Bladder endometriosis, a remarkable resemblance in a monozygotic twin
© The Author(s) 2009
Received: 1 March 2009
Accepted: 1 April 2009
Published: 16 June 2009
It is known for many years that heritability plays a role in the development of endometriosis in many patients. Deep endometriosis of the bladder is a rare presentation of the disease and bladder endometriosis was not reported in monozygotic twin studies so far. Since monozygotic twins share the same genes, concordance and differences in presentation of endometriosis may help to discriminate between genetic and environmental determinants. The remarkable resemblance in the presentation of bladder endometriosis in this monozygotic twin seems to indicate that genetic factors are of importance in the arising of deep endometriosis in the bladder too.
Endometriosis affects 6–10% of women in their reproductive years and affects up to 35–50% of women with pain or infertility . Urogenital tract is superficially involved in about 10–15% of cases but deep endometriosis of the bladder is estimated to be present in 1–2% of the patients only [2–5] Bladder endometriosis is frequently accompanied by other forms of pelvic endometriosis . Frequency, urgency, suprapubic pain and dysuria [3, 6, 7] are the most frequent symptoms of bladder endometriosis and a positive correlation between severity of dysuria and lesion diameter has been described . Haematuria seems to be a less frequent symptom in 20–35% of patients [2, 3, 6].
Heritability of endometriosis is well known from twin studies for many years, but this concerned mainly the increased risk to develop endometriosis and deep bladder endometriosis was not mentioned [8–11]. Despite the rare occurrence of bladder endometriosis, a monozygotic twin presented at our clinic with similar complaints and remarkable resemblance in the presentation of disease.
Because of the predominant complaint of dysuria, both sisters were planned for laparoscopic excision of the bladder nodule by partial cystectomy and excision of the lesion at the backside of the cervix. After excision, the bladder was closed with a running suture vicryl 3 × 0. Complete closure of the bladder was tested with instillation of 150 ml methylene blue dye solution into the bladder at the end of the procedure. Since the sister with adenomyosis wanted to preserve fertility, her uterus was left in situ. The uterus of the sister without child wish was normal. Levonorgestrel IUD remained in situ in both. Prophylactic antibiotics were given for 24 h. Postoperative course was uneventful in both sisters. They were discharged the day after surgery with indwelling catheter. The bladder catheter was removed after a week and micturation proved normal afterwards. Histology confirmed in both cases an adenomyotic lesion through the bladder wall covered with normal bladder endothelium.
At follow-up visit after 6 weeks, dysuria had disappeared in both. At follow-up so far, the sister with the adenomyosis has some dysmenorrhoea still but bearable without pain medication. Her sister has no more complaints at all.
Dysmenorrhoea, cyclic dysuria and suprapubic pain are the most frequent reported symptoms related to bladder endometriosis in literature [2, 3, 6]. In both our patients, dysuria was the predominant complaint with dysmenorrhoea as a second complaint. The dyschezia reported by one of the sisters was probably due to the nodule behind the cervix. Although the bowel was not involved, the complaint had disappeared after resection. The fact that the endometriotic lesions of both sisters were still covered with urothelium will explain the absence of haematuria. This is in agreement with the literature [2, 5].
Ultrasound is the simplest first step in diagnosis of endometriosis. Combination of abdominal, transvaginal and transrectal ultrasound, depending on the complaints, may reveal endometriosis in infrequent sites . In urogenital endometriosis, the bladder is the most frequent involved organ and superficial endometriosis of the bladder is often part of more extended endometriosis . Ultrasound may also be used as a first step to exclude obstruction of the ureters. Although a dimple in the bladder was clear, an IVP is not the first choice to diagnose bladder disease. In case of suspicion of obstruction, however, it may help to localise the place and extent of the obstruction. MRI scanning is more sensitive to diagnose preoperatively the extent of endometriosis especially for retroperitoneal disease and bowel involvement [5, 14]. Cystoscopy and laparoscopy are required for definitive diagnosis .
The pathogenesis of bladder endometriosis has not been clarified. Donnez et al. proposed metaplasia from mullerian remnants , but the histological evidence of mullerian remnants in the urothelium of the bladder has been doubted . Transplantation theory considers the extension of adenomyotic lesions and transport through blood and lymphatic vessels . Finally, post surgery implantation, mainly after Caesarean, may be responsible in a part of the cases [13, 16]. Both twin sisters of this study had adenomyotic lesions of the bladder but only one of the sisters had further adenomyosis.
