Effect of Antidepressants on Sex Hormone Levels and Sexual Functioning

Study Overview
=================
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.

Official Title
-----------------
Effect of Serotonin Reuptake Inhibitors on Gonadal Steroid Hormones

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Fluoxetine
* Drug: Bupropion


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Participants will receive treatment with fluoxetine for 2 months | Drug: Fluoxetine<br>* 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.<br>* Other names: Prozac, Sarafem;|
| Experimental: B<br>Participants will receive treatment with bupropion for 2 months | Drug: Bupropion<br>* 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.<br>* Other names: Wellbutrin, Zyban;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | 
| 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. | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | 
| 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. | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | 
| 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. | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | 
| 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. | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | 
| 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. | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | 
| 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. | Measured in baseline menstrual cycle and during antidepressant treatment for two menstrual cycles | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gonadal Steroid Hormones, Healthy Volunteers, Antidepressant Side Effects, Fluoxetine, Bupropion, Prolactin, Testosterone, Estradiol, Progesterone, Sexual Function, Serotonin Reuptake Inhibitors, 17-OH Pregnenolone