Therapy with oral contraceptive steroids and antibiotics

Abstract

Since 1971 there have been reports of pregnancies and breakthrough bleeding in women using oral contraceptives (OCs) and some antibiotics. Rifampicin appears to induce enzymes that increase the metabolism of estrogens and progesterone in OCs. However, ampicillin, chloramphenicol, and sulphamethoxypyridazine may impair the action of OCs in a potentially more hazardous manner. Synthetic estrogens and progestogens are extensively excreted in bile as glucuronide conjugates. Ordinarily, gut microflora produce a hydrolytic enzyme that splits the conjugates, allowing reabsorption of the steroids from the gastrointestinal tract. Ampicillin and other antibiotics interfere with the hydrolytic process by reducing the population of microflora that produce the enzyme (beta-glucuronidase). In experiments in which rats were given labeled steroids, ampicillin and neomycin reduced biliary excretion of steroids by 70%, and the reduction in biliary excretion correlated well with the reduction in bacterial population. More information on the incidence of antibiotic-OC interactions in practice, controlled studies of changes in plasma levels of steroids produced by common antibiotics, and ways to identify women who are at particular risk of being affected by antibiotics are needed.