Healthy
Conditions
Keywords
Gonadal Steroid Hormones, Healthy Volunteers, Antidepressant Side Effects, Fluoxetine, Bupropion, Prolactin, Testosterone, Estradiol, Progesterone, Sexual Function, Serotonin Reuptake Inhibitors, 17-OH Pregnenolone
Brief summary
This study will evaluate the effect of antidepressants on sex hormone levels in women and if the potential changes in sex hormone levels are related to sexual side effects.
Detailed description
Depression is a leading cause of disability in women, with women being two times more likely than men to develop depression. Depression affects a person's body, thoughts, mood, and behavior, often making normal day-to-day functioning difficult. Fortunately, depression is a condition that is highly treatable with one or more of the antidepressant medications and forms of psychotherapy available. Serotonin reuptake inhibitors (SRIs) are a recent class of antidepressants that have been successful in alleviating symptoms of depression. Although the side effects of SRIs are less than those of other types of antidepressants, a number of people taking SRIs experience sexual dysfunction, including reduced desire and difficulty with orgasm. It is believed that SRI treatment may interfere with gonadal production of steroid hormones, thus leading to changes in sexual function. This study will compare the effects of the SRI fluoxetine with the effects of the non-SRI bupropion on circulating levels of sex hormones in healthy women and on any related sexual side effects. Participation in this study will last 3 months. Potential participants will undergo initial screening, which will involve a blood draw, drug and pregnancy tests, physical exam, electrocardiogram, and psychiatric diagnostic interview. Participants will also complete an interview and questionnaire about sexual functioning. All eligible participants will then be asked to return for a total of 9 study visits over 3 months. Participants will undergo 1 month of baseline hormonal sampling and 2 months of daily treatment with either fluoxetine or bupropion. The study visits will be scheduled around three points in the menstrual cycle (early follicular, ovulatory, and luteal), with each visit including a blood draw and repeat questionnaire on sexual functioning. Participants will be asked to perform daily urine tests, beginning 10 days after the start of menstruation and continuing for up to 8 days until detection of the luteinizing hormone surge, which signals ovulation. Participants will be asked to keep a diary of luteinizing hormone surges, dates of menstruation, and sexual activities. At the Month 3 visit, participants will discontinue their assigned medication and will complete their final blood draw and questionnaire.
Interventions
DRUGFluoxetine
Participants will begin taking 10 mg of fluoxetine, once a day by mouth, on the first day of their second menstrual cycle during the study. Dosage will be increased to 20 mg of fluoxetine once a day after 7 days, to be maintained until the luteal phase (start of ovulation) of menstrual cycle 3. If side effects are intolerable, the dose will be lowered to 10 mg of fluoxetine per day. Participants will undergo a total of 2 months of treatment with fluoxetine.
DRUGBupropion
Participants will begin taking 150 mg of bupropion, once a day by mouth, on the first day of their second menstrual cycle during the study. Dosage will be increased to 300 mg of bupropion once a day after 7 days, to be maintained until the luteal phase of menstrual cycle 3. If side effects are intolerable, the dose will be decreased to 150 mg of bupropion per day. Participants will undergo a total of 2 months of treatment with bupropion.
