Evaluation of the teratogenic potential of Delalutin (17α‐hydroxyprogesterone caproate) in mice

Abstract

Swiss Webster female mice weighing 25-30 gm were injected subcutaneously on days 6-15 of gestation with the synthetic sex steroid Delalutin (17 alpha-hydroxyprogesterone caproate). Treatment was given daily in doses ranging from 42 to 833 mg/kg body weight, or 10, 100, and 200 times the human therapeutic dose. On day 18 fetuses were removed from the uterus and examined for malformations and other fetotoxic effects. Prenatal treatment with the two higher doses resulted in 8 and 13% maternal deaths, and all doses resulted in a slight increase (4-12% above control) in resorption frequency. Treatment with Delalutin did not significantly affect intrauterine growth, sex ratio, or malformation rate of the offspring. The results of the present study confirm other reports that Delalutin is not androgenic, and that it, like progesterone and certain other sex steroids, does not alter the development of nonreproductive organs.

Progestin treatment for the prevention of preterm birth

“…However, there are also some data from animal and human studies suggesting that 17‐OH P may cause fetal harm by fetal toxicity (not teratogenicity). In mice, there was an increased fetal loss with 17‐OH P compared with placebo (51). In rhesus monkeys, total embryo lethality resulted following the administration of 17‐OH P at both one and 10 times the human equivalent dose (52).…”

Guidelines for the management of spontaneous preterm labor: identification of spontaneous preterm labor, diagnosis of preterm premature rupture of membranes, and preventive tools for preterm birth

“…The effects of 17-OHP-C upon pregnancy in experimental animals have been studied in rats, rabbits, mice, and monkeys. Earlier studies found no evidence of androgenic or glucorti-coid activity and no virilising effects on female fetuses [92-96]. It is worth noting that the synthetic 17-OHP-C and natural progesterone are not similar molecules and have different activities in a number of respects including their effects on the myometrium [85,97-100].…”

“…Furthermore, in a recent very large preterm birth prevention study of singleton pregnancies, no cases of miscarriage associated with the use of micronized natural progesterone were observed [102]. On the other hand, 17-OHP-C is associated with an increase in resorption (miscarriage) in pregnant rats [96], total embryo-lethality in pregnant rhesus monkeys [103], a signal for a 30% increase in miscarriage in a meta-analysis of 17-OHP-C clinical studies [81], as well as an imbalance in miscarriage associated with 17-OHP-C in the largest placebo controlled randomized trial published to date [83]. In a study by Rebarber et al [104], patients who received prophylactic treatment with 17-OHP-C had a higher incidence of gestational diabetes (odds ratio 2.9 [95% CI: 2.1-4.1]) than those who were not treated.…”

Population‐based case‐control teratogenic study of hydroxyprogesterone treatment during pregnancy

“…Animal investigations did not find any association between hydroxyprogesterone treatment during pregnancy and the masculinization of female offspring (Suchowsky & Junkmann 1967; Seegmiller et al . 1983), though Seegmiller et al . (1983) gave up to 200 times the human therapeutic dose to mice during organogenesis.…”