Estrogen Receptor Beta and Mood

Study Summary

Background: Our previous studies have found that women who had depression during the perimenopause may have mood symptoms again if they stop estrogen therapy. Estrogen acts in the brain and other tissues by binding to estrogen receptors. There are two main types of estrogen receptors. They are estrogen receptor alpha and beta. Several studies have shown that estrogen receptor beta may play an important role in anxiety- and depressive-like behaviors in animals. Objectives: To examine a possible mechanism mediating the effects of estradiol-withdrawal on mood symptoms in asymptomatic postmenopausal women with a past perimenopausal depression. To evaluate the efficacy and safety of a selective estrogen receptor (ER) beta agonist (Lilly Compound LY500307) to prevent estradiol withdrawal-induced mood symptoms. Eligibility: Healthy, non-depressed postmenopausal women, ages 45 to 65, with a well-documented past perimenopause-related depression (within 12 years) and whose mood systems got better with estradiol Design: Participants will be screened with: Medical history Physical exam Blood tests Psychiatric interview Gynecological exam * Participants able to get pregnant must use effective barrier birth control throughout the study. * During the first 3 weeks, participants will wear an estrogen patch. It is 1x2 inches and will be replaced every 3 days. * For the next 3 weeks, participants will take 3 study capsules every morning. They will not know if they get the study drug or placebo. * Some participants will also take a progesterone-like drug for 1 week at the end of the medication phase of the study. * Participants will have 9 one-hour study visits. They will have blood samples and vital signs taken. They will answer questions about mood and behavior symptoms. * Participants will keep a daily log of these symptoms. * Participants will have 2 transvaginal ultrasounds. A probe is temporarily placed 2-3 inches into the vaginal canal and sound waves are used to c

Primary Outcome

Center for Epidemiologic Studies-Depression (CES-D) Scale is a 20-item questionnaire that asks participants to rate how often over the past week they experienced symptoms associated with depression. Each item is rated from 0 to 3 (0 = Rarely or None of the Time, 1 = Some or Little of the Time, 2 = Moderately or Much of the time, 3 = Most or Almost All the Time). Total scores range from 0 to 60, with high scores indicating greater depressive symptoms. CES-D scores \>8 and \<16 is consistent with

Interventions

• OTHER Placebo
• DRUG Estradiol
• DRUG Provera
• DRUG ER Beta Agonist