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Completed

NCT Number: NCT05903820

Rhythmic Estradiol and Bone Health

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.

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Key information

Conditions

Osteoporosis Risk Menopause

Age range

45 year–60 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Amsterdam UMC

Amsterdam, 1105 AZ, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

Estradiol patch

Drug

Transdermal patch of estradiol

Other names: transdermal17-beta-estradiol

Progesterone

Drug

Oral progesterone capsules 100mg/day

Other names: micronized progesterone

Primary outcomes

  1. Serum P1NP

    Time frame: The difference in P1NP between treatment arms after 2 weeks

    The interaction between treatment and time on serum P1NP

  2. Serum P1NP

    Time frame: The difference in P1NP between treatment arms after 4 weeks

    The interaction between treatment and time on serum P1NP

  3. Serum P1NP

    Time frame: The difference in P1NP between treatment arms after 6 weeks

    The interaction between treatment and time on serum P1NP

  4. Serum P1NP

    Time frame: The difference in P1NP between treatment arms after 8 weeks

    The interaction between treatment and time on serum P1NP

  5. Serum P1NP

    Time frame: The difference in P1NP between treatment arms after 10 weeks

    The interaction between treatment and time on serum P1NP

  6. Serum P1NP

    Time frame: The difference in P1NP between treatment arms after 12 weeks

    The interaction between treatment and time on serum P1NP

  7. Serum P1NP

    Time frame: The difference in P1NP between treatment arms after 14 weeks

    The interaction between treatment and time on serum P1NP

  8. Serum P1NP

    Time frame: The difference in P1NP between treatment arms after 16 weeks

    The interaction between treatment and time on serum P1NP

Secondary outcomes

  1. Serum CTX

    Time frame: The difference in CTX between treatment arms after 2 weeks

    The interaction between treatment and time on serum CTX

  2. Serum CTX

    Time frame: The difference in CTX between treatment arms after 4 weeks

    The interaction between treatment and time on serum CTX

  3. Serum CTX

    Time frame: The difference in CTX between treatment arms after 6 weeks

    The interaction between treatment and time on serum CTX

  4. Serum CTX

    Time frame: The difference in CTX between treatment arms after 8 weeks

    The interaction between treatment and time on serum CTX

  5. Serum CTX

    Time frame: The difference in CTX between treatment arms after 10 weeks

    The interaction between treatment and time on serum CTX

  6. Serum CTX

    Time frame: The difference in CTX between treatment arms after 12 weeks

    The interaction between treatment and time on serum CTX

  7. Serum CTX

    Time frame: The difference in CTX treatment arms after 14 weeks

    The interaction between treatment and time on serum CTX

  8. Serum CTX

    Time frame: The difference in CTX between treatment arms after 16 weeks

    The interaction between treatment and time on serum CTX

Other outcomes

  1. Fasting glucose

    Time frame: The difference between treatment arms in terms of change in fasting glucose after 16 weeks

    Change in fasting glucose

  2. Fasting insulin

    Time frame: The difference between treatment arms in terms of change in fasting insulin after 16 weeks

    Change in fasting insulin

  3. Fasting insulin insulin resistance (HOMA-IR), and post-OGTT outcomes from to baseline until 16 weeks of treatment.

    Time frame: The difference between treatment arms in terms of change in HOMA-IR after 16 weeks

    Change in fasting insulin

  4. Glucose levels after an oral glucose tolerance test (OGTT)

    Time frame: The difference between treatment arms in terms of change in post-OGTT glucose values after 16 weeks

    Change in glucose levels 2 hours after an oral glucose tolerance test (OGTT)

  5. Change in liver steatosis

    Time frame: The difference between treatment arms in terms of change in CAP scores after 16 weeks

    Controlled Attenuation Parameter (CAP) scores, assessed with a Fibroscan

Sponsors and collaborators

Lead sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Other

Registry information

Official study title

The Effect of Low-dose Rhythmic 17-β-estradiol Administration on Bone Turnover in Postmenopausal Women

Acronym: REBEL

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Jun 15, 2023
Registry last updated
Feb 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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