Oral contraceptive steroids--pharmacological issues of interest to the prescribing physician

Abstract

Oral contraceptive steroids (OCS) are well absorbed from the gastrointestinal tract in humans. However, while the progestogens are almost completely bioavailable, ethinylestradiol (EE2) is subject to extensive first pass metabolism consisting chiefly of conjugation with sulfate in the gut wall. Both EE2 and progestogens are well absorbed in patients with an ileostomy or with diseases such as cystic fibrosis or Crohn's disease. However in patients with celiac disease (gluten-sensitive enteropathy) the gut wall is less able to conjugate EE2 and thus its bioavailability is increased. The bioavailability returns to control values as the disease is improved following gluten withdrawal. Other drugs that are conjugated with sulfate, such as vitamin C and paracetamol, compete for available sulfate when coadministered with OCS leading to high plasma levels of EE2. Enzyme-inducing agents such as rifampicin, phenobarbitone, phenytoin and carbamazepine reduce blood levels of the OCS leading to contraceptive failure. In the case of anticonvulsants (but not rifampicin) this can be easily overcome by increasing the dose of OCS used. Broad-spectrum antibiotics are reported to cause failure of contraception by interfering with the enterohepatic circulation of EE2 but limited systematic studies show no evidence of such an interaction. Nevertheless practitioners are advised to recommend the use of alternative contraceptive precautions for women receiving broad-spectrum antibiotics concurrently with their OCS preparation.