Symptomatic endometriosis developing several years after menopause in the absence of increased circulating estrogen concentrations: a systematic review and seven case reports

Abstract

Background: To review women with symptomatic and clinically progressive endometriosis after menopause in the absence of estrogen intake or excessive systemic endogenous production.Design: Seven case reports and a systematic review of the literature from 1995 till February 2018. Results: Only 7 case reports from the authors and 29 cases from the literature described women with either cystic ovarian or deep endometriosis. Severity, symptoms, and localization are highly variable. No case report describes symptomatic superficial typical lesions. In 22 of 36 women (61%), symptoms started more than 10 years after menopause. Conclusions: Symptomatic and clinically progressive endometriosis after menopause in the absence of increased systemic estrogen concentrations or exogenous estrogen intake starts more than 10 years after menopause in the majority of women. This observation suggests that a genetic and/or epigenetic incident caused estrogen-independent progression, increased sensitivity to estrogens or increased local production of estrogens. This observation is important for understanding the pathophysiology of endometriosis, for the management of postmenopausal endometriosis, and for individualization of medical therapy of endometriosis since estrogen-independent endometriosis growth probably also occurs before menopause.

The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights

“…Intracellular production of estrogens has a key role in the pathogenesis of endometriosis, particularly in post-menopausal women [75], as well as of other benign and malignant diseases of the female reproductive tract. Aromatase P450 catalyzes the conversion of androgens to estrogens and is physiologically expressed in different human tissues, including ovaries and adipose tissue, but usually not in the endometrium [76,77].…”

Inflammatory cytokine profile of VEGF and IL-6 from the endometrium of women with and without endometriosis

“…Numerous proposed systems to classify various forms of endometriosis exist mainly in the American Society of Reproductive Medicine (rASRM) (15), which is modified and renamed into Revised American Society for Reproductive Medicine classification of endometriosis. 27,28 All of these classifications divide endometriosis into four stages related to the increasing severity of the ovaries lesions, particularly the number of endometrial implants, their depth, and adhesions; stage I: 1-5 points indicates minimal disease i.e., few superficial implants, stage II: 6-15 points score indicates mild disease which includes more and deeper implants, stage III: 16-40 points for moderate disease having many deep implants, small cysts on one or both ovaries and stage IV: >40 points indicate severe condition with many deep implants, large cysts on one or both ovaries with dense adhesions.…”

“…12,13 More specifically, in the plasma and peritoneal fluid (PF), endometriosis patients display aberrant numbers of immune cells and concentrations of cytokines and chemokines that promote a chronic inflammatory environment compared to healthy women. 2,14,15 The chronic inflammatory environment has also been shown to contribute to the chronic pain and infertility experienced by endometriosis patients. 16,17 Altered function of immune cells are involved in the developmental cause or consequence of endometriosis, especially an immune dysfunction in relation to macrophages and cells within the peritoneum secreting a number of products of monocytes/macrophages, mainly growth factors and cytokines.…”

Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review

“…Estrogen (E 2 ) augmentation and progesterone resistance feature EM pathology, but the mechanism of how this occurs is unclear. Nevertheless, EM has been observed even in the absence of increased E 2 production in postmenopausal women 5 . The pathogenesis of EM is dominated by the theory of ectopic implantation of the endometrium, along with multiple factors, such as endocrine, immunity, invasion, and angiogenesis.…”