NAPROXEN AND NAPROXEN SODIUM IN DYSMENORRHEA: DEVELOPMENT FROM IN VITRO INHIBITION OF PROSTAGLANDIN SYNTHESIS TO SUPPRESSION OF UTERINE CONTRACTIONS IN WOMEN AND DEMONSTRATION OF CLINICAL EFFICACY

Abstract

Abstract. “In vitro” experimentation has shown that naproxen inhibits prostaglandin synthetase generated by uterine microsomes of pregnant rats. In another in vitro system, naproxen inhibited electrically induced contractions of an isolated myometrial strip and abolished the sensitivity of the myometrium to oxytocin.In in vivo experiments, naproxen prevented oxytocin‐induced “writhing” of rats and mice, and delayed parturition when given to pregnant rats.In double‐blind placebo controlled clinical experiments naproxen sodium administration was followed by a steady decrease of intrauterine resting pressure, and the amplitude and frequency of uterine contractions.Clinical trials designed to prove the efficacy and acceptability of naproxen sodium in dysmenorrhea comprised 227 patients followed over a total of 623 painful menstruations. Complete or substantial pain relief was achieved by 77.9% of patients treated with naproxen sodium but only by 23% of placebo treated patients. The use of other analgesic agents was prominently reduced: only 28% naproxen sodium treated patients needed an additional pain medication over 18% painful menstruations while 70% placebo treated patients needed additional analgesics over 54% painful menstruations. Naproxen sodium treatment enabled the patients to continue their daily activities during dysmenorrhea: 77.3% patients who historically had to stay at home from school/work and/or in bed could continue their daily activities, while, in striking contrast 81.8% such patients of the placebo group remained fully incapacitated. Naproxen and naproxen sodium also reduced pain associated with IUD insertion; and in patients with dysmenorrhea secondary to IUD.No meaningful side effects occurred throughout the trials.The mode of naproxen's action in dysmenorrhea is probably by inhibition of microsomal prostaglandin synthetase. The in vitro conversion of arachidonic acid into PGF and PGE by uterine microsomes is reduced by naproxen in a dose‐related manner. Naproxen treatment substantially decreases PGF and PGE concentrations in uterine tissue of pregnant rats. In humans, the PGF content in menstrual blood becomes significantly reduced by naproxen sodium treatment as compared to menstruations with placebo treatment. This suggests causal associations between naproxen treatment, reduction of uterine prostaglandins, inhibition of uterine contractions, and relief of dysmenorrhea. Thus naproxen represents a rational therapy for dysmenorrhea.