NCT05903820

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jul 2023

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 15, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

June 15, 2023

Completed
1 month until next milestone

Study Start

First participant enrolled

July 19, 2023

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 21, 2024

Completed
7 days until next milestone

Study Completion

Last participant's last visit for all outcomes

October 28, 2024

Completed
Last Updated

February 5, 2025

Status Verified

July 1, 2024

Enrollment Period

1.3 years

First QC Date

May 15, 2023

Last Update Submit

February 3, 2025

Conditions

Osteoporosis RiskMenopause

Outcome Measures

Primary Outcomes (8)

  • Serum P1NP

    The interaction between treatment and time on serum P1NP

    The difference in P1NP between treatment arms after 2 weeks

  • Serum P1NP

    The interaction between treatment and time on serum P1NP

    The difference in P1NP between treatment arms after 4 weeks

  • Serum P1NP

    The interaction between treatment and time on serum P1NP

    The difference in P1NP between treatment arms after 6 weeks

  • Serum P1NP

    The interaction between treatment and time on serum P1NP

    The difference in P1NP between treatment arms after 8 weeks

  • Serum P1NP

    The interaction between treatment and time on serum P1NP

    The difference in P1NP between treatment arms after 10 weeks

  • Serum P1NP

    The interaction between treatment and time on serum P1NP

    The difference in P1NP between treatment arms after 12 weeks

  • Serum P1NP

    The interaction between treatment and time on serum P1NP

    The difference in P1NP between treatment arms after 14 weeks

  • Serum P1NP

    The interaction between treatment and time on serum P1NP

    The difference in P1NP between treatment arms after 16 weeks

Secondary Outcomes (8)

  • Serum CTX

    The difference in CTX between treatment arms after 2 weeks

  • Serum CTX

    The difference in CTX between treatment arms after 4 weeks

  • Serum CTX

    The difference in CTX between treatment arms after 6 weeks

  • Serum CTX

    The difference in CTX between treatment arms after 8 weeks

  • Serum CTX

    The difference in CTX between treatment arms after 10 weeks

  • +3 more secondary outcomes

Other Outcomes (5)

  • Fasting glucose

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

  • Fasting insulin

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

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

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

  • +2 more other outcomes

Study Arms (3)

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.

Drug: Estradiol patchDrug: 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.

Drug: Estradiol patchDrug: 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.

Drug: Estradiol patchDrug: Progesterone

Interventions

Estradiol patchDRUG

Transdermal patch of estradiol

Also known as: transdermal17-beta-estradiol
Continuous estradiol 25 mcg/dayContinuous estradiol 50 mcg/dayRhythmic estradiol 25-50 mcg/day
ProgesteroneDRUG

Oral progesterone capsules 100mg/day

Also known as: micronized progesterone
Continuous estradiol 25 mcg/dayContinuous estradiol 50 mcg/dayRhythmic estradiol 25-50 mcg/day

Eligibility Criteria

Age45 Years - 60 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Amsterdam UMC

Amsterdam, 1105 AZ, Netherlands

Location

MeSH Terms

Interventions

Ortho EvraProgesterone

Intervention Hierarchy (Ancestors)

PregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsCorpus Luteum HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsProgesterone CongenersGonadal Steroid Hormones

Study Officials

  • Peter M Bisschop

    Amsterdam UMC

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

May 15, 2023

First Posted

June 15, 2023

Study Start

July 19, 2023

Primary Completion

October 21, 2024

Study Completion

October 28, 2024

Last Updated

February 5, 2025

Record last verified: 2024-07

Data Sharing

IPD Sharing
Will not share

Locations

NL(1)