Effects of St. John's Wort on the Oral Contraceptive Hormone Levonorgestrel

Contraception Clinical Trial

Official title:

Effects of St. John's Wort on Levonorgestrel

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00131885
• Other study ID #: 13430
• Secondary ID: R21AT002297
• Status: Completed
• Phase: Phase 4
• Start date: August 2005
• Est. completion date: May 2008

Study information

• Verified date: November 2023
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will determine the effects of St. John's wort, a common herbal remedy, on metabolism of the female contraceptive hormone levonorgestrel.

Description:

In the last decade, St. John's wort has become one of the most commonly used botanicals. Levonorgestrel is a form of progesterone, a female hormone involved in conception. It can be given as both a pill and an injection and is used for contraception and for the treatment of endometriosis. However, evidence suggests that St. John's wort may reduce the effectiveness of the contraceptive hormone levonorgestrel. This study will determine whether interactions between St. John's wort and levonorgestrel reduce the effectiveness of the hormone. This study will also determine whether a higher dose of levonorgestrel will override the effects of St. John's wort.

All participants will receive a single dose of levonorgestrel between Days 9 and 12 of their first menstrual cycle after entering this study. Blood and urine collection will occur immediately after the levonorgestrel is given and every week until participants' next menstrual cycle to determine the levels of reproductive hormones in participants' bodies.

At the beginning of participants' next menstrual cycle, they will be randomly assigned to one of four groups and receive either St. John's wort or placebo for 6 weeks. Group 1 will receive a placebo; Groups 2 and 3 will receive a standard dose of St. John's wort (900 mg per day); and Group 4 will receive an increased dose of St. John's wort (1500 mg per day). After 6 weeks, Groups 1, 2, and 4 will receive 150 mcg levonorgestrel; and Group 3 will receive 225 mcg levonorgestrel. Blood and urine collection will occur immediately after levonorgestrel is given and every week until participants' next menstrual cycle.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• Body mass index (BMI) between 20 and 25

• Regular menstrual cycles for at least 3 months prior to study entry

Exclusion Criteria:

• Current use of foods, herbs, vitamins, over-the-counter supplements, or any medications that could alter pharmacokinetics of other drugs

• Medical contraindications to the use of contraceptives

Related Conditions & MeSH terms

• Contraception

Intervention

Dietary Supplement:
• Placebo Control (Placebo Herb)
Placebo herb three times daily (ground cellulose) for 4-6 weeks
• St. John's Wort
St. John's Wort (Hypericum perforatum) orally or 4-6 weeks

Drug:
• Levonorgestrel
Levonorgestrel in a single oral dose

Locations

Country	Name	City	State
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	National Center for Complementary and Integrative Health (NCCIH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception. 2005 Jun;71(6):402-8. doi: 10.1016/j.contraception.2004.11.004. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration Versus Time Curve for 0 to 24 Hours After Drug Administration, Done Between Days 9 and 12 of the Menstrual Cycle at Time 1 (Before) and Time 2 (During Treatment With St. John's Wort or Placebo)	Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo). Serum samples drawn at 0, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, and 24 hours, following oral administration of a dose of levonorgestrel.; Treatment between the two time periods was with St. John's Wort or placebo herb, beginning after the Time 1 (baseline) and continued for 5 weeks until Time 2.; Estimates of levonorgestrel clearance were made using a two stage non-compartmental approach to determine individual and group parameters.	Area Under the Concentration versus Time curve for 0 to 24 hours after drug administration, between Days 9 and 12 of the menstrual cycle, done at Time 1 and at Time 2
Primary	Number of Participants With Progesterone Levels Above 3.0 ng/ml at Time 1 (Baseline) and Time 2 (After Intervention With St John's Wort or Placebo).	Serum progesterone levels were drawn at the time of dosing with levonorgestrel and then at weekly intervals until menses occurred. This was done at Time 1 (baseline), and again at Time 2 (after 5 weeks of dosing with St. John's Wort or placebo).; Possible ovulation was defined as a serum progesterone >3ng/ml within 2 weeks of Days 9-12 of the menstrual cycle.	Progesterone levels drawn at weekly intervals after dosing with levonorgestrel between Days 9 and 12 of the menstrual cycle, at each time point until menses
Primary	Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session.	Average and standard deviation for Clearance (L/hr) of Levonorgestrel study for each dosage group and each study session.	Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
Secondary	Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses	Descriptive reporting of secondary outcomes of reproductive hormone levels (including FSH, E2, LH).; Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo).; Weekly means are reported for both time periods at week 0 (day of pharmacokinetic study), week 1 (one week after pharmacokinetic study) and week 2 (2 weeks after pharmacokinetic study).	Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
Secondary	Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses	Descriptive reporting of secondary outcomes of reproductive hormone levels (including FSH, E2, LH).; Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo).; Weekly means are reported for both time periods at week 0 (day of pharmacokinetic study), week 1 (one week after pharmacokinetic study) and week 2 (2 weeks after pharmacokinetic study).	Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
Secondary	Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses	Descriptive reporting of secondary outcomes of reproductive hormone levels (including FSH, E2, LH).; Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo).; Weekly means are reported for both time periods at week 0 (day of pharmacokinetic study), week 1 (one week after pharmacokinetic study) and week 2 (2 weeks after pharmacokinetic study).	Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)