Mood DisorderNCT00001231
Perimenopause-Related Mood and Behavioral Disorders
An observational study of Mood Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 65 years, women only
- Conditions the study is for
- Mood Disorder
- How many people
- 1,158 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Mar 1989to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Both depressed and asymptomatic women who are in the perimenopause.
Who may be able to join
- 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
Show all 15Show fewer
- 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.
- Premenopausal women will be women who meet the following inclusion criteria for the longitudinal study participants:
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: The Evaluation of Women With Perimenopause-Related Mood and Behavioral Disorders
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.
Read more
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.
Read the detailed description
Controversy exists regarding the relevance of changes in gonadal steroids for midlife onset depressions. The purpose of this protocol is to allow for the careful screening of patients and healthy volunteers for participation in research protocols that examine the role of gonadal steroids in depressions occurring during the perimenopause and for the collection of natural history data. Women in this protocol will undergo an evaluation which may include: a psychiatric diagnostic interview; rating scales; a medical history; a physical exam; blood and urine laboratory evaluation; and a request for medical records. The data collected may also be linked with data from other perimenopausal depression protocols (e.g., DNA, psychophysiology tests, treatment studies, etc.) for the purposes of better understanding the diagnosis, pathophysiology, and treatment response of women with depression during the perimenopause.Upon conclusion of the screening process, participants will either be offered entry into a research protocol and will sign the appropriate informed consent, or will be considered not appropriate for participation in research and will be referred back into the community. The second purpose of this protocol is to permit the identification of premenopausal women who are followed longitudinally through the menopause transition in an effort to confirm the association of depression onset with change in reproductive endocrine function. This protocol, then, serves as a screening and evaluation protocol to recruit subjects who are characterized with standard measures in this protocol and then offered participation in related studies.
- Conditions
- Mood Disorder
- Keywords
- Mood, Behavior, Cognition, Midlife, Depression
- Medical subject headings
- Mood Disorders, Behavior, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
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
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start6 Mar 1989
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Mood DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,158 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Peter J Schmidt, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001231
- Sponsor's protocol ID
- 880131
- Other IDs
- 88-M-0131
- Status last verified
- 9 Mar 2026
- First submitted
- 3 Nov 1999
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared with dbGaP, BTRIS and NIMH Data Archive as determined by the Principal Investigator.
Publications
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.
PubMed 8300981Schmidt 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.
PubMed 2053622Schmidt 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.
PubMed 10942479Guerrieri 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.
PubMed 34097071Rudzinskas 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.
PubMed 32788687
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Evaluation of Women With Perimenopause-Related Mood and Behavioral Disorders
- ClinicalTrials.gov ID
- NCT00001231
- Acronym / sponsor ID
- 880131
- Conditions
- Mood Disorder
- Keywords
- Mood, Behavior, Cognition, Midlife, Depression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,158 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 6 Mar 1989 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Controversy exists regarding the relevance of changes in gonadal steroids for midlife onset depressions. The purpose of this protocol is to allow for the careful screening of patients and healthy volunteers for participation in research protocols that examine the role of gonadal steroids in depressions occurring during the perimenopause and for the collection of natural history data. Women in this protocol will undergo an evaluation which may include: a psychiatric diagnostic interview; rating scales; a medical history; a physical exam; blood and urine laboratory evaluation; and a request for medical records. The data collected may also be linked with data from other perimenopausal depression protocols (e.g., DNA, psychophysiology tests, treatment studies, etc.) for the purposes of better understanding the diagnosis, pathophysiology, and treatment response of women with depression during the perimenopause.Upon conclusion of the screening process, participants will either be offered entry into a research protocol and will sign the appropriate informed consent, or will be considered not appropriate for participation in research and will be referred back into the community. The second purpose of this protocol is to permit the identification of premenopausal women who are followed longitudinally through the menopause transition in an effort to confirm the association of depression onset with change in reproductive endocrine function. This protocol, then, serves as a screening and evaluation protocol to recruit subjects who are characterized with standard measures in this protocol and then offered participation in related studies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Both depressed and asymptomatic women who are in the perimenopause.
Key inclusion criteria (15 listed)
- Perimenopausal Subjects:
- 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.
- Premenopausal women will be women who meet the following inclusion criteria for the longitudinal study participants:
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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...
Time frame: Ongoing
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).
1 secondary outcome
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
Time frame: Ongoing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 8300981Kessler 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.
- Background: PubMed 2053622Schmidt 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.
- Background: PubMed 10942479Schmidt 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.
- Derived from this study: PubMed 34097071Guerrieri 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.
- Derived from this study: PubMed 32788687Rudzinskas 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data will be shared with dbGaP, BTRIS and NIMH Data Archive as determined by the Principal Investigator.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter J Schmidt, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mood Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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... (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001231, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.