Trial Outcomes & Findings for Effect of Antidepressants on Sex Hormone Levels and Sexual Functioning (NCT NCT00611975)

NCT ID: NCT00611975

Last Updated: 2020-12-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 83 participants
• Primary outcome timeframe: Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles
• Results posted on: 2020-12-10

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	45	38
Overall Study COMPLETED	40	30
Overall Study NOT COMPLETED	5	8

Reasons for withdrawal

Measure	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.	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.
Overall Study Withdrawal by Subject	3	7
Overall Study Pregnancy	2	1

Baseline Characteristics

Effect of Antidepressants on Sex Hormone Levels and Sexual Functioning

Baseline characteristics by cohort

Measure	Fluoxetine n=45 Participants 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.	Bupropion n=38 Participants 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.	Total n=83 Participants Total of all reporting groups
Age, Continuous	27.4 years STANDARD_DEVIATION 5.5 • n=5 Participants	27.9 years STANDARD_DEVIATION 6.4 • n=7 Participants	27.6 years STANDARD_DEVIATION 5.9 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	38 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	32 Participants n=7 Participants	69 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	14 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	18 Participants n=7 Participants	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Fluoxetine n=45 Participants 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.	Bupropion n=38 Participants 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.
Change in 17-OH Pregnenolone Baseline month follicular	120 ng/dl Standard Error 14	158 ng/dl Standard Error 17
Change in 17-OH Pregnenolone Baseline month ovulation	171 ng/dl Standard Error 46	170 ng/dl Standard Error 23
Change in 17-OH Pregnenolone Baseline month luteal	141 ng/dl Standard Error 18	189 ng/dl Standard Error 22
Change in 17-OH Pregnenolone Treatment month 1 follicular	151 ng/dl Standard Error 15	184 ng/dl Standard Error 39
Change in 17-OH Pregnenolone Treatment month 1 ovulation	122 ng/dl Standard Error 20	142 ng/dl Standard Error 22
Change in 17-OH Pregnenolone Treatment month 1 luteal	109 ng/dl Standard Error 14	163 ng/dl Standard Error 20
Change in 17-OH Pregnenolone Treatment month 2 follicular	101 ng/dl Standard Error 9	138 ng/dl Standard Error 19
Change in 17-OH Pregnenolone Treatment month 2 ovulation	174 ng/dl Standard Error 32	176 ng/dl Standard Error 20
Change in 17-OH Pregnenolone Treatment month 2 luteal	167 ng/dl Standard Error 32	161 ng/dl Standard Error 21

