Dysmenorrhea

Primary dysmenorrhea is menstrual pain without an identifiable pelvic disorder. Its timing reflects the ovarian cycle: after ovulation, progesterone falls in the late luteal phase. That hormonal withdrawal destabilizes endometrial lysosomes and releases phospholipase A2, which liberates arachidonic acid from cell membranes. Cyclooxygenase enzymes then convert arachidonic acid into prostaglandins. COX-1 is constitutively present in many tissues, whereas COX-2 is inducible and becomes upregulated around menstruation. COX-2 is regarded as the principal source of the pain-generating prostaglandins in dysmenorrhea; PGF2-alpha and PGE2 are the major mediators. Leukotrienes may add to symptoms in some patients. PGF2-alpha produces forceful, frequent myometrial contractions. It also constricts uterine vessels, reducing uterine blood flow and producing myometrial ischemia. At the same time, it sensitizes peripheral nerve endings, so contractions that might otherwise be tolerable become painful. Prostaglandin concentration tends to track with pain severity. This mechanism explains the logic of NSAID treatment. NSAIDs inhibit cyclooxygenase and reduce the formation of new prostaglandins. They do not neutralize prostaglandin that has already been released, so taking a dose only after severe cramping begins is less effective than...