This study will evaluate the effects of chronic use of a common herbal remedy, St. John's Wort (Hypericum perforatum), on metabolism of levonorgestrel in a dosing regimen for emergency contraception. Emergency contraception, if taken soon after unprotected intercourse, prevents pregnancy. St. John's Wort induces the P450 enzyme system in the liver, and as such may cause increased metabolism of certain drugs, including contraceptive steroids used as emergency contraception. This will be a randomized, blinded, clinical trial of three groups of reproductive-aged women. First, participants will have pharmacokinetic studies done after a single dose of 1.5 mg levonorgestrel, the standard dose used in emergency contraception. Contraceptive effects will be estimated via progesterone, inhibin A, and glycodelin levels done at 1-week intervals until the end of the menstrual cycle. Participants will be then randomized to one of three groups and take either placebo (one group) or St. John's Wort (two groups) for 6 weeks. The pharmacokinetic studies will be repeated with either the same standard dose of levonorgestrel emergency contraception (in the placebo and first St. John's Wort groups) or after a levonorgestrel dose that has been increased by 50% (in the second St John's Wort group). Contraceptive effects will be measured by progesterone, inhibin A, and glycodelin levels at weekly intervals until the end of the menstrual cycle. Potentially clinically important differences in pharmacokinetic and physiologic parameters between placebo and active treatment groups will be estimated by comparisons to baseline and between groups. Possible effects that may reduce contraceptive efficacy will be identified. Results will be used to estimate parameters for future pharmacokinetic-pharmacodynamic studies that will fully assess the interaction, as well as effects of increasing dosage to compensate for effects. The study protocol will be refined for use in future studies of levonorgestrel and other emergency contraceptive regimens.
