Uterine Activity in Women Receiving 17 α-Hydroxyprogesterone Caproate for the Prevention of Preterm Birth: An Observational Study

ABSTRACT

We evaluated uterine contraction frequency in women receiving 17 α-hydroxyprogesterone caproate (17-OHP-C) for the prevention of preterm delivery. Women with singleton pregnancies and receiving weekly 17-OHP-C and outpatient tococardiography were identified from a database. The mean and maximum contraction frequencies per hour were compared from 3 days before to 3 days after 17-OHP-C dosing. McNemar χ², Mann-Whitney U, and Friedman test statistics were used for analysis. Data were obtained from 388 women. Median contraction frequency was greater for women with subsequent preterm birth versus those delivering at term (1.5 [range 0, 14.5] versus 1.2 [range 0, 21.0] contractions per hour, p < 0.001). No reduction in contraction frequency was observed after 17-OHP-C administration, and in fact, the converse was observed for the average contractions 3 days prior compared with 3 days posttreatment (p < 0.001). In the subgroup of women with a subsequent spontaneous preterm, the proportion who had an average contraction frequency of more than five per hour 1 day preinjection versus 1 day postinjection was not significantly different (2.6% versus 3.0%, p = 1.0). Administration of 17-OHP-C was not associated with a reduction in contraction frequency. To be effective, this drug likely has effects by mechanisms other than tocolysis. Although a statistically significant increase in contractions was identified posttherapy versus pretherapy, the clinical importance of this observation is unknown.

17-hydroxyprogesterone caproate - uterine contractions - preterm birth - drug safety

REFERENCES

• 1 Meis P J, Klebanoff M, Thom E National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.  N Engl J Med. 2003;  348 2379-2385
• 2 Fonseca E B, Celik E, Parra M, Singh M, Nicolaides K H. Fetal Medicine Foundation Second Trimester Screening Group . Progesterone and the risk of preterm birth among women with a short cervix.  N Engl J Med. 2007;  357 462-469
• 3 da Fonseca E B, Bittar R E, Carvalho M H, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study.  Am J Obstet Gynecol. 2003;  188 419-424
• 4 DeFranco E A, O'Brien J M, Adair C D et al.. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial.  Ultrasound Obstet Gynecol. 2007;  30 697-705
• 5 Sharma S, Ou J, Strom S C, Mattison D, Caritis S, Venkataramanan R. Identification of enzymes involved in the metabolism of 17alpha-hydroxyprogesterone caproate: an effective agent for prevention of preterm birth.  Drug Metab Dispos. 2008;  36 1896-1902
• 6 Xu H, Gonzalez J M, Ofori E, Elovitz M A. Preventing cervical ripening: the primary mechanism by which progestational agents prevent preterm birth?.  Am J Obstet Gynecol. 2008;  198 314.e1-314.e8
• 7 Marx S G, Wentz M J, Mackay L B et al.. Effects of progesterone on iNOS, COX-2, and collagen expression in the cervix.  J Histochem Cytochem. 2006;  54 623-639
• 8 Hardy D B, Janowski B A, Corey D R, Mendelson C R. Progesterone receptor plays a major antiinflammatory role in human myometrial cells by antagonism of nuclear factor-kappaB activation of cyclooxygenase 2 expression.  Mol Endocrinol. 2006;  20 2724-2733
• 9 Cakmak H, Schatz F, Huang S T et al.. Progestin suppresses thrombin- and interleukin-1beta-induced interleukin-11 production in term decidual cells: implications for preterm delivery.  J Clin Endocrinol Metab. 2005;  90 5279-5286
• 10 Ou C W, Orsino A, Lye S J. Expression of connexin-43 and connexin-26 in the rat myometrium during pregnancy and labor is differentially regulated by mechanical and hormonal signals.  Endocrinology. 1997;  138 5398-5407
• 11 Facchinetti F, Paganelli S, Comitini G, Dante G, Volpe A. Cervical length changes during preterm cervical ripening: effects of 17-alpha-hydroxyprogesterone caproate.  Am J Obstet Gynecol. 2007;  196 453.e1-453.e4 discussion 421
• 12 Attardi B, Zeleznik A, Simhan H et al.. Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins.  Am J Obstet Gynecol. 2007;  197 599.e1-599.e7
• 13 Ruddock N, Shi S-Q, Jain S et al.. Progesterone, but not 17 alpha hydroxyprogesterone caproate, inhibits human myometrial contractions.  Am J Obstet Gynecol. 2008;  199 391.e1-391.e7
• 14 Sexton D J, O'Reilly M W, Friel A M, Morrison J J. Functional effects of 17alpha-hydroxyprogesterone caproate (17P) on human myometrial contractility in vitro.  Reprod Biol Endocrinol. 2004;  2 80
• 15 Iams J D, Newman R B, Thom E A National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units et al. Frequency of uterine contractions and the risk of spontaneous preterm delivery.  N Engl J Med. 2002;  346 250-255
• 16 Institute of Medicine . Preterm Birth: Causes, Consequences, and Prevention. Behrman RE, Butler AS Washington, DC; National Academies Press 2006