Osteoporosis Risk, Menopause
Conditions
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.
Interventions
DRUGEstradiol patch
Transdermal patch of estradiol
DRUGProgesterone
Oral progesterone capsules 100mg/day
Sponsors
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum P1NP | The difference in P1NP between treatment arms after 2 weeks | The interaction between treatment and time on serum P1NP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum CTX | The difference in CTX between treatment arms after 2 weeks | The interaction between treatment and time on serum CTX |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | Change in fasting insulin |
| Fasting glucose | The difference between treatment arms in terms of change in fasting glucose after 16 weeks | Change in fasting glucose |
| Change in liver steatosis | The difference between treatment arms in terms of change in CAP scores after 16 weeks | Controlled Attenuation Parameter (CAP) scores, assessed with a Fibroscan |
| Glucose levels after an oral glucose tolerance test (OGTT) | 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) |
| Fasting insulin | The difference between treatment arms in terms of change in fasting insulin after 16 weeks | Change in fasting insulin |
Countries
Netherlands
Outcome results
None listed