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.
RCT Entities:
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.
Authors: Ning Zhao; Stephanie O Peacock; Chen Hao Lo; Laine M Heidman; Meghan A Rice; Cale D Fahrenholtz; Ann M Greene; Fiorella Magani; Valeria A Copello; Maria Julia Martinez; Yushan Zhang; Yehia Daaka; Conor C Lynch; Kerry L Burnstein Journal: Sci Transl Med Date: 2019-06-26 Impact factor: 17.956
Authors: Ahmed Haider; Zhiwei Xiao; Xiaotian Xia; Jiahui Chen; Richard S Van; Shi Kuang; Chunyu Zhao; Jian Rong; Tuo Shao; Perla Ramesh; Appu Aravind; Yihan Shao; Chongzhao Ran; Larry J Young; Steven H Liang Journal: Pharmacol Res Date: 2021-09-16 Impact factor: 7.658