Urogenital endometriosis is much more frequent than deep bladder endometriosis . Bladder endometriosis is frequently accompanied by other forms of endometriosis but bladder endometriosis and ureter endometriosis are not associated [4, 18]. Patients with ureter endometriosis usually have more advanced disease [5, 17, 18]. Therefore, the deep endometriosis of the bladder seems to be a different entity within advanced endometriosis.
Genetic factors play a part in the development of endometriosis but inheritance is complex. It is well known that family members of patients with endometriosis have an increased risk to develop endometriosis [10, 19]. The UK–Australian twin examination estimated 51% of the expression to be attributable to genetic factors . The risks between monozygotic twins have been estimated as high as 75–87% [8, 9]. However, this concerned the change of endometriosis for relatives and a correlation in severity, but the localization of the endometriosis often differed between the twin pairs and bladder endometriosis was not described. Bladder endometriosis was mentioned neither in the large genome wide linkage study  nor in the genetic studies of Bischoff . The lesions in the bladder and behind the cervix in the monozygotic twin described here were identical and there were no further peritoneal implants.
The development of endometriosis is multi-factorial and the presentation depends on genetic and extrinsic factors . Apart from resemblance, our twin sisters showed discrepancies too. One of them had fewer complaints, had not been operated on before and had no further adenomyosis. She never had child wish and the levonorgestrel-releasing IUD had been placed about 1 year earlier in her life. It seems unlikely that the short time difference in the placement of the progesterone containing IUD explains the difference in adenomyosis between the sisters. The IUD had not prevented the progression of the bladder and the retro-cervical endometriosis in either of them. Evidence for a beneficial effect of a levonorgestrel-releasing IUD is still limited at this moment . The sister with adenomyosis had been operated on incompletely twice. If this may cause extension of the adenomyosis is unlikely, but no other differences between the sisters is available from their medical histories. Inheritance is complex [1, 10, 19]. Presumably, different genes may influence the development in different ways as by influencing retrograde menstruation, cell differentiation, hormonal misbalance and by detoxification processes [1, 19]. Although this may explain the wide variation in expression of endometriosis, it cannot explain differences in our monozygotic twin.
Symptomatic lesions can be treated hormonally or by surgery. Hormonal treatment for pain will postpone child wish and overall does not improve fertility. It may have different side effects dependant of the medication chosen . For small lesions and in women near menopause hormonal treatment may be considered. For larger and deeper lesions (>5 mm) surgery is recommended generally [2, 3, 17]. Hormonal treatment resulted in temporary relief of symptoms only and previous surgery proved to be inadequate in the first of the twin sisters presented here. In the second sister, the levonorgestrel IUD controlled dysmenorrhoea reasonably but dysuria and dyschezia increased. Radical excision of the lesions relieved all her symptoms. Especially in younger women, surgical treatment of bladder endometriosis should be first choice treatment.
Conflicts of interest
There are no conflicts of interest to disclose.
