title: Actions of progestins for the inhibition of cervical ripening and uterine contractions to prevent preterm birth.
abstract: The importance of progesterone (P4) for maintenance of pregnancy, its role in cervical ripening and uterine contractions is at least partly established and therefore, not surprisingly, the basis for the concept to use P4 as a treatment for preterm birth. Due to the complexity of the condition of preterm birth there are still questions concerning the optimal population that might benefit, timing of treatment, dosage, vehicle and route of administration. Recently vaginal P4 and intramuscular 17-alpha-hydroxyprogesterone caproate (17P) have been used to prevent preterm birth in patients with a high risk for early delivery. The aim of this study was to assess cervical changes throughout pregnancy in rats and the timing of term and preterm delivery after various progestin treatments given by different routes and vehicles in hope of identifying better treatment regimens. This paper presents results that suggest that there are better routes of treatment than the vaginal route (e.g. topical), that the vehicle used in many of the clinical studies (Replens®) is not appropriate due to a low release of the steroid and consequently low uptake of P4, and that inhibition of birth is primarily due to inhibition of uterine contractility that can be achieved by supplementation of P4 but not with 17P.
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, 69115 Heidelberg, Germany.
authors.forename: R-J
authors.initials: RJ
authors.lastname: Kuon
authors.affiliation: Department of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Garfield
keywords: 17-alpha-hydroxyprogesterone; cervical ripening; preterm birth; progesterone; uterine contractions
references.citation: Natl Vital Stat Rep. 2007 Dec 5;56(6):1-103
references.pmid: 18277471
references.citation: Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31
references.pmid: 21472815
references.citation: Obstet Gynecol. 2011 Mar;117(3):663-671
references.pmid: 21446209
references.citation: Endocr Rev. 1994 Oct;15(5):684-706
references.pmid: 7843072
references.citation: J Gen Physiol. 1982 Sep;80(3):353-75
references.pmid: 7142952
references.citation: Acta Obstet Gynecol Scand. 2009;88(11):1180-9
references.pmid: 19900136
references.citation: Arzneimittelforschung. 2002;52(8):615-21
references.pmid: 12236050
references.citation: Am J Obstet Gynecol. 2003 Feb;188(2):419-24
references.pmid: 12592250
references.citation: Am J Obstet Gynecol. 2011 Jul;205(1):82.e15-20
references.pmid: 21497789
references.citation: N Engl J Med. 2007 Aug 2;357(5):462-9
references.pmid: 17671254
references.citation: N Engl J Med. 1975 Oct 2;293(14):675-80
references.pmid: 1099445
references.citation: Am J Obstet Gynecol. 2008 Oct;199(4):391.e1-7
references.pmid: 18928984
references.citation: Menopause. 2005 Mar;12(2):232-7
references.pmid: 15772572
references.citation: Contraception. 2010 Nov;82(5):410-7
references.pmid: 20933114
references.citation: Ultrasound Obstet Gynecol. 2007 Oct;30(5):687-96
references.pmid: 17899572
references.citation: Am J Obstet Gynecol. 2012 Feb;206(2):124.e1-19
references.pmid: 22284156
references.citation: Ultrasound Obstet Gynecol. 2007 Oct;30(5):697-705
references.pmid: 17899571
references.citation: Hum Reprod Update. 1998 Sep-Oct;4(5):673-95
references.pmid: 10027621
references.citation: Br J Dermatol. 2005 Sep;153(3):626-34
references.pmid: 16120154
references.citation: Ultrasound Obstet Gynecol. 2011 Sep;38(3):272-80
references.pmid: 21739497
references.citation: Am J Anat. 1956 Mar;98(2):273-91
references.pmid: 13326855
references.citation: Reprod Biol Endocrinol. 2003 Dec 02;1:122
references.pmid: 14651749
references.citation: Am J Obstet Gynecol. 2012 Mar;206(3):254.e1-5
references.pmid: 22244470
references.citation: Am J Obstet Gynecol. 1986 Mar;154(3):525-9
references.pmid: 3513581
references.citation: Am J Physiol. 1980 Mar;238(3):C81-9
references.pmid: 7369350
references.citation: Reprod Biol Endocrinol. 2004 Dec 07;2:80
references.pmid: 15585068
references.citation: Am J Obstet Gynecol. 2007 Apr;196(4):289-96
references.pmid: 17403397
references.citation: Int J Gynaecol Obstet. 2009 Jan;104(1):40-3
references.pmid: 18929360
references.citation: Maturitas. 2007 May 20;57(1):77-80
references.pmid: 17368973
references.citation: Ann N Y Acad Sci. 1997 Sep 26;828:291-9
references.pmid: 9329850
references.citation: Am J Obstet Gynecol. 2010 May;202(5):455.e1-9
references.pmid: 20452487
references.citation: N Engl J Med. 2003 Jun 12;348(24):2379-85
references.pmid: 12802023
references.citation: Ann N Y Acad Sci. 1994 Sep 30;734:387-413
references.pmid: 7978941
references.citation: Ultrasound Obstet Gynecol. 2011 Jul;38(1):32-7
references.pmid: 21157771
references.citation: Br J Obstet Gynaecol. 1990 Feb;97(2):149-54
references.pmid: 2138496
references.citation: Eur J Obstet Gynecol Reprod Biol. 1991 Jul 25;40(3):203-9
references.pmid: 1879595
references.citation: Am J Obstet Gynecol. 2008 Feb;198(2):235.e1-4
references.pmid: 18226633
references.citation: Ultrasound Obstet Gynecol. 2009 Dec;34(6):653-9
references.pmid: 19918965
references.citation: Am J Obstet Gynecol. 2009 Oct;201(4):410.e1-5
references.pmid: 19716117
references.citation: J Soc Gynecol Investig. 2004 May;11(4):193-202
references.pmid: 15120691
references.citation: Obstet Gynecol. 2000 Mar;95(3):403-6
references.pmid: 10711552
references.citation: Semin Reprod Med. 2007 Jan;25(1):69-79
references.pmid: 17205425
references.citation: Am J Obstet Gynecol. 2007 May;196(5):453.e1-4; discussion 421
references.pmid: 17466698
references.citation: Obstet Gynecol. 2008 Oct;112(4):963-5
references.pmid: 18827143
references.citation: Fertil Steril. 2005 Jun;83(6):1641-9
references.pmid: 15950631