Perimenopausal DepressionNCT00060736
The Effects of Estrogen Withdrawal on Mood Symptoms in Women
An observational study of Perimenopausal Depression and Post Menopausal, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study evaluates the effects on mood when stopping estrogen replacement therapy. The purpose of this study is to investigate the effects of estrogen levels on perimenopausal depression. This study will examine short-term withdrawal of estrogen in women whose mood had improved with estrogen therapy. Read more about this study
- Who is it for?
- Ages 45 to 65 years, women only
- Conditions the study is for
- Perimenopausal Depression, Post Menopausal, Healthy
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 5 May 2003to 27 Apr 2016
- 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 45 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All subjects for this protocol will be either self-referred in response to newspaper advertisements or referred by their personal physician. The women participating in this protocol will have previously completed the screening protocol # 88-M-0131 and, therefore, will have had the presence or absence of perimenopausal or menopausal reproductive status evaluated and documented.
- Women with a past perimenopause-related depression (within 12 years) and whose depression responded to ET will be recruited to participate in this randomized, parallel-design, double-blind, placebo-controlled study. Women with histories of either perimenopausal depression that was not responsive to ET or hormone replacement therapy-induced dysphoria due to either the estrogen or the progesterone components of their hormone replacement will be excluded. The diagnosis of perimenopause-related depression will be based on a history of a past depressive episode (major or minor depression confirmed by Structured Clinical Interview for DSM-IV (SCID) or Schedule of Affective Disorders and Schizophrenia-Lifetime Version (SADS-L), respectively) at midlife in association with menstrual cycle irregularity and the history of remission (also confirmed by SCID or SADS-L) of this depression after ET. Additionally, all women will report that they were placed on HRT for the treatment of perimenopausal symptoms, including depression.
- Age 45 to 65
- In good medical health
- <TAB>
- Women without past perimenopausal depression -
Show all 11Show fewer
- To control for the effects of the hormonal manipulations in this protocol, we will also recruit a group of asymptomatic controls who are either currently on ET or were prescribed ET previously and with no previous history of perimenopause-related depression or HRT-induced dysphoria. Women who participate in this study as the asymptomatic comparison group will meet the following criteria:
- Women who received hormone therapy (HT) with no previous history of perimenopause-related depression or HT-induced dysphoria
- No current mood or behavioral problems
- Age 45 to 65
- In good medical health
Who cannot join
- past history of severe major depression with suicidal ideation
- current treatment with antidepressant medications
- history of ischemic cardiac disease, pulmonary embolism, or thrombophlebitis
- renal disease
- hepatic dysfunction
- women with a history of carcinoma of the breast
Show all 10Show fewer
- women with a history of uterine cancer, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding
- pregnant women
- cerebrovascular disease (stroke)
- recurrent migraine headaches
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Effects of Acute Withdrawal of Estradiol on Mood Symptoms in Women With Perimenopausal Depression
This study evaluates the effects on mood when stopping estrogen replacement therapy.
The purpose of this study is to investigate the effects of estrogen levels on perimenopausal depression. This study will examine short-term withdrawal of estrogen in women whose mood had improved with estrogen therapy.
Read more
Perimenopause-related mood disorders cause significant distress in a large number of women. Evidence suggests that estradiol may have beneficial effects in women with perimenopausal depression. However, the effect of declining estradiol secretion during perimenopause has not been fully examined.
Peri- and post-menopausal women who experience a remission of perimenopause-related depression symptoms while on estrogen therapy and a control group of healthy volunteers on hormone replacement therapy (HRT) will be switched from their current form of HRT to estradiol for a 3-week period; volunteers will also complete symptom ratings to confirm the absence of mood symptoms. Participants will then be randomly assigned to either continue estradiol or take a placebo (an inactive pill) for an additional 3 weeks. Mood ratings will be used to determine response to estradiol withdrawal.
...