Sponsors
National Institute of Mental Health (NIMH)
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Regular menstrual cycles that are 25 to 35 days in length during the 1 year prior to study entry * Willing to engage in sexual activity, alone or with a partner, at least weekly for the duration of the study * Willing to use effective birth control (e.g., condom, diaphragm with spermicide, tubal ligation, nonhormonal intrauterine device,, partner with vasectomy) for the duration of the study
Exclusion criteria
* Medical illness that may contribute to sexual dysfunction or affect steroid hormone levels * Body mass index (BMI) greater than 30 * Elevated testosterone at screening * History of seizure disorder * Consumes more than 10 alcoholic beverages per week
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 17-OH Pregnenolone | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Effects of the two antidepressant treatments and menstrual cycle on hormone level were examined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Free Testosterone | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | Free testosterone was calculated from total testosterone ng/ml divided by sex hormone binding globulin (SHBG) nmol/l multiplied by 100. Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined. |
| Change in Estradiol | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined. |
| Change in Prolactin | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined. |
| Change in Progesterone | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | Hormone levels at early follicular, ovulation, and luteal phase of the cycle were averaged for the baseline pre-treatment month and compared to average values during the 1st and 2nd months of antidepressant treatment. |
| Change in Arizona Sexual Experiences Scale (ASEX) | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | A five-item scale with each item scored from 1 to 6. Score range is 5 to 30. Higher scores indicate more sexual dysfunction. Scores at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on ASEX scores were examined. |
| Change in Androstenedione | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined. |
| C-reactive Protein | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | — |
| Inflammatory Cytokines | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | — |
| Lymphocyte Activation Markers | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | — |
| Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluoxetine Participants will receive treatment with fluoxetine for 2 months
Fluoxetine: Participants will begin taking 10 mg of fluoxetine, once a day by mouth, on the first day of their second menstrual cycle during the study. Dosage will be increased to 20 mg of fluoxetine once a day after 7 days, to be maintained until the luteal phase (start of ovulation) of menstrual cycle 3. If side effects are intolerable, the dose will be lowered to 10 mg of fluoxetine per day. Participants will undergo a total of 2 months of treatment with fluoxetine. | 45 |
| Bupropion Participants will receive treatment with bupropion for 2 months
Bupropion: Participants will begin taking 150 mg of bupropion, once a day by mouth, on the first day of their second menstrual cycle during the study. Dosage will be increased to 300 mg of bupropion once a day after 7 days, to be maintained until the luteal phase of menstrual cycle 3. If side effects are intolerable, the dose will be decreased to 150 mg of bupropion per day. Participants will undergo a total of 2 months of treatment with bupropion. | 38 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Pregnancy | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 7 |
Baseline characteristics
| Characteristic | Bupropion | Total | Fluoxetine |
|---|---|---|---|
| Age, Continuous | 27.9 years STANDARD_DEVIATION 6.4 | 27.6 years STANDARD_DEVIATION 5.9 | 27.4 years STANDARD_DEVIATION 5.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 14 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 69 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 14 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 24 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 43 Participants | 25 Participants |
| Sex: Female, Male Female | 38 Participants | 83 Participants | 45 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 38 |
| other Total, other adverse events | 33 / 45 | 21 / 38 |
| serious Total, serious adverse events | 1 / 45 | 2 / 38 |
Outcome results
Primary
Change in 17-OH Pregnenolone
Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Effects of the two antidepressant treatments and menstrual cycle on hormone level were examined.
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: All subjects enrolled were included in the mixed model analysis. For mean results at each timepoint in the data table below, some subjects were not included due to missing blood samples or samples collected outside the specified cycle phase window.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluoxetine | Change in 17-OH Pregnenolone | Treatment month 2 luteal | 167 ng/dl | Standard Error 32 |
| Fluoxetine | Change in 17-OH Pregnenolone | Baseline month follicular | 120 ng/dl | Standard Error 14 |
| Fluoxetine | Change in 17-OH Pregnenolone | Baseline month ovulation | 171 ng/dl | Standard Error 46 |
| Fluoxetine | Change in 17-OH Pregnenolone | Baseline month luteal | 141 ng/dl | Standard Error 18 |
| Fluoxetine | Change in 17-OH Pregnenolone | Treatment month 1 follicular | 151 ng/dl | Standard Error 15 |
| Fluoxetine | Change in 17-OH Pregnenolone | Treatment month 1 ovulation | 122 ng/dl | Standard Error 20 |
| Fluoxetine | Change in 17-OH Pregnenolone | Treatment month 1 luteal | 109 ng/dl | Standard Error 14 |
| Fluoxetine | Change in 17-OH Pregnenolone | Treatment month 2 follicular | 101 ng/dl | Standard Error 9 |
| Fluoxetine | Change in 17-OH Pregnenolone | Treatment month 2 ovulation | 174 ng/dl | Standard Error 32 |
| Bupropion | Change in 17-OH Pregnenolone | Treatment month 2 follicular | 138 ng/dl | Standard Error 19 |
| Bupropion | Change in 17-OH Pregnenolone | Treatment month 1 ovulation | 142 ng/dl | Standard Error 22 |
| Bupropion | Change in 17-OH Pregnenolone | Baseline month follicular | 158 ng/dl | Standard Error 17 |
| Bupropion | Change in 17-OH Pregnenolone | Treatment month 2 luteal | 161 ng/dl | Standard Error 21 |
| Bupropion | Change in 17-OH Pregnenolone | Baseline month ovulation | 170 ng/dl | Standard Error 23 |
| Bupropion | Change in 17-OH Pregnenolone | Treatment month 1 luteal | 163 ng/dl | Standard Error 20 |
| Bupropion | Change in 17-OH Pregnenolone | Baseline month luteal | 189 ng/dl | Standard Error 22 |
| Bupropion | Change in 17-OH Pregnenolone | Treatment month 2 ovulation | 176 ng/dl | Standard Error 20 |
| Bupropion | Change in 17-OH Pregnenolone | Treatment month 1 follicular | 184 ng/dl | Standard Error 39 |
Comparison: Blood draws were scheduled for early follicular, ovulatory and luteal phases. Menstrual phase for blood samples were re-assigned to phase based on time to onset of next menstrual period. Early follicular(35-21 days before next menstrual period (NMP)), Ovulatory (16-12 before NMP) luteal (11-3 days before NMP).p-value: >0.8Mixed Models Analysis
Comparison: This secondary analysis examined main effect of menstrual cycle phase on hormone levelsp-value: >0.4Mixed Models Analysis
Secondary
Change in Androstenedione
Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined.
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: All subjects enrolled were included in the mixed model analysis. For mean results at each timepoint in the data table below, some subjects were not included due to missing blood samples or samples collected outside the specified cycle phase window.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluoxetine | Change in Androstenedione | Treatment month 2 luteal | 1.13 ng/ml | Standard Error 0.09 |
| Fluoxetine | Change in Androstenedione | Baseline month follicular | 0.84 ng/ml | Standard Error 0.05 |
| Fluoxetine | Change in Androstenedione | Baseline month ovulation | 1.13 ng/ml | Standard Error 0.07 |
| Fluoxetine | Change in Androstenedione | Baseline month luteal | 1.31 ng/ml | Standard Error 0.1 |
| Fluoxetine | Change in Androstenedione | Treatment month 1 follicular | 0.89 ng/ml | Standard Error 0.07 |
| Fluoxetine | Change in Androstenedione | Treatment month 1 ovulation | 1.13 ng/ml | Standard Error 0.1 |
| Fluoxetine | Change in Androstenedione | Treatment month 1 luteal | 1.04 ng/ml | Standard Error 0.06 |
| Fluoxetine | Change in Androstenedione | Treatment month 2 follicular | 0.79 ng/ml | Standard Error 0.05 |
| Fluoxetine | Change in Androstenedione | Treatment month 2 ovulation | 1.07 ng/ml | Standard Error 0.12 |
| Bupropion | Change in Androstenedione | Treatment month 2 follicular | .85 ng/ml | Standard Error 0.06 |
| Bupropion | Change in Androstenedione | Treatment month 1 ovulation | 0.96 ng/ml | Standard Error 0.06 |
| Bupropion | Change in Androstenedione | Baseline month follicular | 0.89 ng/ml | Standard Error 0.05 |
| Bupropion | Change in Androstenedione | Treatment month 2 luteal | 1.12 ng/ml | Standard Error 0.12 |
