Adenomyosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun M.D. PhD.[2], Dina Elantably, MD[3]

Overview

Adenomyosis is a medical condition characterized by the presence of ectopic endometrial tissue (the inner lining of the uterus) within the myometrium (the thick, muscular layer of the uterus). The condition is typically found in women between the ages between 35 and 50. Patients with adenomyosis can have painful and/or profuse menses (dysmenorrhea & menorrhagia, respectively). Adenomyosis may involve the uterus focally, creating an adenomyoma, or diffusely. With diffuse involvement, the uterus becomes bulky and heavier.

Historical Perspective

  • Adenomyosis was first discovered by Carl von Rokitansky, a German pathologist, in 1860 when he found endometrial glands in the myometrium and designated this finding as 'cystosarcoma adenoids uterinum'[1].
  • In 1892 the first systematic investigation of adenomyosis was carried out by 'Thomas Stephen Cullen', a gynecologist. He distinguished 3 types of adenomyoma: intramural, subperitoneal and submucous adenomyoma[1].
  • In 1893, Kelly and Cullen described the pathogenesis of adenomyoma. The 'gradual ascendancy of Cullen’s mucosal theory' stated that endometrium invades the inner myometrium through the presence in it of ‘chinks’, or fissures.
  • In 1892, Cullen described that abdominal hysterectomy is indicated for treatment as the endometrial growths are interwoven with the normal muscle of the uterus.

Classification

  • Adenomyosis can be classified according to its histopathology into 2 groups:
  • Diffuse adenomyosis: Uniformly enlarged boggy uterus.
  • Focal adenomyosis (adenomyoma): Grossly it resembles fibroid but without a surrounding pseudocapsule.
  • Other variants of adenomyosis include juvenile cystic adenomyosis; which is the presence of endometrial cysts > 1cm in diameter within the myometrium. It is usually seen in young women <30 years old [2].

Pathophysiology

  1. Endomyometrial invagination of the endometrium; due to weakness of the uterine smooth muscles.
  2. De novo development of adenomyosis from mullerian rests due to metaplasia.

Causes

The cause of adenomyosis is unknown, although it has been associated with any sort of uterine trauma that may break the barrier between the endometrium and myometrium, such as:

Differentiating adenomyosis from other Diseases

For further information about the differential diagnosis, click here.

Epidemiology and Demographics

  • It is generally estimated that adenomyosis is present in 20-35% of women[10].
  • The incidence and prevalence of adenomyosis are, however, difficult to be accurately estimated and biased by studying only women undergoing hysterectomy, so the total population of women having the disease is not known[11].

Age

Race

  • There is no racial predilection for adenomyosis.
  • Almost all cases of adenomyosis present in multiparous women, however there is no clear causal relationship between multiparty and the development of the disease[9]

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

Adenomyosis is a histopathological diagnosis that is made after hysterectomy. The preoperative diagnosis is suggested by pelvic imaging such as transvaginal ultrasound and MRI along with the classical presentation of heavy menstrual bleeding, dysmenorrhea, and uniformly enlarged globular uterus.

Symptoms

Physical Examination

  • Diffusely enlarged uterus (Boggy soft uterus)
  • Uterus is mobile (not fixed as in endometriosis)
  • Uterine tenderness may be noted.

Pelvic Imaging

The uterus may be imaged using ultrasound (US) or magnetic resonance imaging (MRI). Transvaginal ultrasound is the most cost-effective and most available. Either modality will show an enlarged uterus. On ultrasound, the uterus will have a heterogeneous texture, without the focal well-defined masses that characterize uterine fibroids.

Ultrasonography

Image courtesy of RadsWiki

Computed Tomography

Images courtesy of RadsWiki

Magnetic Resonance Imaging

  • Adenomyosis appears as either diffuse or focal thickening (greater than 12 mm )of the junctional zone forming an ill-defined area of low signal intensity, occasionally with embedded bright foci on T2-weighted images.

