Adenomyosis: Epidemiology, Risk Factors, Clinical Phenotype and Surgical and Interventional Alternatives to Hysterectomy

Abstract

Adenomyosis is an important clinical challenge in gynecology and healthcare economics; in its fully developed form, hysterectomy is often used to treat it in premenopausal and perimenopausal women. Symptoms of adenomyosis typically include menorrhagia, pelvic pain and dysmenorrhea. Moreover, adenomyosis and leiomyomas commonly coexist in the same uterus, and differentiating the symptoms for each pathological process can be problematic. Although it has been recognized for over a century, reliable epidemiological studies on this condition are limited, because only postoperative diagnoses were possible in the past. Minimally invasive surgical techniques (endometrial ablation/resection, myometrial excision/reduction, myometrial electrocoagulation, uterine artery ligation) have had limited success in the treatment of adenomyosis, and the reported data for these procedures have been obtained from case reports or small case series with only short follow-up times. However, newer techniques including uterine artery embolization (UAE) and magnetic resonance imaging guided focused ultrasound (MRgFUS) show promise in treating adenomyosis. The data is strongest for UAE; these studies have the largest patient cohorts. However, none of the UAE studies were randomized or controlled. Thus, despite the clinical importance of adenomyosis, there is little evidence on which to base treatment decisions. The objective of this review is to summarize the epidemiology, risk factors, clinical phenotype and to evaluate the accrued experience with surgical and interventional alternatives to hysterectomy.

Zusammenfassung

Die Adenomyosis uteri stellt eine große klinische Herausforderung für sowohl Gynäkologie als auch Gesundheitsökonomie dar. Oftmals ist sie bei symptomatischen prä- und perimenopausalen Frauen Indikation zur Hysterektomie. Typische Symptome der Adenomyosis uteri werden mit Menorrhagie, Unterbauchschmerzen und Dysmenorrhö beschrieben. Bei den benignen Erkrankungen des Uterus kommen die Adenomyosis und die Leiomyome häufig gleichzeitig vor und erschweren so eine eindeutige Zuordnung der Symptomatik. Obgleich die Erstbeschreibung der Adenomyosis uteri aus dem letzten Jahrhundert stammt, existieren zu diesem Krankheitsbild nach wie vor keine verlässlichen epidemiologischen Daten. Dies liegt auch in der Tatsache begründet, dass in der Vergangenheit nur eine postoperative Diagnose dieser Erkrankung möglich war. Minimalinvasive chirurgische Therapieansätze (Endometriumablation/-resektion, myometrane Exzision/Reduktion, myometrane Elektrokoagulation, Ligatur der Aa. uterinae) haben nur begrenzte Erfolge in der Behandlung der Adenomyosis uteri zeigen können. Darüber hinaus stammt die Evidenz zu diesen Therapieansätzen ausschließlich aus Studien mit geringen Fallzahlen und Fallberichten. Dennoch zeigen neuere, interventionelle Techniken einschließlich der Uterusarterienembolisation (UAE) und der Magnetresonanztomografie-gesteuerten fokussierten Ultraschalltherapie (MRgFUS) aussichtsreiche Ergebnisse in der uteruserhaltenden Behandlung der Adenomyosis. Obwohl die meisten Ergebnisse diesbezüglich für die UAE vorhanden sind, waren diese Arbeiten weder randomisiert noch kontrolliert. Trotz der großen klinischen Bedeutung der Adenomyosis uteri gibt es nach wie vor keine ausreichende Evidenz für nachhaltige Therapieempfehlungen. Ziel dieser Übersichtsarbeit ist eine Zusammenfassung der epidemiologischen Daten, der Risikofaktoren, des klinischen Erscheinungsbilds der Adenomyosis uteri sowie eine Analyse der eigenen Erfahrung mit chirurgischen und interventionellen Therapiemodalitäten in der Behandlung der Adenomyosis.

