Interindividual variation and drug interactions with hormonal steroid contraceptives

Large interindividual differences occur in the plasma concentration of contraceptive steroids. With the present tendency to decrease the dose of progestagen and oestrogen any factor which reduces the bioavailability of the lower dose preparations becomes very important. The possibility that other drugs and environmental chemicals may interact with contraceptive steroids is currently being investigated. Clinical reports suggest that the most important interacting drugs are the antituberculosis agent rifampicin, anticonvulsants and antibiotics. In the case of the first two, evidence is available suggesting that microsomal enzyme induction, either in the liver or the gut wall, is the operative mechanism. Antibiotics interfere with the pharmacokinetics of contraceptive steroids by interfering with their enterohepatic circulation in animal species: whether this is operative in man is still unclear. Other environmental and constitutional factors such as smoking, variations in diet, and concurrent disease may alter the disposition of contraceptive steroids and affect response accordingly. Additional studies are needed to estimate the significance of such interactions.