Osteoporosis RiskPhase 4REBELNCT05903820
Rhythmic Estradiol and Bone Health
A Phase 4 study testing Estradiol patch and Progesterone in people with Osteoporosis Risk and Menopause, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
The goal of this randomized-controlled trial is to compare the effect of rhythmic estrogen treatment to continuous estrogen treatment on bone turnover in healthy postmenopausal women. Read more about this study
- Who is it for?
- Ages 45 to 60 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis Risk, Menopause
- What is being tested?
- Estradiol patch and Progesterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteNetherlands
- Study dates
- 19 Jul 2023to 28 Oct 2024
- Phase
- Phase 4
- 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 60 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Postmenopausal, defined as final menstrual cycle more than 1 years prior to inclusion and FSH>30 IU/L
- Final menstrual cycle < 10 years prior to inclusion
Who cannot join
- Contra-indication for estrogen and/or progesterone therapy
- First-grade family member with inherited thrombophilia or history of venous thromboembolism under the age of 60 years
- Hysterectomy
- Premature menopause (menopause age <40 years)
- Known hypersensitivity to the excipients in the estradiol patch or progesterone capsule
- Hormonal contraception or hormone replacement therapy use (estradiol with or without progesterone) in the past 12 months
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- Presence or history of any clinically relevant metabolic, endocrinological, hepatic, renal, cardiovascular, gastrointestinal, or respiratory conditions, history of bone disease or bone marrow disease, known vitamin D deficiency (25-OH vitamin D <30 nmol/L)
- Recent fracture (<12 months)
- BMI <20 or BMI ≥30
- Use of drugs including herbal medicine known to affect bone metabolism (e.g. corticosteroids) or to interfere with cytochrome P450 enzyme (CYP) pathways. Exceptions are occasional use of paracetamol, ibuprofen, acetylsalicylic acid or topical medication
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Low-dose Rhythmic 17-β-estradiol Administration on Bone Turnover in Postmenopausal Women
The goal of this randomized-controlled trial is to compare the effect of rhythmic estrogen treatment to continuous estrogen treatment on bone turnover in healthy postmenopausal women. The main question it aims to answer are:
- Does rhythmic estrogen lead to increased bone formation in healthy postmenopausal women, compared to continuous estrogen?
Read more
Participants will receive one of the following treatments for a duration of 16 weeks:
- Rhythmic estradiol: Alternating 4-week cycles consisting of transdermal 17-β-estradiol 25μg/24hrs for two weeks, followed by two weeks of transdermal 17-β-estradiol 50μg/24hrs. Estradiol therapy will be combined with continuous oral micronized progesterone 100mg once daily.
- Low-dose continuous estradiol: Continuous transdermal 17-β-estradiol 25μg/24hrs, combined with continuous oral micronized progesterone 100mg daily once daily.
- Standard-dose continuous estradiol: Continuous transdermal 17-β-estradiol 50μg/24hrs, combined with continuous oral micronized progesterone 100mg daily once daily.
If there is a comparison group: Researchers will compare rhythmic estradiol to continuous estradiol to see if rhythmic estradiol improves bone formation in postmenopausal women.
