Perimenopause-Related Mood and Behavioral Disorders

NCT00001231 | Completed

• 2 other identifiers: 88013188-M-0131
• Study Type: observational
• Target: 1,158
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate mood and behavior changes in the time period surrounding and including menopause. This is an observational study; volunteers who participate will not receive any new or experimental therapies. Controversy exists regarding the relationship between estrogen and progesterone (gonadal steroid) changes and midlife-onset depression. This study will examine the role of gonadal steroids in perimenopausal mood and behavioral disorders. Perimenopausal women with depression symptoms and a control group of healthy perimenopausal volunteers will be compared to identify correlates of the occurrence of depression. Participants with depressive symptoms may also participate in companion studies that will test the antidepressant efficacy of phytoestrogens and selective estrogen receptor modulators (SERMS). A group of younger pre-perimenopausal women with normal menstrual cycle functioning will be followed through menopause in an effort to confirm the association of depression onset with changes in reproductive endocrine functioning.

Conditions

Mood Disorder

Keywords

Mood; Behavior; Cognition; Midlife; Depression

Outcome Measures

Primary Outcomes (1)

• Standardized cross-sectional rating scales (Beck Depression Inventory, Hamilton Depression and Anxiety Scales, and the Center for Epidemiologic Studies-Depression Scale), symptom rating scales completed daily, and plasma hormone measures (includ...

  Standardized cross-sectional rating scales (Beck Depression Inventory, Hamilton Depression and Anxiety Scales, and the Center for Epidemiologic Studies-Depression Scale), symptom rating scales completed daily, and plasma hormone measures (including neurosteroid levels).

  Ongoing

Secondary Outcomes (1)

• Plasma ACTH and cortisol response to the o-CRH stimulation tests, selected variants in genomic profile (e.g., SNPs) and genome/exome sequencing, and the results of the SCID interviews

  Ongoing

Study Arms (2)

Healthy Women

The purpose of this protocol is to allow for the careful screening of healthy volunteers for participation in research protocols.

premenopausal depressed women patients

The purpose of this protocol is to allow for the careful screening of patients for participation in research protocols.

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Both depressed and asymptomatic women who are in the perimenopause.

You may qualify if:

• Perimenopausal Subjects:
• History within the last one year of at least one month with perimenopause-related mood or behavioral disturbances of at least moderate severity - that is, disturbances that are distinct in appearance and associated with a notable degree of functional impairment;
• Age 40-65;
• History of the onset of menstrual irregularity during the past six months but not greater than one year of amenorrhea (i.e., not postmenopausal);
• Biological evidence of a deterioration of normal ovarian activity, specifically, plasma FSH levels persistently elevated (\> 14IU/L) (as recommended by the Stages of Reproductive Aging Workshop criteria (106)) drawn at two week intervals over a period of eight weeks;
• No prior estrogen replacement therapy for treatment of perimenopausal physical or emotional symptoms within the last six months; and
• In good medical health;
• Subjects must be competent to comprehend the purpose of the screening process and to provide written informed consent and be willing to participate in NIMH IRB approved research protocols.
• A control group of age-matched perimenopausal women who meet patient selection criteria with the exception of the presence of mood or behavioral disorders will also be sought.
• Regular menstrual cycle function (21-34 days);
• Absence of current mood or behavioral disturbance as determined by a structured diagnostic interview;
• Plasma gonadotropin levels in pre-perimenopausal range (\<14 IU/L);
• In good medical health; and
• Medication free.

You may not qualify if:

• Primary general medical illness (i.e., appears to be causing the mood disorder);
• Current antidepressant therapy (since this is a screening protocol for subsequent treatment studies in which participants must be untreated). Antidepressants will not be withheld from participants who need or want them;
• Current alcohol or substance abuse or dependence (excluding nicotine) of sufficient magnitude to require independent, concurrent treatment intervention (e.g., antabuse or opiate treatment, but not including self-help groups);
• Pregnant or lactating women;
• Subjects who are unable to provide informed consent.
• NIMH employees, staff and their immediate family members will be excluded from the study per NIMH policy.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Kessler RC, McGonagle KA, Swartz M, Blazer DG, Nelson CB. Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence. J Affect Disord. 1993 Oct-Nov;29(2-3):85-96. doi: 10.1016/0165-0327(93)90026-g.

  PMID: 8300981 BACKGROUND

• Schmidt PJ, Rubinow DR. Menopause-related affective disorders: a justification for further study. Am J Psychiatry. 1991 Jul;148(7):844-52. doi: 10.1176/ajp.148.7.844.

  PMID: 2053622 BACKGROUND

• Schmidt PJ, Nieman L, Danaceau MA, Tobin MB, Roca CA, Murphy JH, Rubinow DR. Estrogen replacement in perimenopause-related depression: a preliminary report. Am J Obstet Gynecol. 2000 Aug;183(2):414-20. doi: 10.1067/mob.2000.106004.

  PMID: 10942479 BACKGROUND

• Guerrieri GM, Ben Dor R, Li X, Wei SM, Martinez PE, Neiman LK, Rubinow DR, Schmidt PJ. The Cortisol and ACTH Response to Dex/CRH Testing in Women With and Without Perimenopausal Depression. J Clin Endocrinol Metab. 2021 Sep 27;106(10):3007-3018. doi: 10.1210/clinem/dgab407.

  PMID: 34097071 DERIVED

• Rudzinskas S, Hoffman JF, Martinez P, Rubinow DR, Schmidt PJ, Goldman D. In vitro model of perimenopausal depression implicates steroid metabolic and proinflammatory genes. Mol Psychiatry. 2021 Jul;26(7):3266-3276. doi: 10.1038/s41380-020-00860-x. Epub 2020 Aug 12.

  PMID: 32788687 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Mood Disorders; Behavior; Depression

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms

Study Officials

• Peter J Schmidt, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: March 6, 1989
• Last Updated: April 14, 2026

Record last verified: 2026-03-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting 24 months after final publication
• Access Criteria: Data will be shared with dbGaP, BTRIS and NIMH Data Archive as determined by the Principal Investigator.

Locations

US (1)