Inadvertent pregnancies in combined pill users are not uncommon, and are usually due to errors of tablet taking. However, many factors may contribute to 'pill failure'. In this review the endocrine pharmacology of pill use and the changes reported with missed pills have been considered in detail. The influences of other factors including drug interactions have been reviewed and a series of recommendations made for reducing the risk of pregnancy in each of these circumstances.
PIP: The efficacy of oral contraceptives (OCs) is influenced by any factor that affects circulating blood levels of exogenous estrogen or progesterone or that interferes with their action at a cellular level. Inadvertent pregnancies are not uncommon in combined pill users, and are usually due to errors of tablet taking. Estrogen-progestogen combinations work mainly by hypothalamic suppression; basal plasma levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) are usually repressed and their cyclical surges eliminated. Progestogen-only formulations have much less effect on central control and depend more on effects on the cervical mucus, endometrium, and possibly tubal function. Significant increases in FSH and LH levels may occur in the pill-free week among combined pill users. Reduction in dosage of some newer preparations appears to reduce the margin of error and, in low-dose progestogen-only pills, progestogen may reach inadequate levels for contraceptive effect before the expected time of the next pill. Higher failure rates in the 1st rather than in subsequent treatment cycles are mainly due to user failure, but method failures also may be more common, possibly because hypothalamic suppression increases over the 1st few cycles. 3 studies on pituitary and ovarian function in women who deliberately missed pills at specific stages showed an increase in breakthrough ovulation. Other clinical factors which may affect pill efficacy included vomiting, diarrhea, changing to a lower dose formulation, obesity, and drug interaction, especially with the antituberculosis drug rifampicin, some anticonvulsants, and antibiotics. Breakthrough ovulation from drug interaction is more likely to occur when OCs are administered early or late in the cycle. Analogously, the most hazardous times to miss pills are at the beginning or end of a monthly course.