- Conditions
- Osteoporosis Risk, Menopause
- Being tested
- Estradiol patch, Progesterone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol patchDrug
Also called transdermal17-beta-estradiol
Transdermal patch of estradiol
ProgesteroneDrug
Also called micronized progesterone
Oral progesterone capsules 100mg/day
| Study group | Role | What they receive |
|---|---|---|
| Continuous estradiol 50 mcg/day | Active comparator | The continuous standard-dose 17-β-estradiol group will receive the standard therapy for prevention of osteoporosis. A transdermal patch that releases 50ug/24 hrs of 17-β-estradiol will be administered continuously during the 16 weeks of treatment. Receives: Drug: Estradiol patch; Drug: Progesterone |
| Continuous estradiol 25 mcg/day | Active comparator | The continuous low-dose 17-β-estradiol group will receive a transdermal patch that releases 25ug/24 hrs of 17-β-estradiol administered continuously during the 16 weeks of treatment. Receives: Drug: Estradiol patch; Drug: Progesterone |
| Rhythmic estradiol 25-50 mcg/day | Experimental | The rhythmic 17-β-estradiol group will receive a transdermal patch for two weeks that releases 25ug/24hrs of 17-β-estradiol, and a patch of 50ug/24hrs for 2 weeks in each 4-week cycle. Receives: Drug: Estradiol patch; Drug: Progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum P1NP
The interaction between treatment and time on serum P1NP
Measured: The difference in P1NP between treatment arms after 2 weeks
Serum P1NP
The interaction between treatment and time on serum P1NP
Measured: The difference in P1NP between treatment arms after 4 weeks
Serum P1NP
The interaction between treatment and time on serum P1NP
Measured: The difference in P1NP between treatment arms after 6 weeks
Serum P1NP
The interaction between treatment and time on serum P1NP
Measured: The difference in P1NP between treatment arms after 8 weeks
Serum P1NP
The interaction between treatment and time on serum P1NP
Measured: The difference in P1NP between treatment arms after 10 weeks
Serum P1NP
The interaction between treatment and time on serum P1NP
Measured: The difference in P1NP between treatment arms after 12 weeks
Serum P1NP
The interaction between treatment and time on serum P1NP
Measured: The difference in P1NP between treatment arms after 14 weeks
Serum P1NP
The interaction between treatment and time on serum P1NP
Measured: The difference in P1NP between treatment arms after 16 weeks
Secondary outcomes (8)
Serum CTX
The interaction between treatment and time on serum CTX
Measured: The difference in CTX between treatment arms after 2 weeks
Serum CTX
The interaction between treatment and time on serum CTX
Measured: The difference in CTX between treatment arms after 4 weeks
Serum CTX
The interaction between treatment and time on serum CTX
Measured: The difference in CTX between treatment arms after 6 weeks
Serum CTX
The interaction between treatment and time on serum CTX
Measured: The difference in CTX between treatment arms after 8 weeks
Serum CTX
The interaction between treatment and time on serum CTX
Measured: The difference in CTX between treatment arms after 10 weeks
Serum CTX
The interaction between treatment and time on serum CTX
Measured: The difference in CTX between treatment arms after 12 weeks
Serum CTX
The interaction between treatment and time on serum CTX
Measured: The difference in CTX treatment arms after 14 weeks
Serum CTX
The interaction between treatment and time on serum CTX
Measured: The difference in CTX between treatment arms after 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start19 Jul 2023
- Primary completion21 Oct 2024
- Study completion28 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoporosis RiskStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter H. Bisschop, Amsterdam UMC, location AMC
- Investigators
- Peter M Bisschop, Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05903820
- Sponsor's protocol ID
- NL83336.018.23
- Acronym
- REBEL
- Status last verified
- Jul 2024
- First submitted
- 15 May 2023
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Low-dose Rhythmic 17-β-estradiol Administration on Bone Turnover in Postmenopausal Women
- ClinicalTrials.gov ID
- NCT05903820
- Acronym / sponsor ID
- REBEL / NL83336.018.23
- Conditions
- Osteoporosis Risk, Menopause
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 19 Jul 2023 (actual)
- Primary completion
- 21 Oct 2024 (actual)
- Study completion
- 28 Oct 2024 (actual)
- First posted
- 15 Jun 2023 (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.
The goal of this randomized-controlled trial is to compare the effect of rhythmic estrogen treatment to continuous estrogen treatment on bone turnover in healthy postmenopausal women. The main question it aims to answer are:
- Does rhythmic estrogen lead to increased bone formation in healthy postmenopausal women, compared to continuous estrogen?
Participants will receive one of the following treatments for a duration of 16 weeks:
- Rhythmic estradiol: Alternating 4-week cycles consisting of transdermal 17-β-estradiol 25μg/24hrs for two weeks, followed by two weeks of transdermal 17-β-estradiol 50μg/24hrs. Estradiol therapy will be combined with continuous oral micronized progesterone 100mg once daily.
- Low-dose continuous estradiol: Continuous transdermal 17-β-estradiol 25μg/24hrs, combined with continuous oral micronized progesterone 100mg daily once daily.
- Standard-dose continuous estradiol: Continuous transdermal 17-β-estradiol 50μg/24hrs, combined with continuous oral micronized progesterone 100mg daily once daily.
