Kauppila, A., Hartikainen-Sorri, A. L., Jänne, O., Tuimala, R., & Järvinen, P. A. (1980). Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine. American journal of obstetrics and gynecology, 138(4), 404-408. https://doi.org/10.1016/0002-9378(80)90137-4
Kauppila A, Hartikainen-Sorri AL, Jänne O, Tuimala R, Järvinen PA. Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine. Am J Obstet Gynecol. 1980;138(4):404-408. doi:10.1016/0002-9378(80)90137-4
Kauppila, A., et al. "Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine." American journal of obstetrics and gynecology, vol. 138, no. 4, 1980, pp. 404-408.
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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%).
The low-molecular-mass insulin-like growth factor-binding protein (IGF-BP) and placental protein 12 (PP12) are identical proteins that are present in human serum, amniotic fluid, secretory endometrium and decidua. IGF-BP/PP12 is believed to act as an autocrine or paracrine regulator of cell growth. A cDNA clone encompassing the entire protein coding region of this protein was isolated from a human decidual cDNA library. The authenticity of the cDNA was verified by in vitro transcription/translation experiments and by the identity of the 10 N-terminal amino acids deduced for the mature peptide with those obtained by direct protein sequencing. The amino acid sequence indicates that pre-IGF-BP/PP12 consists of 259 amino acid residues. The putative signal peptide is 25 residues long, and the mature protein thus contains 234 amino acids and has a molecular mass of 25293 Da. The sequence is very cysteine-rich at the N-terminus after which there are regions of clustered Pro, Glu, Ser and Thr residues (so-called PEST regions), which exist in proteins with short half-lives. The amino acid sequence also includes an Arg-Gly-Asp tripeptide that may function as a cell recognition signal. The IGF-BP/PP12 gene encodes a single 1.6 kb mRNA species that is expressed in decidua, secretory endometrium, liver and a human hepatoma cell line (HepG2). Southern blot analysis suggests that there is a single IGF-BP/PP12 gene in the human genome.
Luteinizing hormone (LH) receptor concentrations in ovarian follicles and corpora lutea were measured in 51 patients with histologically proven endometriosis and in 41 control patients. The LH receptor concentrations in cases of endometriosis were lower during the early (0.43 +/- 0.11 [mean +/- standard error] versus 1.31 +/- 0.27 fmol/mg protein; P less than 0.001) and late (0.48 +/- 0.10 versus 1.59 +/- 0.22 fmol/mg protein; P less than 0.001) follicular phase, and during the late luteal phase (2.62 +/- 0.55 versus 4.62 +/- 0.65 fmol/mg protein; P less than 0.05) of the cycle than in control patients. In contrast to the control patients, the LH receptor concentration during the follicular phase remained constant in endometriosis, being lower in patients with extensive or severe disease than in patients with moderate or mild disease (0.28 +/- 0.07 versus 0.61 +/- 0.21 fmol/mg protein; P less than 0.05). Endometriosis-associated infertility might be a consequence of a defect in the mechanism mediating LH action in the ovaries.
Wedge resection was performed in 12 patients with polycystic ovarian disease, and cell samples from the cystic follicles were assayed for LH(hCG) receptor using [125I]iodo-hCG as a ligand hormone. Simultaneously to wedge resection, blood samples were taken for serum FSH, LH, 17 beta-estradiol, progesterone, and testosterone RIA measurements. Serum LH was regularly elevated (16.0-57.1 U/liter), whereas FSH (5.2-11.5 U/liter) was within the normal reference range. The LH to FSH ratio was between 2.1-7.8. The 17 beta-estradiol concentrations (0.12-0.23 nmol/liter) were within the normal reference range found during the early follicular phase. Only 3 patients had progesterone levels exceeding the assay sensitivity limit of 0.1 nmol/liter. Ony 3 of the 11 patients assayed for serum testosterone had values exceeding the upper limit of the reference range. Seventy-seven percent of the ovarian follicular samples showed specific binding of [125I]iodo-hCG. The number of receptors in positive samples averaged 0.67 +/- 0.11 fmol/mg homogenate protein, which is clearly lower than that in normal preovulatory follicles. Scatchard analyses revealed a single class of binding sites, with a mean equilibrium association constant of 5.4 X 10(9) M-1 at 37 C. These results suggest that the derangement of follicular development in patients with polycystic ovarian disease probably is not due to the lack of appearance of the LH(hCG) receptor. It is possible that the tonic elevation of serum LH results in a decrease in the number of available receptor sites; this would be one step in the process leading to ovarian changes characteristic of this disease.
