Advertisement

23: Progestins do not modulate the uterine response to tocolytics or oxytocin

      Objective

      Progestins have been used to prevent preterm birth in various high-risk conditions. One of the suggested mechanisms for this beneficial effect involves modulation of uterine response to excitatory or inhibitory agents. Our objective was to evaluate the effect of progestins on uterine contractile responses to tocolytics and oxytocin in vitro.

      Study Design

      Biopsies were obtained from the lower uterine segment from term, non-laboring women undergoing cesarean section (n=15), and collected in Hanks Balanced Salt Solution (HBSS). Tissue strips (8 per biopsy) were suspended in organ chambers for isometric tension recording and incubated for 60 min with either progesterone (P4; 10-7M), 17-alpha hydroxyprogesterone caproate (17P; 10-7M), or solvent. After further equilibration, responses were determined to cumulative concentrations (10-10 to 10-5M) of nifedipine, indomethacin, or oxytocin. Solvent time-controls were also run in parallel. Area under the contraction curve over 20 min was calculated at baseline, and after addition of each concentration. KCl 60 mM, a non-specific hyperpolarizing agent, was added at the end. ANOVA was used for statistical analysis (significance: p<0.05)

      Results

      Indocin did not have an effect on spontaneous uterine contractility or response to KCl, whether by itself or in combination with progestins. Nifedipine significantly inhibited spontaneous contractility, as well as response to KCl, without any potentiation by progestins (Figure). Pre-incubation with progestins did not have an effect on the response to oxytocin.

      Conclusion

      Progestins do not potentiate the effects of tocolytics, or decrease the response to oxytocin in tissues from term non-laboring women. The beneficial effects of progestins in preventing preterm birth may not be due to a direct effect on uterine response to oxytocin or tocolytics.