Read the detailed description
Perimenopause-related mood disorders cause significant distress to a large number of women. Recent studies have reported the therapeutic benefits of estradiol in women with these mood disorders; however, a relevant pathophysiologic role of declining estradiol secretion during the perimenopause has not been demonstrated. In this protocol we wish to investigate the effects of acute withdrawal of estradiol on mood under placebo controlled conditions. Thus, mood and behavior symptoms may be precipitated by the experimental conditions of this protocol. This protocol will address the following hypothesis: women with a past history of perimenopause-related depression but not women without such a history will experience a recurrence of mood and behavioral symptoms during acute estradiol withdrawal but not during continued estradiol administration. The nature of the relationship between the declining secretion of estradiol and mood in perimenopausal depressed women will be examined as follows: Peri- and postmenopausal women reporting the onset of depression during the perimenopause and who report remission of depressive symptoms on estrogen therapy (ET) will be withdrawn from ET under blinded and placebo-controlled conditions. We will recruit as a comparison group asymptomatic women on hormone replacement and without a history of perimenopause-related depression. During a three week baseline phase, all women will be switched from their current form of hormone replacement therapy to estradiol and will complete symptom ratings to confirm the absence of mood symptoms prior to entry into the study. After the screening, all women will be randomized to receive either estradiol or placebo for an additional three weeks. Comparison of mood ratings during these contrasting treatment conditions will allow us to examine the specific role of estrogen withdrawal in depression that is responsive to ET.
- Conditions
- Perimenopausal Depression, Post Menopausal, Healthy, Depression
- Keywords
- Hormone Replacement, Gonadal Steroids, Estrogen, Major Depression, Minor Depression, Perimenopause, Estradiol, Depression, Perimenopausal Depression
- Medical subject headings
- Depression, Depressive Disorder, Major
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2003 (estimated)
- Study start5 May 2003
- Study completion27 Apr 2016
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 Perimenopausal DepressionStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- 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
- Enrolment
- 60 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
- NCT00060736
- Sponsor's protocol ID
- 030175
- Other IDs
- 03-M-0175
- Status last verified
- 27 Apr 2016
- First submitted
- 9 May 2003
- Last updated
- 16 Dec 2019
- Results posted
- No
Publications
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. doi: 10.1001/jama.288.3.321.
PubMed 12117397Serin IS, Ozcelik B, Basbug M, Aygen E, Kula M, Erez R. Long-term effects of continuous oral and transdermal estrogen replacement therapy on sex hormone binding globulin and free testosterone levels. Eur J Obstet Gynecol Reprod Biol. 2001 Dec 1;99(2):222-5. doi: 10.1016/s0301-2115(01)00398-0.
PubMed 11788176Schmidt 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 10942479Rudzinskas 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 32788687Schmidt PJ, Ben Dor R, Martinez PE, Guerrieri GM, Harsh VL, Thompson K, Koziol DE, Nieman LK, Rubinow DR. Effects of Estradiol Withdrawal on Mood in Women With Past Perimenopausal Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2015 Jul;72(7):714-26. doi: 10.1001/jamapsychiatry.2015.0111.
PubMed 26018333
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Acute Withdrawal of Estradiol on Mood Symptoms in Women With Perimenopausal Depression
- ClinicalTrials.gov ID
- NCT00060736
- Acronym / sponsor ID
- 030175
- Conditions
- Perimenopausal Depression, Post Menopausal, Healthy, Depression
- Keywords
- Hormone Replacement, Gonadal Steroids, Estrogen, Major Depression, Minor Depression, Perimenopause, Estradiol, Depression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 5 May 2003
- Study completion
- 27 Apr 2016
- First posted
- 12 May 2003 (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.
This study evaluates the effects on mood when stopping estrogen replacement therapy.
The purpose of this study is to investigate the effects of estrogen levels on perimenopausal depression. This study will examine short-term withdrawal of estrogen in women whose mood had improved with estrogen therapy.
Perimenopause-related mood disorders cause significant distress in a large number of women. Evidence suggests that estradiol may have beneficial effects in women with perimenopausal depression. However, the effect of declining estradiol secretion during perimenopause has not been fully examined.
Peri- and post-menopausal women who experience a remission of perimenopause-related depression symptoms while on estrogen therapy and a control group of healthy volunteers on hormone replacement therapy (HRT) will be switched from their current form of HRT to estradiol for a 3-week period; volunteers will also complete symptom ratings to confirm the absence of mood symptoms. Participants will then be randomly assigned to either continue estradiol or take a placebo (an inactive pill) for an additional 3 weeks. Mood ratings will be used to determine response to estradiol withdrawal.
