Jeffrey ELLIS, MD Dr. Smith is professor of OBG at the University of Missouri–Kansas City Truman Medical Center in Kansas City, Mo. Dr. Ellis is in private practice in Plymouth, Ind.
Sites of inflammation (neoplastic tissue, small intestine, ovary, uterus, brain)
Function
Homeostasis
Inflammation and repair, neoplasia, modulation of immune response
Conclusion
It is apparent from the multitude of published studies and the breadth of clinical experience with NSAID therapy for primary dysmenorrhea that most of these drugs provide relief for the majority of dysmenorrheic women. The success rates reported from both subjective and objective studies of the use of mefenamic acid in dysmenorrhea support its potential superiority. The physiology of primary dysmenorrhea would suggest that the ability of the fenamates to block the action of preformed prostaglandins—as well as the 5-lipooxygenase pathway—gives them a therapeutic edge. Interestingly, one investigation of the level of selectivity of multiple NSAIDs found that mefenamic acid had a selectivity (preferential COX-2 inhibition) comparable to some of the newest selective COX-2 inhibitors.43 This may account for the low incidence of GI and other side effects reported with mefenamic acid.
The history of NSAIDs has involved the sequential introduction of agents designed to reduce side effects or increase efficacy, often through the modification of existing compounds. Many of these products have failed to meet expectations and have been withdrawn from the market. Notable recent examples include benoxaprofen, suprofen, oxyphenbutazone, and zomepirac.
Thus, it is ironic that mefenamic acid, the first agent introduced to overcome the drawbacks of aspirin, has proved to be so robust in efficacy and tolerability. In addition, it is one of the only agents objectively shown to reduce menstrual blood loss in women with menorrhagia,44-47 and to ease menstrual migraine48 and the physical and emotional symptoms of premenstrual syndrome.49-51 In fact, the combination of dysmenorrhea, premenstrual syndrome, and menorrhagia experienced by many women would seem to support the use of mefenamic acid over other agents.
Unfortunately, no direct comparisons of various drugs have definitively resolved the question of which agent is “best” for the treatment of dysmenorrhea. Until there is further refinement of our knowledge of uterine prostaglandins, menstrual function, and the physiology of dysmenorrhea, it would seem wise to rely on agents that have been studied most extensively.
Dr. Smith reports no financial relationship with any companies whose products are mentioned in this article. Dr. Ellis reports that he is on the speakers’ bureau for First Horizon Pharmaceutical Company.
