Pathophysiological Basis of Endometriosis-Linked Stress Associated with Pain and Infertility: A Conceptual Review

Abstract

Women with endometriosis are often under stress due to the associated pain, infertility, inflammation-related and other comorbidities including cancer. Additionally, these women are also under stress due to taboos, myths, inter-personal troubles surrounding infertility and pain of the disease as well as due to frequent incidences of missed diagnosis and treatment recurrence. Often these women suffer from frustration and loss of valuable time in the prime phase of life. All these complexities integral to endometriosis posit a hyperstructure of integrative stress physiology with overt differentials in effective allostatic state in women with disease compared with disease-free women. In the present review, we aim to critically examine various aspects of pathophysiological basis of stress surrounding endometriosis with special emphasis on pain and subfertility that are known to affect the overall health and quality of life of women with the disease and promising pathophysiological basis for its effective management.

Progesterone Resistance in Endometriosis

“…of reproductive age have endometriosis, with more than 70% of them affected by chronic pelvic pain. 65 Endometriosis is also a wellacknowledged cause of infertility, which is seen in 50% of patients with endometriosis with normal ovulation and normo-spermic partners.…”

“…Severe endometriosis is associated with poor embryo implantation rates and pregnancy rates in women undergoing in vitro fertilisation treatment. 65 Females with endometriosis often have several inflammation-linked and other comorbidities like uterine fibroid, adenomyosis, pelvic inflammatory disorder, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, fibromyalgia and cardiovascular diseases. 65 Endometriosis is generally considered benign; however, unmanaged endometriosis with atypia may result in ovarian and extra-ovarian cancers.…”

“…65 Females with endometriosis often have several inflammation-linked and other comorbidities like uterine fibroid, adenomyosis, pelvic inflammatory disorder, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, fibromyalgia and cardiovascular diseases. 65 Endometriosis is generally considered benign; however, unmanaged endometriosis with atypia may result in ovarian and extra-ovarian cancers. 66 Based on generally known progesterone actions in target tissues as discussed above and shown in Figure 5, it appears that resistance of progesterone action may cause the abovementioned endometriosis-associated conditions in patients.…”

Examining Diagnostic Options and Classification Systems Available for Endometriosis

“…The EFI provides a classification system on the basis of scores obtained from the assessment of surgical factors and historical factors, and projects to predict the clinical outcome of pregnancy in patients who are infertile .2,62 EFI is considered a valid clinical tool to predict fertility outcome for people following surgical staging of endometriosis and may be used for suitable treatment plans for infertile women with endometriosis. 2,62,63 The Foci-Ovarian endometrioma-Adhesion-Tubal endometriosis-Inflammationadenomyosis-Recto-Vaginal Space (FOATIaRVS) system of classification takes into consideration the histology of ectopic lesions and functional repercussions for tubal and ovarian functions along with the nature of inflammation. Collectively, it may help to identify the nature of medical and surgical treatments to be undertaken in patients who are infertile and have endometrioma; and the chances of malignant proliferation.…”

Overexpression of ErbB-1 (EGFR) Protein in Eutopic Endome-Trium of Infertile Women with Severe Ovarian Endometriosis during the ‘Implantation Window’ of Menstrual Cycle

“…Thus, it is possible that the primary defect exists in eutopic endometrium of women diagnosed with endometriosis as it bears significant differences with control endometrium from endometriosis-free women [3,4]. There exists a strong association between endometriosis and infertility; in infertile women, the prevalence of endometriosis may be as high as 50%, and at least one woman of three women with endometriosis is infertile [5,6]. It appears that the pathophysiological basis of endometriosisassociated infertility is multifactorial, and that inadequate endometrial preparation causing implantation defect is an important one [7].…”