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Completed

NCT Number: NCT00131885

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

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

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Key information

Conditions

Contraception

Age range

18 year–30 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

University of Utah

Salt Lake City, Utah, 84112, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Placebo Control (Placebo Herb)

Dietary Supplement

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

St. John's wort

Dietary Supplement

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

Levonorgestrel

Drug

Levonorgestrel in a single oral dose

Primary outcomes

  1. 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)

    Time frame: 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

    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.

  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).

    Time frame: 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

    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.

  3. Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session.

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

    Average and standard deviation for Clearance (L/hr) of Levonorgestrel study for each dosage group and each study session.

Secondary outcomes

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

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

    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).

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

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

    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).

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

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

    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).

Sponsors and collaborators

Lead sponsor

University of Utah

Other

Collaborators

  • National Center for Complementary and Integrative Health (NCCIH)

Registry information

Official study title

Effects of St. John's Wort on Levonorgestrel

Important dates

Study start
2005
Primary completion
2008
Study completion
2008
First posted
Aug 19, 2005
Registry last updated
Nov 13, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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