Key words

adenomyosis - hysterectomy - endometrial ablation - uterine artery embolization - magnetic resonance guided focused ultrasound

Schlüsselwörter

Adenomyosis - Hysterektomie - Endometriumsablation - Uterusarterienembolisation - Magnetresonanztomografie-gesteuerte fokussierte Ultraschalltherapie

• References

• 1 Benagiano G, Brosens I. History of adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006; 20: 449-463
• 2 Renner SP, Lermann J, Hackl J et al. Chronische Erkrankung. Endometriose. Geburtsh Frauenheilk 2012; 72: 914-919
• 3 Gordts S, Brosens JJ, Fusi L et al. Uterine adenomyosis: a need for uniform terminology and consensus classification. Reprod Biomed Online 2008; 17: 244-248
• 4 Garcia L, Isaacson K. Adenomyosis: review of the literature. J Minim Invasive Gynecol 2011; 18: 428-437
• 5 Popovic M, Puchner S, Berzaczy D et al. Uterine artery embolization for the treatment of adenomyosis: a review. J Vasc Interv Radiol 2011; 22: 901-909
• 6 Rabinovici J, Stewart EA. New interventional techniques for adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006; 20: 617-636
• 7 Fernandez H, Farrugia M, Jones SE et al. Rate, type, and cost of invasive interventions for uterine myomas in Germany, France, and England. J Minim Invasive Gynecol 2009; 16: 40-46
• 8 Cardozo ER, Clark AD, Banks NK et al. The estimated annual cost of uterine leiomyomata in the United States. Am J Obstet Gynecol 2012; 20: 211.e1-211.e9
• 9 Azziz R. Adenomyosis: current perspectives. Obstet Gynecol Clin North Am 1989; 16: 221-235
• 10 Vercellini P, Parazzini F, Oldani S et al. Adenomyosis at hysterectomy: a study on frequency distribution and patient characteristics. Hum Reprod 1995; 10: 1160-1162
• 11 Parazzini FVP, Panazza S, Chatenoud L et al. Risk factors for adenomyosis. Hum Reprod 1997; 12: 1275-1279
• 12 Bergholt T, Eriksen L, Berendt N et al. Prevalence and risk factors of adenomyosis at hysterectomy. Hum Reprod 2001; 16: 2418-2421
• 13 Vercellini P, Vigano P, Somigliana E et al. Adenomyosis: epidemiological factors. Best Pract Res Clin Obstet Gynaecol 2006; 20: 465-477
• 14 Parazzini F, Mais V, Cipriani S et al. Determinants of adenomyosis in women who underwent hysterectomy for benign gynecological conditions: results from a prospective multicentric study in Italy. Eur J Obstet Gynecol Reprod Biol 2009; 143: 103-106
• 15 Wallwiener M, Taran FA, Rothmund R et al. Laparoscopic supracervical hysterectomy (LSH) versus total laparoscopic hysterectomy (TLH): an implementation study in 1,952 patients with an analysis of risk factors for conversion to laparotomy and complications, and of procedure-specific re-operations. Arch Gynecol Obstet 2013; Jun 18 [Epub ahead of print]
• 16 Bird CC, McElin T, Manalo-Estrella P. The elusive adenomyosis of the uterus. Am J Obstet Gynecol 1972; 112: 583-593
• 17 Taran FA, Weaver AL, Coddington CC et al. Understanding adenomyosis: a case control study. Fertil Steril 2010; 94: 1223-1228
• 18 Taran FA, Weaver AL, Coddington CC et al. Characteristics indicating adenomyosis coexisting with leiomyomas: a case-control study. Hum Reprod 2010; 25: 1177-1182
• 19 Taran FA, Wallwiener M, Kabashi D et al. Clinical characteristics indicating adenomyosis at the time of hysterectomy: a retrospective study in 291 patients. Arch Gynecol Obstet 2012; 285: 1571-1576
• 20 Siedentopf P. Chronic pain syndromes in gynaecological practice: endometriosis and fibromyalgia. Geburtsh Frauenheilk 2012; 72: 1092-1098
• 21 Burghaus S, Klingsiek P, Fasching PA et al. Risk factors for endometriosis in a German case–control study. Geburtsh Frauenheilk 2011; 71: 1073-1079
