• Arizona Sexual Experiences Scale (ASEX) [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
• Free testosterone [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
• Estradiol [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
• Prolactin [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
• Progesterone [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
• Dehydroepiandrosterone Sulfate (DHEA-S) [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
• Androstenedione [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
• C-reactive protein [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
• Inflammatory cytokines [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]
• Lymphocyte activation markers [ Time Frame: Measured at Month 3 ] [ Designated as safety issue: No ]

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.

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.

• Drug: Fluoxetine
• Drug: Bupropion

• Experimental: Participants will receive treatment with fluoxetine for 2 months
• Experimental: Participants will receive treatment with bupropion for 2 months

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 IUD, 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