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Uterine adenomyosis is a common chronic disorder frequently encountered in reproductive-age women, causing heavy menstrual bleeding, intense pelvic pain, and infertility. Despite its high prevalence, its etiopathogenesis is not yet fully understood, so there are currently no specific drugs to treat the disease. A number of dysregulated mechanisms are believed to contribute to adenomyosis development and symptoms, including sex steroid signaling, endometrial proliferation and invasiveness, and aberrant immune response. Abnormal sex steroid signaling, particularly hyperestrogenism and subsequent progesterone resistance, are known to play a pivotal role in its pathogenesis, which is why various antiestrogenic agents have been used to manage adenomyosis-related symptoms. Among them, gonadotropin-releasing hormone (GnRH) antagonists are swiftly gaining ground, with recent studies reporting efficient lesion regression and symptom alleviation. The aim of the present review is to compile available information on the pathogenesis of adenomyosis, explore the etiology and mechanisms of hyperestrogenism, and discuss the potential of antiestrogenic therapies for treating the disease and improving patient quality of life.

Uterine adenomyosis is a benign disease, commonly encountered in reproductive-age women and responsible for chronic pelvic pain, abnormal uterine bleeding, and infertility. Although the exact origin and pathogenic mechanisms involved in adenomyosis still need to be elucidated, significant progress has been made over recent years. Ever since the theory of endometrium invaginating the myometrium via a traumatized interface was first proposed, numerous molecular mechanisms have been reported to participate in this process. At the same time, an alternative theory has suggested de novo development of adenomyotic lesions from metaplasia of Müllerian remnants or adult stem cells. Hence, our understanding of the pathogenesis of adenomyosis has been greatly enhanced and is anticipated to pave the way for development of an effective and safe treatment. The goal of this review is to analyze current knowledge on the origin and pathogenic mechanisms of adenomyosis, ranging from the most widely accepted theories to newly reported data., (© 2020. Society for Reproductive Investigation.)