• 22 Wölfler MM, Stadermann M, Rath W et al. Anamnestisches Screening bei symptomatischen Patientinnen mit und ohne Endometriose. Geburtsh Frauenheilk 2011; 71: 53-58
• 23 Parker JD, Leondires M, Sinaii N et al. Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Fertil Steril 2006; 86: 711-715
• 24 Ryan GL, Stolpen A, Van Voorhis BJ. An unusual cause of adolescent dysmenorrhea. Obstet Gynecol 2006; 108: 1017-1022
• 25 Templeman C, Marshall SF, Ursin G et al. Adenomyosis and endometriosis in the California Teachers Study. Fertil Steril 2008; 90: 415-424
• 26 Weiss G, Maseelall P, Schott LL et al. Adenomyosis a variant, not a disease? Evidence from hysterectomized menopausal women in the Study of Womenʼs Health Across the Nation (SWAN). Fertil Steril 2009; 91: 201-206
• 27 Levgur M, Abadi MA, Tucker A. Adenomyosis: symptoms, histology, and pregnancy terminations. Obstet Gynecol 2000; 95: 688-691
• 28 Panganamamula UR, Harmanli OH, Isik-Akbay EF et al. Is prior uterine surgery a risk factor for adenomyosis?. Obstet Gynecol 2004; 104: 1034-1038
• 29 Whitted R, Verma U, Voigl B et al. Does cesarean delivery increase the prevalence of adenomyosis? A retrospective review. Obstet Gynecol 2000; 95: S83
• 30 Harris WJ, Daniell JF, Baxter JW. Prior cesarean section. A risk factor for adenomyosis?. J Reprod Med 1985; 30: 173-175
• 31 Van Voorhis BJ, Dawson JD, Stovall DW et al. The effects of smoking on ovarian function and fertility during assisted reproduction cycles. Obstet Gynecol 1996; 88: 785-791
• 32 Kitawaki J. Adenomyosis: the pathophysiology of an oestrogen-dependent disease. Best Pract Res Clin Obstet Gynaecol 2006; 20: 493-502
• 33 Yeniel O, Cirpan T, Ulukus M et al. Adenomyosis: prevalence, risk factors, symptoms and clinical findings. Clin Exp Obstet Gynecol 2007; 34: 163-167
• 34 Lu HF, Sheu BC, Shih JC et al. Intramural ectopic pregnancy. Sonographic picture and its relation with adenomyosis. Acta Obstet Gynecol Scand 1997; 76: 886-889
• 35 Ginsburg KA, Quereshi F, Thomas M et al. Intramural ectopic pregnancy implanting in adenomyosis. Fertil Steril 1989; 51: 354-356
• 36 Saraiya M, Berg CJ, Kendrick JS et al. Cigarette smoking as a risk factor for ectopic pregnancy. Am J Obstet Gynecol 1998; 178: 493-498
• 37 Mori T, Singtripop T, Kawashima S. Animal model of uterine adenomyosis: Is prolactin a potent inducer of adenomyosis in mice?. Am J Obstet Gynecol 1991; 165: 232-234
• 38 Yamashita M, Matsuda M, Mori T. In situ detection of prolactin receptor mRNA and apoptotic cell death in mouse uterine tissues with adenomyosis. In Vivo 1999; 13: 57-60
• 39 Ficicioglu C, Tekin HI, Arioglu PF et al. A murine model of adenomyosis: the effects of hyperprolactinemia induced by fluoxetine hydrochloride, a selective serotonin reuptake inhibitor, on adenomyosis induction in Wistar albino rats. Acta Eur Fertil 1995; 26: 75-79
• 40 Molitch ME. Medication-induced hyperprolactinemia. Mayo Clin Proc 2005; 80: 1050-1057
• 41 Greaves P, White IN. Experimental adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006; 20: 503-510
• 42 Walters CA, Daly DC, Chapitis J et al. Human myometrium: a new potential source of prolactin. Am J Obstet Gynecol 1983; 147: 639-644
• 43 Daly DC, Walters CA, Prior JC et al. Prolactin production from proliferative phase leiomyoma. Am J Obstet Gynecol 1984; 148: 1059-1063
• 44 Mora S, Diehl T, Stewart EA et al. Prolactin is an autocrine growth regulator for human myometrial and leyomyoma cells. J Soc Gynecol Invest 1995; 2: 396
• 45 Khan KN, Kitajima M, Fujishita A et al. Toll-like receptor system and endometriosis. J Obstet Gynaecol Res 2013; 39: 1281-1292
