Embryotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate

Andrew G Hendrickx, R. Korte, F. Leuschner, B. W. Neumann, A. Poggel, P. Binkerd, S. Prahalada, P. Günzel

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Two sex steroid compounds which have been used clinically for parenteral supportive therapy of pregnancy were examined for embryotoxic effects in rhesus and cynomolgus macaques. Hydroxyprogesterone caproate (HPC) alone or in combination with estradiol valerate (EV) were administered intramuscularly (i.m.) to pregnant monkeys at 7‐day intervals between 20 and 146 days of gestation and fetuses were examined following cesarean section at 150 ± 2 days. HPC alone was tested in both species at doses ranging from 0.01 × to 10 × the human dose equivalent (HDE); only rhesus monkeys were exposed to the HPC + EV combination at 0.1 × to 10 × HDE. Total embryole‐thality resulted following the administration of HPC alone and combined with EV at 1 × and 10 × HDE in rhesus monkeys; the level of abortions in cynomolgus monkeys exposed to HPC (0.1 × to 1 × HDE) was comparable to controls. A small number of nonspecific malformations and developmental variations observed in cynomolgus fetuses after HPC exposure were considered to be incidental findings. No anomalies were found in surviving rhesus monkey fetuses treated with HPC + EV. The results indicate that long‐term in utero exposure to the progestin, HPC, alone or in combination with EV in rhesus and cynomolgus monkeys, is embryolethal but not teratogenic at doses up to ten times the human therapeutic dose.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalTeratology
Volume35
Issue number1
DOIs
StatePublished - 1987

Fingerprint

estradiol valerate
Gonadal Steroid Hormones
Primates
Hormones
Macaca mulatta
Fetus
Macaca fascicularis
Pregnancy
Incidental Findings
17-alpha-hydroxy-progesterone caproate
Progestins
Cesarean Section

ASJC Scopus subject areas

  • Embryology
  • Toxicology
  • Developmental Biology
  • Health, Toxicology and Mutagenesis

Cite this

Hendrickx, A. G., Korte, R., Leuschner, F., Neumann, B. W., Poggel, A., Binkerd, P., ... Günzel, P. (1987). Embryotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate. Teratology, 35(1), 129-136. https://doi.org/10.1002/tera.1420350116

Embryotoxicity of sex steroidal hormones in nonhuman primates : II. Hydroxyprogesterone caproate, estradiol valerate. / Hendrickx, Andrew G; Korte, R.; Leuschner, F.; Neumann, B. W.; Poggel, A.; Binkerd, P.; Prahalada, S.; Günzel, P.

In: Teratology, Vol. 35, No. 1, 1987, p. 129-136.

Research output: Contribution to journalArticle

Hendrickx, AG, Korte, R, Leuschner, F, Neumann, BW, Poggel, A, Binkerd, P, Prahalada, S & Günzel, P 1987, 'Embryotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate', Teratology, vol. 35, no. 1, pp. 129-136. https://doi.org/10.1002/tera.1420350116
Hendrickx, Andrew G ; Korte, R. ; Leuschner, F. ; Neumann, B. W. ; Poggel, A. ; Binkerd, P. ; Prahalada, S. ; Günzel, P. / Embryotoxicity of sex steroidal hormones in nonhuman primates : II. Hydroxyprogesterone caproate, estradiol valerate. In: Teratology. 1987 ; Vol. 35, No. 1. pp. 129-136.
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