Hydroxyprogesterone

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

other: publications

Adequacy of study:

other information

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Genital Abnormalities in Infants Associated with Administration of Progesteroids to Their Mothers

Author:

Leibow S.G. and Gardner L.I.

Year:

1960

Bibliographic source:

Pediatrics, 26, 151

Reference 2

Reference Type:

publication

Title:

A Population-based Case Control Study of Congenital Abnormalities and Medication Use During Pregnancy Using the Czech National Register of Congenital Abnormalities

Author:

Maskova J., Sipek A., Kollar P.

Year:

2011

Bibliographic source:

Central European Journal of Medicine, 6 (4), 435-441

Reference 3

Reference Type:

publication

Title:

Embryo–fetal toxicity signals for 17a-hydroxyprogesterone caproate in high-risk pregnancies: A review of the non-clinical literature for embryo–fetal toxicity with progestins

Author:

Christian M.S., Brent R.L., Calda P.

Year:

2007

Bibliographic source:

The Journal of Maternal-Fetal and Neonatal Medicine, 20(2): 89–112

Reference 4

Reference Type:

publication

Title:

‘‘Natural’’ Progesterone: Information on Fetal Effects

Author:

Golub M.S., Kaufman F.L., Campbell M.A., Li L.-H., Donald J.M.

Year:

2006

Bibliographic source:

Birth Defects Research (Part B) 77:455–470

Reference 5

Reference Type:

publication

Title:

Drugs in infertility and fetal safety

Author:

Elizur S.E., Tulandi T.

Year:

2008

Bibliographic source:

Fertility and Sterility, 89(6), 1595-1602

Applicant's summary and conclusion

Conclusions:

Due to the low gestagenic potency of 17-OHP and the limited oral bioavailability of OHPA very rare clinical data of both compounds are reported.
Regarding TRGS 905 (version 12.03.2020 and the justification document for Steroid Hormones, version Sept 1999) OHPA is classified as gestagen (group 7) with a reproduction toxicity RF= 1A and RD=1B (CLP), but 17-OHP is not listed here. RTECS shows a reproductive toxicity entry for 17-OHP based on a case study in 1960 reporting on genital abnormality of a child which mother was treated with 250 mg intramuscularly during pregnancy every second week (Leibow, 1960). It is unclear whether 17-OHP or its caproate OHPC was administered, the latter introduced for medical use in 1954/55 and typically applied until today as intramuscular depot with 250 mg/ml (Proluton®, Makena®) to prevent preterm birth. Nevertheless, a derived TDLo 65 mg/kg for 17-OHP is cited in RTECS.
Other case control studies revealed no conclusive evidence for higher incidences of congenital abnormalities or neural-tube defects after therapeutical administration of hydroxyprogesterone (no further data on substance identity) during pregnancy (Leibow, 1960; Medveczky, 2004). Consequently, after a history of precautionary labeling for therapeutic exposure of progestational drugs more recent epidemiologic analyses, animal studies and basic scientific principles disproved the risks and led 1987 to the FDA removing the warning label on oral contraceptives regarding nongenital malformation (Brent, 2005). Recent publications conclude even for the therapeutic use during pregnancy with almost no concern or signal for reproductive toxicity in association with progesterone or 17-hydroxyprogesterone (Christian et.al, 2007; Golub et al., 2006; Elizur et.al., 2008).


Leibow SG, Gardner LI, Pediatrics 1960, July:151-160
Maskova et al., Cent Eur J Med 2011; 6(4):435-441
Medveczky, Pharmacoepidem Drug Safety 2004; 13:443-455
Brent, Birth Defects Research (Part A) 2005; 73
Elizur et.al., Fertility and Sterility 2008; 89 (6):1595-1602
Christian et.al., J Mat-Fet Neonat Med 2007; 20(2):89-112
Golub et al., Birth Defects Res B Dev Reprod Toxicol, 2006 Oct;77(5):455-70