If there is a comparison group: Researchers will compare rhythmic estradiol to continuous estradiol to see if rhythmic estradiol improves bone formation in postmenopausal women.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Continuous estradiol 50 mcg/day | Active comparator | Drug: Estradiol patch, Drug: ProgesteroneThe continuous standard-dose 17-β-estradiol group will receive the standard therapy for prevention of osteoporosis. A transdermal patch that releases 50ug/24 hrs of 17-β-estradiol will be administered continuously during the 16 weeks of treatment. |
| Continuous estradiol 25 mcg/day | Active comparator | Drug: Estradiol patch, Drug: ProgesteroneThe continuous low-dose 17-β-estradiol group will receive a transdermal patch that releases 25ug/24 hrs of 17-β-estradiol administered continuously during the 16 weeks of treatment. |
| Rhythmic estradiol 25-50 mcg/day | Experimental | Drug: Estradiol patch, Drug: ProgesteroneThe rhythmic 17-β-estradiol group will receive a transdermal patch for two weeks that releases 25ug/24hrs of 17-β-estradiol, and a patch of 50ug/24hrs for 2 weeks in each 4-week cycle. |
Who may qualify
- Ages
- 45 to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Postmenopausal, defined as final menstrual cycle more than 1 years prior to inclusion and FSH>30 IU/L
- Final menstrual cycle < 10 years prior to inclusion
Key exclusion criteria (10 listed)
- Contra-indication for estrogen and/or progesterone therapy
- First-grade family member with inherited thrombophilia or history of venous thromboembolism under the age of 60 years
- Hysterectomy
- Premature menopause (menopause age <40 years)
- Known hypersensitivity to the excipients in the estradiol patch or progesterone capsule
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 |
|---|---|---|
| Estradiol patchAlso: transdermal17-beta-estradiolTransdermal patch of estradiol | Drug | Continuous estradiol 25 mcg/day, Continuous estradiol 50 mcg/day, Rhythmic estradiol 25-50 mcg/day |
| ProgesteroneAlso: micronized progesteroneOral progesterone capsules 100mg/day | Drug | Continuous estradiol 25 mcg/day, Continuous estradiol 50 mcg/day, Rhythmic estradiol 25-50 mcg/day |
Primary outcome
Serum P1NP
Time frame: The difference in P1NP between treatment arms after 2 weeks
The interaction between treatment and time on serum P1NP
Serum P1NP
Time frame: The difference in P1NP between treatment arms after 4 weeks
The interaction between treatment and time on serum P1NP
Serum P1NP
Time frame: The difference in P1NP between treatment arms after 6 weeks
The interaction between treatment and time on serum P1NP
Serum P1NP
Time frame: The difference in P1NP between treatment arms after 8 weeks
The interaction between treatment and time on serum P1NP
Serum P1NP
Time frame: The difference in P1NP between treatment arms after 10 weeks
The interaction between treatment and time on serum P1NP
Serum P1NP
Time frame: The difference in P1NP between treatment arms after 12 weeks
The interaction between treatment and time on serum P1NP
Serum P1NP
Time frame: The difference in P1NP between treatment arms after 14 weeks
The interaction between treatment and time on serum P1NP
Serum P1NP
Time frame: The difference in P1NP between treatment arms after 16 weeks
The interaction between treatment and time on serum P1NP
8 secondary outcomes
Serum CTX
Time frame: The difference in CTX between treatment arms after 2 weeks
Serum CTX
Time frame: The difference in CTX between treatment arms after 4 weeks
Serum CTX
Time frame: The difference in CTX between treatment arms after 6 weeks
Serum CTX
Time frame: The difference in CTX between treatment arms after 8 weeks
Serum CTX
Time frame: The difference in CTX between treatment arms after 10 weeks
Serum CTX
Time frame: The difference in CTX between treatment arms after 12 weeks
Serum CTX
Time frame: The difference in CTX treatment arms after 14 weeks
Serum CTX
Time frame: The difference in CTX between treatment arms after 16 weeks
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 Oct 2026.
- Individual participant dataSharing planned: No
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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 M Bisschop principal investigator
Amsterdam UMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Estradiol patch and Progesterone in people with Osteoporosis Risk and Menopause, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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 2 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 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 Netherlands. 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.
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?
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?
Serum P1NP (time frame: The difference in P1NP between treatment arms after 2 weeks). The study lists 8 primary outcomes in all. 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 16 Oct 2026.