This trial is active, not recruiting.

Conditions perimenopause, menopause, depression
Treatments estradiol, placebo
Phase phase 2/phase 3
Sponsor University of North Carolina, Chapel Hill
Collaborator National Institute of Mental Health (NIMH)
Start date October 2010
End date February 2016
Trial size 382 participants
Trial identifier NCT01308814, 10-0542, R01MH087619


Study Background and Objectives: In the U.S. the majority of heart disease deaths are in women, not men. Much of the gender disparity in CVD rates relate to the burden of CV risk in women after the menopause. Depression has been associated with an increased risk for CVD morbidity and mortality. Even histories of recurrent depression in euthymic individuals are associated with elevated CV risk. Understanding the depression-CVD link may have particular relevance for women since women experience depression at a rate twice that of men. Substantial convergent evidence indicates that ovarian failure (estrogen deprivation) is one likely mechanism contributing to both CVD and depression in women. The perimenopause, a time associated with a two-fold increase in rates of depression, may provide an ideal opportunity for studying the pathophysiology of CV risk and depression in women.

The primary objective of this study is to examine the prophylactic role of estradiol in the development of depressive symptoms and the progression of cardiovascular risk in perimenopausal women with or without histories of depression. The investigators predict that women susceptible to depression will be particularly vulnerable to the acceleration of CVD in the context of the perimenopause and, consequently, will show differentially greater benefit of estradiol treatment during the menopause transition for both indices of CV risk (e.g. inflammation, endothelial function, stress reactivity), as well as depressive symptoms.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
(Placebo Comparator)
Placebo patches for 12 months and placebo pills for 12 days every 2 months.
Placebo patches for 12 months, to be worn continuously and replaced once a week. Also, placebo pills will be administered for 12 days every 2 months.
Transdermal 17β-estradiol (100 ug/day) for 12 months and oral micronized progesterone (200 mg/day) for 12 days every two months.
estradiol Climara and Prometrium.
Transdermal 17β-estradiol (100 ug/day) for 12 months, administered as patches to be worn continuously and replaced once a week. Also, every 2 months, oral micronized progesterone (200 mg/day x 12 days) will be administered.

Primary Outcomes

Change in Depressive Symptoms as Indicated by The Center for Epidemiologic Studies Depression Scale (CES-D)
time frame: Baseline, month 1, 2, 4, 6, 8, 10, 12
Change in Psychiatric Diagnosis as Assessed by the Structured Clinical Interview for DSM Disorders I/NP
time frame: Baseline and when prompted by CES-D score
Change in Stress Reactivity during Laboratory Session including Trier Social Stress Test
time frame: Baseline, month 6 and 12

Secondary Outcomes

Change in Functional Well-being as Assessed by the Medical Outcomes Study 36-item Short form (SF-36)
time frame: Baseline, month 6 and 12
Change in Metabolic risk
time frame: Baseline, month 6 and 12
Change in Flow Mediated Vasodilatation
time frame: Baseline, month 6 and 12
Change in Baroreceptor sensitivity
time frame: Baseline, month 6 and 12

Eligibility Criteria

Female participants from 45 years up to 60 years old.

Inclusion Criteria: - must be between 45 and 60 years of age - must be in the menopause transition (irregular/ absent menstrual cycles or hot flashes) - must be are medically healthy Exclusion Criteria: - currently taking antidepressant medication

Additional Information

Official title Depression, Estrogen Replacement, and Cardiovascular Health in the Perimenopause
Principal investigator Susan Girdler, PH.D.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by University of North Carolina, Chapel Hill.