Images courtesy of RadsWiki

Images courtesy of RadsWiki

MR: T2 image demonstrates adenomyosis


MR: T2 image demonstrates adenomyosis


Treatment

Surgery

Medical Therapy

Uterine artery embolization

References

  1. 1.0 1.1 Benagiano G, Brosens I (2006). "History of adenomyosis". Best Pract Res Clin Obstet Gynaecol. 20 (4): 449–63. doi:10.1016/j.bpobgyn.2006.01.007. PMID 16515887.
  2. Takeuchi H, Kitade M, Kikuchi I, Kumakiri J, Kuroda K, Jinushi M (2010). "Diagnosis, laparoscopic management, and histopathologic findings of juvenile cystic adenomyoma: a review of nine cases". Fertil Steril. 94 (3): 862–8. doi:10.1016/j.fertnstert.2009.05.010. PMID 19539912.
  3. Ferenczy A (1998). "Pathophysiology of adenomyosis". Hum Reprod Update. 4 (4): 312–22. doi:10.1093/humupd/4.4.312. PMID 9825847.
  4. Propst AM, Quade BJ, Gargiulo AR, Nowak RA, Stewart EA (2001). "Adenomyosis demonstrates increased expression of the basic fibroblast growth factor receptor/ligand system compared with autologous endometrium". Menopause. 8 (5): 368–71. doi:10.1097/00042192-200109000-00012. PMID 11528364.
  5. Green AR, Styles JA, Parrott EL, Gray D, Edwards RE, Smith AG; et al. (2005). "Neonatal tamoxifen treatment of mice leads to adenomyosis but not uterine cancer". Exp Toxicol Pathol. 56 (4–5): 255–63. doi:10.1016/j.etp.2004.10.001. PMID 15816354.
  6. Guo SW, Mao X, Ma Q, Liu X (2013). "Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis". Fertil Steril. 99 (1): 231–240. doi:10.1016/j.fertnstert.2012.08.038. PMID 22999795.
  7. Stewart EA (2001). "Gonadotropins and the uterus: is there a gonad-independent pathway?". J Soc Gynecol Investig. 8 (6): 319–26. PMID 11750866.
  8. Mori T, Singtripop T, Kawashima S (1991). "Animal model of uterine adenomyosis: is prolactin a potent inducer of adenomyosis in mice?". Am J Obstet Gynecol. 165 (1): 232–4. doi:10.1016/0002-9378(91)90258-s. PMID 1853904.
  9. 9.0 9.1 9.2 9.3 Bergeron C, Amant F, Ferenczy A (2006). "Pathology and physiopathology of adenomyosis". Best Pract Res Clin Obstet Gynaecol. 20 (4): 511–21. doi:10.1016/j.bpobgyn.2006.01.016. PMID 16563870.
  10. Vercellini P, Viganò P, Somigliana E, Daguati R, Abbiati A, Fedele L (2006). "Adenomyosis: epidemiological factors". Best Pract Res Clin Obstet Gynaecol. 20 (4): 465–77. doi:10.1016/j.bpobgyn.2006.01.017. PMID 16563868.
  11. 11.0 11.1 Abbott JA (2017). "Adenomyosis and Abnormal Uterine Bleeding (AUB-A)-Pathogenesis, diagnosis, and management". Best Pract Res Clin Obstet Gynaecol. 40: 68–81. doi:10.1016/j.bpobgyn.2016.09.006. PMID 27810281.
  12. 12.0 12.1 Parker JD, Leondires M, Sinaii N, Premkumar A, Nieman LK, Stratton P (2006). "Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis". Fertil Steril. 86 (3): 711–5. doi:10.1016/j.fertnstert.2006.01.030. PMID 16782099.
  13. Panganamamula UR, Harmanli OH, Isik-Akbay EF, Grotegut CA, Dandolu V, Gaughan JP (2004). "Is prior uterine surgery a risk factor for adenomyosis?". Obstet Gynecol. 104 (5 Pt 1): 1034–8. doi:10.1097/01.AOG.0000143264.59822.73. PMID 15516398.
  14. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y (2019). "Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis". Hum Reprod Update. 25 (5): 592–632. doi:10.1093/humupd/dmz012. PMID 31318420.
  15. Maheshwari A, Gurunath S, Fatima F, Bhattacharya S (2012). "Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes". Hum Reprod Update. 18 (4): 374–92. doi:10.1093/humupd/dms006. PMID 22442261.
  16. 16.0 16.1 McElin TW, Bird CC (1974). "Adenomyosis of the uterus". Obstet Gynecol Annu. 3 (0): 425–41. PMID 4608783.
  17. 17.0 17.1 Vannuccini S, Petraglia F (2019). "Recent advances in understanding and managing adenomyosis". F1000Res. 8. doi:10.12688/f1000research.17242.1. PMC 6419978. PMID 30918629.
  18. Wood C (1998). "Surgical and medical treatment of adenomyosis". Hum Reprod Update. 4 (4): 323–36. doi:10.1093/humupd/4.4.323. PMID 9825848.
  19. Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD; et al. (2020). "Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids". N Engl J Med. 382 (4): 328–340. doi:10.1056/NEJMoa1904351. PMID 31971678.
  20. Bragheto AM, Caserta N, Bahamondes L, Petta CA (2007). "Effectiveness of the levonorgestrel-releasing intrauterine system in the treatment of adenomyosis diagnosed and monitored by magnetic resonance imaging". Contraception. 76 (3): 195–9. doi:10.1016/j.contraception.2007.05.091. PMID 17707716.
  21. 21.0 21.1 Zhou J, He L, Liu P, Duan H, Zhang H, Li W; et al. (2016). "Outcomes in Adenomyosis Treated with Uterine Artery Embolization Are Associated with Lesion Vascularity: A Long-Term Follow-Up Study of 252 Cases". PLoS One. 11 (11): e0165610. doi:10.1371/journal.pone.0165610. PMC 5091759. PMID 27806072.

