Inflammatory Markers in Dysmenorrhea and Therapeutic Options

Abstract

Dysmenorrhea often significantly reduces the quality of women’s life and is still an important public health problem. Despite numerous studies, the pathomechanism of dysmenorrhea is not fully understood. Previous research indicates the complexity of biochemical reactions between the endocrine, vascular, and immune systems. Prostaglandins play a major role in the pathomechanism of dysmenorrhea. In contrast, cytokines and other proinflammatory factors in primary dysmenorrhea are less studied. In addition to the applied pharmacotherapy, more and more studies proving the effectiveness of non-pharmacological methods appear. Therefore, the present work contains a review of the latest research concerning factors involved in dysmenorrhea, as well as therapeutic options. In the literature search, authors used online databases, PubMed, and clinitrials.gov and browsed through individual gynecology, physiotherapy journals and books.

Primary Dysmenorrhea in Relation to Oxidative Stress and Antioxidant Status: A Systematic Review of Case-Control Studies

“…Two years later, it has been suggested that inflammation and endothelial dysfunction may be characterized by lipid peroxidation [ 25 ]. Nowadays, one of the convincing mechanisms that stand behind elevated markers of inflammation is based on the role of progesterone in the menstrual cycle [ 8 , 16 ] ( Figure 2 ). During the first half of secretory (luteal) phase in the menstrual cycle, the level of progesterone increases, which has anti-inflammatory and regulating (prostaglandins and leukocytes synthesis) effects on endometrial tissue [ 8 , 16 ].…”

“…Nowadays, one of the convincing mechanisms that stand behind elevated markers of inflammation is based on the role of progesterone in the menstrual cycle [ 8 , 16 ] ( Figure 2 ). During the first half of secretory (luteal) phase in the menstrual cycle, the level of progesterone increases, which has anti-inflammatory and regulating (prostaglandins and leukocytes synthesis) effects on endometrial tissue [ 8 , 16 ]. In the second half of the luteal phase, the progesterone level begins to fall, which causes the secretion of arachidonic acid and its metabolites, such as prostaglandins and leukotrienes [ 6 , 12 , 16 , 57 ].…”

“…During the first half of secretory (luteal) phase in the menstrual cycle, the level of progesterone increases, which has anti-inflammatory and regulating (prostaglandins and leukocytes synthesis) effects on endometrial tissue [ 8 , 16 ]. In the second half of the luteal phase, the progesterone level begins to fall, which causes the secretion of arachidonic acid and its metabolites, such as prostaglandins and leukotrienes [ 6 , 12 , 16 , 57 ]. Prostaglandin and leukotrienes cause vasoconstriction and myometrial contraction, leading to uterine ischemia, which results in pain and also other complaints, such as vomiting or headache [ 6 , 17 ].…”

“…Progesterone withdrawal at the late luteal phase leads to the secretion of arachidonic acid and release of prostaglandins (especially PGF2a and PGE2) and leukotrienes during endometrial sloughing, which may cause myometrial hypercontractility. Moreover, vasoconstriction and myometrial contractions result in the ischemia and hypoxia of the uterine muscle, which causes pain and systemic symptoms [ 6 , 16 , 17 ]. During the luteal phase, increased levels of prostaglandins (compared to the follicular phase) are observed in all women; however, dysmenorrheal women have higher levels of these hormones than controls, especially during the first two days of menses [ 1 , 4 , 8 ].…”

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

“…It has been reported that inflammation potently mediates the pathological process of PD. Activated macrophages produce a wide array of inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α, which stimulate the synthesis and release of PG, leading to excessive contraction of uterine smooth muscles and ischemic injury in PD [7,8]. As a core part of inflammation, the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is involved in a wide array of acute and chronic diseases, such as coronary heart disease, stroke, pneumonia, acute kidney injury, and viral hepatitis [9].…”