MenopausePhase 4NCT06306404
Sleeping Through Menopause
A Phase 4 study testing Estrogens and Progestogens and Cognitive behavioral therapy for insomnia (CBTi), and circadian rhythm therapy in people with Menopause and Insomnia, run by VU University of Amsterdam.
Trial summary
Sleepless nights during the menopausal period: what treatment works? About half of the women have trouble sleeping during the years around the menopause, the perimenopause. This is a period characterised by fluctuating sex hormones. Read more about this study
- Who is it for?
- Ages 40 to 55 years, women only
- What is being tested?
- Estrogens and Progestogens and Cognitive behavioral therapy for insomnia (CBTi), and circadian rhythm therapy
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2025to 1 Jan 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age between 40-55 years old
- Insomnia severity index score =>10
- Green Climacteric Score =>13
- Self-considered capability of completing online questionnaires and diaries in Dutch/English
- Presence of a menstruation (whether regular or not) and the last menstruation must be less than 12 months ago
Who cannot join
- CBTi treatment in past year
- Bipolar disorder or psychotic disorder
- Contra-indication for Menopausal Hormone Therapy
- Alcohol or drugs dependency (scores of ≥ 20 on the AUDIT and ≥25 on the DUDIT)
- Women using thyroid medication, lamotrigine, aromatase, tamoxifen, because of interaction effects with MHT
- Use of drugs known to interfere with cytochrome P450 enzyme (CYP) 3A4
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- Known hypersensitivity to the excipients in the estradiol patch: acrylate copolymer, polyethylene terephthalate, alfa-tocopherol, soy allergy (component of progesterone capsule).
- All women on hormonal contraceptives will be excluded.
- All women already on MHT will be excluded.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: The Role of Online Sleep Intervention and Hormone Therapy on Sleep, Climacteric Symptoms and Mood in the Perimenopause
Sleepless nights during the menopausal period: what treatment works? About half of the women have trouble sleeping during the years around the menopause, the perimenopause. This is a period characterised by fluctuating sex hormones. Insomnia during the perimenopause can make women more likely to develop more severe climacteric symptoms and other mental health problems. It is therefore important to find the right treatment to treat insomnia. Currently, we do not know what the best treatment is for managing insomnia during the perimenopause. The Sleeping Through Menopause study is the first to evaluate, side by side, two interventions: menopausal hormone therapy (MHT) and combined cognitive behavioural and circadian therapy for insomnia (CBCTi). The study aims to evaluate how well these treatments alleviate insomnia and climacteric symptoms including hot flashes, and by doing so alleviate or prevent other mental health issues. It will also explore how personal factors might affect treatment success.
In the study, 222 women with both insomnia and climacteric symptoms will be randomly assigned to one of four groups: MHT, CBCTi, a combination of both MHT and CBCTi, or a group with no treatment. The main goal is to evaluate how each treatment alleviates insomnia after 8 and 15 weeks. Secondary outcomes are sleep quality, climacteric symptoms including hot flashes, mental health, and daily functioning.
This study will help us understand the best ways to treat sleep problems during menopause and whether better sleep can improve other mental health and menopausal symptoms as well.
Read the detailed description
The perimenopause is known as a vulnerable period for some women, with noticeable somatic and psychological issues. Aside from climacteric symptoms, insomnia and depression are common. About half of women during the peri-menopausal period experience sleep problems like problems falling asleep, awakening during the night and being unable to return to sleep. This is often attributed to vasomotor symptoms, but this is not the only reason of poor sleep. Also, the peri-menopausal period is a critical time for the occurrence of new onset and recurrent depressions. It has been suggested that fluctuations in estradiol may increase the risk for depression by altering neuronal functions in the brain. But there are also indications that the risk for depression increases by indirect effects, such as the increase in insomnia. Poor sleep has increasingly been recognized as the key modifiable factor affecting mental issues like depression. While antidepressants and psychotherapies continue to be the treatments of choice for depression, and Cognitive Behavioral Therapy for sleep (CBTi) for insomnia, preclinical and clinical data support the benefits of estrogen-based therapies to improve mood, sleep and other menopause-related symptoms. Transdermal estradiol patches, which provide a stable release of estradiol and lead to more stable blood levels, have been suggested to have a positive effect on sleep and depressive symptoms in randomized controlled trials. However, it is currently unclear if the relation between improvement in mood and estradiol patches is mediated by improvement in sleep problems, and if the effect of estradiol patches on sleep problems is more effective during peri-menopause than the current evidence-based sleep interventions of CBTi, preferably in combination with Circadian Rhythm Support (CRS). The aim of the study is to pinpoint the determinants of complaints about sleep and mood and how they respond to Menopausal Hormone Treatment (MHT) with and without the addition of a guided eHealth sleep intervention that combines CBTi + CRS.
