Clinical trial NCT00131885: Effects of St. John's Wort on the Oral Contraceptive Hormone Levonorgestrel
Official title: Effects of St. John's Wort on Levonorgestrel
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Contraception
Keywords: Menstruation
Complementary Therapies
Pharmacokinetics
Hypericum
St. John's wort
Levonorgestrel
Women
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2005-08-19
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 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
measure: 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).
timeFrame: 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
measure: Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session.
timeFrame: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
Secondary outcomes:
measure: Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses
timeFrame: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
measure: Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses
timeFrame: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
measure: Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses
timeFrame: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: College of Nursing, University of Utah
name: Patricia A. Murphy, DrPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.