OBJECTIVE:Increased intra-uterine pressure due to exaggerated myometrial contractions is an important factor in the pathogenesis of dysmenorrhea, its treatment being associated with uterine muscle relaxation. Diminished synthesis of endogenous nitric oxide has been shown to induce myometrial contractions and, conversely, the administration of exogenous nitric oxide has successfully resulted in uterine relaxation in a variety of obstetrical/gynecological disorders. The objective of this study was to determine the role of transdermal glyceryl trinitrate, as a source of exogenous nitric oxide, in the management of primary dysmenorrhea. METHOD: This was a multi-national, double-blind, randomized and cross-over study in patients with primary dysmenorrhea. Eighty-eight patients from six countries were evaluated during three menstrual cycles while receiving glyceryl trinitrate patches, 0.1 mg/h (x) or matching placebo patches. Pain intensity scores assessed on a visual analog scale and the time-weighted sum of the pain intensity differences (SPID) were evaluated during days 1, 2 and 3 of each cycle using an analysis of variance (ANOVA) model. Overall assessment of efficacy and the incidence of adverse events were analyzed by the Stuart-Maxwell or the McNemar tests as appropriate. RESULTS:Efficacy was determined for the first day of each cycle, all days/all cycles and for patients who completed at least one cycle in each treatment modality. In all three analyses, SPIDs were statistically superior (P<0.01) for the glyceryl trinitrate patches. Pain intensity differences from hours 1 to 6 also showed statistically significant differences in favor of the active treatment. In the overall assessment of efficacy, glyceryl trinitrate patches were statistically superior as well. The incidence of headache was 26% for the active drug and 6.1% for placebo (P<0.01). CONCLUSIONS: The data indicate that transdermal glyceryl trinitrate, as a source of exogenous nitric oxide, is useful as a modulator of uterine contractility representing, therefore, a new and mechanistically different therapeutic alternative for the management of primary dysmenorrhea.
RCT Entities:
OBJECTIVE: Increased intra-uterine pressure due to exaggerated myometrial contractions is an important factor in the pathogenesis of dysmenorrhea, its treatment being associated with uterine muscle relaxation. Diminished synthesis of endogenous nitric oxide has been shown to induce myometrial contractions and, conversely, the administration of exogenous nitric oxide has successfully resulted in uterine relaxation in a variety of obstetrical/gynecological disorders. The objective of this study was to determine the role of transdermal glyceryl trinitrate, as a source of exogenous nitric oxide, in the management of primary dysmenorrhea. METHOD: This was a multi-national, double-blind, randomized and cross-over study in patients with primary dysmenorrhea. Eighty-eight patients from six countries were evaluated during three menstrual cycles while receiving glyceryl trinitrate patches, 0.1 mg/h (x) or matching placebo patches. Pain intensity scores assessed on a visual analog scale and the time-weighted sum of the pain intensity differences (SPID) were evaluated during days 1, 2 and 3 of each cycle using an analysis of variance (ANOVA) model. Overall assessment of efficacy and the incidence of adverse events were analyzed by the Stuart-Maxwell or the McNemar tests as appropriate. RESULTS: Efficacy was determined for the first day of each cycle, all days/all cycles and for patients who completed at least one cycle in each treatment modality. In all three analyses, SPIDs were statistically superior (P<0.01) for the glyceryl trinitrate patches. Pain intensity differences from hours 1 to 6 also showed statistically significant differences in favor of the active treatment. In the overall assessment of efficacy, glyceryl trinitrate patches were statistically superior as well. The incidence of headache was 26% for the active drug and 6.1% for placebo (P<0.01). CONCLUSIONS: The data indicate that transdermal glyceryl trinitrate, as a source of exogenous nitric oxide, is useful as a modulator of uterine contractility representing, therefore, a new and mechanistically different therapeutic alternative for the management of primary dysmenorrhea.