Functional effects of 17alpha-hydroxyprogesterone caproate (17P) on human myometrial contractility in vitro

BACKGROUND 17 alpha-hydroxyprogesterone caproate (17P) administration reportedly improves outcome for women with a previous spontaneous preterm delivery. This study, using in vitro strips of human uterine smooth muscle, aimed to investigate the direct non-genomic effects of 17P on spontaneous and induced contractions in tissues obtained during pregnancy, and in the non-pregnant state. METHODS Biopsies of human myometrium were obtained at elective cesarean section, and from hysterectomy specimens, and dissected strips suspended for isometric recordings. The effects of 17P (1 nmol/L -10 micro mol/L) on spontaneous and agonist-induced (oxytocin 0.5 nmol/L for pregnant, phenylephrine 10 micromol/L for non-pregnant) contractions were measured. Integrals of contractile activity, including the mean maximal inhibition values (MMI) observed at the maximal concentration, were compared with those from simultaneously run control strips. RESULTS There was no significant direct effect exerted by 17P on pregnant or non-pregnant human myometrial contractility. The MMI +/- SEM for spontaneous contractions in pregnant myometrium was 4.9% +/- 7.2 (n = 6; P = 0.309) and for oxytocin-induced contractions was 2.2% +/- 1.3 (n = 6; P = 0.128). For non-pregnant myometrium, the MMI +/- SEM for spontaneous contractions was 8.8% +/- 11.0 (n = 6; P = 0.121) and for phenylephrine induced contractions was -7.9% +/- 6.5 (n = 6; P = 0.966). CONCLUSIONS The putative benefits of 17P for preterm labor prevention are not achieved, even partially, by a direct utero-relaxant effect. These findings outline the possibility that genomic effects of 17P, achieved over long periods of administration, are required for its reported therapeutic benefits.