Six female olive baboons (Papio cynocephalus anubis) were treated with a single dose of 150 mg of Depo-Provera i.m. at day 30 of pregnancy, approximately three times the human dose equivalent on a body weight basis. Fetectomies were performed at day 100 of gestation. The body weights and measurements of the five live fetuses were comparable to age-matched controls and no gross or histologic abnormalities were seen. The dead fetus was in an advanced state of decomposition. This preliminary study suggests that, at levels up to three times that used for human contraception, Depo-Provera does not appear to have any adverse effects on fetal development.
PMID 6238440 6238440 DOI 10.1002/tera.1420300205 10.1002/tera.1420300205
Cite this article
Tarara, R. P. (1984). The effect of medroxyprogesterone acetate (Depo-Provera) on prenatal development in the baboon (Papio anubis): a preliminary study. Teratology, 30(2), 181-185. https://doi.org/10.1002/tera.1420300205
Tarara RP. The effect of medroxyprogesterone acetate (Depo-Provera) on prenatal development in the baboon (Papio anubis): a preliminary study. Teratology. 1984;30(2):181-185. doi:10.1002/tera.1420300205
Tarara, Ross P. "The effect of medroxyprogesterone acetate (Depo-Provera) on prenatal development in the baboon (Papio anubis): a preliminary study." Teratology, vol. 30, no. 2, 1984, pp. 181-185.
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.
Pregnant mice were treated with a single subcutaneous injection of either cyproterone acetate (CA) or medroxyprogesterone acetate (MPA). In the first experiment the animals received 5-900 mg/kg of the hormone before implantation (day 2 of pregnancy). CA treatment on day 2 caused a dose-dependent decrease in fetal weight and a significant dose-dependent increase in the rates of cleft palate and urinary tract abnormalities. Exencephaly and heart abnormalities were also significantly more frequent, but this increase was not dose-dependent. MPA treatment on day 2 was followed by sporadic increases in dead and resorbed fetuses, a decrease in fetal weight and an increase in the rates of cleft palate, and malformed or abnormally developed fetuses. None of these effects, however, was dose-dependent. In the second experiment the mice were given one single injection (30 mg/kg) of CA or MPA on any one of days 1-12 of gestation. Treatment with CA on one day between days 1 and 12 revealed that the specific sensitivity for abnormalities of the urinary tract was on days 5 and 6, for the respiratory tract on days 8 and 9, and for cleft palate on days 10 and 11. Treatment with MPA on one day between days 1 and 12 only revealed a high rate of respiratory and urinary tract abnormalities on day 9. After treatment with MPA cleft palate was again significantly more frequent in all treated groups, however, days of peak sensitivity were not detected. The long half-life of CA (60 hours) explains the teratogenic effect of high doses of this progestin after treatment on day 2 and also the pattern of abnormal development found after treatment with a single dose of CA on one of the days between day 1 and day 12.
Medroxyprogesterone acetate (MPA; Provera) was given orally to 449 women from the 5th to 7th week of pregnancy until at least the 18th week. Data are recorded from two treatment groups (recurrent abortion and threatened abortion) and are compared to a matched series. A total of 1,016 pregnancies are included in the study, and all patients were recruited from a subfertile population conceiving from a range of infertility treatments. Early pregnancy wastage was high throughout the groups and was significantly elevated (43%; P less than .001) in those women who had vaginal bleeding in early pregnancy. The study focuses on the question of potential teratogenicity of progestagens administered in the first trimester. There were 15/366 (4.1%) infants with congenital abnormalities in the MPA-treated group and 15/428 in the untreated group (3.5%). The difference was not significant, and MPA is considered to have no embryopathic risk, nor is it likely to retain an abnormal fetus that might otherwise abort. It appears that MPA is a safe drug to use in pregnancy although the question of efficacy has not been addressed in this report. Considering other recent negative epidemiologic studies with regard to teratogenicity, we add to the conclusion that MPA cannot be demonstrated to have a measurable teratogenic risk and certainly does not present a risk for congenital heart disease and limb reduction defects.
A single dose of MPA (Depo-Provera; Upjohn Co., Kalamazoo, Michigan) was administered intramuscularly to 12 time-mated pregnant cynomolgus monkeys on day 27 (+/- 2) of gestation at 25 mg/kg or at 100 mg/kg. Maternal blood samples were collected immediately prior to MPA injection and then at regular intervals until cesarean section at term (day 152 +/- 3). Infants in both dose groups had external genital abnormalities. Female infants in the low-dose groups had partial or complete labial fusion, prominent median raphe, and clitoral hypertrophy; at high doses (100 mg/kg), the female infants had complete labial fusion and a distinct penile urethra. MPA had an opposite effect on external genitalia of male infants. The penis was short and the scrotal swelling was absent or less conspicuous, and two males had hypospadias. The adrenal glands were significantly smaller (P less than 0.05) in infants of both sexes treated with 100 mg/kg. One of the infants treated with 25 mg/kg of MPA had a muscular ventricular septal defect. Serum concentrations of MPA were determined by radioimmunoassay in eight pregnant monkeys. In the 25 mg/kg group the patterns of MPA profiles in the serum were similar in all four animals. An initial peak occurred at 24-48 hr postinjection (2.7-9.6 ng/ml), followed by a slight decrease at 3 days postinjection (gestational day 30), and then a steady increase to maximum levels of 10-14 ng/ml occurring between gestational days 37 and 50. Serum levels gradually declined to concentrations below 5 ng/ml by midgestation in three of four monkeys. By comparison, both the patterns and magnitude of MPA concentration showed great interanimal variation in the 100 mg/kg group. MPA was present in cord blood at measurable concentrations in infants at both dose groups; the levels ranged from 0.6 to 8.3 ng/ml, corresponding to 40-72% of the maternal concentrations. These results demonstrate that a single injection of MPA during early pregnancy causes selective embryotoxicity in both male and female fetuses. Presence of high levels of MPA in maternal sera during the critical period of genital development can cause specific genital defects; however, the exact mechanism by which MPA causes these paradoxical genital abnormalities is unknown.