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- Giudice LC, Kao LC (2004) Endometriosis. Lancet 364:1789–1799View ArticlePubMedGoogle Scholar
- Zugor V, Krot D, Rösch WH, Schott GE (2007) Endometriose von Ureter und Harnblase. Der Urologe 1:71–79View ArticleGoogle Scholar
- Pastor-Navarro H, Giménez-Bachs JM, Donate-Moreno MJ, Pastor-Guzman JM, Ruiz-Mondéjar R, Atienzar-Tobarra M, alinas-Sánchez AS, Virserda-Rodriguez JA (2007) Update on the diagnosis and treatment of bladder endometriosis. Int Urogynaecol J 18:949–954View ArticleGoogle Scholar
- Somigliana E, Vercellini P, Gattei U, Chopin N, Chiodo I, Chapron C (2007) Bladder endometriosis: getting closer and closer to the unifying metatstic hypothesis. Fertil Steril 87(6):1287–1290View ArticlePubMedGoogle Scholar
- Donnez J, Squuifflet J, Smets M, Jadoul P (2006) Severe endometriosis involving the urogenital system. In: Sutton J, Jones K, Adamson GD (eds) Modern management of endometriosis. Tailor & Francis, New York, pp 205–214Google Scholar
- Fedele L, Bianchi S, Carmignani L, Berlanda N, Fontana E, Frontino G (2007) Evaluation of a new questionnaire for the presurgical diagnosis of bladder endometriosis. Hum Reprod 22(10):2698–2701View ArticlePubMedGoogle Scholar
- Villa G, Mabrouk M, Guerrini M, Montanari G, Fabbri E, Venturoli S, Seracchioli R (2007) Relationship between site and size of bladder endometriotic nodules and severity of dysuria. J Minim Invasive Gynecol 14(5):628–632View ArticlePubMedGoogle Scholar
- Moen MH (1994) Endometriosis in monozygotic twins. Acta Obstet Gynecol Scand 73:59–62View ArticlePubMedGoogle Scholar
- Hadfield RM, Mardon HJ, Barlow DH, Kennedy SH (1997) Endometriosis in monozygotic twins. Fertil Steril 68(5):941–942View ArticlePubMedGoogle Scholar
- Stefanson H, Geirsson RT, Steinthorsdottr V, Jonsson H, Manolescu A, Kong A, Ingadottir G, Gulcher J, Stefansson K (2002) Genetic factors contribute to the risk of developing endoemtriosis. Hum Reprod 17(3):555–559View ArticleGoogle Scholar
- Treloar SA, Wicks J, Nyholt DR, Montgomery GW, Bahlo M, Smith V, Dawson G, Mackay IJ, Weeks DE, Bennet ST, Carey A, Ewen-White KR, Duffy DL, O’Connor DT, Barlow DH, Martin NG, Kennedy SH (2005) Genomewide Linkage Study in 1176 Affected Sister Pair families Identifies a Significant Susceptibility Locus for Endometriosis on Chromosome 10q26. Am J Hum Genet 77:365–376View ArticlePubMedGoogle Scholar
- Park SB, Kim JK, Cho KS (2008) Sonography of Endometriosis in Infrequent Sites. J Clin Ultrasound 36(2):91–97View ArticlePubMedGoogle Scholar
- Donnez J, Spada F, Squifflet J, Nisolle M (2000) Bladder endometriosis must be considered as bladder adenomyosis. Fertil Steril 76(1):213–214View ArticleGoogle Scholar
- Kinkel K, Brosens J, Brosens I (2006) Preoperative investigations. In: Sutton J, Jones K, Adamson GD (eds) Modern management of endometriosis. Tailor & Francis, New York, pp 71–85Google Scholar
- Vitagliano G, Viletta M, Castillo O (2006) Laparoscopic partial cystectomy in the management of bladder endoemtriosis: report of two cases. J Endourol 20(12):1072–1074View ArticlePubMedGoogle Scholar
- Fedele L, Piazzola E, Raffaelli R, Bianchi S (1998) Bladder endoemtriosis: deep infiltrating endoemtriosis or adenomyosis? Fertil Steril 69(50):972–975View ArticlePubMedGoogle Scholar
- Langebrekke A, Istre O, Busund B, Johannessen HO, Qvistad E (2006) Endoscopic treatment of deep infiltrating endometriosis (DIE) involving the bladder and rectosigmoid colon. Acta Obstet Gynecol 85:712–715View ArticleGoogle Scholar
- Abrao MS, Dias JA Jr, Bellelis P, Podgaec S, Bautzer CR, Gromatsky C (2009) Endometriosis of the ureter and bladder are not associated. Fertil Steril 91(5):1662–1667Google Scholar
- Bisschoff FZ, Simpson JL (2000) Heritability and molecular genetis studies of endometriosis. Hum Reprod Updat 6(1):37–44View ArticleGoogle Scholar
- Abou-Setta AM, Al-Innany HG, Farquhar C (2006) Levonorgestrel-releasing intrauterine devoce (LNG-IUD) for symptomatic endometriosis following surgery. Cochrane Database Syst Rev 4:CD005072. doi:10.1002/14651858.CD005072.pub2 PubMedGoogle Scholar
- Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, Vanderkerckhove P (2007) Ovulation suppression for endometriosis. Cochrane Database Syst Rev 3:CD000155. doi:10.1002/14651858.CD000155.pub2 PubMedGoogle Scholar