Rhythmic Estradiol and Bone Health

NCT ID: NCT05903820

Last Updated: 2025-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-19
• Study Completion Date: 2024-10-28

Brief 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. 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.

Conditions

Osteoporosis Risk; Menopause

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Continuous estradiol 50 mcg/day

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.

Group Type: ACTIVE_COMPARATOR

Estradiol patch

Intervention Type: DRUG

Transdermal patch of estradiol

Progesterone

Intervention Type: DRUG

Oral progesterone capsules 100mg/day

Continuous estradiol 25 mcg/day

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.

Group Type: ACTIVE_COMPARATOR

Estradiol patch

Intervention Type: DRUG

Transdermal patch of estradiol

Progesterone

Intervention Type: DRUG

Oral progesterone capsules 100mg/day

Rhythmic estradiol 25-50 mcg/day

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.

Group Type: EXPERIMENTAL

Estradiol patch

Intervention Type: DRUG

Transdermal patch of estradiol

Progesterone

Intervention Type: DRUG

Oral progesterone capsules 100mg/day

Interventions

Estradiol patch

Transdermal patch of estradiol

Intervention Type: DRUG

Progesterone

Oral progesterone capsules 100mg/day

Intervention Type: DRUG

Other Intervention Names

transdermal17-beta-estradiol; micronized progesterone

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Peter H. Bisschop

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter M Bisschop

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

Locations

Amsterdam UMC

Amsterdam, , Netherlands

Countries

Netherlands

Other Identifiers

NL83336.018.23

Identifier Type: -

Identifier Source: org_study_id