Measurements will be conducted at baseline (T0), 2 months (T1) and 4 months (T3), with questionnaires, sleep measurements (EEG sleepband and actigraph) and skin conductance (to measure hot flushes). Participants will be recruited via www.slaapregister.nl and via OLVG outpatient clinic population of peri-menopausal women seeking help for climacteric complaints (like hot flushes, feeling bloated, increase in weight), including sleep problems. The participants are adults between 40-55 years old, with an Insomnia Severity Index score ≥10 and Climacteric Green Scale score ≥ 13.They have the self-considered capability to complete online questionnaires and diaries in Dutch.
The intervention will be MHT (estradiol transdermal patches 50 mcg (Systen), in combination with 200 mg progesterone (Utrogestan tablets for 2 weeks, adjusted to the menstrual cycle to prevent endometrium carcinoma according to the international MHT guidelines), with and without the addition of a guided eHealth sleep intervention that combines CBTi + CRS.
- Being tested
- Estrogens and Progestogens, Cognitive behavioral therapy for insomnia (CBTi), and circadian rhythm therapy
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estrogens and ProgestogensDrug
Also called Hormone replacement therapy
Menopausal Hormone Therapy, formerly known as Hormone Replacement Therapy (HRT), is a medical treatment that involves the use of hormones to relieve the symptoms of menopause and to reduce the risk of certain long-term health conditions associated with menopause. Menopause is a natural biological process that occurs when a women's ovaries stop producing effects, and her estrogen and progesteron hormone levels subsequently decrease. MHT typically involves administration of a combination of sec steroids.
In this study MHT consists of estradiol transdermal patches (50 mcg (Systen), which provide a stable release of estradiol and lead to more stable blood levels. This is combined with 200 mg progesterone (Utrogestan tablets for 2 weeks) adjusted to the menstrual cycle to prevent endometrium carcinoma according to the international MHT guidelines.
Cognitive behavioral therapy for insomnia (CBTi), and circadian rhythm therapyBehavioural
CBTi is a guided, internet-based cognitive behavioral therapy program for insomnia, containing information and exercises on sleep. It consists of five online sessions:
- Psycho-education on sleep, disordered sleep and sleep hygiene (i.e. general guidelines about health and environmental factors influencing sleep),
- Sleep restriction (i.e. restrict time in bed to the average sleep time) and stimulus control training (i.e. reinforce association of bed with sleeping),
- Rumination and relaxation techniques,
- Cognitive restructuring (i.e. changing misconceptions about sleep),
- Relapse prevention.
| Study group | Role | What they receive |
|---|---|---|
| MHT | Experimental | Participants will receive the standard care menopausal hormone therapy. Receives: Drug: Estrogens and Progestogens |
| Sleep modules | Experimental | Participants will receive the sleep modules, which includes cognitive behavioral therapy for insomnia, and circadian rhythm therapy. |
| MHT and Sleep modules | Experimental | Participants will receive both the sleep modules, which includes cognitive behavioral therapy for insomnia, and circadian rhythm therapy, and the standard care menopausal hormone therapy. Receives: Drug: Estrogens and Progestogens; Behavioral: Cognitive behavioral therapy for insomnia (CBTi), and circadian rhythm therapy |
| No intervention | No intervention | The control group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome variable is the difference between the groups in the within-subject change in insomnia severity at T1 (2 months) and T2 (4 months) relative to T0 (baseline).
The Insomnia Severity Index (ISI) is composed of seven items that evaluate the severity of sleep disturbance during the past 2 weeks. Each item is rated on a five-point Likert scale and the total score indicates the severity of insomnia. The higher the more severe.
