Clinical meaning
Dysmenorrhea is classified as primary (no underlying pelvic pathology) or secondary (identifiable organic cause such as endometriosis, adenomyosis, or fibroids).
Primary dysmenorrhea results from excessive prostaglandin production by the secretory endometrium at the time of menstruation. Following progesterone withdrawal at the end of the luteal phase, membrane phospholipids are cleaved by phospholipase A2 (PLA2) to release arachidonic acid. Arachidonic acid is then converted by cyclooxygenase-2 (COX-2) to prostaglandin H2 (PGH2), which is subsequently converted to prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) by tissue-specific synthases.
PGF2α is the primary mediator of dysmenorrhea. It causes potent myometrial smooth muscle hypercontractility, increasing intrauterine pressure above 150-180 mmHg (resting: 10 mmHg) and exceeding arterial perfusion pressure. This produces myometrial ischemia with anaerobic metabolism and lactic acid accumulation, activating pain-sensitive nerve fibers. PGF2α also sensitizes type C pain afferents to bradykinin and histamine. PGE2 contributes through vasodilation, edema, and further nociceptor sensitization. Vasopressin (AVP) independently increases myometrial contractility via V1a receptors and exacerbates uterine ischemia through vasoconstriction of uterine arterioles.
Secondary dysmenorrhea involves structural or inflammatory pathology. Endometriosis causes ectopic endometrial implants that produce prostaglandins, cytokines (IL-1β, IL-6, TNF-α), and nerve growth factor, creating peripheral and central sensitization. Adenomyosis involves ectopic endometrial glands within the myometrium, disrupting normal contractile patterns and causing diffuse uterine enlargement with heavy, painful menses.