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Fluoxetine n=45 Participants 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.	Bupropion n=38 Participants 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.
Change in Arizona Sexual Experiences Scale (ASEX) Baseline month follicular	13.1 score on a scale Standard Error .5	12.9 score on a scale Standard Error .7
Change in Arizona Sexual Experiences Scale (ASEX) Baseline month ovulation	11.3 score on a scale Standard Error 0.6	12.1 score on a scale Standard Error 1.1
Change in Arizona Sexual Experiences Scale (ASEX) Baseline month luteal	14.0 score on a scale Standard Error 0.8	12.4 score on a scale Standard Error 0.7
Change in Arizona Sexual Experiences Scale (ASEX) Treatment month 1 follicular	15.1 score on a scale Standard Error .9	13.6 score on a scale Standard Error 10.9
Change in Arizona Sexual Experiences Scale (ASEX) Treatment month 1 ovulation	15.0 score on a scale Standard Error 1.0	12.6 score on a scale Standard Error 1.0
Change in Arizona Sexual Experiences Scale (ASEX) Treatment month 1 luteal	14.8 score on a scale Standard Error .7	13.8 score on a scale Standard Error 0.8
Change in Arizona Sexual Experiences Scale (ASEX) Treatment month 2 follicular	14.4 score on a scale Standard Error 0.7	14.3 score on a scale Standard Error 0.9
Change in Arizona Sexual Experiences Scale (ASEX) Treatment month 2 ovulation	13.6 score on a scale Standard Error 1.2	15.2 score on a scale Standard Error 1.4
Change in Arizona Sexual Experiences Scale (ASEX) Treatment month 2 luteal	15.1 score on a scale Standard Error 0.7	14.4 score on a scale Standard Error 1.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Fluoxetine n=45 Participants 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.	Bupropion n=38 Participants 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.
Change in Free Testosterone Baseline month luteal	.47 calculated ratio Standard Error .04	.47 calculated ratio Standard Error .04
Change in Free Testosterone Treatment month 1 ovulation	.41 calculated ratio Standard Error .04	.65 calculated ratio Standard Error .13
Change in Free Testosterone Treatment month 1 luteal	.49 calculated ratio Standard Error .04	.48 calculated ratio Standard Error .05
Change in Free Testosterone Baseline month follicular	.41 calculated ratio Standard Error .03	.44 calculated ratio Standard Error .02
Change in Free Testosterone Baseline month ovulation	.52 calculated ratio Standard Error .05	.69 calculated ratio Standard Error .09
Change in Free Testosterone Treatment month 1 follicular	.39 calculated ratio Standard Error .02	.51 calculated ratio Standard Error .04
Change in Free Testosterone Treatment month 2 follicular	.36 calculated ratio Standard Error .03	.40 calculated ratio Standard Error .04
Change in Free Testosterone Treatment month 2 ovulation	.50 calculated ratio Standard Error .04	.81 calculated ratio Standard Error .20
Change in Free Testosterone Treatment month 2 luteal	.50 calculated ratio Standard Error .07	.44 calculated ratio Standard Error .06

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Fluoxetine n=45 Participants 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.	Bupropion n=38 Participants 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.
Change in Estradiol Baseline Month Luteal	107 pg/ml Standard Error 7	109 pg/ml Standard Error 8
Change in Estradiol Baseline month follicular	42 pg/ml Standard Error 5	38 pg/ml Standard Error 3
Change in Estradiol Baseline month ovulation	131 pg/ml Standard Error 14	134 pg/ml Standard Error 20
Change in Estradiol Treatment month 1 follicular	41 pg/ml Standard Error 5	42 pg/ml Standard Error 6
Change in Estradiol Treatment month 1 ovulation	91 pg/ml Standard Error 12	121 pg/ml Standard Error 19
Change in Estradiol Treatment month 1 luteal	126 pg/ml Standard Error 11	108 pg/ml Standard Error 12
Change in Estradiol Treatment month 2 follicular	40 pg/ml Standard Error 6	35 pg/ml Standard Error 3
Change in Estradiol Treatment month 2 ovulation	122 pg/ml Standard Error 19	113 pg/ml Standard Error 13
Change in Estradiol Treatment month 2 luteal	112 pg/ml Standard Error 9	101 pg/ml Standard Error 10

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Fluoxetine n=45 Participants 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.	Bupropion n=38 Participants 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.
Change in Prolactin Baseline month follicular	11.2 ng/ml Standard Error 0.7	11.0 ng/ml Standard Error 1.2
Change in Prolactin Baseline month ovulation	15.9 ng/ml Standard Error 1.7	14.1 ng/ml Standard Error 1.6
Change in Prolactin Baseline month luteal	16.4 ng/ml Standard Error 1.4	15.4 ng/ml Standard Error 1.6
Change in Prolactin Treatment month 1 follicular	12.1 ng/ml Standard Error 1.1	11.7 ng/ml Standard Error 1.5
Change in Prolactin Treatment month 1 ovulation	12.9 ng/ml Standard Error 1.4	16.0 ng/ml Standard Error 2.9
Change in Prolactin Treatment month 1 luteal	14.0 ng/ml Standard Error 1.4	16.6 ng/ml Standard Error 1.9
Change in Prolactin Treatment month 2 follicular	12.8 ng/ml Standard Error 1.0	10.8 ng/ml Standard Error 1.4
Change in Prolactin Treatment month 2 ovulation	17.1 ng/ml Standard Error 3.3	18.3 ng/ml Standard Error 4.4
Change in Prolactin Treatment month 2 luteal	13.7 ng/ml Standard Error 1.0	12.1 ng/ml Standard Error 0.8

