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

NCT00131885 | Completed Phase 4 Results DMC

• 2 other identifiers: 13430R21AT002297
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Contraception

Keywords

Menstruation; Complementary Therapies; Pharmacokinetics; Hypericum; St. John's wort; Levonorgestrel; Women

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (3)

• Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses

  Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)

• Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses

  Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)

• Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses

  Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)

Study Arms (4)

Levonorgestrel 1.5 with Placebo Herb

PLACEBO COMPARATOR

This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took a placebo herb daily for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 1.5 mg

Dietary Supplement: Placebo Control (Placebo Herb); Drug: Levonorgestrel

Levonorgestrel 1.5 with SJW 900 mg

ACTIVE COMPARATOR

This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took St. John's Wort (SJW) 900 mg a Day orally for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 1.5 mg

Dietary Supplement: St. John's Wort; Drug: Levonorgestrel

Levonorgestrel 2.25 with SJW 900 mg

ACTIVE COMPARATOR

This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took a St. Johns's Wort 300 mg capsules three times daily for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 2.25 mg

Dietary Supplement: St. John's Wort; Drug: Levonorgestrel

Levonorgestrel 1.5 with SJW 1500 mg

ACTIVE COMPARATOR

This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took a St. Johns's Wort 300 mg capsules five times daily for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 1.5 mg

Dietary Supplement: St. John's Wort; Drug: Levonorgestrel

Interventions

Placebo Control (Placebo Herb) DIETARY_SUPPLEMENT

Placebo herb three times daily (ground cellulose) for 4-6 weeks

Levonorgestrel 1.5 with Placebo Herb

St. John's Wort DIETARY_SUPPLEMENT

St. John's Wort (Hypericum perforatum) orally or 4-6 weeks

Levonorgestrel 1.5 with SJW 1500 mg; Levonorgestrel 1.5 with SJW 900 mg; Levonorgestrel 2.25 with SJW 900 mg

Levonorgestrel DRUG

Levonorgestrel in a single oral dose

Levonorgestrel 1.5 with Placebo Herb; Levonorgestrel 1.5 with SJW 1500 mg; Levonorgestrel 1.5 with SJW 900 mg; Levonorgestrel 2.25 with SJW 900 mg

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index (BMI) between 20 and 25
• Regular menstrual cycles for at least 3 months prior to study entry

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Utah: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related 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.

  PMID: 15914127 BACKGROUND

MeSH Terms

Interventions

Hypericum extract LI 160; Levonorgestrel

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Patricia Murphy, DrPH
• Organization: University of Utah

patricia.murphy@nurs.utah.edu

801-793-5729

Study Officials

• Patricia A. Murphy, DrPH

  College of Nursing, University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 17, 2005
• First Posted: August 19, 2005
• Study Start: August 1, 2005
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: November 13, 2023
• Results First Posted: June 9, 2010

Record last verified: 2023-11

Locations

US (1)