Adenomyosis: Mechanisms and Pathogenesis

Junyu Zhai; Silvia Vannuccini; Felice Petraglia; Linda C. Giudice

doi:10.1055/s-0040-1716687

Seminars in Reproductive Medicine, Table of Contents

Semin Reprod Med 2020; 38(02/03): 129-143
DOI: 10.1055/s-0040-1716687

Review Article

Adenomyosis: Mechanisms and Pathogenesis

Junyu Zhai

¹Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California

²Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China

³Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, People's Republic of China

,

Silvia Vannuccini

⁴Division of Obstetrics and Gynecology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Careggi University Hospital, Florence, Italy

⁵Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy

,

Felice Petraglia

⁴Division of Obstetrics and Gynecology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Careggi University Hospital, Florence, Italy

,

Linda C. Giudice

¹Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California

› Author Affiliations

Abstract

Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is characterized by endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells. While both the mechanistic processes and the pathogenesis of adenomyosis are uncertain, several theories have been put forward addressing how this disease develops. These include intrinsic or induced (1) microtrauma of the endometrial–myometrial interface; (2) enhanced invasion of endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4) infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and pituitary hormones; and (6) abnormal uterine development in response to genetic and epigenetic modifications. Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components. Elucidating mechanisms underlying the pathogenesis of adenomyosis raise possibilities to develop targeted therapies to ameliorate symptoms beyond the current agents that are largely ineffective. Herein, we address these possible etiologies and data that support underlying mechanisms.

Keywords

adenomyosis - mechanisms - pathogenesis - metaplasia - endometrial–myometrial interface

Full Text

References

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