- Elizabeth A Stewart, MD
Elizabeth A Stewart, MD
- Consultant and Professor of Obstetrics and Gynecology
- Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology
- Mayo Clinic and Mayo Medical School
Adenomyosis refers to a disorder in which endometrial glands and stroma are present within the uterine musculature (uterine adenomyomatosis). The ectopic endometrial tissue appears to induce hypertrophy and hyperplasia of the surrounding myometrium, which results in a diffusely enlarged uterus (often termed "globular" enlargement) analogous to the concentric enlargement of the pregnant uterus. However, some women have only small areas of diffuse disease that are only apparent by microscopy, whereas others develop nodules (termed adenomyomas), which clinically resemble leiomyomas. The uterus only rarely exceeds the size of a pregnant uterus at 12 weeks of gestation.
EPIDEMIOLOGY AND RISK FACTORS
The incidence of adenomyosis has not been determined accurately since the diagnosis can only be made with certainty by microscopic examination of the uterus, typically following hysterectomy. Although generally estimated to affect 20 percent of women, the incidence was approximately 65 percent in one study in which meticulous histopathological analysis of multiple myometrial sections was performed .
A full understanding of the epidemiology of the disease is limited by the difficulty in making the diagnosis. Until recently, adenomyosis was only diagnosed at the time of hysterectomy. Most studies suggest that women undergoing hysterectomy for adenomyosis are in the later part of their reproductive years. However, this results in a lack of information about early stages of disease. Studies that use pelvic imaging, rather than hysterectomy, for diagnosis suggest that adenomyosis can be found in adolescents.
In addition, the fact that adenomyosis coexists with other uterine diseases, primarily uterine leiomyomas and endometriosis, contributes to the gaps in the understanding of this disease. As an example, persistence of pelvic pain following optimal endometriosis surgical therapy may be confounded by the presence of adenomyosis [2,3].
On the other hand, one study argued that adenomyosis was a variant and not a true disease because the presenting symptoms for hysterectomy were similar with and without the finding of adenomyosis . However, at the time of recruitment, all women were at least 42 years old and women were followed for 10 years, so the cohort represented only perimenopausal women.
- McElin TW, Bird CC. Adenomyosis of the uterus. Obstet Gynecol Annu 1974; 3:425.
- Ryan GL, Stolpen A, Van Voorhis BJ. An unusual cause of adolescent dysmenorrhea. Obstet Gynecol 2006; 108:1017.
- 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.
- Weiss G, Maseelall P, Schott LL, et al. Adenomyosis a variant, not a disease? Evidence from hysterectomized menopausal women in the Study of Women's Health Across the Nation (SWAN). Fertil Steril 2009; 91:201.
- Templeman C, Marshall SF, Ursin G, et al. Adenomyosis and endometriosis in the California Teachers Study. Fertil Steril 2008; 90:415.
- Taran FA, Weaver AL, Coddington CC, Stewart EA. Understanding adenomyosis: a case control study. Fertil Steril 2010; 94:1223.
- Molitor JJ. Adenomyosis: a clinical and pathological appraisal. Am J Obstet Gynecol 1971; 110:275.
- Panganamamula UR, Harmanli OH, Isik-Akbay EF, et al. Is prior uterine surgery a risk factor for adenomyosis? Obstet Gynecol 2004; 104:1034.
- Ferenczy A. Pathophysiology of adenomyosis. Hum Reprod Update 1998; 4:312.
- 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.
- Enatsu A, Harada T, Yoshida S, et al. Adenomyosis in a patient with the Rokitansky-Kuster-Hauser syndrome. Fertil Steril 2000; 73:862.
- Ota H, Igarashi S, Sato N, et al. Distribution of tissue macrophages in uterine muscle layers in patients with adenomyosis. Med Sci Res 1991; 19:473.
- Matsumoto Y, Iwasaka T, Yamasaki F, Sugimori H. Apoptosis and Ki-67 expression in adenomyotic lesions and in the corresponding eutopic endometrium. Obstet Gynecol 1999; 94:71.
- Ota H, Igarashi S, Hatazawa J, Tanaka T. Immunohistochemical assessment of superoxide dismutase expression in the endometrium in endometriosis and adenomyosis. Fertil Steril 1999; 72:129.
- Propst AM, Quade BJ, Gargiulo AR, et al. Adenomyosis demonstrates increased expression of the basic fibroblast growth factor receptor/ligand system compared with autologous endometrium. Menopause 2001; 8:368.
