ultrasound with doppler assessment, percutan-eous uterine needle biopsy, and histology ofexcised endo-myometrial or needle myometrialbiopsy at the time of hysteroscopy or laparoscopy,resulted in 63% of women being symptom free 2years later and 12% requiring hysterectomy duringthe same time period because of persistence orrecurrence of severe symptoms. Each of the tech-niques had a success rate greater than 50%. Nine

of 16 women attempting pregnancy conceived, 4 of7 after myometrial electrocoagulation and 5 of 9after myometrial excision. One woman who hadtwo electrocoagulation treatments, includingone associated myometrial excision, subsequentlyruptured her uterus in the twelfth week of preg-nancy.MRI and uterine biopsy were used to diagnose

nodular adenomyosis by Phillips et al. [14].Preoperative GnRH analogue, endomyometrialresection and bipolar coagulation were used in14 women. One year after treatment menorrhagiawas cured in 12 and dysmenorrhoea in 8. Twoproceeded to hysterectomy. The advantage ofpreoperative use of GnRH analogue was shownby a 50.8% mean reduction of uterine volume afterleuprolide acetate treatment for 3 months.

GnRH Analogues

A GnRH analogue, leuprolide acetate has beenused to produce a constant hypoestrogenic statein a woman with histologically proven adenomyo-sis [14]. Dysmenorrhoea and desire for conceptionwere the two complaints. This produced amenor-rhoea, control of pain and uterine shrinkage, andconception resulted.A pure antiestrogen may offer some advantage

in the treatment of adenomyosis and trials areplanned to assess its usefulness in the human.

Topical Danazol/Progestogen Therapy

Adenomyosis has been treated by 200 mg of dana-zol contained in an intrauterine device (DIUD)[15]. Blood danazol levels are undetectable, ovula-tion was not inhibited, and side effects did notoccur. The DIUD was effective in 9 of 10 cases inreducing uterine size and dysmenorrhoea andpregnancy occurred in 3 cases after removal ofthe DIUD. Another study of the DIUD containing300tg of danazol produced similar results over6-12 months [10]. Symptoms improved in morethan 70% of patients especially for dysmenor-rhoea, the DIUD was shown to be active after

94 C. WOOD

12 months use, mean CA125 levels decreased from295U/m1 to 115U/m1, and mean uterine vol-ume decreased from 369cm to 264cm3. Usingthe DIUD in Australian women 3 of 4 expelledthe DIUD and a larger IUD would be required totest its efficacy.The levonorgestrel intrauterine device (LNIUD)

has proven to be effective not only as a contra-

ceptive but also in the control of menorrhagia. Itsaction is to produce an atrophic endometrium. Itmay be useful in the control of menorrhagia in thepresence of adenomyosis, and possibly the reduc-tion of dysmenorrhoea. The antioestrogenic effectmay reduce the growth of the adenomyotic tissue.A study of 25 women with menorrhagia associatedwith adenomyosis diagnosed by vaginal ultra-sound has shown that 23 had relief of menorrhagiapersisting for year after use of the LNIUD[16]. Reduction of menstrual pain was lessfrequent. Spotting in the first 3 months was themost common side effect, one patient asking tohave the device removed because of this. Sixpatients reported headaches, three breast tender-ness, six greasy hair, seborrhoea or acne, and sevenweight gain. Spotting was well tolerated.

Arterial Embolization

Arterial uterine artery embolization has the poten-tial to reduce blood flow to part or the whole ofthe uterus. Two patients with diffuse adenomyosishave been treated by embolization with cure orcontrol of menstrual pain and menorrhagia; followup is only short term. Angiography and dopplerultrasound demonstrates more than 50% reduc-tion of uterine blood flow. The technique will betried on all patients who would otherwise requirehysterectomy. In both patients the posteriormyometrial thickness was reduced by 45 and58%, small myometrial cystic spaces were presentin one and myometrial scarring increased in theother.The major advantage of arterial embolization is

that the angiogram localizes the site of adenomyo-sis by indicating increased vascularization often

associated with adenomyotic areas, which can thenbe targeted by precise embolization of the arteriessupplying the involved areas.

It may not be suitable for patients wishing toconceive, as large areas of scarred myometriummay weaken the uterus and result in uterinerupture in pregnancy.The limitation of uterine artery embolization is

the possibility of early regrowth of the adenomyo-sis and the limited availability of the technique. Itsincreasing use in treating certain types of fibroidsmay encourage exploration of the techniques’effectiveness or not in adenomyosis. Complica-tions are unproven. The cure rate for menorrhagiain women with fibroids is more than 50% [17,18].Pain may occur for up to 1-2 months which issimilar to that after laparoscopic excision ofadenomyosis. The technique has to be done byskilled radiologists e.g. those already treating brainaneurysms. Two cases in a review of all 2000 casesperformed in the USA resulted in ovarian failurein three patients.

