The effects of medroxyprogesterone acetate on the maintenance of pregnancy in ovariectomized rats and rabbits

Bruce, Neville; Bartholomeusz, R. K.

doi:10.1002/tera.1420130311

Cited by 9 publications

(2 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yochim andZarrow (1961} and have reported that placental overgrowth in ovariectomized rats is accompanied by small but significant increases in foetal weight, but Callard and Leathem (1971) did not observe any associated increases in foetal growth. Ovariectomy also induces placental overgrowth in the rabbit (Abdul-Karim et ale 1971; Bruce and Bartholomeusz 1976). However, it remains unclear whether this pheno-menon occurs in mammals other than the rat and rabbit, and the physiological significance of ovariectomy-induced placental overgrowth; in relation to the maintenance of gestation and foetal growth, is unknown (Callard and Leathem 1971;Chan and Leathem 1977).…”

Section: Introductionmentioning

confidence: 99%

Effects of Ovarian Hormones on Foetal and Placental Growth in the Mouse

Miller¹

1978

Aust. Jnl. Of Bio. Sci.

View full text Add to dashboard Cite

The effects of ovariectomy and treatment with progesterone and oestradiol on foetal and placental growth were examined. The occurrence of cellular hypertrophy and hyperplasia in the placenta in response to treatments was determined by measuring protein, DNA and RNA: DNA ratios. In control mice, which had not been ovariectomized, the daily administration of O·01-2' 56 J1g oestradiol on days 10-15 of pregnancy caused only small decreases in the number of live foetuses and foetal and placental weights on day 16. When mice were ovariectomized on day 10, gestation was maintained by administering 5 mg progesterone daily, but terminated when only 1 mg progesterone was given daily. However, when ovariectomized mice receiving 1 mg progesterone were also given O'OlJ1g oestradiol on days 10-15, gestation was maintained and the number of live foetuses and foetal and placental weights on day 16 were normal. Increasing the daily dose of oestradiol up to 2· 56J1g in mice receiving 1 mg progesterone on days 10-15 had no effect on foetal and placental growth. In contrast, the daily administration of 0·64-2· 56J1g oestradiol to ovariectomized mice receiving 5 mg progesterone on days 10-15 terminated gestation in some mice and considerably reduced the number of live foetuses and foetal and placental weights in those mice which remained pregnant on day 16.None of the treatments increased protein, DNA or the RNA : DNA ratio in the placenta to levels above those seen in control mice. The results are discussed in relation to ovariectomy-induced placental overgrowth in the rat.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of Ovarian Hormones on Foetal and Placental Growth in the Mouse

Miller¹

1978

Aust. Jnl. Of Bio. Sci.

View full text Add to dashboard Cite

show abstract

“…Learner et al (1962) had similar results in the rat using a dose of 5 mg/kg of MPA, which is 80 times the HDE. Bruce and Bartholomeusz (1976) studied fetal survival, the malformation rate, and fetal and placental weights in pregnant rats and rabbits treated with MPA. In 28 pregnant rabbits, the malformation rate was not increased in the MPA-treated rabbits.…”

Section: Have Investigators Been Able To Develop a Teratogenic Animalmentioning

confidence: 99%

Nongenital malformations following exposure to progestational drugs: The last chapter of an erroneous allegation

Brent

2005

Birth Defect Res A

View full text Add to dashboard Cite

In the late 1960s and 1970s, a number of epidemiological studies were published indicating that pregnant women who were exposed to an array of sex steroids delivered infants with an increased incidence of nongenital congenital malformations. Because of these publications, the Food and Drug Administration (FDA), in conjunction with various pharmaceutical companies, labeled the therapeutic exposure of progestational drugs and contraceptives in pregnant women as a risk factor for limb-reduction defects (LRDs) and congenital heart defects (CHDs). Subsequently there was a rapid decrease in the exposure of pregnant women to these drugs and the initiation of numerous lawsuits alleging that a particular progestational drug was responsible for a child's nongenital congenital malformation. Wilson and Brent (1981) published an article indicating that epidemiological and animal studies of these drugs, and basic science did not support the package insert's warnings. Many new and previous animal and epidemiological studies did not support the FDA box warning. In 1987 the FDA held a hearing in which the FDA, the Teratology Society, the Centers for Disease Control and Prevention, the American College of Obstetrics and Gynecology, and other organizations supported the position that progestational agents did not result in nongenital malformations. An editorial appeared in Teratology congratulating the FDA for removing the warning label on oral contraceptives regarding nongenital malformations. In 1999 the FDA published new wording for package inserts that removed warnings for nongenital malformations for all progestational agents. In spite of the recent changes in the package inserts, lawsuits have alleged that progestational drugs cause nongenital malformations. It took 22 years from the time a box warning was required by the FDA until the warnings were removed in 1999. The 1999 FDA publication, which is a scholarly and objective document, should put an end to 2 decades of concern and anxiety for pregnant women or women of reproductive age. Could scientists, the pharmaceutical companies, or the FDA have prevented the mislabeling of progestational drugs with regard to their teratogenic risks? Was the epidemiological or teratology community at fault because they did not critique and respond to the early publications? Did the FDA act too slowly? The epidemiologic analyses, animal studies, and basic science principles have been reviewed, and it is obvious that clinically utilized progestational drugs do not cause nongenital malformations (i.e., LRDs and CHDs).

show abstract

Corpus luteum growth and plasma progesterone levels in unilaterally ovariectomized pregnant rats

Meyer

Bruce

1979

Anat. Rec.

View full text Add to dashboard Cite

Unilateral ovariectomy (ULO) was carried out on rats at Day 8 of gestation: term is Day 23. The effect on peripheral plasma progesterone levels at Day 16 and on growth and cellular changes in the remaining corporalutea (CL) at Day 17 was determined by comparison with results from control and sham-operated rats. ULO increased the volume of remaining CL by 18% at Day 17. At Day 16 this effect was only apparent in rats with three or fewer CL remaining. CL hypertrophy was due to an increase in the volume of individual luteal cells and not to cell hyperplasia. Luteal cell nuclear volume also increased as did the number of endothelial cells per corpus luteum. The proportion of the corpus luteum occupied by vascular space did not alter. ULO had little effect on mean plasma progesterone levels at Day 16 (92 +/- 7 ng/ml treated; 86 +/- 11 ng/ml controls). In rats with three or fewer CL remaining, however, progesterone levels were low (51 +/- 7 ng/ml). It was concluded that ULO can enhance the growth of corpora lutea and perhaps increase their rate of progesterone production.

show abstract

The effects of medroxyprogesterone acetate on the maintenance of pregnancy in ovariectomized rats and rabbits

Cited by 9 publications

References 7 publications

Effects of Ovarian Hormones on Foetal and Placental Growth in the Mouse

Effects of Ovarian Hormones on Foetal and Placental Growth in the Mouse

Nongenital malformations following exposure to progestational drugs: The last chapter of an erroneous allegation

Corpus luteum growth and plasma progesterone levels in unilaterally ovariectomized pregnant rats

Contact Info

Product

Resources

About