- Propst AM, Quade BJ, Nowak RA, Stewart EA. Granulocyte macrophage colony-stimulating factor in adenomyosis and autologous endometrium. J Soc Gynecol Investig 2002; 9:93.
- Brosens JJ, de Souza NM, Barker FG. Uterine junctional zone: function and disease. Lancet 1995; 346:558.
- Zhang Y, Yu P, Sun F, et al. Expression of oxytocin receptors in the uterine junctional zone in women with adenomyosis. Acta Obstet Gynecol Scand 2015; 94:412.
- Ibrahim MG, Chiantera V, Frangini S, et al. Ultramicro-trauma in the endometrial-myometrial junctional zone and pale cell migration in adenomyosis. Fertil Steril 2015; 104:1475.
- Wang S, Duan H, Zhang Y, Sun FQ. Abnormal Activation of RhoA/ROCK-I Signaling in Junctional Zone Smooth Muscle Cells of Patients With Adenomyosis. Reprod Sci 2016; 23:333.
- Yamamoto T, Noguchi T, Tamura T, et al. Evidence for estrogen synthesis in adenomyotic tissues. Am J Obstet Gynecol 1993; 169:734.
- Ishihara H, Kitawaki J, Kado N, et al. Gonadotropin-releasing hormone agonist and danazol normalize aromatase cytochrome P450 expression in eutopic endometrium from women with endometriosis, adenomyosis, or leiomyomas. Fertil Steril 2003; 79 Suppl 1:735.
- Green AR, Styles JA, Parrott EL, et al. Neonatal tamoxifen treatment of mice leads to adenomyosis but not uterine cancer. Exp Toxicol Pathol 2005; 56:255.
- Nowak RA, Mora S, Diehl T, et al. Prolactin is an autocrine or paracrine growth factor for human myometrial and leiomyoma cells. Gynecol Obstet Invest 1999; 48:127.
- Stewart EA. Gonadotropins and the uterus: is there a gonad-independent pathway? J Soc Gynecol Investig 2001; 8:319.
- Danilovich N, Roy I, Sairam MR. Emergence of uterine pathology during accelerated biological aging in FSH receptor-haploinsufficient mice. Endocrinology 2002; 143:3618.
- Fiçicioğlu C, Tekin HI, Arioğlu PF, Okar I. 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.
- Schindl M, Birner P, Obermair A, et al. Increased microvessel density in adenomyosis uteri. Fertil Steril 2001; 75:131.
- Kang S, Zhao J, Liu Q, et al. Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis. Environ Mol Mutagen 2009; 50:361.
- Wang F, Li H, Yang Z, et al. Expression of interleukin-10 in patients with adenomyosis. Fertil Steril 2009; 91:1681.
- Yang JH, Wu MY, Chen MJ, et al. Increased matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 secretion but unaffected invasiveness of endometrial stromal cells in adenomyosis. Fertil Steril 2009; 91:2193.
- Zhou YF, Mori T, Kudo H, et al. Effects of angiogenesis inhibitor TNP-470 on the development of uterine adenomyosis in mice. Fertil Steril 2003; 80 Suppl 2:788.
- Takeuchi H, Kitade M, Kikuchi I, et al. Diagnosis, laparoscopic management, and histopathologic findings of juvenile cystic adenomyoma: a review of nine cases. Fertil Steril 2010; 94:862.
- Troiano RN, Flynn SD, McCarthy S. Cystic adenomyosis of the uterus: MRI. J Magn Reson Imaging 1998; 8:1198.
- Levgur M. Diagnosis of adenomyosis: a review. J Reprod Med 2007; 52:177.
- Juang CM, Chou P, Yen MS, et al. Adenomyosis and risk of preterm delivery. BJOG 2007; 114:165.
- Maheshwari A, Gurunath S, Fatima F, Bhattacharya S. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Hum Reprod Update 2012; 18:374.
- Tomassetti C, Meuleman C, Timmerman D, D'Hooghe T. Adenomyosis and subfertility: evidence of association and causation. Semin Reprod Med 2013; 31:101.
- Barrier BF, Malinowski MJ, Dick EJ Jr, et al. Adenomyosis in the baboon is associated with primary infertility. Fertil Steril 2004; 82 Suppl 3:1091.
- Kunz G, Beil D, Huppert P, et al. Adenomyosis in endometriosis--prevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod 2005; 20:2309.