• 46 Cohen I, Beyth Y, Tepper R et al. Adenomyosis in postmenopausal breast cancer patients treated with tamoxifen: a new entity?. Gynecol Oncol 1995; 58: 86-91
• 47 Cohen I, Beyth Y, Shapira J et al. High frequency of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen. Gynecol Obstet Invest 1997; 44: 200-205
• 48 Cohen I, Shapira J, Beyth Y et al. Estrogen and progesterone receptors of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen. Gynecol Obstet Invest 1998; 45: 126-131
• 49 McCluggage WG, Desai V, Manek S. Tamoxifen-associated postmenopausal adenomyosis exhibits stromal fibrosis, glandular dilatation and epithelial metaplasias. Histopathology 2000; 37: 340-346
• 50 Deligdisch L. Effects of hormone therapy on the endometrium. Mod Pathol 1993; 6: 94-106
• 51 Owolabi TO, Strickler RC. Adenomyosis: a neglected diagnosis. Obstet Gynecol 1977; 50: 424-427
• 52 Shaikh H, Khan KS. Adenomyosis in Pakistani women: four year experience at the Aga Khan University Medical Centre, Karachi. J Clin Pathol 1990; 43: 817-819
• 53 Vavilis D, Agorastos T, Tzafetas J et al. Adenomyosis at hysterectomy: prevalence and relationship to operative findings and reproductive and menstrual factors. Clin Exp Obstet Gynecol 1997; 24: 36-38
• 54 Thomas jr. JS, Clark JF. Adenomyosis: a retrospective view. J Natl Med Assoc 1989; 81: 969-972
• 55 Peddada SD, Laughlin SK, Miner K et al. Growth of uterine leiomyomata among premenopausal black and white women. Proc Natl Acad Sci U S A 2008; 105: 19887-19892
• 56 Levgur M. Therapeutic options for adenomyosis: a review. Arch Gynecol Obstet 2007; 276: 1-15
• 57 Wallwiener D, Rimbach S, Kaufmann M et al. Hysteroscopic endometrial ablation to avoid hysterectomy in high-risk patients. Geburtsh Frauenheilk 1994; 54: 498-501
• 58 Wood C, Maher P, Hill D. Biopsy diagnosis and conservative surgical treatment of adenomyosis. Aust N Z J Obstet Gynaecol 1993; 33: 319-321
• 59 Wood C, Maher P, Hill D. Biopsy diagnosis and conservative surgical treatment of adenomyosis. J Am Assoc Gynecol Laparosc 1994; 1: 313-316
• 60 Vancaillie TG. Electrocoagulation of the endometrium with the ball-end resectoscope. Obstet Gynecol 1989; 74: 425-427
• 61 Daniell JF, Kurtz BR, Ke RW. Hysteroscopic endometrial ablation using the rollerball electrode. Obstet Gynecol 1992; 80: 329-332
• 62 Unger JB, Meeks GR. Hysterectomy after endometrial ablation. Am J Obstet Gynecol 1996; 175: 1432-1436
• 63 El-Nashar SA, Hopkins MR, Creedon DJ et al. Prediction of treatment outcomes after global endometrial ablation. Obstet Gynecol 2009; 113: 97-106
• 64 Pepas L, Deguara C, Davis C. Update on the surgical management of adenomyosis. Curr Opin Obstet Gynecol 2012; 24: 259-264
• 65 Fedele L, Bianchi S, Zanotti F et al. Fertility after conservative surgery for adenomyomas. Hum Reprod 1993; 8: 1708-1710
• 66 Wang PH, Liu WM, Fuh JL et al. Comparison of surgery alone and combined surgical-medical treatment in the management of symptomatic uterine adenomyoma. Fertil Steril 2009; 92: 876-885
• 67 Fujishita A, Masuzaki H, Khan KN et al. Modified reduction surgery for adenomyosis. A preliminary report of the transverse H incision technique. Gynecol Obstet Invest 2004; 57: 132-138
• 68 Osada H, Silber S, Kakinuma T et al. Surgical procedure to conserve the uterus for future pregnancy in patients suffering from massive adenomyosis. Reprod Biomed Online 2011; 22: 94-99
• 69 Wang CJ, Yen CF, Lee CL et al. Laparoscopic uterine artery ligation for treatment of symptomatic adenomyosis. J Am Assoc Gynecol Laparosc 2002; 9: 293-296
• 70 Wood C. Adenomyosis: difficult to diagnose, and difficult to treat. Diagn Ther Endosc 2001; 7: 89-95
