An example of OCs affecting the metabolism of other drugs is seen with diazepam and related compounds. Oral contraceptive use reduces the metabolic clearance and increases the half-life of those benzodiazepines that are metabolized primarily by oxidation: chlordiazepoxide, alprazolam, diazepam, and nitrazepam. Caffeine and theophylline are metabolized in the liver by two of the P450 isozymes, and their clearance is reduced in OC users. Cyclosporine is hydroxylated by another of the P450 isozymes, and its plasma concentrations are increased by OCs. Plasma levels of some analgesic drugs are decreased in OC users. Salicylic acid and morphine clearances are enhanced by OC use; therefore, higher doses could be needed for adequate therapeutic effect. Clearance of ethanol may be reduced in OC users.
The interactions of antiretroviral drugs with contraceptive steroids are complex. Some of the drugs increase plasma steroid levels and some reduce them. A complete list of interactions is available in the Centers for Disease Control and Prevention’s “U.S. Medical Eligibility for Contraception” (7).
Oral contraceptives have the potential to alter a number of clinical laboratory tests as a result of estrogen-induced changes in hepatic synthesis; however, a large study comparing OC users with pregnant and nonpregnant controls found minimal changes (209). Hormone users took a variety of OCs containing 50 to 100 μg of estrogen, higher doses than are used today. Compared with nonpregnant women who were not using OCs, the OC users had an increase in T4 that is explained by increased circulating thyroid-binding protein, no change in creatinine and globulin levels, slight reduction in mean fasting glucose values and serum glutamic oxaloacetic transaminase, and a decrease in total bilirubin and alkaline phosphatase.
Choice of Oral Contraceptives