Acta Obstet Gynecol Scand – 2023 – Knez – Natural progression of deep pelvic endometriosis in women who opt for expectant

Abstract


Introduction: The natural history of endometriosis is poorly understood, and despite
numerous studies, the rate of the disease progression and optimal treatment planning
in women who are asymptomatic or experience mild symptoms not requiring
treatment are unknown. The aim of this study was to assess the behavior of deep
endometriosis in women who are managed expectantly without any medical or surgical
intervention.

Abstract

Endometriosis and adenomyosis are closely related disorders. Their pathophysiologies are extremely similar. Both tissues originate from the eutopically located intracavitary endometrium. Oligoclones of endometrial glandular epithelial cells with somatic mutations and attached stromal cells may give rise to endometriosis if they travel to peritoneal surfaces or the ovary via retrograde menstruation and/or may be entrapped in the myometrium to give rise to adenomyosis. In both instances, the endometrial cell populations possess survival and growth capabilities conferred by somatic epithelial mutations and epigenetic abnormalities in stromal cells. Activating mutations of KRAS are the most commonly found genetic variant in endometriotic epithelial cells, whereas the adenomyotic epithelial cells almost exclusively bear KRAS mutations. Epigenetic abnormalities in the stromal cells of endometriosis and adenomyosis are very similar and involve an abnormal expression pattern of nuclear receptors, including the steroid receptors. These epigenetic defects give rise to excessive local estrogen biosynthesis by aromatase and abnormal estrogen action via estrogen receptor-β. Deficient progesterone receptor expression results in progesterone resistance in both endometriosis and adenomyosis.

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.

Abstract

The aim of this review is to clarify the relative association between adenomyosis and infertility and the possible treatment for an infertile patient. Although adenomyosis is detected more often in women of late reproductive age, its influence on pregnancy rates is important, especially considering the tendency to delay pregnancy among women in developed countries. In this article, we present a critical analysis of the literature data concerning the impact of adenomyosis on fertility. The possible effects of treatment on the pregnancy rate will also be discussed. We conducted a literature search; publications from Pubmed, Embase and Cochrane databases published from 1982 to 2019 were retrieved using terms ’adenomyosis and infertility’ and ’adenomyosis and pregnancy outcomes’, extensively studied in the aspects of diagnosis, pathogenesis of infertility and possible treatment methods. Molecular studies have given deep insight into the pathogenesis of adenomyosis in the recent few years, but there is a huge discrepancy between in vitro studies and praxis. Oral contraceptive pills, anti-prostaglandins, oral or parenteral progestins, danazol and gonadotrophin-releasing hormone (GnRH) analogues have all been used to control menstrual pain and menorrhagia in women with adenomyosis, but they temporarily suppress the menstrual cycle. Additionally, endometrial ablation and hysterectomy used to alleviate pain caused by adenomyosis exclude pregnancy planning. The development of imaging techniques—ultrasound and MRI—enables the diagnosis of adenomyosis with very high accuracy nowadays, but the methods of treatment mentioned above have not given satisfactory results in women planning pregnancy. For these patients, the high-intensity-focused ultrasound method (HIFU) and combined treatment before assisted reproductive techniques can prove beneficial in adenomyosis patients.

Abstract

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.