Objective: To investigate the clinical effect of SR49059 when given shortly before the onset of menstruation as a preventative treatment of dysmenorrhoea.
Design: A double-blind, randomised, placebo-controlled, cross-over trial in complete block design (three periods, three treatments).
Setting: A clinical research organisation in Paris, France.
Participants: Women aged 18-35 years suffering from primary dysmenorrhoea.
Interventions: In each of three menstrual cycles, women reported to the study centre and were given a daily dose of either placebo, 100 mg or 300 mg SR49059 from a minimum of 4 hours up to a maximum of three days before the onset of bleeding and/or menstrual pain. If this did not control the pain, women were allowed once a day to take a second dose of study treatment providing that at least 4 hours had passed since the first drug intake.
Main outcome measures: Intensity of menstrual pain recorded by means of a visual analogue scale. Rating of symptoms of dysmenorrhoea (mainly back and pelvic pain) in relation to functional capacity (Sultan score). Self-assessment of menstrual blood loss in a menstrual diary record.
Results: Analysis of intensity of menstrual pain, as recorded by visual analogue scale and Sultan pain score (back and pelvic pain) during the first 24 hours of dysmenorrhoea, showed a dose-related effect of SR49059. The 300 mg dose of SR49059 was significantly more effective than placebo. Similarly, a dose-related effect of SR49059 was shown on total Sultan score. SR49059 was well tolerated and no significant effect on the bleeding pattern was noted.
Conclusions: This study showed for the first time a therapeutic effect of an orally active vasopressin V1a receptor antagonist in the prevention of dysmenorrhoea. Further studies are required to examine effect mechanisms and determine effective doses.