References

[1] Wood, C. Surgical and Medical Treatment of Adenomyosis.Hum. Reprod. Update 1998; 4(4): 323-336.

[2] Wood, C., Maher, P. and Hill, D. Biopsy Diagnosis andConservative Surgical Treatment of Adenomyosis. J. Am.Assoc. Gynecol. Laparosc. 1994; 1(4): 313-316.

[3] Brosens, J.J., de Souza, N.M., Barker, F.G. et al. Endo-vaginal ultrasonography in the diagnosis of adenomyosisuteri: identifying the predictive characteristics. Br. J.Obstet. Gynaecol. 1995; 102(6): 471-474.

[4] Fedele, L., Bianchi, S., Dorta, M. et al. Transvaginalultrasonography in the diagnosis of diffuse adenomyosis.Fertil. Steril. 1992; 58(1): 94-97.

[5] McCausland, A.M. Hysteroscopic myometrial biopsy: itsuse in diagnosing adenomyosis and its clinical applica-tion. Am. J. Obstet. Gyneeol. 1992; 166: 1619-1626.

[6] Popp, L.W., Schwiedessen, J.P. and Gaetje, R. Myometrialbiopsy in the diagnosis of adenomyosis uteri. Am. J. Obstet.Gyneeol. 1993; 169(3): 546-549.

[7] Kang, S., Turner, D.A., Foster, G.S. et al. Adenomyosis:specificity of 5 mm as the maximum normal uterine junc-tional zone thickness in MR images. Am. J. Roentgenol.1996; 166(5): 1145-1150.

[8] Reinhold, C., McCarthy, S., Bret, P.M. et al. Diffuseadenomyosis: comparison of endovaginal US and MRimaging with histopathologic correlation. Radiology 1996;199(1): 151-158.


[9] Brosens, J.J. and Barker, F.G. The role of myometrialneedle biopsies in the diagnosis of adenomyosis. Fertil.Steril. June 1995; 63(6): 1347-1349.

[10] Tanaoka, Y., Slo, R., Yamamoto, Y. et al. Investigationof treatment of adenomyosis by intrauterine device thatcontains danazol. Fifth World Congress on Endometriosis.Abstracts 21-24 October, Yokohama, Japan 0-156,1996, p. 80.

[11] Koninckx, P.R., Riittinen, L., Sepfili, M. and Cornillie,F.J. CA-125 and placental protein 14 concentration inplasma and peritoneal fluid of women with deeply infiltrat-ing pelvic endometriosis. Fertil. Steril. 1992; 7: 523-530.

[12] Brosens, J.J., de Souza, R.N. and Barker, F.G. Uterinejunctional zone: function and disease. Lancet, August 26,1995; 346: 558-560.

[13] Kang, S., Turner, D.A., Foster, G.S. et al. Adenomyosis:specificity of 5 mm as the maximum normal uterine junc-tional zone thickness in MR images. Am. J. Roentgenol.1996; 166(5): 1145-1150.

[14] Phillips, D.R., Nathanson, H.G., Milim, S.J. et al.Laparoscopic bipolar coagulation for the conservativetreatment of adenomyomata. J. Am. Assoc. Gynecol.Laparosc. 1996; 4(1): 19-24.

[15] Igarashi, M., Iizuka, M., Ahe, Y., et al. A new therapy foruterine adenomyosis. Fifth World Congress on Endo-metrisois. Abstracts 21-24 October, Yokohama, Japan0-155, 1996.

[16] Fedele, L., Bianchi, S., Raffaeli, R. et al. Treatment ofadenomyosis- associated menorrhagia with a levonorges-trel-releasing intrauterine device. Fertil. Steril. 1997; 68(3):426-429.

[17] Hutchins, F.L. Jr., and Worthington-Kirsh, R.L. Initialexperience with uterine artery embolization for themanagement of symptomatic uterine fibroids. J. Am.Assoc. Gynecol. Laparosc. 1997; 4: 27.

[18] Vedanthen, S., Goodwin, S.C., McLucas, B. andForno, A.E. Uterine artery embolization for uterinefibroids. J. Am. Assoc. Gynecol. Laparosc. 1997; 4: 39.

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Adenomyosis: Difficult to Diagnose, and Difficult to Treatdownloads.hindawi.com/journals/dte/2001/340321.pdf · 90 C. WOOD women having MRI and uterine histology have adenomyosis[12]