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Fluoxetine n=45 Participants 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.	Bupropion n=38 Participants 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.
Change in Progesterone Baseline month follicular	0.66 ng/ml Standard Error 0.2	0.5 ng/ml Standard Error 0.4
Change in Progesterone Baseline month ovulation	2.4 ng/ml Standard Error 0.6	2.8 ng/ml Standard Error 0.9
Change in Progesterone Baseline month luteal	9.5 ng/ml Standard Error 0.9	9.6 ng/ml Standard Error 1.1
Change in Progesterone Treatment month 1 follicular	0.7 ng/ml Standard Error 0.2	0.7 ng/ml Standard Error 0.2
Change in Progesterone Treatment month 1 ovulation	2.4 ng/ml Standard Error 0.7	3.9 ng/ml Standard Error 1.2
Change in Progesterone Treatment month 1 luteal	8.4 ng/ml Standard Error 1.1	7.4 ng/ml Standard Error 1.0
Change in Progesterone Treatment month 2 follicular	0.6 ng/ml Standard Error 0.2	0.6 ng/ml Standard Error 0.08
Change in Progesterone Treatment month 2 ovulation	2.9 ng/ml Standard Error 0.8	3.2 ng/ml Standard Error 1.2
Change in Progesterone Treatment month 2 luteal	8.6 ng/ml Standard Error 1.2	8.1 ng/ml Standard Error 1.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Fluoxetine n=45 Participants 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.	Bupropion n=38 Participants 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.
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Baseline month follicular	1.6 ug/ml Standard Error 0.1	1.8 ug/ml Standard Error 0.1
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Baseline month ovulation	1.8 ug/ml Standard Error 0.2	2.0 ug/ml Standard Error 0.2
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Baseline month luteal	1.6 ug/ml Standard Error 0.1	1.9 ug/ml Standard Error .01
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Treatment month 1 follicular	1.6 ug/ml Standard Error 0.1	1.9 ug/ml Standard Error 0.1
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Treatment month 1 ovulation	1.7 ug/ml Standard Error 0.2	1.9 ug/ml Standard Error 0.2
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Treatment month 1 luteal	1.7 ug/ml Standard Error 0.2	1.9 ug/ml Standard Error 0.2
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Treatment month 2 follicular	1.6 ug/ml Standard Error 0.2	1.8 ug/ml Standard Error 0.2
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Treatment month 2 ovulation	1.9 ug/ml Standard Error 0.3	1.8 ug/ml Standard Error 0.2
Change in Dehydroepiandrosterone Sulfate (DHEA-S) Treatment month 2 luteal	1.9 ug/ml Standard Error 0.2	1.9 ug/ml Standard Error 0.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Fluoxetine n=45 Participants 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.	Bupropion n=38 Participants 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.
Change in Androstenedione Baseline month follicular	0.84 ng/ml Standard Error 0.05	0.89 ng/ml Standard Error 0.05
Change in Androstenedione Baseline month ovulation	1.13 ng/ml Standard Error 0.07	1.28 ng/ml Standard Error 0.10
Change in Androstenedione Baseline month luteal	1.31 ng/ml Standard Error 0.10	1.14 ng/ml Standard Error 0.07
Change in Androstenedione Treatment month 1 follicular	0.89 ng/ml Standard Error 0.07	0.84 ng/ml Standard Error 0.06
Change in Androstenedione Treatment month 1 ovulation	1.13 ng/ml Standard Error 0.10	0.96 ng/ml Standard Error 0.06
Change in Androstenedione Treatment month 1 luteal	1.04 ng/ml Standard Error 0.06	1.13 ng/ml Standard Error 0.08
Change in Androstenedione Treatment month 2 follicular	0.79 ng/ml Standard Error 0.05	.85 ng/ml Standard Error .06
Change in Androstenedione Treatment month 2 ovulation	1.07 ng/ml Standard Error 0.12	1.00 ng/ml Standard Error 0.13
Change in Androstenedione Treatment month 2 luteal	1.13 ng/ml Standard Error 0.09	1.12 ng/ml Standard Error 0.12

