Dysmenorrhoea and prostaglandins: pharmacological and therapeutic considerations

Primary dysmenorrhoea is characterised by painful menstrual cramps which appear to have no macroscopically identifiable pelvic pathology. 50% of postpubescent females suffer from dysmenorrhoea, and 10% are incapacitated for 1 to 3 days each month. Many of these patients have an increased synthesis of prostaglandins in their endometrial tissue with increased prostaglandin release in the menstrual fluid. The increased amount of prostaglandins induces incoordinate hyperactivity of the uterine muscle resulting in uterine ischaemia and pain. Recent clinical and laboratory studies have shown that many of the non-steroidal anti-inflammatory drugs such as ibuprofen, naproxen, flufenamic acid, mefenamic acid and indomethacin are capable of relieving primary dysmenorrhoea. These drugs are inhibitors of the prostaglandin synthetase enzymes which are necessary for prostaglandin biosynthesis. Thus, with ibuprofen it has been shown that clinical relief of the dysmenorrhoeic symptoms accompanies the reduction of menstrual fluid prostaglandins. With the oral contraceptive pill there is good relief of primary dysmenorrhoea, significant decrease in menstrual fluid prostaglandins, but no reduction in menstrual fluid volume; this suggests that the reduction in prostaglandins is secondary to the inhibition of endometrial growth and development. In some forms of secondary dysmenorrhoea elevated prostaglandin levels have been implicated. However, the evidence is less conclusive for dysmenorrhoea secondary to endometriosis and uterine myomas than for dysmenorrhoea associated with intrauterine devices. With the intrauterine device, prostaglandin synthetase inhibitors such as flufenamic acid, ibuprofen and naproxen are able not only to relieve dysmenorrhoea but also to reduce menstrual blood loss to normal levels. Thus, the use of appropriately selected prostaglandin synthetase inhibitors can offer effective relief from the miseries of some types of dysmenorrhoea with subsequent restoration of normal daily activities.