| Bupropion | Change in Androstenedione | Baseline month ovulation | 1.28 ng/ml | Standard Error 0.1 |
| Bupropion | Change in Androstenedione | Treatment month 1 luteal | 1.13 ng/ml | Standard Error 0.08 |
| Bupropion | Change in Androstenedione | Baseline month luteal | 1.14 ng/ml | Standard Error 0.07 |
| Bupropion | Change in Androstenedione | Treatment month 2 ovulation | 1.00 ng/ml | Standard Error 0.13 |
| Bupropion | Change in Androstenedione | Treatment month 1 follicular | 0.84 ng/ml | Standard Error 0.06 |
Comparison: Blood draws were scheduled for early follicular, ovulatory and luteal phases. Menstrual phase for blood samples were re-assigned to phase based on time to onset of next menstrual period. Early follicular(35-21 days before next menstrual period (NMP)), Ovulatory (16-12 before NMP) luteal (11-3 days before NMP).p-value: >0.1Mixed Models Analysis
Comparison: This secondary analysis examined main effect of menstrual cycle phase on hormone levelsp-value: >0.7Mixed Models Analysis
Secondary
Change in Arizona Sexual Experiences Scale (ASEX)
A five-item scale with each item scored from 1 to 6. Score range is 5 to 30. Higher scores indicate more sexual dysfunction. Scores at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on ASEX scores were examined.
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: All subjects enrolled were included in the mixed model analysis. For mean results at each timepoint in the data table below, some subjects were not included due to missing questionnaire samples or samples collected outside the specified cycle phase window.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluoxetine | Change in Arizona Sexual Experiences Scale (ASEX) | Baseline month follicular | 13.1 score on a scale | Standard Error 0.5 |
| Fluoxetine | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 1 luteal | 14.8 score on a scale | Standard Error 0.7 |
| Fluoxetine | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 1 follicular | 15.1 score on a scale | Standard Error 0.9 |
| Fluoxetine | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 2 follicular | 14.4 score on a scale | Standard Error 0.7 |
| Fluoxetine | Change in Arizona Sexual Experiences Scale (ASEX) | Baseline month luteal | 14.0 score on a scale | Standard Error 0.8 |
| Fluoxetine | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 2 ovulation | 13.6 score on a scale | Standard Error 1.2 |
| Fluoxetine | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 1 ovulation | 15.0 score on a scale | Standard Error 1 |
| Fluoxetine | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 2 luteal | 15.1 score on a scale | Standard Error 0.7 |
| Fluoxetine | Change in Arizona Sexual Experiences Scale (ASEX) | Baseline month ovulation | 11.3 score on a scale | Standard Error 0.6 |
| Bupropion | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 2 luteal | 14.4 score on a scale | Standard Error 1 |
| Bupropion | Change in Arizona Sexual Experiences Scale (ASEX) | Baseline month follicular | 12.9 score on a scale | Standard Error 0.7 |
| Bupropion | Change in Arizona Sexual Experiences Scale (ASEX) | Baseline month ovulation | 12.1 score on a scale | Standard Error 1.1 |
| Bupropion | Change in Arizona Sexual Experiences Scale (ASEX) | Baseline month luteal | 12.4 score on a scale | Standard Error 0.7 |
| Bupropion | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 1 follicular | 13.6 score on a scale | Standard Error 10.9 |
| Bupropion | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 1 ovulation | 12.6 score on a scale | Standard Error 1 |
| Bupropion | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 1 luteal | 13.8 score on a scale | Standard Error 0.8 |
| Bupropion | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 2 follicular | 14.3 score on a scale | Standard Error 0.9 |
| Bupropion | Change in Arizona Sexual Experiences Scale (ASEX) | Treatment month 2 ovulation | 15.2 score on a scale | Standard Error 1.4 |
Comparison: Asex questionnaires were scheduled for early follicular, ovulatory and luteal phases. Menstrual phase for ASEX scores were re-assigned to phase based on time to onset of next menstrual period. Follicular(35-21 days before next menstrual period (NMP)), Ovulatory (16-12 before NMP) luteal (11-2 days before NMP).p-value: >0.6Mixed Models Analysis
Comparison: This secondary analysis examined main effect of menstrual cycle phase on ASEX scoresp-value: >0.6Mixed Models Analysis
Secondary
Change in Dehydroepiandrosterone Sulfate (DHEA-S)
Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined.
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: All subjects enrolled were included in the mixed model analysis. For mean results at each timepoint in the data table below, some subjects were not included due to missing blood samples or samples collected outside the specified cycle phase window.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluoxetine | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Baseline month ovulation | 1.8 ug/ml | Standard Error 0.2 |
| Fluoxetine | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 1 luteal | 1.7 ug/ml | Standard Error 0.2 |
| Fluoxetine | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 1 follicular | 1.6 ug/ml | Standard Error 0.1 |
| Fluoxetine | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 2 follicular | 1.6 ug/ml | Standard Error 0.2 |
| Fluoxetine | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Baseline month luteal | 1.6 ug/ml | Standard Error 0.1 |
| Fluoxetine | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 2 ovulation | 1.9 ug/ml | Standard Error 0.3 |
| Fluoxetine | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 1 ovulation | 1.7 ug/ml | Standard Error 0.2 |
| Fluoxetine | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 2 luteal | 1.9 ug/ml | Standard Error 0.2 |
| Fluoxetine | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Baseline month follicular | 1.6 ug/ml | Standard Error 0.1 |
| Bupropion | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 2 luteal | 1.9 ug/ml | Standard Error 0.2 |
| Bupropion | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Baseline month follicular | 1.8 ug/ml | Standard Error 0.1 |
| Bupropion | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Baseline month ovulation | 2.0 ug/ml | Standard Error 0.2 |
| Bupropion | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Baseline month luteal | 1.9 ug/ml | Standard Error 0.01 |
| Bupropion | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 1 follicular | 1.9 ug/ml | Standard Error 0.1 |
| Bupropion | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 1 ovulation | 1.9 ug/ml | Standard Error 0.2 |
| Bupropion | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 1 luteal | 1.9 ug/ml | Standard Error 0.2 |
| Bupropion | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 2 follicular | 1.8 ug/ml | Standard Error 0.2 |
| Bupropion | Change in Dehydroepiandrosterone Sulfate (DHEA-S) | Treatment month 2 ovulation | 1.8 ug/ml | Standard Error 0.2 |
Comparison: Blood draws were scheduled for early follicular, ovulatory and luteal phases. Menstrual phase for blood samples were re-assigned to phase based on time to onset of next menstrual period. Early follicular(35-21 days before next menstrual period (NMP)), Ovulatory (16-12 before NMP) luteal (11-3 days before NMP).p-value: >0.9Mixed Models Analysis
Comparison: This secondary analysis examined main effect of menstrual cycle phase on hormone levelsp-value: >0.9Mixed Models Analysis
Secondary
Change in Estradiol
Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined.
