Clinical trial NCT05903820: Rhythmic Estradiol and Bone Health
Official title: The Effect of Low-dose Rhythmic 17-β-estradiol Administration on Bone Turnover in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoporosis Risk
Menopause
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2023-06-15
Enrollment: 48
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Serum P1NP
timeFrame: The difference in P1NP between treatment arms after 2 weeks
measure: Serum P1NP
timeFrame: The difference in P1NP between treatment arms after 4 weeks
measure: Serum P1NP
timeFrame: The difference in P1NP between treatment arms after 6 weeks
measure: Serum P1NP
timeFrame: The difference in P1NP between treatment arms after 8 weeks
measure: Serum P1NP
timeFrame: The difference in P1NP between treatment arms after 10 weeks
measure: Serum P1NP
timeFrame: The difference in P1NP between treatment arms after 12 weeks
measure: Serum P1NP
timeFrame: The difference in P1NP between treatment arms after 14 weeks
measure: Serum P1NP
timeFrame: The difference in P1NP between treatment arms after 16 weeks
Secondary outcomes:
measure: Serum CTX
timeFrame: The difference in CTX between treatment arms after 2 weeks
measure: Serum CTX
timeFrame: The difference in CTX between treatment arms after 4 weeks
measure: Serum CTX
timeFrame: The difference in CTX between treatment arms after 6 weeks
measure: Serum CTX
timeFrame: The difference in CTX between treatment arms after 8 weeks
measure: Serum CTX
timeFrame: The difference in CTX between treatment arms after 10 weeks
measure: Serum CTX
timeFrame: The difference in CTX between treatment arms after 12 weeks
measure: Serum CTX
timeFrame: The difference in CTX treatment arms after 14 weeks
measure: Serum CTX
timeFrame: The difference in CTX between treatment arms after 16 weeks
Other outcomes:
measure: Fasting glucose
timeFrame: The difference between treatment arms in terms of change in fasting glucose after 16 weeks
measure: Fasting insulin
timeFrame: The difference between treatment arms in terms of change in fasting insulin after 16 weeks
measure: Fasting insulin insulin resistance (HOMA-IR), and post-OGTT outcomes from to baseline until 16 weeks of treatment.
timeFrame: The difference between treatment arms in terms of change in HOMA-IR after 16 weeks
measure: Glucose levels after an oral glucose tolerance test (OGTT)
timeFrame: The difference between treatment arms in terms of change in post-OGTT glucose values after 16 weeks
measure: Change in liver steatosis
timeFrame: The difference between treatment arms in terms of change in CAP scores after 16 weeks
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
affiliation: Amsterdam UMC
name: Peter M Bisschop
role: PRINCIPAL_INVESTIGATOR
References: