Perimenopause-Related DepressionPhase 2NCT03689543
Estrogen Receptor Beta and Mood
A Phase 2 study testing Estradiol, ER Beta Agonist and Provera in people with Perimenopause-Related Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: Our previous studies have found that women who had depression during the perimenopause may have mood symptoms again if they stop estrogen therapy. Estrogen acts in the brain and other tissues by binding to estrogen receptors. There are two main types of estrogen receptors. Read more about this study
- Who is it for?
- Ages 45 to 65 years, women only
- Conditions the study is for
- Perimenopause-Related Depression
- What is being tested?
- Estradiol, ER Beta Agonist and Provera
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- 23 May 2019to 9 Sep 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women with a past perimenopause-related depression (within 12 years). 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 Diagnostic and Statistical Manual (DSM)-V (SCID)) at midlife in association with menstrual cycle irregularity (and possibly hot flushes and/or vaginal dryness) and in whom menopausal hormone therapy was reported to improve their depression at any time within the prior twelve years. All women participating in this protocol will be screened with psychiatric, medical, and reproductive evaluations to confirm they are in good medical health.
- Age 45 to 65
- Medication free (including no mood stabilizers, no sleep medication) except for the following: women on menopausal hormone therapy who will discontinue these medications at the start of this study and have their hormone therapy replaced with estradiol 100mcg per day (as described below), women who are on stable doses of thyroid replacement for at least six months prior to study enrollment, or women who occasionally take non-steroidal anti-inflammatory drugs [NSAIDs] or allergy medications (although we will ask women to minimize the use of these medications during the study).
- Subjects must have consent capacity
Who cannot join
- The following conditions will constitute contraindications to participate in this protocol:
- Any current Axis 1 psychiatric illness or any clinically significant sleep disorder;
- Women with histories of hormone replacement therapy-induced dysphoria due to either the estrogen or the progesterone components of their hormone replacement;
- Past history of major depression with suicidal ideation;
- History of ischemic cardiac disease, pulmonary embolism, or thrombophlebitis;
- Renal disease; hepatic dysfunction; history of cholecystitis; hypertension;
Show all 13Show fewer
- Women with a history of carcinoma of the breast or any undiagnosed breast nodule/mass;
- Women with a history of uterine cancer, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding;
- Pregnant women; sexually active women will be required to employ barrier contraceptive methods;
- Cerebrovascular disease (stroke);
- Recurrent migraine headaches;
- Women who have had a hysterectomy before one year after their last menstrual period.
- National Institute of Mental Health (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 Effects of an ER Beta Agonist (Lilly Compound LY500307) on Estradiol-withdrawal-induced Mood Symptoms in Women With Past Perimenopausal Depression
Background:
Our previous studies have found that women who had depression during the perimenopause may have mood symptoms again if they stop estrogen therapy. Estrogen acts in the brain and other tissues by binding to estrogen receptors. There are two main types of estrogen receptors. They are estrogen receptor alpha and beta. Several studies have shown that estrogen receptor beta may play an important role in anxiety- and depressive-like behaviors in animals.
Read more
Objectives:
To examine a possible mechanism mediating the effects of estradiol-withdrawal on mood symptoms in asymptomatic postmenopausal women with a past perimenopausal depression. To evaluate the efficacy and safety of a selective estrogen receptor (ER) beta agonist (Lilly Compound LY500307) to prevent estradiol withdrawal-induced mood symptoms.
Eligibility:
Healthy, non-depressed postmenopausal women, ages 45 to 65, with a well-documented past perimenopause-related depression (within 12 years) and whose mood systems got better with estradiol
Design:
Participants will be screened with:
Medical history
Physical exam
Blood tests
Psychiatric interview
Gynecological exam
- Participants able to get pregnant must use effective barrier birth control throughout the study.
- During the first 3 weeks, participants will wear an estrogen patch. It is 1x2 inches and will be replaced every 3 days.
- For the next 3 weeks, participants will take 3 study capsules every morning. They will not know if they get the study drug or placebo.
