Estrogen Receptor Beta and Mood

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 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.

Conditions

• Perimenopause-Related Depression

Interventions

DRUG

Estradiol

Estradiol patch 0.1 mg transdermal every three days for three weeks

DRUG

ER Beta Agonist

Lilly Compound LY500307, a selective estrogen receptor (ER) beta agonist

OTHER

Placebo

Placebo orally once daily

DRUG

Provera

Provera 5 mg orally once a day for one week after completion of randomization

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  lead NIH

Principal Investigators

• Peter J Schmidt, M.D. · National Institute of Mental Health (NIMH)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

45 Years

Max Age

65 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-05-23

Primary Completion

2024-09-09

Completion

2024-09-09

FDA Drug

Yes

Countries

• United States

Study Locations