Measured: month 2 vs. month 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start1 Oct 2025 (estimated)
- Primary completion1 Oct 2029 (estimated)
- Study completion1 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MenopauseStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 222 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VU University of Amsterdam
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Birit Broekman, VU University of Amsterdam
- Investigators
- Birit Broekman, Prof., Principal investigator, OLVG and Amsterdam UMC, VUEus van Someren, Prof., Principal investigator, Netherlands Institute for Neuroscience
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06306404
- Sponsor's protocol ID
- 2024-512071-12-00
- Status last verified
- Aug 2025
- First submitted
- 5 Mar 2024
- Last updated
- 24 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Online Sleep Intervention and Hormone Therapy on Sleep, Climacteric Symptoms and Mood in the Perimenopause
- ClinicalTrials.gov ID
- NCT06306404
- Acronym / sponsor ID
- 2024-512071-12-00
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 222 participants (estimated)
- Lead sponsor
- VU University of AmsterdamUniversity, hospital or other
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- 1 Oct 2029 (estimated)
- Study completion
- 1 Jan 2030 (estimated)
- First posted
- 12 Mar 2024 (actual)
- 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.
Sleepless nights during the menopausal period: what treatment works? About half of the women have trouble sleeping during the years around the menopause, the perimenopause. This is a period characterised by fluctuating sex hormones. Insomnia during the perimenopause can make women more likely to develop more severe climacteric symptoms and other mental health problems. It is therefore important to find the right treatment to treat insomnia. Currently, we do not know what the best treatment is for managing insomnia during the perimenopause. The Sleeping Through Menopause study is the first to evaluate, side by side, two interventions: menopausal hormone therapy (MHT) and combined cognitive behavioural and circadian therapy for insomnia (CBCTi). The study aims to evaluate how well these treatments alleviate insomnia and climacteric symptoms including hot flashes, and by doing so alleviate or prevent other mental health issues. It will also explore how personal factors might affect treatment success.
In the study, 222 women with both insomnia and climacteric symptoms will be randomly assigned to one of four groups: MHT, CBCTi, a combination of both MHT and CBCTi, or a group with no treatment. The main goal is to evaluate how each treatment alleviates insomnia after 8 and 15 weeks. Secondary outcomes are sleep quality, climacteric symptoms including hot flashes, mental health, and daily functioning.
This study will help us understand the best ways to treat sleep problems during menopause and whether better sleep can improve other mental health and menopausal symptoms as well.
Detailed description
The perimenopause is known as a vulnerable period for some women, with noticeable somatic and psychological issues. Aside from climacteric symptoms, insomnia and depression are common. About half of women during the peri-menopausal period experience sleep problems like problems falling asleep, awakening during the night and being unable to return to sleep. This is often attributed to vasomotor symptoms, but this is not the only reason of poor sleep. Also, the peri-menopausal period is a critical time for the occurrence of new onset and recurrent depressions. It has been suggested that fluctuations in estradiol may increase the risk for depression by altering neuronal functions in the brain. But there are also indications that the risk for depression increases by indirect effects, such as the increase in insomnia. Poor sleep has increasingly been recognized as the key modifiable factor affecting mental issues like depression. While antidepressants and psychotherapies continue to be the treatments of choice for depression, and Cognitive Behavioral Therapy for sleep (CBTi) for insomnia, preclinical and clinical data support the benefits of estrogen-based therapies to improve mood, sleep and other menopause-related symptoms. Transdermal estradiol patches, which provide a stable release of estradiol and lead to more stable blood levels, have been suggested to have a positive effect on sleep and depressive symptoms in randomized controlled trials. However, it is currently unclear if the relation between improvement in mood and estradiol patches is mediated by improvement in sleep problems, and if the effect of estradiol patches on sleep problems is more effective during peri-menopause than the current evidence-based sleep interventions of CBTi, preferably in combination with Circadian Rhythm Support (CRS). The aim of the study is to pinpoint the determinants of complaints about sleep and mood and how they respond to Menopausal Hormone Treatment (MHT) with and without the addition of a guided eHealth sleep intervention that combines CBTi + CRS.
Measurements will be conducted at baseline (T0), 2 months (T1) and 4 months (T3), with questionnaires, sleep measurements (EEG sleepband and actigraph) and skin conductance (to measure hot flushes). Participants will be recruited via www.slaapregister.nl and via OLVG outpatient clinic population of peri-menopausal women seeking help for climacteric complaints (like hot flushes, feeling bloated, increase in weight), including sleep problems. The participants are adults between 40-55 years old, with an Insomnia Severity Index score ≥10 and Climacteric Green Scale score ≥ 13.They have the self-considered capability to complete online questionnaires and diaries in Dutch.
