The basic pharmacology pharmacokinetics and drug interactions of hormonal contraceptives.

This review article summarizes the pharmacology of hormonal contraceptives available in the UK. The most popular oral contraceptives are the combined estrogen (ethinyl estradiol) and progestagen preparations; there are 2 mestranol-containing pills mestranol being converted in the body to ethinyl estradiol. These preparations mimic the hormonal fluctuation of the normal menstrual cycle and reduce the total dose of steroid. A 3rd preparation is the progestagen only "minipill" suitable for use when estrogen is contraindicated. Other forms or progestagen preparations are available such as Depo-provera (1 dose every 12 weeks) and progesterone impregnated coils and loops. The usual contraceptive doses of estrogen inhibit ovulation by preventing the release of gonadotropin releasing hormone; progestagens act in several additional ways rendering the endometrium semi-atrophic and increasing the viscosity of cervical mucus. Because of its complex metabolism and disposition other drugs may interact with ethinyl estradiol at a number of sites: ascorbic acid by competing with ethinyl estradiol for gut wall sulphation leads to an increase in steroid bioavailability found to increase hemostatic parameters in the direction of thrombosis; drugs inhibiting cytochrome p450 mediated metabolism could increase the toxic effects of estrogen. The practically important drug interactions which occur with steroids nearly all relate to contraceptive failure. The action of antibiotics on gut flora can reduce the bacterially mediated hydrolysis of ethinyl estradiol conjugates causing a drop in the circulating level of the steroid however contraceptive failure due to this is rarely documented. Other drugs which have caused contraceptive failure include phenytoin carbamazepine and phenobarbitone.