- Some participants will also take a progesterone-like drug for 1 week at the end of the medication phase of the study.
- Participants will have 9 one-hour study visits. They will have blood samples and vital signs taken. They will answer questions about mood and behavior symptoms.
- Participants will keep a daily log of these symptoms.
- Participants will have 2 transvaginal ultrasounds. A probe is temporarily placed 2-3 inches into the vaginal canal and sound waves are used to create pictures of the lining of the uterus.
- Participants will have a final visit 4 weeks after stopping the study drug. They will answer questions about mood and side effects.
Read the detailed description
OBJECTIVE:
Depression risk increases during the perimenopause, and depression is cited as a primary reason for resuming menopausal hormone therapy (HT). Community-based epidemiologic studies document a 1.5-3 fold greater risk of first onset and recurrent depressions in women during the perimenopause compared with those who are premenopausal (or who are several years postmenopausal). Observational studies report the emergence of depressive symptoms after the discontinuation of HT in 5-10% of women. The role of estradiol (E2) - either declining or low levels - in the precipitation of perimenopausal depression (PMD) is unknown, largely due to the associational and indirect nature of the evidence linking ovarian function and depression. In study 03-M-0175, our results demonstrated that estradiol withdrawal was associated with a significant increase in depressive symptoms in those women with a past depression during the perimenopause. Of note, the effects of estradiol primarily occur through activation of two receptor subtypes, often with opposing outcomes: estrogen receptor (ER) alpha, and ER beta. Therefore, in this protocol, we examined the ability of a selective ER beta agonist (LY500307) to prevent estradiol withdrawal- induced mood symptoms in women with past perimenopausal depression. We focused on ER beta because the beta estrogen receptor is reported to mediate the effects of estradiol on the serotonergic system and mediate the antidepressant-like effects of estradiol in the forced-swim test. Moreover, selective agonists of estrogen receptor beta have been demonstrated to attenuate the behavioral and hypothalamic-pituitary-adrenal (HPA) axis response to stress.
Our objective is to examine the specific role of estrogen receptor beta in the effects of estrogen withdrawal in women with a past perimenopause-related depression. Results of this study will determine the role of ER beta in estradiol withdrawal-induced mood symptoms and can provide preliminary data to support the efficacy and safety of this compound as a treatment for depression during the perimenopausal transition.
STUDY POPULATION:
Healthy, non-depressed postmenopausal women, ages 45 to 65, with a well-documented past perimenopause-related depression (within 12 years) and whose mood systems got better with estradiol
DESIGN:
The medication phase of this study is a seven-week randomized, double blind, placebo controlled study and there is a four week follow-up evaluation phase to monitor all women for the emergence of adverse effects post-medication exposure. Participants will have weekly outpatient visits, weekly blood draws and will also complete daily symptom rating scales. The study involves a three week baseline phase in which all women receive open label (OL) estradiol therapy (ET) at a dose of 100 micrograms per day by transdermal skin patch, after which all women receive three weeks of double blind (DB) medication (i.e., LY500307 [at a daily dose of either 25 mg or 75 mg] or placebo). All participants will receive three capsules of LY500307 or placebo each morning consisting of the following formulations: 1) women randomized to 75 mg LY500307 will receive three capsules each containing 25 mg LY500307; 2) women randomized to 25 mg LY500307 will receive one capsule containing 25 mg LY500307 and two capsules of placebo; and 3) women randomized to placebo will receive three capsules each containing placebo. Then, in non-menstruating women (i.e., the absence of reported menstrual bleeding of greater than 1-2 days during the double blind phase of this study), the double blind phase will be followed by one week of Provera to precipitate a progestin-induced menses. The week of Provera is not a research-related intervention but is clinically-indicated to induce endometrial shedding that will eliminate potentially abnormal endometrial tissue consequent to the three weeks of unopposed estradiol exposure.
- Conditions
- Perimenopause-Related Depression
- Being tested
- Estradiol, ER Beta Agonist, Placebo, Provera
- Keywords
- Perimenopause-related depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Estradiol patch 0.1 mg transdermal every three days for three weeks
ER Beta AgonistDrug
Also called LY500307
Lilly Compound LY500307, a selective estrogen receptor (ER) beta agonist
PlaceboOther
Placebo orally once daily
ProveraDrug
Provera 5 mg orally once a day for one week after completion of randomization
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: High dose LY500307 compound | Experimental | Female participants received open label estradiol 0.1mg transdermal patch per day for three weeks. Then participants received LY500307 compound 75mg orally once per day for three weeks under double blind conditions. Participants with a uterus received Provera 5mg orally once a day for one week after completion of randomization. Receives: Drug: Estradiol; Drug: ER Beta Agonist; Drug: Provera |
| Arm 2: Low dose LY500307 compound | Active comparator | Female participants received open label estradiol 0.1mg transdermal patch per day for three weeks. Then participants received a combination of LY500307 compound 25mg and placebo orally once per day for three weeks under double blind conditions. Participants with a uterus received Provera 5mg orally once a day for one week after completion of randomization. Receives: Drug: Estradiol; Drug: ER Beta Agonist; Other: Placebo; Drug: Provera |
| Arm 3: Placebo | Placebo comparator | Female participants received open label estradiol 0.1mg transdermal patch per day for three weeks. Then participants received placebo orally once per day for three weeks under double blind conditions. Participants with a uterus received Provera 5mg orally once a day for one week after completion of randomization. Receives: Drug: Estradiol; Other: Placebo; Drug: Provera |
What is being measured
The primary outcome is the main question the study is designed to answer.
Center for Epidemiologic Studies-Depression (CES-D) Scale Mean Total Score
Center for Epidemiologic Studies-Depression (CES-D) Scale is a 20-item questionnaire that asks participants to rate how often over the past week they experienced symptoms associated with depression. Each item is rated from 0 to 3 (0 = Rarely or None of the Time, 1 = Some or Little of the Time, 2 = Moderately or Much of the time, 3 = Most or Almost All the Time). Total scores range from 0 to 60, with high scores indicating greater depressive symptoms. CES-D scores >8 and <16 is consistent with subsyndromal depression. CES-D scores > 16 are consistent with clinically significant depressive symptoms of at least moderate severity. Participants completed the CES-D at baseline and every week for six weeks during each of the study phases (open label estradiol patch, double blind placebo or LY500307 compound). Analysis was calculated as the mean of scores for baseline (week 0) and weekly through week six (6).
Measured: Baseline, then weekly through end of week six
Hamilton Rating Scale of Depression (HRSD) Mean Total Score
The Hamilton Rating Scale of Depression (HRSD) is a 21-item scale used by clinicians to assess the severity of depressive symptoms administered through a structured interview. The HRSD contains 21 items, but four questions are not added to the numerical total score. The first 17 items are scored on a 3 (0-2) or 5 (0-4) point scale, with total score range between 0 and 52. Higher score indicates greater depressive symptom. Scores of 0-7 are considered normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression. Participants completed the HRSD at baseline and every week for six weeks during each of the study phases (open label estradiol patch, double blind placebo or LY500307 compound). Analysis was calculated as the mean of scores for baseline (week 0) and weekly through week six (6).
Measured: Baseline, then weekly through end of week six
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2018
- Study start23 May 2019
- Primary completion9 Sep 2024
- Study completion9 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Perimenopause-Related DepressionStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 74 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
- NCT03689543
- Sponsor's protocol ID
- 180144
- Other IDs
- 18-M-0144
- Status last verified
- 15 Aug 2025
- First submitted
- 26 Sep 2018
- Last updated
- 16 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared with database of Genotypes and Phenotypes (dbGaP), Biomedical Translational Research Information System (BTRIS) and NIMH Data Archive as determined by the Principal Investigator.
Publications
Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch Gen Psychiatry. 2006 Apr;63(4):385-90. doi: 10.1001/archpsyc.63.4.385.
PubMed 16585467Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006 Apr;63(4):375-82. doi: 10.1001/archpsyc.63.4.375.
PubMed 16585466Freeman EW. Associations of depression with the transition to menopause. Menopause. 2010 Jul;17(4):823-7. doi: 10.1097/gme.0b013e3181db9f8b.
PubMed 20531231
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of an ER Beta Agonist (Lilly Compound LY500307) on Estradiol-withdrawal-induced Mood Symptoms in Women With Past Perimenopausal Depression
- ClinicalTrials.gov ID
- NCT03689543
- Acronym / sponsor ID
- 180144
- Conditions
- Perimenopause-Related Depression
- Keywords
- Perimenopause-related depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 23 May 2019 (actual)
- Primary completion
- 9 Sep 2024 (actual)
- Study completion
- 9 Sep 2024 (actual)
- First posted
- 28 Sep 2018 (actual)
- Results
- Posted 16 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Our previous studies have found that women who had depression during the perimenopause may have mood symptoms again if they stop estrogen therapy. Estrogen acts in the brain and other tissues by binding to estrogen receptors. There are two main types of estrogen receptors. They are estrogen receptor alpha and beta. Several studies have shown that estrogen receptor beta may play an important role in anxiety- and depressive-like behaviors in animals.
Objectives:
To examine a possible mechanism mediating the effects of estradiol-withdrawal on mood symptoms in asymptomatic postmenopausal women with a past perimenopausal depression. To evaluate the efficacy and safety of a selective estrogen receptor (ER) beta agonist (Lilly Compound LY500307) to prevent estradiol withdrawal-induced mood symptoms.
Eligibility:
Healthy, non-depressed postmenopausal women, ages 45 to 65, with a well-documented past perimenopause-related depression (within 12 years) and whose mood systems got better with estradiol
Design:
Participants will be screened with:
Medical history
Physical exam
Blood tests
Psychiatric interview
Gynecological exam
- Participants able to get pregnant must use effective barrier birth control throughout the study.
- During the first 3 weeks, participants will wear an estrogen patch. It is 1x2 inches and will be replaced every 3 days.
- For the next 3 weeks, participants will take 3 study capsules every morning. They will not know if they get the study drug or placebo.
- Some participants will also take a progesterone-like drug for 1 week at the end of the medication phase of the study.
- Participants will have 9 one-hour study visits. They will have blood samples and vital signs taken. They will answer questions about mood and behavior symptoms.
- Participants will keep a daily log of these symptoms.
- Participants will have 2 transvaginal ultrasounds. A probe is temporarily placed 2-3 inches into the vaginal canal and sound waves are used to create pictures of the lining of the uterus.
- Participants will have a final visit 4 weeks after stopping the study drug. They will answer questions about mood and side effects.
Detailed description
OBJECTIVE:
Depression risk increases during the perimenopause, and depression is cited as a primary reason for resuming menopausal hormone therapy (HT). Community-based epidemiologic studies document a 1.5-3 fold greater risk of first onset and recurrent depressions in women during the perimenopause compared with those who are premenopausal (or who are several years postmenopausal). Observational studies report the emergence of depressive symptoms after the discontinuation of HT in 5-10% of women. The role of estradiol (E2) - either declining or low levels - in the precipitation of perimenopausal depression (PMD) is unknown, largely due to the associational and indirect nature of the evidence linking ovarian function and depression. In study 03-M-0175, our results demonstrated that estradiol withdrawal was associated with a significant increase in depressive symptoms in those women with a past depression during the perimenopause. Of note, the effects of estradiol primarily occur through activation of two receptor subtypes, often with opposing outcomes: estrogen receptor (ER) alpha, and ER beta. Therefore, in this protocol, we examined the ability of a selective ER beta agonist (LY500307) to prevent estradiol withdrawal- induced mood symptoms in women with past perimenopausal depression. We focused on ER beta because the beta estrogen receptor is reported to mediate the effects of estradiol on the serotonergic system and mediate the antidepressant-like effects of estradiol in the forced-swim test. Moreover, selective agonists of estrogen receptor beta have been demonstrated to attenuate the behavioral and hypothalamic-pituitary-adrenal (HPA) axis response to stress.
Our objective is to examine the specific role of estrogen receptor beta in the effects of estrogen withdrawal in women with a past perimenopause-related depression. Results of this study will determine the role of ER beta in estradiol withdrawal-induced mood symptoms and can provide preliminary data to support the efficacy and safety of this compound as a treatment for depression during the perimenopausal transition.
STUDY POPULATION:
Healthy, non-depressed postmenopausal women, ages 45 to 65, with a well-documented past perimenopause-related depression (within 12 years) and whose mood systems got better with estradiol
DESIGN:
The medication phase of this study is a seven-week randomized, double blind, placebo controlled study and there is a four week follow-up evaluation phase to monitor all women for the emergence of adverse effects post-medication exposure. Participants will have weekly outpatient visits, weekly blood draws and will also complete daily symptom rating scales. The study involves a three week baseline phase in which all women receive open label (OL) estradiol therapy (ET) at a dose of 100 micrograms per day by transdermal skin patch, after which all women receive three weeks of double blind (DB) medication (i.e., LY500307 [at a daily dose of either 25 mg or 75 mg] or placebo). All participants will receive three capsules of LY500307 or placebo each morning consisting of the following formulations: 1) women randomized to 75 mg LY500307 will receive three capsules each containing 25 mg LY500307; 2) women randomized to 25 mg LY500307 will receive one capsule containing 25 mg LY500307 and two capsules of placebo; and 3) women randomized to placebo will receive three capsules each containing placebo. Then, in non-menstruating women (i.e., the absence of reported menstrual bleeding of greater than 1-2 days during the double blind phase of this study), the double blind phase will be followed by one week of Provera to precipitate a progestin-induced menses. The week of Provera is not a research-related intervention but is clinically-indicated to induce endometrial shedding that will eliminate potentially abnormal endometrial tissue consequent to the three weeks of unopposed estradiol exposure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1: High dose LY500307 compound | Experimental | Drug: Estradiol, Drug: ER Beta Agonist, Drug: ProveraFemale participants received open label estradiol 0.1mg transdermal patch per day for three weeks. Then participants received LY500307 compound 75mg orally once per day for three weeks under double blind conditions. Participants with a uterus received Provera 5mg orally once a day for one week after completion of randomization. |
| Arm 2: Low dose LY500307 compound | Active comparator | Drug: Estradiol, Drug: ER Beta Agonist, Other: Placebo, Drug: ProveraFemale participants received open label estradiol 0.1mg transdermal patch per day for three weeks. Then participants received a combination of LY500307 compound 25mg and placebo orally once per day for three weeks under double blind conditions. Participants with a uterus received Provera 5mg orally once a day for one week after completion of randomization. |
| Arm 3: Placebo | Placebo comparator | Drug: Estradiol, Other: Placebo, Drug: ProveraFemale participants received open label estradiol 0.1mg transdermal patch per day for three weeks. Then participants received placebo orally once per day for three weeks under double blind conditions. Participants with a uterus received Provera 5mg orally once a day for one week after completion of randomization. |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Women with a past perimenopause-related depression (within 12 years). 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 Diagnostic and Statistical Manual (DSM)-V (SCID)) at midlife in association with menstrual cycle irregularity (and possibly hot flushes and/or vaginal dryness) and in whom menopausal hormone therapy was reported to improve their depression at any time within the prior twelve years. All women participating in this protocol will be screened with psychiatric, medical, and reproductive evaluations to confirm they are in good medical health.
- Age 45 to 65
- Medication free (including no mood stabilizers, no sleep medication) except for the following: women on menopausal hormone therapy who will discontinue these medications at the start of this study and have their hormone therapy replaced with estradiol 100mcg per day (as described below), women who are on stable doses of thyroid replacement for at least six months prior to study enrollment, or women who occasionally take non-steroidal anti-inflammatory drugs [NSAIDs] or allergy medications (although we will ask women to minimize the use of these medications during the study).
- Subjects must have consent capacity
Key exclusion criteria (13 listed)
- The following conditions will constitute contraindications to participate in this protocol:
- Any current Axis 1 psychiatric illness or any clinically significant sleep disorder;
- Women with histories of hormone replacement therapy-induced dysphoria due to either the estrogen or the progesterone components of their hormone replacement;
- Past history of major depression with suicidal ideation;
- History of ischemic cardiac disease, pulmonary embolism, or thrombophlebitis;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EstradiolEstradiol patch 0.1 mg transdermal every three days for three weeks | Drug | Arm 1: High dose LY500307 compound, Arm 2: Low dose LY500307 compound, Arm 3: Placebo |
| ER Beta AgonistAlso: LY500307Lilly Compound LY500307, a selective estrogen receptor (ER) beta agonist | Drug | Arm 1: High dose LY500307 compound, Arm 2: Low dose LY500307 compound |
| PlaceboPlacebo orally once daily | Other | Arm 2: Low dose LY500307 compound, Arm 3: Placebo |
| ProveraProvera 5 mg orally once a day for one week after completion of randomization | Drug | Arm 1: High dose LY500307 compound, Arm 2: Low dose LY500307 compound, Arm 3: Placebo |
Primary outcome
Center for Epidemiologic Studies-Depression (CES-D) Scale Mean Total Score
Time frame: Baseline, then weekly through end of week six
Center for Epidemiologic Studies-Depression (CES-D) Scale is a 20-item questionnaire that asks participants to rate how often over the past week they experienced symptoms associated with depression. Each item is rated from 0 to 3 (0 = Rarely or None of the Time, 1 = Some or Little of the Time, 2 = Moderately or Much of the time, 3 = Most or Almost All the Time). Total scores range from 0 to 60, with high scores indicating greater depressive symptoms. CES-D scores >8 and <16 is consistent with subsyndromal depression. CES-D scores > 16 are consistent with clinically significant depressive symptoms of at least moderate severity. Participants completed the CES-D at baseline and every week for six weeks during each of the study phases (open label estradiol patch, double blind placebo or LY500307 compound). Analysis was calculated as the mean of scores for baseline (week 0) and weekly through week six (6).
Hamilton Rating Scale of Depression (HRSD) Mean Total Score
Time frame: Baseline, then weekly through end of week six
The Hamilton Rating Scale of Depression (HRSD) is a 21-item scale used by clinicians to assess the severity of depressive symptoms administered through a structured interview. The HRSD contains 21 items, but four questions are not added to the numerical total score. The first 17 items are scored on a 3 (0-2) or 5 (0-4) point scale, with total score range between 0 and 52. Higher score indicates greater depressive symptom. Scores of 0-7 are considered normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression. Participants completed the HRSD at baseline and every week for six weeks during each of the study phases (open label estradiol patch, double blind placebo or LY500307 compound). Analysis was calculated as the mean of scores for baseline (week 0) and weekly through week six (6).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16585467Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch Gen Psychiatry. 2006 Apr;63(4):385-90. doi: 10.1001/archpsyc.63.4.385.
- Background: PubMed 16585466Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006 Apr;63(4):375-82. doi: 10.1001/archpsyc.63.4.375.
- Background: PubMed 20531231Freeman EW. Associations of depression with the transition to menopause. Menopause. 2010 Jul;17(4):823-7. doi: 10.1097/gme.0b013e3181db9f8b.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data will be shared with database of Genotypes and Phenotypes (dbGaP), Biomedical Translational Research Information System (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?
A Phase 2 study testing Estradiol, ER Beta Agonist and Provera in people with Perimenopause-Related Depression, 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 4 inclusion and 13 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 Sep 2025. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Center for Epidemiologic Studies-Depression (CES-D) Scale Mean Total Score (time frame: Baseline, then weekly through end of week six). The study lists 2 primary outcomes in all. 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 NCT03689543, which also lists 3 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 Sep 2025.