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: All subjects enrolled were included in the mixed model analysis. For mean results at each timepoint in the data table below, some subjects were not included due to missing blood samples or samples collected outside the specified cycle phase window.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluoxetine | Change in Estradiol | Baseline month follicular | 42 pg/ml | Standard Error 5 |
| Fluoxetine | Change in Estradiol | Baseline Month Luteal | 107 pg/ml | Standard Error 7 |
| Fluoxetine | Change in Estradiol | Treatment month 1 ovulation | 91 pg/ml | Standard Error 12 |
| Fluoxetine | Change in Estradiol | Baseline month ovulation | 131 pg/ml | Standard Error 14 |
| Fluoxetine | Change in Estradiol | Treatment month 1 luteal | 126 pg/ml | Standard Error 11 |
| Fluoxetine | Change in Estradiol | Treatment month 1 follicular | 41 pg/ml | Standard Error 5 |
| Fluoxetine | Change in Estradiol | Treatment month 2 follicular | 40 pg/ml | Standard Error 6 |
| Fluoxetine | Change in Estradiol | Treatment month 2 luteal | 112 pg/ml | Standard Error 9 |
| Fluoxetine | Change in Estradiol | Treatment month 2 ovulation | 122 pg/ml | Standard Error 19 |
| Bupropion | Change in Estradiol | Treatment month 2 luteal | 101 pg/ml | Standard Error 10 |
| Bupropion | Change in Estradiol | Treatment month 2 ovulation | 113 pg/ml | Standard Error 13 |
| Bupropion | Change in Estradiol | Baseline month follicular | 38 pg/ml | Standard Error 3 |
| Bupropion | Change in Estradiol | Baseline month ovulation | 134 pg/ml | Standard Error 20 |
| Bupropion | Change in Estradiol | Baseline Month Luteal | 109 pg/ml | Standard Error 8 |
| Bupropion | Change in Estradiol | Treatment month 1 follicular | 42 pg/ml | Standard Error 6 |
| Bupropion | Change in Estradiol | Treatment month 2 follicular | 35 pg/ml | Standard Error 3 |
| Bupropion | Change in Estradiol | Treatment month 1 ovulation | 121 pg/ml | Standard Error 19 |
| Bupropion | Change in Estradiol | Treatment month 1 luteal | 108 pg/ml | Standard Error 12 |
Comparison: Blood draws were scheduled for early follicular, ovulatory and luteal phases. Menstrual phase for blood samples were re-assigned to phase based on time to onset of next menstrual period. Early follicular(35-21 days before next menstrual period (NMP)), Ovulatory (16-12 before NMP) luteal (11-3 days before NMP).p-value: >0.4Mixed Models Analysis
Comparison: This secondary analysis examined main effect of menstrual cycle phase on hormone levelsp-value: <0.0001Mixed Models Analysis
Secondary
Change in Free Testosterone
Free testosterone was calculated from total testosterone ng/ml divided by sex hormone binding globulin (SHBG) nmol/l multiplied by 100. Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined.
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: All subjects enrolled were included in the mixed model analysis. For mean results at each timepoint in the data table below, some subjects were not included due to missing blood samples or samples collected outside the specified cycle phase window.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluoxetine | Change in Free Testosterone | Baseline month ovulation | .52 calculated ratio | Standard Error 0.05 |
| Fluoxetine | Change in Free Testosterone | Treatment month 1 luteal | .49 calculated ratio | Standard Error 0.04 |
| Fluoxetine | Change in Free Testosterone | Treatment month 1 follicular | .39 calculated ratio | Standard Error 0.02 |
| Fluoxetine | Change in Free Testosterone | Treatment month 2 follicular | .36 calculated ratio | Standard Error 0.03 |
| Fluoxetine | Change in Free Testosterone | Baseline month luteal | .47 calculated ratio | Standard Error 0.04 |
| Fluoxetine | Change in Free Testosterone | Treatment month 2 ovulation | .50 calculated ratio | Standard Error 0.04 |
| Fluoxetine | Change in Free Testosterone | Treatment month 1 ovulation | .41 calculated ratio | Standard Error 0.04 |
| Fluoxetine | Change in Free Testosterone | Treatment month 2 luteal | .50 calculated ratio | Standard Error 0.07 |
| Fluoxetine | Change in Free Testosterone | Baseline month follicular | .41 calculated ratio | Standard Error 0.03 |
| Bupropion | Change in Free Testosterone | Treatment month 2 luteal | .44 calculated ratio | Standard Error 0.06 |
| Bupropion | Change in Free Testosterone | Baseline month follicular | .44 calculated ratio | Standard Error 0.02 |
| Bupropion | Change in Free Testosterone | Baseline month ovulation | .69 calculated ratio | Standard Error 0.09 |
