The results of a study concerning the treatment of acute menace of preterm labor are given: beta-mimetics were administered intravenously in all cases (44) and micronized progesterone or placebo was administered orally after classical double-blind randomization (22 cases in each group). The mean index of pregnancy prolongation was the same in both groups. However the mean duration of the intravenous perfusion and the mean quantity of beta-mimetics administered intravenously were significantly reduced in the progesterone group (P less than 0.01). The mean duration of hospital stay was also significantly reduced (P less than 0.05). Cost and risks are finally significantly lessened.
PMID 1879595 1879595 DOI 10.1016/0028-2243(91)90118-5 10.1016/0028-2243(91)90118-5 Noblot et al. 1991, Noblot 1991
Cite this article
Noblot, G., Audra, P., Dargent, D., Faguer, B., & Mellier, G. (1991). The use of micronized progesterone in the treatment of menace of preterm delivery. European journal of obstetrics, gynecology, and reproductive biology, 40(3), 203-209. https://doi.org/10.1016/0028-2243(91)90118-5
Noblot G, Audra P, Dargent D, Faguer B, Mellier G. The use of micronized progesterone in the treatment of menace of preterm delivery. Eur J Obstet Gynecol Reprod Biol. 1991;40(3):203-209. doi:10.1016/0028-2243(91)90118-5
Noblot, G., et al. "The use of micronized progesterone in the treatment of menace of preterm delivery." European journal of obstetrics, gynecology, and reproductive biology, vol. 40, no. 3, 1991, pp. 203-209.
The potential tocolytic effect of natural progesterone administration on premature labor was investigated in a double-blind study. An oral progesterone formulation was used because its ability to increase both plasma and myometrial concentration of progesterone in pregnant women had been previously demonstrated. Furthermore, no commercial intravenous or intramuscular natural progesterone formulation is currently available in France. Fifty-seven patients in two obstetric clinics, admitted because of the risk of premature delivery, were included in the study, and uterine contractility and fetal cardiac rhythm were monitored in all of them. At random and after 30 minutes' rest, 29 women absorbed four capsules of 100 mg of progesterone each and 28 women absorbed four capsules of a placebo. Plasma progesterone levels were evaluated in all cases after 30 minutes' rest and 1 hour after absorption of the capsules. The results showed that bed rest and placebo administration decrease uterine activity in 42% of the cases and oral progesterone decreases activity in 75% to 88% of cases, depending on the initial severity of the menace of premature delivery. The difference between the effects of progesterone and of placebo is significant. The tocolytic effect of oral progesterone is not as intense or as rapid as the effect of intravenous beta-mimetics but is sufficient in 80% of cases, on the average, to stop the premature labor without any detectable side effects. This tocolytic effect of oral progesterone is related not just to an increase in plasma progesterone levels but probably to an increase in myometrial progesterone concentration.
A shift in progesterone-to-estradiol balance to estradiol dominance is assumed to be a prerequisite for regular uterine contractions. To antagonize this effect in premature labor 24 consecutive women were treated with intravenous cortisol for 3 days and with weekly intramuscular injections of 17 alpha-hydroxyprogesterone caproate (17 OHP-C). Twenty-four similar patients treated with ritodrine served as a reference group. The delivery was postponed by at least 1 week in 21 patients (87.5%) in the steroid treatment group and in 18 patients (75%) in the ritodrine group. The premature labor lasted for 5.1 +/- 0.4 hours (mean +/- SEM) with steroid therapy and for 2.2 +/- 0.3 hours with ritodrine. In singleton pregnancies the gestational length and birth weight of the newborn infants were greater in the steroid treatment group (N = 23, 39.1 +/- 0.3 weeks, 3,460 +/- 119 gm) than in the ritodrine group (N = 24, 37.7 +/- 0.4 weeks, 3,106 +/- 118 gm). Steroid treatment suppressed serum estradiol concentrations (maximally by 60%) and, to a lesser extent, testosterone, estriol, and progresterone levels (maximally by 30%).
Progesterone support in pregnancy has been in use for over 60 years, having received its start in the 1940s. Its initial use was in patients who had habitual spontaneous abortion caused by luteal phase deficiency. More recently, the administration of progesterone later in pregnancy has been considered to be justified because of an observed decrease in circulating progesterone with the onset of labor, an association of premature labor with decreased progesterone concentrations, and the observation that progesterone has a tocolytic effect. A considerable boost to the use of progestational agents to reduce preterm delivery was received with the publication of two papers which showed a significant reduction in preterm delivery rates with the prophylactic administration of either progesterone or 17-a hydroxyprogesterone caproate. Recently it has been shown, however, that its use is not universal. This may be related to the significant late sequelae that were documented following the in utero exposure of the fetus to the potent steroid diethylstilbestrol (DES) and that this bad experience cast “a long shadow,” In spite of this, the use of progesterone, at least in early pregnancy, is widespread in the various artificial reproductive programs and is growing in its use as an agent to reduce prematurity. Over the years, there has been an extraordinary amount of confusion related to the use of progesterone support in pregnancy. The Food & Drug Administration (FDA) created some of this confusion. In various labeling of progesterone products by the FDA, one of the contraindications to the use of oral progesterone is listed as “known or suspected pregnancy.” And, yet, no such contraindication is identified for the use of progesterone gel. In fact, progesterone gel is indicated for progesterone supplementation or replacement as a part of an assisted reproductive technology (ART) treatment program for infertile women with a progesterone deficiency. To make this even more confusing, oral progesterone, while it was contraindicated in “known or suspected pregnancy,” its official labeling stated that it “should be used during pregnancy only if indicated (see contraindications).” Also, up until very recently, there was a dire “warning” contained in the labeling for USP progesterone injection in sesame seed oil regarding an increased possibility of birth defects. An analysis of the fetal safety of isomolecular progesterone (Pregn-4-ene-3,20-dione) administration during the course of 1,310 pregnancies over a 35-year period of time (1979-2014) was undertaken to address this confusion.
The role of human chorionic gonadatropin (hCG) in the maintenance of early pregnancy is well known. Recent data suggests that hCG may play a role in the maintenance of the later stages of pregnancy as well, by directly and indirectly promoting uterine quiescence. If hCG acts as an endogenous tocolytic in normal pregnancy, then it may be an ideal candidate for therapy of preterm labor as well. We present compelling in vitro as well as in vivo data, which support the role of hCG in the maintenance of normal uterine quiescence. Additionally, we will present in vivo and in vitro data that confirms the ability of hCG to directly promote relaxation of uterine contractions. This review provides a basis for future study of the use of hCG in clinical obstetrics. Given the limited effectiveness of tocolytic therapies available at the time, hCG may provide a promising pharmacological approach to the pervasive problem of preterm labor in human pregnancy. While further work is needed, initial data strongly support this novel use of hCG in clinical obstetrics.