Oral contraceptive hormones (OCs) are metabolized by the hepatic cytochrome p450 system; thus, inducers of the p450 system may increase OC metabolism. Whether decreased OC levels, associated with p450 inducer exposure, increase the risk of pregnancy is widely suspected but remains unknown. For chronically ill women, who undergo prolonged exposure to p450 inducers, effects on OC metabolism are especially important. p450 inducers can be teratogenic, and maternal risks associated with pregnancy in this group are high. This study examines the effects of carbamazepine on OC metabolism and contraceptive efficacy. Carbamazepine is widely used in reproductive age women for seizures, bipolar disease and pain syndromes. Healthy volunteers (n=25) will participate in a double blind, randomized, placebo-controlled crossover study. After one cycle of OCs, subjects will receive one month of either placebo or carbamazepine with OCs. After a one-cycle OC only washout, subjects will receive the other treatment with OCs. The primary aim will be to compare results during the OC+placebo cycle with results from the OC+ carbamazepine cycle on the following parameters: 1) Twenty-four hour pharmacokinetic [PK] studies of OC metabolism and 2) Surrogate markers of pregnancy risk: a) ovarian follicular development, b) endometrial stripe thickness, c) serum progesterone level and d) bleeding patterns. This will be the first study to examine risk of ovulation using sensitive markers of ovarian function during exposure to a p450 inducer in OC users. Secondary aims include: 1) obtaining pilot data on PK variability to inform sample size calculations in future studies and 2) identifying the most important end-points in order to design simpler and more cost-efficient future studies. ? ?
|Davis, Anne R; Westhoff, Carolyn L; Stanczyk, Frank Z (2011) Carbamazepine coadministration with an oral contraceptive: effects on steroid pharmacokinetics, ovulation, and bleeding. Epilepsia 52:243-7|