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Pharmacology: Mode of action: COCs suppress gonadotropins in a manner that inhibits ovulation, which leads to contraception.
Pharmacodynamics, clinical efficacy: When taken consistently and correctly, the probable failure rate of COCs is 0.1% per year; however, the failure rate during typical use is 5% per year for all types of oral contraceptives. The efficacy of most methods of contraception depends upon the reliability with which they are used. Method failure is more likely if COC tablets are missed.
Pharmacokinetics: Ethinyl estradiol and gestodene are rapidly and almost completely absorbed from the gastrointestinal tract.
Peak plasma levels of each drug are reached within 1-2 hours. Post maximum concentration curves show two phases with half-lives of 1 and 15 hours in the case of gestodene and 1-3 and approximately 24 hours in the case of ethinyl estradiol.
After oral administration, gestodene unlike ethinyl estradiol is not subject to first-pass metabolism. Following oral administration, gestodene is completely bioavailable, ethinyl estradiol about 40%.
Gestodene is extensively plasma protein bound to sex hormone binding globulin (SHBG). Ethinyl estradiol is bound in plasma to albumin and enhances the binding capacity of SHBG.
The elimination half-life for ethinyl is approximately 25 hours. It is primarily metabolized by aromatic hydroxylation but a wide variety of hydroxylated and methylated metabolites are formed, and these are present both free and as conjugates with glucuronide and sulfate. Conjugated ethinyl estradiol is excreted in bile and subject to enterohepatic recirculation. About 40% of the drug is excreted in the urine and 60% is eliminated in the feces.
The elimination half-life for gestodene is approximately 16-18 hours after multiple oral doses. The drug is primarily metabolized by reduction of the A ring followed by glucuronidation. About 50% of gestodene is excreted in the urine and 33% is eliminated in the feces.
Cycle Control In Clinical Trials: In clinical trials with MINULET including 14,281 cycles of treatment, the overall incidence of spotting was 5.0% and breakthrough bleeding was 0.7%. (See Table 1.)
Click on icon to see table/diagram/imageAmenorrhea (absence of expected withdrawal bleeding), occurred in 68 of 14,281 treatment cycles, an incidence of 0.5%.
Influence of Missed Tablets: The following table shows that the rate of intermenstrual bleeding is increased by intake errors, i.e., when one or more tablets are omitted. (See Table 2.)
Click on icon to see table/diagram/image