Evidence supports the concept that dysmenorrhea arises through the excess in prostaglandin synthesis from the endometrium itself: elevated levels of PGF_2α have been found in the menstrual fluid, as well as in the blood, of adolescents with dysmenorrhea. In the uterus, phospholipids from the dead cell membranes are converted to arachidonic acid which can be metabolized by cyclooxygenase, leading to the synthesis of endoperoxides. These endoperoxides are then converted to prostaglandins (PGD₂, PGE₂, PGF_2α). PGF_2α mediates the pain sensation and stimulates endometrium contraction (

fig. 1), while abnormal uterine smooth muscle contractility and modifications of the local blood flow are responsible for abdominal pain.

The role of PGs has been strengthened by the observation that the NSAIDs that inhibit PG synthesis can relieve dysmenorrhea and associated symptoms.

Rofecoxib, a specific cyclooxygenase-2 inhibitor, effectively treated primary dysmenorrhea, and cyclooxygenase-2-derived prostanoids play a role in the pathophysiology of primary dysmenorrhea. Increased urinary excretion of leukotrienes E(4), inflammatory mediators known to cause potent vasoconstriction and uterine contractions, suggests that these mediators may also be involved in generating dysmenorrhea symptoms in adolescents.