Rhythmic Estradiol and Bone Health (REBEL)

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

Status and phase: Completed; Phase 4

Conditions: Osteoporosis Risk; Menopause

Treatments: Drug: Estradiol patch; Drug: Progesterone

Study type: Interventional

Funder types: Other

Identifiers

NCT05903820

NL83336.018.23

Details and patient eligibility

About

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.

Enrollment: 48 patients

Sex: Female

Ages: 45 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 3 patient groups

Continuous estradiol 50 mcg/day

Active Comparator group

Description:

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.

Treatment:

Drug: Progesterone

Drug: Estradiol patch

Continuous estradiol 25 mcg/day

Active Comparator group

Description:

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.

Treatment:

Drug: Progesterone

Drug: Estradiol patch

Rhythmic estradiol 25-50 mcg/day

Experimental group

Description:

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.

Treatment:

Drug: Progesterone

Drug: Estradiol patch