Effects in vitro of progesterone and two 5α-reduced progestins, 5α-pregnane-3,20-dione and 5α-pregnane-3α-ol-20-one, on contracting human myometrium at term

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Abstract
Progesterone is known to prevent labour at term in domestic animals, but its effect in primates is uncertain. 5α-reduced progesterone metabolites are more potent central nervous system depressants than progesterone is itself. Progesterone and its 5α-reduced metabolites also relax pregnant rat myometrium in vitro. The serum concentration of the initial 5α-reduced metabolite, 5α-pregnane-3,20-dione, is high during pregnancy, but decreases significantly prior to parturition. The next metabolite, 5α-pregnane-3α-ol-20-one, has anaesthetic properties in human beings. The purpose of this study was to ascertain whether these progesterone metabolites also suppress contracting human uterine muscle at term. An in vitro model was devised. Strips of human myometrial muscle were mounted in organ chambers and after regular contractions had become established, the strips were superfused with progestin solutions. The progestins were dissolved in the buffer using an ultrasound bath. Progesterone, used as reference substance, slightly reduced the measured amount of muscular work performed per contraction, recordable after 18 min of exposure (p<0.05). Similar results have been reported previously in the literature; 5α-pregnane-3α-ol-20-one showed the same tendency though not significant at the 5% level. 5α-pregnane-3,20-dione evidently reduced the contraction frequency after 10 min of exposure (p<0.05). None of the substances affected the duration of the contraction. These 5α-reduced progesterone metabolites are thus not potent inhibitors of contracting human term myometrium in vitro.

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