Estrogen Receptor Beta and Mood

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 create pictures of the lining of the uterus. * Participants will have a final visit 4 weeks after stopping the study drug. They will answer questions about mood and side effects.