Validation of a test model of induced dysmenorrhea

Abstract

The myometrial hyperactivity and reduced uterine blood flow of primary dysmenorrhea is to a large extent caused by increased vasopressin secretion. A new therapeutic approach for this condition is to develop antagonists of uterine vasopressin V1a receptors. We studied a test model of vasopressin-induced dysmenorrhea in healthy, sterilized women and compared responses against those in dysmenorrheic subjects. Eight women with primary dysmenorrhea and eight sterilized, healthy women participated in recordings of intrauterine pressure and experienced pain on days 1-2 of two menstruations. We tried to identify biochemical markers in plasma of uterine ischemia. Furthermore, the effects of repeated bolus injections of 10 pmol/kg b w of vasopressin or placebo on these parameters were assessed. The vasopressin injections caused statistically significant increases in the area under the intrauterine pressure curve (AUC) in both healthy volunteers and patients with dysmenorrhea, the overall responses being greater in healthy volunteers. The experienced pain measured by visual analog scale in individual dysmenorrheic subjects tended to show higher maximal post-dose scores for the vasopressin injections than for placebo. Maximum visual analog scale scores and maximum AUCs in individual subjects tended to be related. Mean creatine kinase MB levels were higher in women with dysmenorrhea than in healthy subjects both before and after vasopressin administration, the converse being observed for C-reactive protein levels. The present model appears to be useful for evaluating new drugs for the treatment of primary dysmenorrhea.