| Bupropion | Change in Free Testosterone | Baseline month luteal | .47 calculated ratio | Standard Error 0.04 |
| Bupropion | Change in Free Testosterone | Treatment month 1 follicular | .51 calculated ratio | Standard Error 0.04 |
| Bupropion | Change in Free Testosterone | Treatment month 1 ovulation | .65 calculated ratio | Standard Error 0.13 |
| Bupropion | Change in Free Testosterone | Treatment month 1 luteal | .48 calculated ratio | Standard Error 0.05 |
| Bupropion | Change in Free Testosterone | Treatment month 2 follicular | .40 calculated ratio | Standard Error 0.04 |
| Bupropion | Change in Free Testosterone | Treatment month 2 ovulation | .81 calculated ratio | Standard Error 0.2 |
Comparison: Blood draws were scheduled for early follicular, ovulatory and luteal phases. Menstrual phase for blood samples were re-assigned to phase based on time to onset of next menstrual period. Early follicular(35-21 days before next menstrual period (NMP)), Ovulatory (16-12 before NMP) luteal (11-3 days before NMP).p-value: <0.01Mixed Models Analysis
Comparison: This secondary analysis examined main effect of menstrual cycle phase on hormone levelsp-value: <0.01Mixed Models Analysis
Secondary
Change in Progesterone
Hormone levels at early follicular, ovulation, and luteal phase of the cycle were averaged for the baseline pre-treatment month and compared to average values during the 1st and 2nd months of antidepressant treatment.
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: All subjects enrolled were included in the mixed model analysis. For mean results at each timepoint in the data table below, some subjects were not included due to missing blood samples or samples collected outside the specified cycle phase window.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluoxetine | Change in Progesterone | Baseline month ovulation | 2.4 ng/ml | Standard Error 0.6 |
| Fluoxetine | Change in Progesterone | Treatment month 1 ovulation | 2.4 ng/ml | Standard Error 0.7 |
| Fluoxetine | Change in Progesterone | Baseline month follicular | 0.66 ng/ml | Standard Error 0.2 |
| Fluoxetine | Change in Progesterone | Treatment month 2 follicular | 0.6 ng/ml | Standard Error 0.2 |
| Fluoxetine | Change in Progesterone | Treatment month 1 luteal | 8.4 ng/ml | Standard Error 1.1 |
| Fluoxetine | Change in Progesterone | Treatment month 2 ovulation | 2.9 ng/ml | Standard Error 0.8 |
| Fluoxetine | Change in Progesterone | Treatment month 1 follicular | 0.7 ng/ml | Standard Error 0.2 |
| Fluoxetine | Change in Progesterone | Treatment month 2 luteal | 8.6 ng/ml | Standard Error 1.2 |
| Fluoxetine | Change in Progesterone | Baseline month luteal | 9.5 ng/ml | Standard Error 0.9 |
| Bupropion | Change in Progesterone | Treatment month 2 luteal | 8.1 ng/ml | Standard Error 1.2 |
| Bupropion | Change in Progesterone | Treatment month 1 luteal | 7.4 ng/ml | Standard Error 1 |
| Bupropion | Change in Progesterone | Baseline month follicular | 0.5 ng/ml | Standard Error 0.4 |
| Bupropion | Change in Progesterone | Baseline month ovulation | 2.8 ng/ml | Standard Error 0.9 |
| Bupropion | Change in Progesterone | Baseline month luteal | 9.6 ng/ml | Standard Error 1.1 |
| Bupropion | Change in Progesterone | Treatment month 1 follicular | 0.7 ng/ml | Standard Error 0.2 |
| Bupropion | Change in Progesterone | Treatment month 1 ovulation | 3.9 ng/ml | Standard Error 1.2 |
| Bupropion | Change in Progesterone | Treatment month 2 follicular | 0.6 ng/ml | Standard Error 0.08 |
| Bupropion | Change in Progesterone | Treatment month 2 ovulation | 3.2 ng/ml | Standard Error 1.2 |
Comparison: Blood draws were scheduled for early follicular, ovulatory and luteal phases. Menstrual phase for blood samples were re-assigned to phase based on time to onset of next menstrual period. Early follicular(35-21 days before next menstrual period (NMP)), Ovulatory (16-12 before NMP) luteal (11-3 days before NMP).p-value: >0.9Mixed Models Analysis
Comparison: This secondary analysis examined main effect of menstrual cycle phase on hormone levelsp-value: <0.0001Mixed Models Analysis
Secondary
Change in Prolactin
Hormone levels at early follicular, ovulation, and luteal phase of 3 menstrual cycles which included baseline month, month 1 of daily antidepressant treatment and month 2 of daily antidepressant treatment. Differential effects of the two antidepressant treatments and menstrual cycle on hormone levels were examined.
