New Perspectives on Adenomyosis

Elizabeth A. Stewart, MD

Linda C. Giudice, MD, PhD, MSc

Lisa M. Halvorson, MD

Luk Rombauts, PhD, FRANZCOG, MD

Adenomyosis, defined as the presence of endometrial tissue within the uterine myometrium, may be associated with substantial dysmenorrhea, chronic pelvic pain, menorrhagia, bowel and bladder pressure, infertility, and pregnancy complications. Of note, similar to endometriosis, there is a wide variation in morbidity across patients and may be poor correlation with extent of disease. Current prevalence estimates range from approximately 1% when based on ICD codes to 20% by ultrasound in symptomatic women to as high as 60% in hysterectomy specimens.[1] [2] With improved awareness and increased utilization of pelvic ultrasound, it is becoming clear that adenomyosis presents earlier and may be a more common cause of gynecologic and obstetric complications than previously appreciated.

As disorders of ectopic endometrium, adenomyosis and endometriosis have previously been designated “endometriosis interna” and “endometriosis externa,” respectively. Although they share common features and frequently coexist, some experts believe they should be considered distinct entities due to differences in pathogenesis, risk factors, and clinical presentations. Others highlight similarities between adenomyosis and deep infiltrating endometriosis and emphasize the many ways in which adenomyosis can be viewed as “myometrial endometriosis.”

The etiology of adenomyosis is poorly defined and may differ between focal adenomyosis and diffuse forms of the disease. Current thinking focuses on two primary models, either breakdown of the endometrial–myometrial border allowing endometrial cell migration or metaplasia of embryonic Mullerian remnants. Similarly, little is known about the contribution of genomic or epigenomic variants or of stem cell dysfunction to the pathogenesis of this disorder.[3] [4] Treatment is primarily hysterectomy, although medical management and less aggressive surgical and interventional radiologic approaches are emerging.[5]

The “benign” nature of adenomyosis is frequently emphasized in the literature and in discussions with patients. This terminology minimizes the substantial morbidity experienced by patients and, as for other noncancerous gynecologic conditions, may have diminished the intensity of the search for adequate diagnosis and treatment.

Recognizing the significant need to better understand this disorder, the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) sponsored a meeting entitled “Adenomyosis: Diagnosis, Pathogenesis, and Treatment” on April 24, 2019. This issue is the extension of this workshop which was attended by many of the authors who have contributed here. The following articles are designed to review the current state-of-the science in adenomyosis research and clinical care, including the epidemiology, diagnosis, pathogenesis, pathophysiology, and treatment of this disorder. The overlap of adenomyosis and its clinical presentation with other gynecologic disorders, particularly endometriosis, is presented to emphasize the high potential for misdiagnosis and, as a result, suboptimal treatment. The currently available in vitro and in vivo models are analyzed for their ability to address ongoing research questions. Throughout, authors highlight gaps in our knowledge and suggest research tools, models, and investigative approaches which are poised to advance research in this field.

We hope that this issue will be a useful resource for clinicians and investigators, and spur enthusiasm for the increased study of this highly prevalent and morbid disorder. While many questions remain, the emerging interest in this field promises great hope for the future care of these patients.

Publication History

Article published online:
24 November 2020

• References

• 1 Yu O, Schulze-Rath R, Grafton J, Hansen K, Scholes D, Reed SD. Adenomyosis incidence, prevalence and treatment: United States population-based study 2006-2015. Am J Obstet Gynecol 2020; 223 (01) 94.e1-94.e10
• 2 Munro MG. Classification and reporting systems for adenomyosis. J Minim Invasive Gynecol 2020; 27 (02) 296-308
• 3 García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia?. Fertil Steril 2018; 109 (03) 371-379
• 4 Vannuccini S, Tosti C, Carmona F. et al. Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod Biomed Online 2017; 35 (05) 592-601
• 5 Rabinovici J, Stewart EA. New interventional techniques for adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006; 20 (04) 617-636