The use of progestational agents during the first four months of pregnancy is not recommended.
Progestational agents have been used beginning within the first trimester of pregnancy in an attempt to prevent habitual abortion or treat threatened abortion. There is no adequate evidence that such use is effective and there is evidence of potential harm to the fetus when such drugs are given during the first four months of pregnancy. Furthermore, in the vast majority of women, the cause of abortion is a defective ovum, which progestational agents could not be expected to influence. In addition, the use of progestational agents, with their uterine-relaxant properties, in patients with fertilized defective ova may cause a delay in spontaneous abortion.
Therefore, the use of such drugs during the first four months of pregnancy is not recommended.
Several reports suggest an association between intrauterine exposure to female sex hormones and congenital anomalies, including congenital heart defects and limb reduction defects. One study estimated a 4.7-fold increased risk of limb reduction defects in infants exposed in utero to sex hormones (oral contraceptives, hormone withdrawal tests for pregnancy, or attempted treatment for threatened abortion). Some of these exposures were very short and involved only a few days of treatment. The data suggest that the risk of limb reduction defects in exposed fetuses is somewhat less than 1 in 1,000. If the patient is exposed to APO-MEGESTROL (megestrol acetate) during the first four months of pregnancy or if she becomes pregnant while taking the drug, she should be apprised of the potential risks to the fetus.
Administration for up to 7 years of megestrol acetate to female dogs is associated with an increased incidence of both benign and malignant tumours of the breast. Comparable studies in the monkey are not associated with an increased incidence of malignant tumours. The relationship of the dog tumours to humans is unknown but should be considered in assessing the benefit-to-risk ratio when prescribing megestrol acetate and in surveillance of patients on therapy.