Toxicology of depot medroxyprogesterone acetate.

ABSTRACT

PIP: This paper reviews Depo-Provera (depot-medroxyprogesterone acetate or DMPA) toxicologic and carcinogenic studies and addresses possible reasons why animal-derived data failed to raise concerns for use in women. DMPA was found to be nontoxic following single-dose treatments in rats (8 g/kg body weight) and mice (4 g/kg body weight). Chronic toxicity studies in female rabbits and Rhesus monkeys indicated that DMPA has a low toxicity at the doses given. For rabbits, intramuscular injections of DMPA were given every 3 months for 1 year at dosages of 3, 10, and 30 mg/kg body weight. For Rhesus monkeys, the treatment regime was the same as stated above for the rabbits, except that the treatment period lasted for 28 months. Reproductive effects have been studied in a number of pregnant animals. The effects of DMPA on reproductive tissue have been inconsistent, but there appear to be some effects on both the male and female reproductive organs. Studies on DMPA mutagenic and carcinogenic potentials indicate that chromosomal aberrations occur in hamsters and dogs. DMPA was found to produce tumors in dogs. It was concluded that a dose-related effect for the tumor production response in dogs was evident. Different test animal species responded differently to the levels of DMPA dosages. All available toxicological and pharmacokinetic data collected throughout the extensive testing of DMPA suggests that DMPA meets the overall safety standards as established by the US Food and Drug Administration.