Clinical trial NCT01308814: Perimenopausal Estrogen Replacement Therapy Study
Official title: Depression, Estrogen Replacement, and Cardiovascular Health in the Perimenopause
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Perimenopause
Menopause
Depression
Keywords: Perimenopause
Menopause
Depression
Cardiovascular health
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2011-03-04
Enrollment: 172
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Depressive Symptoms as Indicated by The Center for Epidemiologic Studies Depression Scale (CES-D)
timeFrame: Baseline, month 12
measure: Change in Psychiatric Diagnosis as Assessed by the Structured Clinical Interview for DSM Disorders I/NP
timeFrame: Baseline and when prompted by CES-D score
measure: Change in Stress Reactivity During Laboratory Session Including Trier Social Stress Test
timeFrame: Baseline, month 12
Secondary outcomes:
measure: Change in Functional Well-being as Assessed by the Medical Outcomes Study 36-item Short Form (SF-36)
timeFrame: Baseline, month 12
measure: Percentage Meeting Criteria for Metabolic Risk [Baseline and Month 12]
timeFrame: Baseline, month 12
measure: Change in Percentage of Brachial Artery Diameter
timeFrame: Baseline, month 12
measure: Change in Baroreceptor Sensitivity
timeFrame: Baseline, month 12
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: UNC
name: Susan Girdler, PH.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vaisar T, Gordon JL, Wimberger J, Heinecke JW, Hinderliter AL, Rubinow DR, Girdler SS, Rubinow KB. Perimenopausal transdermal estradiol replacement reduces serum HDL cholesterol efflux capacity but improves cardiovascular risk factors. J Clin Lipidol. 2021 Jan-Feb;15(1):151-161.e0. doi: 10.1016/j.jacl.2020.11.009. Epub 2020 Nov 24.
citation: Zannas AS, Gordon JL, Hinderliter AL, Girdler SS, Rubinow DR. IL-6 Response to Psychosocial Stress Predicts 12-month Changes in Cardiometabolic Biomarkers in Perimenopausal Women. J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3757-65. doi: 10.1210/clinem/dgaa476.
citation: Gordon JL, Rubinow DR, Watkins L, Hinderliter AL, Caughey MC, Girdler SS. The Effect of Perimenopausal Transdermal Estradiol and Micronized Progesterone on Markers of Risk for Arterial Disease. J Clin Endocrinol Metab. 2020 May 1;105(5):e2050-60. doi: 10.1210/clinem/dgz262.
citation: Gordon JL, Rubinow DR, Eisenlohr-Moul TA, Xia K, Schmidt PJ, Girdler SS. Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):149-157. doi: 10.1001/jamapsychiatry.2017.3998.