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Fluoxetine

Serious events: 1 serious events

Other events: 33 other events

Deaths: 0 deaths

Bupropion

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fluoxetine n=45 participants at risk 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.	Bupropion n=38 participants at risk 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.
Nervous system disorders seizure	0.00% 0/45 • Each subject was assessed for 3 months.	2.6% 1/38 • Each subject was assessed for 3 months.
Pregnancy, puerperium and perinatal conditions pregnancy	2.2% 1/45 • Each subject was assessed for 3 months.	2.6% 1/38 • Each subject was assessed for 3 months.

Other adverse events

Measure	Fluoxetine n=45 participants at risk 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.	Bupropion n=38 participants at risk 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.
Reproductive system and breast disorders reduced orgasm	22.2% 10/45 • Number of events 10 • Each subject was assessed for 3 months.	15.8% 6/38 • Number of events 6 • Each subject was assessed for 3 months.
Reproductive system and breast disorders reduced libido	20.0% 9/45 • Number of events 9 • Each subject was assessed for 3 months.	7.9% 3/38 • Number of events 3 • Each subject was assessed for 3 months.
Gastrointestinal disorders reduced appetite	20.0% 9/45 • Number of events 9 • Each subject was assessed for 3 months.	28.9% 11/38 • Number of events 11 • Each subject was assessed for 3 months.
Gastrointestinal disorders dry mouth	11.1% 5/45 • Number of events 5 • Each subject was assessed for 3 months.	26.3% 10/38 • Number of events 10 • Each subject was assessed for 3 months.
Psychiatric disorders anxiety	6.7% 3/45 • Number of events 3 • Each subject was assessed for 3 months.	5.3% 2/38 • Number of events 2 • Each subject was assessed for 3 months.
Nervous system disorders yawning	17.8% 8/45 • Number of events 8 • Each subject was assessed for 3 months.	10.5% 4/38 • Number of events 4 • Each subject was assessed for 3 months.
Gastrointestinal disorders diarrhea	13.3% 6/45 • Number of events 6 • Each subject was assessed for 3 months.	13.2% 5/38 • Number of events 5 • Each subject was assessed for 3 months.
General disorders fatigue	24.4% 11/45 • Number of events 11 • Each subject was assessed for 3 months.	18.4% 7/38 • Number of events 7 • Each subject was assessed for 3 months.
Nervous system disorders headache	31.1% 14/45 • Number of events 14 • Each subject was assessed for 3 months.	15.8% 6/38 • Number of events 6 • Each subject was assessed for 3 months.
Gastrointestinal disorders nausea	20.0% 9/45 • Number of events 9 • Each subject was assessed for 3 months.	31.6% 12/38 • Number of events 12 • Each subject was assessed for 3 months.
General disorders insomnia	13.3% 6/45 • Number of events 6 • Each subject was assessed for 3 months.	10.5% 4/38 • Number of events 4 • Each subject was assessed for 3 months.
Nervous system disorders tinnitus	6.7% 3/45 • Number of events 3 • Each subject was assessed for 3 months.	10.5% 4/38 • Number of events 4 • Each subject was assessed for 3 months.

Additional Information

Margaret Altemus

Yale School of Medicine

Phone: 646-209-6277

Email: margaret.altemus@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place