...
Detailed description
Perimenopause-related mood disorders cause significant distress to a large number of women. Recent studies have reported the therapeutic benefits of estradiol in women with these mood disorders; however, a relevant pathophysiologic role of declining estradiol secretion during the perimenopause has not been demonstrated. In this protocol we wish to investigate the effects of acute withdrawal of estradiol on mood under placebo controlled conditions. Thus, mood and behavior symptoms may be precipitated by the experimental conditions of this protocol. This protocol will address the following hypothesis: women with a past history of perimenopause-related depression but not women without such a history will experience a recurrence of mood and behavioral symptoms during acute estradiol withdrawal but not during continued estradiol administration. The nature of the relationship between the declining secretion of estradiol and mood in perimenopausal depressed women will be examined as follows: Peri- and postmenopausal women reporting the onset of depression during the perimenopause and who report remission of depressive symptoms on estrogen therapy (ET) will be withdrawn from ET under blinded and placebo-controlled conditions. We will recruit as a comparison group asymptomatic women on hormone replacement and without a history of perimenopause-related depression. During a three week baseline phase, all women will be switched from their current form of hormone replacement therapy to estradiol and will complete symptom ratings to confirm the absence of mood symptoms prior to entry into the study. After the screening, all women will be randomized to receive either estradiol or placebo for an additional three weeks. Comparison of mood ratings during these contrasting treatment conditions will allow us to examine the specific role of estrogen withdrawal in depression that is responsive to ET.
Study design
Who may qualify
- Ages
- 45 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- All subjects for this protocol will be either self-referred in response to newspaper advertisements or referred by their personal physician. The women participating in this protocol will have previously completed the screening protocol # 88-M-0131 and, therefore, will have had the presence or absence of perimenopausal or menopausal reproductive status evaluated and documented.
- Women with a past perimenopause-related depression (within 12 years) and whose depression responded to ET will be recruited to participate in this randomized, parallel-design, double-blind, placebo-controlled study. Women with histories of either perimenopausal depression that was not responsive to ET or hormone replacement therapy-induced dysphoria due to either the estrogen or the progesterone components of their hormone replacement will be excluded. The diagnosis of perimenopause-related depression will be based on a history of a past depressive episode (major or minor depression confirmed by Structured Clinical Interview for DSM-IV (SCID) or Schedule of Affective Disorders and Schizophrenia-Lifetime Version (SADS-L), respectively) at midlife in association with menstrual cycle irregularity and the history of remission (also confirmed by SCID or SADS-L) of this depression after ET. Additionally, all women will report that they were placed on HRT for the treatment of perimenopausal symptoms, including depression.
- Age 45 to 65
- In good medical health
- <TAB>
Key exclusion criteria (10 listed)
- past history of severe major depression with suicidal ideation
- current treatment with antidepressant medications
- history of ischemic cardiac disease, pulmonary embolism, or thrombophlebitis
- renal disease
- hepatic dysfunction
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
Not reported in the source record.
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 16 Dec 2019.
- Background: PubMed 12117397Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. doi: 10.1001/jama.288.3.321.
- Background: PubMed 11788176Serin IS, Ozcelik B, Basbug M, Aygen E, Kula M, Erez R. Long-term effects of continuous oral and transdermal estrogen replacement therapy on sex hormone binding globulin and free testosterone levels. Eur J Obstet Gynecol Reprod Biol. 2001 Dec 1;99(2):222-5. doi: 10.1016/s0301-2115(01)00398-0.
- 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 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.
- Derived from this study: PubMed 26018333Schmidt PJ, Ben Dor R, Martinez PE, Guerrieri GM, Harsh VL, Thompson K, Koziol DE, Nieman LK, Rubinow DR. Effects of Estradiol Withdrawal on Mood in Women With Past Perimenopausal Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2015 Jul;72(7):714-26. doi: 10.1001/jamapsychiatry.2015.0111.
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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 Perimenopausal Depression and Post Menopausal, 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 11 inclusion and 10 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 16 Dec 2019. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00060736, 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 16 Dec 2019.