Additional Resources

  • Atri M, Reinhold C, Mehio AR. Adenomyosis: US features with histologic correlation in an in-vitro study. Radiology. Jun 2000;215(3):783-90.
  • Batzer FR, Hansen L. Bizarre sonographic appearance of an adenomyoma and its presentation. J Ultrasound Med. Aug 1996;15(8):599-602.
  • Bazot M, Daraï E. [Evaluation of pelvic endometriosis: the role of MRI.]. J Radiol. Nov 2008;89(11 Pt 1):1695-6.
  • Byun JY, Kim SE, Choi BG, et al. Diffuse and focal adenomyosis: MR imaging findings. Radiographics. Oct 1999;19 Spec No:S161-70.
  • Chiang CH, Chang MY, Hsu JJ. Tumor vascular pattern and blood flow impedance in the differential diagnosis of leiomyoma and adenomyosis by color Doppler sonography. J Assist Reprod Genet. May 1999;16(5):268-75.
  • Guilbeault H, Wilson SR, Lickrish GM. Massive uterine enlargement with necrosis: an unusual manifestation of adenomyosis. J Ultrasound Med. Apr 1994;13(4):326-8.
  • Haimovici JB, Tempany CM. MR of the female pelvis: benign disease. Appl Radiol. Jun 1994;7:21.
  • Huang HY. Medical treatment of endometriosis. Chang Gung Med J. Sep-Oct 2008;31(5):431-40.
  • Iribarne C, Plaza J, De la Fuente P, et al. Intramyometrial cystic adenomyosis. J Clin Ultrasound. Jun 1994;22(5):348-50.
  • Jarlot C, Anglade E, Paillocher N, Moreau D, Catala L, Aubé C. [MR imaging features of deep pelvic endometriosis: correlation with laparoscopy.]. J Radiol. Nov 2008;89(11 Pt 1):1745-54.
  • Kang S, Turner DA, Foster GS, et al. Adenomyosis: specificity of 5 mm as the maximum normal uterine junctional zone thickness in MR images. AJR Am J Roentgenol. May 1996;166(5):1145-50.
  • Kim MD, Lee HS, Lee MH, Kim HJ, Cho JH, Cha SH. Long-term results of symptomatic fibroids treated with uterine artery embolization: In conjunction with MR evaluation. Eur J Radiol. Dec 10 2008;
  • Ostrzenski A. Extensive iatrogenic adenomyosis after laparoscopic myomectomy. Fertil Steril. Jan 1998;69(1):143-5.
  • Piketty M, Chopin N, Dousset B, Millischer-Bellaische AE, Roseau G, Leconte M, et al. Preoperative work-up for patients with deeply infiltrating endometriosis: transvaginal ultrasonography must definitely be the first-line imaging examination. Hum Reprod. Dec 17 2008;
  • Piketty M, Chopin N, Dousset B, Millischer-Bellaische AE, Roseau G, Leconte M, et al. Preoperative work-up for patients with deeply infiltrating endometriosis: transvaginal ultrasonography must definitely be the first-line imaging examination. Hum Reprod. Dec 17 2008;
  • Reinhold C, Atri M, Mehio A, et al. Diffuse uterine adenomyosis: morphologic criteria and diagnostic accuracy of endovaginal sonography. Radiology. Dec 1995;197(3):609-14.
  • Reinhold C, Tafazoli F, Mehio A, et al. Uterine adenomyosis: endovaginal US and MR imaging features with histopathologic correlation. Radiographics. Oct 1999;19 Spec No:S147-60.
  • Tamai K, Koyama T, Umeoka S, et al. Spectrum of MR features in adenomyosis. Best Pract Res Clin Obstet Gynaecol. Aug 2006;20(4):583-602.
  • Tamai K, Togashi K, Ito T, et al. MR imaging findings of adenomyosis: correlation with histopathologic features and diagnostic pitfalls. Radiographics. Jan-Feb 2005;25(1):21-40.
  • Utsunomiya D, Notsute S, Hayashida Y, et al. Endometrial carcinoma in adenomyosis: assessment of myometrial invasion on T2-weighted spin-echo and gadolinium-enhanced T1-weighted images. AJR Am J Roentgenol. Feb 2004;182(2):399-404.

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