• 71 Ravina JH, Herbreteau D, Ciraru-Vigneron N et al. Arterial embolisation to treat uterine myomata. Lancet 1995; 346: 671-672
• 72 Goodwin SC, McLucas B, Lee M et al. Uterine artery embolization for the treatment of uterine leiomyomata midterm results. J Vasc Interv Radiol 1999; 10: 1159-1165
• 73 Smith SJ, Sewall LE, Handelsman A. A clinical failure of uterine fibroid embolization due to adenomyosis. J Vasc Interv Radiol 1999; 10: 1171-1174
• 74 Siskin GP, Tublin ME, Stainken BF et al. Uterine artery embolization for the treatment of adenomyosis: clinical response and evaluation with MR imaging. AJR Am J Roentgenol 2001; 177: 297-302
• 75 Jha RC, Takahama J, Imaoka I et al. Adenomyosis: MRI of the uterus treated with uterine artery embolization. AJR Am J Roentgenol 2003; 181: 851-856
• 76 Toh CH, Wu CH, Tsay PK et al. Uterine artery embolization for symptomatic uterine leiomyoma and adenomyosis. J Formos Med Assoc 2003; 102: 701-706
• 77 Kim MD, Won JW, Lee DY et al. Uterine artery embolization for adenomyosis without fibroids. Clin Radiol 2004; 59: 520-526
• 78 Pelage JP, Jacob D, Fazel A et al. Midterm results of uterine artery embolization for symptomatic adenomyosis: initial experience. Radiology 2005; 234: 948-953
• 79 Kitamura Y, Allison SJ, Jha RC et al. MRI of adenomyosis: changes with uterine artery embolization. AJR Am J Roentgenol 2006; 186: 855-864
• 80 Kim MD, Kim S, Kim NK et al. Long-term results of uterine artery embolization for symptomatic adenomyosis. AJR Am J Roentgenol 2007; 188: 176-181
• 81 Bratby MJ, Walker WJ. Uterine artery embolisation for symptomatic adenomyosis–mid-term results. Eur J Radiol 2009; 70: 128-132
• 82 Liang E, Brown B, Kirsop R et al. Efficacy of uterine artery embolisation for treatment of symptomatic fibroids and adenomyosis – an interim report on an Australian experience. Aust N Z J Obstet Gynaecol 2012; 52: 106-112
• 83 Smeets AJ, Nijenhuis RJ, Boekkooi PF et al. Long-term follow-up of uterine artery embolization for symptomatic adenomyosis. Cardiovasc Intervent Radiol 2012; 35: 815-819
• 84 Yu L, Wu T, Spain J et al. Uterine artery embolization for the treatment of adenomyosis: questions for long-term efficacy. J Vasc Interv Radiol 2012; 23: 430-432
• 85 Taran FA, Tempany CM, Regan L et al. Magnetic resonance-guided focused ultrasound (MRgFUS) compared with abdominal hysterectomy for treatment of uterine leiomyomas. Ultrasound Obstet Gynecol 2009; 34: 572-578
• 86 Al Hilli MM, Stewart EA. Magnetic resonance-guided focused ultrasound surgery. Semin Reprod Med 2010; 28: 242-249
• 87 Rabinovici J, Inbar Y, Eylon SC et al. Pregnancy and live birth after focused ultrasound surgery for symptomatic focal adenomyosis: a case report. Hum Reprod 2006; 21: 1255-1259
• 88 Yoon SW, Kim KA, Cha SH et al. Successful use of magnetic resonance-guided focused ultrasound surgery to relieve symptoms in a patient with symptomatic focal adenomyosis. Fertil Steril 2008; 90: 2018.e13-2018.e15
• 89 Fukunishi H, Funaki K, Sawada K et al. Early results of magnetic resonance-guided focused ultrasound surgery of adenomyosis: analysis of 20 cases. J Minim Invasive Gynecol 2008; 15: 571-579
• 90 Polina L, Nyapathy V, Mishra A et al. Noninvasive treatment of focal adenomyosis with MR-guided focused ultrasound in two patients. Indian J Radiol Imaging 2012; 22: 93-97
• 91 Kim KA, Yoon SW, Lee C et al. Short-term results of magnetic resonance imaging-guided focused ultrasound surgery for patients with adenomyosis: symptomatic relief and pain reduction. Fertil Steril 2011; 95: 1152-1155
• 92 Mohan PP, Hamblin MH, Vogelzang RL. Uterine artery embolization and its effect on fertility. J Vasc Interv Radiol 2013; 24: 925-930