Contraception
Conditions
Keywords
Menstruation, Complementary Therapies, Pharmacokinetics, Hypericum, St. John's wort, Levonorgestrel, Women
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.
Interventions
DIETARY_SUPPLEMENTPlacebo Control (Placebo Herb)
Placebo herb three times daily (ground cellulose) for 4-6 weeks
DIETARY_SUPPLEMENTSt. John's Wort
St. John's Wort (Hypericum perforatum) orally or 4-6 weeks
DRUGLevonorgestrel
Levonorgestrel in a single oral dose
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 30 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
| 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). | 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. |
| Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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). |
| 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) | 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). |
| 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) | 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). |
Countries
United States
Participant flow
Recruitment details
Eligible participants were recruited via local advertising.
Pre-assignment details
No enrolled participants were excluded
Participants by arm
| Arm | Count |
|---|---|
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg Group 1: one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by placebo herb and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study | 9 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg Group 2: One-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day, and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study | 9 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose Group 3: A one-time oral dose of levonorgestrel 1.5 mg mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day (900 mg total) and a one-time oral dose of levonorgestrel 2.25 mg at the second pharmacokinetic study | 9 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG Group 4: A one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, then St. John's Wort 300 mg orally five times per day (total 1500 mg daily) and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study | 9 |
| Total | 36 |
Baseline characteristics
| Characteristic | LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 36 Participants |
| Age, Continuous | 22.4 years STANDARD_DEVIATION 3.1 | 23 years STANDARD_DEVIATION 3.5 | 23.1 years STANDARD_DEVIATION 3.6 | 22.9 years STANDARD_DEVIATION 3.4 | 22.9 years STANDARD_DEVIATION 3.3 |
| Region of Enrollment United States | 9 participants | 9 participants | 9 participants | 9 participants | 36 participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 36 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
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.
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | 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) | AUC 0-24 hours after drug administration Time 1 | 586.3 ng*hr/mL | Standard Deviation 530.6 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | 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) | AUC 0-24 hours after drug administration Time 2 | 478.2 ng*hr/mL | Standard Deviation 374 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | 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) | AUC 0-24 hours after drug administration Time 2 | 317.4 ng*hr/mL | Standard Deviation 171.6 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | 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) | AUC 0-24 hours after drug administration Time 1 | 379.4 ng*hr/mL | Standard Deviation 201.3 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | 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) | AUC 0-24 hours after drug administration Time 1 | 339.4 ng*hr/mL | Standard Deviation 201.2 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | 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) | AUC 0-24 hours after drug administration Time 2 | 439.4 ng*hr/mL | Standard Deviation 320.1 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | 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) | AUC 0-24 hours after drug administration Time 1 | 253.3 ng*hr/mL | Standard Deviation 114.4 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | 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) | AUC 0-24 hours after drug administration Time 2 | 210.1 ng*hr/mL | Standard Deviation 100.4 |
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 Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Clearance (L/hr) Time 1 | 4.06 L/hr | Standard Deviation 2.6 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Clearance L/hr Time 2 | 4.64 L/hr | Standard Deviation 2.44 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Clearance L/hr Time 2 | 5.63 L/hr | Standard Deviation 2.08 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Clearance (L/hr) Time 1 | 4.93 L/hr | Standard Deviation 2.19 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Clearance (L/hr) Time 1 | 6.39 L/hr | Standard Deviation 4.23 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Clearance L/hr Time 2 | 7.68 L/hr | Standard Deviation 4.97 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Clearance (L/hr) Time 1 | 6.85 L/hr | Standard Deviation 2.51 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Clearance L/hr Time 2 | 8.92 L/hr | Standard Deviation 4.6 |
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.