- Champaneria R, Abedin P, Daniels J, et al. Ultrasound scan and magnetic resonance imaging for the diagnosis of adenomyosis: systematic review comparing test accuracy. Acta Obstet Gynecol Scand 2010; 89:1374.
- Reinhold C, Tafazoli F, Mehio A, et al. Uterine adenomyosis: endovaginal US and MR imaging features with histopathologic correlation. Radiographics 1999; 19 Spec No:S147.
- Gordts S, Brosens JJ, Fusi L, et al. Uterine adenomyosis: a need for uniform terminology and consensus classification. Reprod Biomed Online 2008; 17:244.
- Tocci A, Greco E, Ubaldi FM. Adenomyosis and 'endometrial-subendometrial myometrium unit disruption disease' are two different entities. Reprod Biomed Online 2008; 17:281.
- Byun JY, Kim SE, Choi BG, et al. Diffuse and focal adenomyosis: MR imaging findings. Radiographics 1999; 19 Spec No:S161.
- Katsumata Y, Noda M, Tanaka M, et al. [CT appearance of uterine adenomyosis]. Rinsho Hoshasen 1989; 34:227.
- Fong YF, Singh K. Medical treatment of a grossly enlarged adenomyotic uterus with the levonorgestrel-releasing intrauterine system. Contraception 1999; 60:173.
- Huang FJ, Kung FT, Chang SY, Hsu TY. Effects of short-course buserelin therapy on adenomyosis. A report of two cases. J Reprod Med 1999; 44:741.
- Fedele L, Bianchi S, Raffaelli R, et al. Treatment of adenomyosis-associated menorrhagia with a levonorgestrel-releasing intrauterine device. Fertil Steril 1997; 68:426.
- Kitawaki J. Adenomyosis: the pathophysiology of an oestrogen-dependent disease. Best Pract Res Clin Obstet Gynaecol 2006; 20:493.
- Bragheto AM, Caserta N, Bahamondes L, Petta CA. Effectiveness of the levonorgestrel-releasing intrauterine system in the treatment of adenomyosis diagnosed and monitored by magnetic resonance imaging. Contraception 2007; 76:195.
- Sheng J, Zhang WY, Zhang JP, Lu D. The LNG-IUS study on adenomyosis: a 3-year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis. Contraception 2009; 79:189.
- Igarashi M, Abe Y, Fukuda M, et al. Novel conservative medical therapy for uterine adenomyosis with a danazol-loaded intrauterine device. Fertil Steril 2000; 74:412.
- Shaaban OM, Ali MK, Sabra AM, Abd El Aal DE. Levonorgestrel-releasing intrauterine system versus a low-dose combined oral contraceptive for treatment of adenomyotic uteri: a randomized clinical trial. Contraception 2015; 92:301.
- Wood C. Surgical and medical treatment of adenomyosis. Hum Reprod Update 1998; 4:323.
- McCausland V, McCausland A. The response of adenomyosis to endometrial ablation/resection. Hum Reprod Update 1998; 4:350.
- Scarperi S, Pontrelli G, Campana C, et al. Laparoscopic Radiofrequency Thermal Ablation for Uterine Adenomyosis. JSLS 2015; 19.
- Hai N, Hou Q, Ding X, et al. Ultrasound-guided transcervical radiofrequency ablation for symptomatic uterine adenomyosis. Br J Radiol 2017; 90:20160119.
- 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.
- Huang X, Huang Q, Chen S, et al. Efficacy of laparoscopic adenomyomectomy using double-flap method for diffuse uterine adenomyosis. BMC Womens Health 2015; 15:24.
- Pelage JP, Jacob D, Fazel A, et al. Midterm results of uterine artery embolization for symptomatic adenomyosis: initial experience. Radiology 2005; 234:948.
- Nijenhuis RJ, Smeets AJ, Morpurgo M, et al. Uterine artery embolisation for symptomatic adenomyosis with polyzene F-coated hydrogel microspheres: three-year clinical follow-up using UFS-QoL questionnaire. Cardiovasc Intervent Radiol 2015; 38:65.
- Kitamura Y, Allison SJ, Jha RC, et al. MRI of adenomyosis: changes with uterine artery embolization. AJR Am J Roentgenol 2006; 186:855.
- 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.
- 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.
- 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.
- Zhou M, Chen JY, Tang LD, et al. Ultrasound-guided high-intensity focused ultrasound ablation for adenomyosis: the clinical experience of a single center. Fertil Steril 2011; 95:900.