The intervention will be MHT (estradiol transdermal patches 50 mcg (Systen), in combination with 200 mg progesterone (Utrogestan tablets for 2 weeks, adjusted to the menstrual cycle to prevent endometrium carcinoma according to the international MHT guidelines), with and without the addition of a guided eHealth sleep intervention that combines CBTi + CRS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MHT | Experimental | Drug: Estrogens and ProgestogensParticipants will receive the standard care menopausal hormone therapy. |
| Sleep modules | Experimental | –Participants will receive the sleep modules, which includes cognitive behavioral therapy for insomnia, and circadian rhythm therapy. |
| MHT and Sleep modules | Experimental | Drug: Estrogens and Progestogens, Behavioral: Cognitive behavioral therapy for insomnia (CBTi), and circadian rhythm therapyParticipants will receive both the sleep modules, which includes cognitive behavioral therapy for insomnia, and circadian rhythm therapy, and the standard care menopausal hormone therapy. |
| No intervention | No intervention | –The control group. |
Who may qualify
- Ages
- 40 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age between 40-55 years old
- Insomnia severity index score =>10
- Green Climacteric Score =>13
- Self-considered capability of completing online questionnaires and diaries in Dutch/English
- Presence of a menstruation (whether regular or not) and the last menstruation must be less than 12 months ago
Key exclusion criteria (9 listed)
- CBTi treatment in past year
- Bipolar disorder or psychotic disorder
- Contra-indication for Menopausal Hormone Therapy
- Alcohol or drugs dependency (scores of ≥ 20 on the AUDIT and ≥25 on the DUDIT)
- Women using thyroid medication, lamotrigine, aromatase, tamoxifen, because of interaction effects with MHT
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 |
|---|---|---|
| Estrogens and ProgestogensAlso: Hormone replacement therapyMenopausal Hormone Therapy, formerly known as Hormone Replacement Therapy (HRT), is a medical treatment that involves the use of hormones to relieve the symptoms of menopause and to reduce the risk of certain long-term health conditions associated with menopause. Menopause is a natural biological process that occurs when a women's ovaries stop producing effects, and her estrogen and progesteron hormone levels subsequently decrease. MHT typically involves administration of a combination of sec steroids. In this study MHT consists of estradiol transdermal patches (50 mcg (Systen), which provide a stable release of estradiol and lead to more stable blood levels. This is combined with 200 mg progesterone (Utrogestan tablets for 2 weeks) adjusted to the menstrual cycle to prevent endometrium carcinoma according to the international MHT guidelines. | Drug | MHT, MHT and Sleep modules |
| Cognitive behavioral therapy for insomnia (CBTi), and circadian rhythm therapyCBTi is a guided, internet-based cognitive behavioral therapy program for insomnia, containing information and exercises on sleep. It consists of five online sessions: 1. Psycho-education on sleep, disordered sleep and sleep hygiene (i.e. general guidelines about health and environmental factors influencing sleep), 2. Sleep restriction (i.e. restrict time in bed to the average sleep time) and stimulus control training (i.e. reinforce association of bed with sleeping), 3. Rumination and relaxation techniques, 4. Cognitive restructuring (i.e. changing misconceptions about sleep), 5. Relapse prevention. | Behavioural | MHT and Sleep modules |
Primary outcome
The primary outcome variable is the difference between the groups in the within-subject change in insomnia severity at T1 (2 months) and T2 (4 months) relative to T0 (baseline).
Time frame: month 2 vs. month 4
The Insomnia Severity Index (ISI) is composed of seven items that evaluate the severity of sleep disturbance during the past 2 weeks. Each item is rated on a five-point Likert scale and the total score indicates the severity of insomnia. The higher the more severe.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2025.
- Individual participant dataSharing planned: Yes
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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.
Birit Broekman, Prof. principal investigator
OLVG and Amsterdam UMC, VU
Eus van Someren, Prof. principal investigator
Netherlands Institute for Neuroscience
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Estrogens and Progestogens and Cognitive behavioral therapy for insomnia (CBTi), and circadian rhythm therapy in people with Menopause and Insomnia, run by VU University of Amsterdam.
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 5 inclusion and 9 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: opening soon, as of the sponsor's last update on 24 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anne-Sophie Koning, Dr. (+31 20 566 5500, a.koning@nin.knaw.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome variable is the difference between the groups in the within-subject change in insomnia severity at T1 (2 months) and T2 (4 months) relative to T0 (baseline). (time frame: month 2 vs. month 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Aug 2025.