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: All subjects enrolled were included in the mixed model analysis. For mean results at each timepoint in the data table below, some subjects were not included due to missing blood samples or samples collected outside the specified cycle phase window.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluoxetine | Change in Prolactin | Baseline month ovulation | 15.9 ng/ml | Standard Error 1.7 |
| Fluoxetine | Change in Prolactin | Treatment month 1 luteal | 14.0 ng/ml | Standard Error 1.4 |
| Fluoxetine | Change in Prolactin | Treatment month 1 follicular | 12.1 ng/ml | Standard Error 1.1 |
| Fluoxetine | Change in Prolactin | Treatment month 2 follicular | 12.8 ng/ml | Standard Error 1 |
| Fluoxetine | Change in Prolactin | Baseline month luteal | 16.4 ng/ml | Standard Error 1.4 |
| Fluoxetine | Change in Prolactin | Treatment month 2 ovulation | 17.1 ng/ml | Standard Error 3.3 |
| Fluoxetine | Change in Prolactin | Treatment month 1 ovulation | 12.9 ng/ml | Standard Error 1.4 |
| Fluoxetine | Change in Prolactin | Treatment month 2 luteal | 13.7 ng/ml | Standard Error 1 |
| Fluoxetine | Change in Prolactin | Baseline month follicular | 11.2 ng/ml | Standard Error 0.7 |
| Bupropion | Change in Prolactin | Treatment month 2 luteal | 12.1 ng/ml | Standard Error 0.8 |
| Bupropion | Change in Prolactin | Baseline month follicular | 11.0 ng/ml | Standard Error 1.2 |
| Bupropion | Change in Prolactin | Baseline month ovulation | 14.1 ng/ml | Standard Error 1.6 |
| Bupropion | Change in Prolactin | Baseline month luteal | 15.4 ng/ml | Standard Error 1.6 |
| Bupropion | Change in Prolactin | Treatment month 1 follicular | 11.7 ng/ml | Standard Error 1.5 |
| Bupropion | Change in Prolactin | Treatment month 1 ovulation | 16.0 ng/ml | Standard Error 2.9 |
| Bupropion | Change in Prolactin | Treatment month 1 luteal | 16.6 ng/ml | Standard Error 1.9 |
| Bupropion | Change in Prolactin | Treatment month 2 follicular | 10.8 ng/ml | Standard Error 1.4 |
| Bupropion | Change in Prolactin | Treatment month 2 ovulation | 18.3 ng/ml | Standard Error 4.4 |
Comparison: Blood draws were scheduled for early follicular, ovulatory and luteal phases. Menstrual phase for blood samples were re-assigned to phase based on time to onset of next menstrual period. Early follicular(35-21 days before next menstrual period (NMP)), Ovulatory (16-12 before NMP) luteal (11-3 days before NMP).p-value: >0.7Mixed Models Analysis
Comparison: This secondary analysis examined main effect of menstrual cycle phase on hormone levelsp-value: <0.0001Mixed Models Analysis
Secondary
C-reactive Protein
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: This measure was not performed due to lack of anticipated supplementary funding.
Secondary
Inflammatory Cytokines
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: This measure was not performed due to lack of anticipated supplementary funding.
Secondary
Lymphocyte Activation Markers
Time frame: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
Population: This measure was not performed due to lack of anticipated supplementary funding.