Role of inflammation in benign gynecologic disorders: from pathogenesis to novel therapies†

Abstract

Emerging evidence supports the notion that inflammation fosters the development of common benign gynecologic disorders, including uterine leiomyoma, endometriosis, and adenomyosis. Numerous cytokines, chemokines, and growth and transcription factors have indisputable roles in the establishment and maintenance of benign gynecologic disorders by initiating complex cascades that promote proliferation, angiogenesis, and lesion progression. The interaction between inflammation and benign gynecologic disorders is orchestrated by a plethora of factors, including sex steroids, genetics, epigenetics, extracellular matrix, stem cells, cardiometabolic risk factors, diet, vitamin D, and the immune system. The role of inflammation in these disorders is not limited to local pathobiology but also extends to involve clinical sequelae that range from those confined to the reproductive tract, such as infertility and gynecologic malignancies, to systemic complications such as cardiovascular disease. Enhanced understanding of the intricate mechanisms of this association will introduce us to unvisited pathophysiological perspectives and guide future diagnostic and therapeutic implications aimed at reducing the burden of these disorders. Utilization of inflammatory markers, microRNA, and molecular imaging as diagnostic adjuncts may be valuable, non-invasive techniques for prompt detection of benign gynecologic disorders. Further, use of novel as well as previously established therapeutics, such as immunomodulators, hormonal treatments, cardiometabolic medications, and cyclooxygenase-2 and NF-κB inhibitors, can target inflammatory pathways involved in their pathogenesis. In this comprehensive review, we aim to dissect the existing literature on the role of inflammation in benign gynecologic disorders, including the proposed underlying mechanisms and complex interactions, its contribution to clinical sequelae, and the clinical implications this role entails.

Huayu Sanjie Enema Liquid Relieves Pain in Endometriosis Model Rats by Inhibiting Inflammation, Peripheral Sensitization, and Pelvic Adhesion

“…EMs has long been considered an aseptic inflammatory disease [ 35 ]. Its occurrence and development and the production of pelvic pain are related to the mediation of many inflammatory factors [ 36 , 37 ]. In this study, we measured the expression levels of PGE2, IL-6, TNF- α , and MIP-2 to evaluate the effects of Huayu Sanjie enema on inflammation.…”

Uterine leiomyoma is associated with the risk of developing endometriosis: A nationwide cohort study involving 156,195 women

“…Endometriosis and uterine fibroids are common disorders that affect significant numbers of women. Previous studies have identified incidence rates of between 12% and 20% for concomitant fibroids and endometriosis [ 25 , 30 ]. In a US study, 87% of 208 patients who underwent surgical treatment for symptomatic leiomyoma were found to have endometriosis [ 31 ].…”

“…Promisingly, in vitro and preclinical investigations have indicated that some phytochemicals demonstrate strong phytoestrogenic effects capable of modulating estrogen and inflammatory activity, which could help to reduce endometriosis symptoms, although randomized controlled trial data are lacking [ 21 , 24 ]. Interestingly, increasing clinical and pathophysiological evidence supports the notion that chronic inflammation is associated with benign gynecological disorders such as uterine leiomyoma and endometriosis [ 25 ]. These associations have been comprehensively reviewed [ 25 ], although basic and clinical investigations have yet to clearly define the mechanism responsible for the development of endometriosis.…”

“…Interestingly, increasing clinical and pathophysiological evidence supports the notion that chronic inflammation is associated with benign gynecological disorders such as uterine leiomyoma and endometriosis [ 25 ]. These associations have been comprehensively reviewed [ 25 ], although basic and clinical investigations have yet to clearly define the mechanism responsible for the development of endometriosis. Up until now, research has focused on altered immune responses and other regulatory factors that may mediate the histogenesis of endometriosis.…”

Diet and Nutrition in Gynecological Disorders: A Focus on Clinical Studies

“…Although surgical removal of the endometriotic lesions is an alternate treatment modality, the recurrence rate is up to 50% within five years of surgery. An increasing number of studies have explored diet as a therapeutic strategy for endometriosis, especially in the light of current evidence suggesting an association between benign gynecological conditions, including endometriosis, and cardiometabolic risk and systemic inflammation [ 23 , 60 ]. In the following section, we review the current evidence regarding the association of nutrition and diet with endometriosis, focusing on clinical studies ( Figure 2 ).…”