Prostaglandins and Nonsteroidal Antiinflammatory Drugs in Dysmenorrhea

Abstract

INTRODUCTIONDysmenorrhea, commonly known as menstrual pain or cramps, is classifi ed into primary and secondary dysmenorrhea. Generally, primary dysmenorr hea has its inception at the onset of or soon after menarche and characteris tically has no identifiable macroscopical pathology. In contrast, secondary dysmenorrhea usually has its onset in adulthood and is associated with specific pelvic pathology. Some of the causes of secondary dysmenorrhea are endometriosis, uterine polyps, pelvic inflamm atory diseases, uterogeni tal anatomical anomaly, and intrauterine device. Primary dysmenorrhea is by far the more prevalent form.The incidence and prevalence of primary dysmenorrhea have not been established, but it has been estimated that as many as 50% of women of reproductive age, particularly nulliparas, suffer from dysmenorrhea at one time or other. In approximately 10% of these dysmenorrheic subjects, the symptoms are disabling enough to cause incapacitation for one to two days a month (1-4). Primary dysmenorrhea is the most common gynecologic complaint. Because of its cyclic recurring nature, the medical and socioeco nomic impact of dysmenorrhea is enormous. It is the greatest single cause of lost work hours and school days among women (5-8), with more than 140 million work hours estimated to be lost annually (4). With increasing numbers of women entering the work force, dysmenorrhea may cause an even greater economic loss to society. 131Annu. Rev. Pharmacol. Toxicol. 1983.23:131-149. Downloaded from www.annualreviews.org Access provided by University of California -Davis on 02/03/15. For personal use only. Quick links to online content Further ANNUAL REVIEWS 132 CHAN Despite the prevalence of dysmenorrhea, until very recently, medicine has made very little headway either toward the understanding of the patho physiology of dysmenorrhea or the discovery of a specifi c and effective therapy for this female malady. The introduction of oral contraceptives in the 19608 marked the advent of the first effective therapeutic agent for the treatment of primary dysmenorrhea. Oral contraceptives, however, are not specific agents for dysmenorrhea. Until that time, treatments for dys menorrhea were primarily symptomatic, involving strong analgesics, an tidepressants, alcohol, and a variety of home remedies. These therapeutic approaches have not been successful, because of either lack of efficacy or unacceptable side effects. The first rational therapy for dySmenorrhea ap peared on the medical scene as late as the mid 19708, when the relationship between prostaglandin (pG) and dysmenorrhea was recognized and the newer nonsteroidal anti-in1lamm atory drugs (NSAIDs) with PG synthetase inhibitory activity were being introduced to the general medical practice.This review focuses on the etiologic role of PO in primary dysmenorrhea and therapeutic suppression of uterine PG production as a specifi c therapy for dysmenorrhea. PATHOPHYSIOLOGY OF PRIMARY DYSMENORRHEAMany theories have been proposed for the cause of dysmenorrhea. These inc...

Menstrual migraine: a clinical review

“…When an excessive amount of prostaglandins gain entrance to the circulation, other systemic symptoms occur that are characteristically associated with menorrhagia and/or dysmenorrhoea such as headache and nausea. 66,67 Plasma taken during the premenstrual phase from women with dysmenorrhoea and re-infused post-menstruation into the same women resulted in premenstrual symptoms, including headache. 68 Thus prostaglandins may have a specific role in migraine associated with dysmenorrhoea and/or menorrhagia.…”

Measurement of phospholipase A2 activity in human endometrium during the menstrual cycle

“…Further evidence came from the observation that PGF2oc will induce menstrual bleeding (Wiquist, Bygdeman & Kirton, 1971) and that inhibi¬ tors of prostaglandin synthesis, e.g. indomethacin and mefanamic acid, will reduce menstrual blood loss and relieve dysmennorhoea (Anderson, Haynes, Guillebaud & Turnbull, 1976;Chan, 1983). Prosta¬ glandin F2a is known to promote vasoconstriction (Malik & McGiff, 1976) whereas PGE2 has vasodilatory properties (Moneada & Vane, 1978) and it is thought that normal menstrual bleeding is dependent on the balance between the two.…”

Pharmacokinetics of the thromboxane A2 receptor antagonist sulotroban (BM 13.177) in renal failure.

“…They could be understood causally by similar mechanisms. Sulotroban is a selective antagonist of TXA2, but also of prostaglandin F2a (Stegmeier et al, 1984), which controls the perfusion of the uterine mucosa in equilibrium with prostaglandin E2 (Chan 1983;Ylikorkala & Makila, 1985). An excess of prostaglandin E2 caused by sulotroban could lead to diapedetic haemorrhages if the platelet function dependent on TXA2 is simultaneously blocked.…”