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | 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). | Ovulation (Progesterone Levels > 3.0 ng/ml) Time 1 | 3 Participants |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | 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). | Ovulation (Progesterone Levels >3.0 ng/ml) Time 2 | 3 Participants |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | 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). | Ovulation (Progesterone Levels >3.0 ng/ml) Time 2 | 2 Participants |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | 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). | Ovulation (Progesterone Levels > 3.0 ng/ml) Time 1 | 1 Participants |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | 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). | Ovulation (Progesterone Levels >3.0 ng/ml) Time 2 | 2 Participants |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | 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). | Ovulation (Progesterone Levels > 3.0 ng/ml) Time 1 | 1 Participants |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | 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). | Ovulation (Progesterone Levels >3.0 ng/ml) Time 2 | 2 Participants |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | 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). | Ovulation (Progesterone Levels > 3.0 ng/ml) Time 1 | 3 Participants |
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 Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL, Time 1, week 0 | 133.3 pg/mL | Standard Deviation 64.3 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL, Time 1, week 1 | 142.2 pg/mL | Standard Deviation 90 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 1, week 2 | 132.4 pg/mL | Standard Deviation 103.9 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 0 | 134.2 pg/mL | Standard Deviation 73.9 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 1 | 210.7 pg/mL | Standard Deviation 227.1 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 2 | 146.3 pg/mL | Standard Deviation 80.5 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 2 | 192.0 pg/mL | Standard Deviation 101.2 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 0 | 102.0 pg/mL | Standard Deviation 44.2 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL, Time 1, week 0 | 137.2 pg/mL | Standard Deviation 76.9 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 1, week 2 | 107.9 pg/mL | Standard Deviation 39.3 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL, Time 1, week 1 | 154.7 pg/mL | Standard Deviation 117.1 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 1 | 121.6 pg/mL | Standard Deviation 57.5 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL, Time 1, week 1 | 138.4 pg/mL | Standard Deviation 77.7 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 1, week 2 | 132.6 pg/mL | Standard Deviation 73.3 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 0 | 119.3 pg/mL | Standard Deviation 77.9 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 2 | 102.9 pg/mL | Standard Deviation 75.1 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 1 | 113.9 pg/mL | Standard Deviation 71.1 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL, Time 1, week 0 | 131.1 pg/mL | Standard Deviation 75 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 1 | 118.0 pg/mL | Standard Deviation 86.3 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 2 | 108.7 pg/mL | Standard Deviation 47.6 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL, Time 1, week 1 | 290.6 pg/mL | Standard Deviation 34.8 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 2, week 0 | 123.4 pg/mL | Standard Deviation 60.2 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL, Time 1, week 0 | 103.5 pg/mL | Standard Deviation 52.2 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Estradiol, pg/mL,Time 1, week 2 | 230.4 pg/mL | Standard Deviation 34.2 |
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 Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 0 | 14.9 IU/mL | Standard Deviation 5.7 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 1 | 14.5 IU/mL | Standard Deviation 5 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 2 | 13.8 IU/mL | Standard Deviation 4.2 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 0 | 12.9 IU/mL | Standard Deviation 3.5 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 1 | 11.8 IU/mL | Standard Deviation 3 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 2 | 11.3 IU/mL | Standard Deviation 4.4 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 2 | 14.1 IU/mL | Standard Deviation 4.5 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 0 | 13.0 IU/mL | Standard Deviation 3.6 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 0 | 14.0 IU/mL | Standard Deviation 4.8 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 2 | 13.4 IU/mL | Standard Deviation 4.3 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 1 | 14.7 IU/mL | Standard Deviation 4.8 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 1 | 15.9 IU/mL | Standard Deviation 5 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 1 | 13.9 IU/mL | Standard Deviation 5.2 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 2 | 20.4 IU/mL | Standard Deviation 12 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 0 | 17.5 IU/mL | Standard Deviation 10.1 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 2 | 14.8 IU/mL | Standard Deviation 4.7 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 1 | 17.7 IU/mL | Standard Deviation 8.8 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 0 | 15.8 IU/mL | Standard Deviation 8 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 1 | 13.8 IU/mL | Standard Deviation 4.5 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 2 | 16.8 IU/mL | Standard Deviation 10.1 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 1 | 13.6 IU/mL | Standard Deviation 4.4 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 2, week 0 | 14.7 IU/mL | Standard Deviation 4.1 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 0 | 13.9 IU/mL | Standard Deviation 4.3 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | FSH, IU/mL, Time 1, week 2 | 15.4 IU/mL | Standard Deviation 9.9 |
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 Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 2, week 2 | 29.1 IU/mL | Standard Deviation 22.5 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 0 | 24.7 IU/mL | Standard Deviation 10.1 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 1 | 35.1 IU/mL | Standard Deviation 16.1 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 2 | 36.2 IU/mL | Standard Deviation 20.1 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 2, week 1 | 30.1 IU/mL | Standard Deviation 20 |
| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH IU/L, Time 2, week 0 | 33.2 IU/mL | Standard Deviation 16.5 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 2, week 1 | 27.5 IU/mL | Standard Deviation 17.9 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 2, week 2 | 27.7 IU/mL | Standard Deviation 19.1 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 1 | 30.2 IU/mL | Standard Deviation 21.8 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 0 | 20.9 IU/mL | Standard Deviation 10.4 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 2 | 23.1 IU/mL | Standard Deviation 14.7 |
| LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH IU/L, Time 2, week 0 | 28.4 IU/mL | Standard Deviation 14.9 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 0 | 26.4 IU/mL | Standard Deviation 15.7 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 2, week 1 | 40.0 IU/mL | Standard Deviation 46.5 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH IU/L, Time 2, week 0 | 31.9 IU/mL | Standard Deviation 27.5 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 1 | 24.6 IU/mL | Standard Deviation 16.3 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 2, week 2 | 27.7 IU/mL | Standard Deviation 19.1 |
| LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 2 | 25.6 IU/mL | Standard Deviation 22.1 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 2, week 2 | 39.1 IU/mL | Standard Deviation 18 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 0 | 25.3 IU/mL | Standard Deviation 15.7 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 1 | 25.3 IU/mL | Standard Deviation 15.7 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 1, week 2 | 23.2 IU/mL | Standard Deviation 18.4 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH IU/L, Time 2, week 0 | 46.3 IU/mL | Standard Deviation 25.8 |
| LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | LH, IU/L, Time 2, week 1 | 28.8 IU/mL | Standard Deviation 11.4 |