Eighty pregnant women at high risk of giving birth prematurely were divided randomly into two groups. Treatment with either 17 alpha-hydroxyprogesterone caproate, 250 mg by intramuscular injection once a week, or a placebo was given in a double-blind fashion. Imminent premature labor occurred in 29.0% of the treated group and in 59.4% of the control group (p less than 0.025). The rate of premature deliveries was also significantly lower in the treated group (16.1%) than in the control group (37.82%) (p less than 0.05). There were no cases of perinatal death or fetal malformations in either group. The mean birth weight of all infants of the treated group was significantly higher than in those of the control group (3111.9 +/- 905 gm versus 2680 +/- 813.4 gm, p less than 0.05). The results support treatment with progesterone caproate for the prevention of premature labor.
We conducted a double-blind study to determine the efficacy of 17alpha-hydroxyprogesterone caproate in preventing premature delivery in 43 high-risk patients. Premature delivery did not occur in 18 patients receiving the progestational agent, whereas 41 per cent of the 22 receiving the palcebo had premature delivery (P less than 0.01). The mean duration of pregnancy and the mean birth weight in the former group (38.6 weeks +/- 1.6 S.D., and 2836 g +/- 412 S.D.) were both significantly greater (P less than 0.025) than that in the latter (35.2 weeks +/- 6.7 S.D.; 2361 g +/- 1085 S.D.). The perinatal mortality rate in the group given the progestational agent (O per cent) was significantly less than that observed in the placebo group (27 per cent) (P less than 0.05). Although there were no complications attributable to the progestational drug, the study population was too small for assessment of immediate or long term safety. However, the results indicate a possible obstetric use for this drug.
Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen. Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants.
Studies have been undertaken regarding the efficacy and modus operandi of 17 alpha-hydroxyprogesterone caproate (17 alpha-OHP-C) in preventing premature labor in high-risk patients. In a total of 70 patients, the treated patient population had a prematurity rate (12.8%) and a perinatal mortality rate (5%) which were significantly lower than those of the total placebo or untreated patient group (40.9 and 25%, respectively). In addition, sequential plasma steroid values were determined in 21 patients, 10 of whom delivered prematurely. The results indicate that low plasma progesterone (P) and 17 alpha-hydroxyprogesterone (17 alpha-OHP) levels precede the onset of preterm labor by weeks. Successful treatment with 17 alpha-OHP-C was characterized by elevated P levels. Plasma estradiol (E2) and cortisol (C) values did not vary with time of delivery or treatment. These findings support the progesterone block theory as an important mechanism affecting preterm delivery in this high-risk population.
Pregnancy › Preterm Birth › Tocolytic Therapy · Birth and Delivery › Labor and Birth › Physiologic Birth · Therapeutics › Hormonal Agents › Progesterone and Progestins
PMID 7424996 7424996 DOI 10.1016/0002-9378(80)90137-4 10.1016/0002-9378(80)90137-4 Kauppila et al. 1980, Kauppila 1980
Cite this article
Kauppila, A., Hartikainen-Sorri, A. L., Jänne, O., Tuimala, R., & Järvinen, P. A. (1980). Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine. American journal of obstetrics and gynecology, 138(4), 404-408. https://doi.org/10.1016/0002-9378(80)90137-4
Kauppila A, Hartikainen-Sorri AL, Jänne O, Tuimala R, Järvinen PA. Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine. Am J Obstet Gynecol. 1980;138(4):404-408. doi:10.1016/0002-9378(80)90137-4
Kauppila, A., et al. "Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine." American journal of obstetrics and gynecology, vol. 138, no. 4, 1980, pp. 404-408.
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