Effect of medroxyprogesterone acetate on hepatic and placental drug metabolism in rats.

Medroxyprogesterone acetate (MPA: Depo-Provera) is a long-acting synthetic progestin that has been used as a contraceptive for more than 11 million women-years in 80 nations [1]. The U.S. Food and Drug Administration has denied approval of MPA as a contraceptive because of concern about its safety, especially teratogenicity and carcinogenicity [2.3]. In addition to its contraceptive action, MPA has been used clinically at high doses for the treatment of breast [4]. kidney [5] and prostate cancer [6]. It has also been used for slowing sexual development in children with precocious puberty [7]. A few studies have shown that MPA at high levels induces hepatic drug metabolism in rats [8-10] and humans [11]. Morevoer, MPA increases the rate of steroid metabolism in several species [12, 13]. In contrast, pregnancy is known to decrease hepatic drug metabolism particularly in late pregnancy [14]. Because some women to whom MPA is administered as a contraceptive may be unknowingly pregnant, it is important to know the nature of the combined effects of MPA and pregnancy on drug metabolism. There is no published information on the effect of MPA on either hepatic or placental drug metabolism in pregnant animals. The present study was undertaken to evaluate the combined influences of pregnancy and MPA administration on hepatic and placental drug metabolism in the rat.