The third S.K. & F. Prize lecture, University of London, December 1981. The clinical pharmacology of oral contraceptive steroids.

Abstract

Oral contraceptive steroids have been in regular use for some 20 years and are taken by about 50 million women worldwide. It is therefore surprising to find that information on the clinical pharmacology of such commonly used drugs is so lacking. There are a number of possible reasons for this state of affairs, but at least partly this is due to the fact that oral contraceptive steroids occupy a unique position in therapeutics in being given to a healthy group of women. In addition, oral contraceptive steroids were, for a long time, given in supratherapeutic doses. With the realisation that side effects were occurring, and that some of these were clearly dose related, the dose of steroid in the combined preparations was gradually reduced. As the dose has been reduced, the problems associated with interindividual variations in elimination have become apparent, thus highlighting our previous lack of knowledge. The first combination preparation to undergo large scale clinical trial was Enovid which contained 150 ,tg of oestrogen (mestranol) and 10 mg of progestogen (norethynodrel). Most combined preparations now contain 1 mg or less of progestogen and about 30 ,ug of the oestrogen (ethinyloestradiol). The latest triphasic preparations contain an even lower total dose of steroid.We are now at such a stage that it would be difficult to reduce the total dose level much further without impairing the contraceptive efficacy of the preparation. Any factor which interferes with the bioavailability of the contraceptive steroids is likely to cause failure of contraception and this is reflected in the increasing interest in drug interactions with the contraceptive steroids. Pharmacokinetics of contraceptive steroidsThere is a wide inter-individual range in the plasma concentrations of steroids, measured in blood samples taken 10-12 h after dosing in women on long term treatment. Figure 1 shows the plasma concentrations of ethinyloestradiol and levonorgestrel given at two dose levels to groups of women. There is a 20-30 fold variation in the steady state plasma concentration of each steroid.