Menopausal OsteoporosisPhase 2COMPASSNCT07254429
COMPASS - COpenhagen MenoPAuSe Study
A Phase 2 study testing Triptorelin 11.25 mg, Sodium Chloride 0.9% and Estradiol (E2) in people with Menopausal Osteoporosis and Bone Markers, run by Martin Blomberg Jensen at 1 site in Denmark.
Trial summary
During menopause, estrogen levels drop while the level of another hormone - LH (luteinizing hormone) substantially increases. This hormonal shift is linked to bone Loss and other complications. Estrogen therapy can help, but some women avoid it due to the increased risk of blood clots and cancer. Read more about this study
- Who is it for?
- Ages 40 to 65 years, women only
- Conditions the study is for
- Menopausal Osteoporosis, Bone Markers
- What is being tested?
- Triptorelin 11.25 mg, Sodium Chloride 0.9% and Estradiol (E2)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 192 participants
- Where
- 1 siteDenmark
- Study dates
- 2 Oct 2025to May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women >40 years and ≤65 at screening visit
- A body mass index between 18-35
- Confirmed menopause
- Method 1
- Spontaneous amenorrhea for ≥12 consecutive months
- Negative urine hCG test
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- Method 2
- Spontaneous amenorrhea for ≥6 months
- FSH >30 mIU/L
- Negative urine hCG test
- Moderate to severe vasomotor symptoms (VMS)
- Within the 7 days prior to randomization, participants must report ≥ 14 moderate to severe VMS per week
Who cannot join
- Current or previous hormone replacement therapy (HRT)
- Vaginal estradiol/vaginal inserts (e.g. Vagifem®) can be used, but will have to be pause 2 weeks prior to randomization and throughout the study period
- Menopausal Hormone Therapy (MHT) can be used by participants, but must be paused 6 weeks prior to inclusion.
- Current or previous cancer diagnosis
- Except for basal cell carcinoma
- Known BRCA gene mutation
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- Current hyperthyroid disease
- Osteoporosis
- Major psychiatric diagnosis including ongoing medication e.g. selective serotonin re-uptake inhibitors (SSRIs)
- Known prolonged QT or other known clinically significant abnormal ECG, including taking medication that can prolong QT interval (e.g. sotalol, dronedarone, amiodarone, methadone, and several antipsychotic drugs)
- Previous myocardial infarction or heart failure
- Previous thromboembolic event
- The use of opioids, anticoagulating treatment or unwilling to pause fish oil/Omega-3 supplements 3 days prior visit 1 and 3
- Current alcohol or drug abuse
- Hypertension treated with more than two drugs
- Severe history of allergy, hypersensitivity, or intolerance to drugs
- Moderate to severe liver and kidney disease (eGFR <60 mL/min)
- Diagnosed with type 1 or 2 diabetes
- Chronic diseases requiring immunomodulatory treatments such as rheumatoid arthritis, inflammatory bowel disease, and vasculitis etc.
- Known uterine fibroids, Endometriosis, Systemic lupus erythematosus (SLE), otosclerosis, severe migraine or sleep apnea
- Known Epilepsy or previous seizures or convulsive disorder
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital Herlev.
Herlev
Nadia Poulsen, MD, +45 38 68 63 64, nadia.nicholine.poulsen.02@regionh.dk
About this study
Official title: Copenhagen Menopause Study (COMPASS): A Randomized Clinical Trial
During menopause, estrogen levels drop while the level of another hormone - LH (luteinizing hormone) substantially increases. This hormonal shift is linked to bone Loss and other complications. Estrogen therapy can help, but some women avoid it due to the increased risk of blood clots and cancer. This project will investigate whether blocking LH could offer a safe alternative to alleviate symptoms and complications of menopause since it is known from previous research that high LH levels contribute to both bone deterioration and metabolic issues. The goal is to explore new treatment options that can improve health and quality of life for women both during and after menopause. This randomized clinical trial is a single center, sponsor-investigator-initiated single-blinded 8 weeks clinical trial with four parallel groups comparing the effect of an gonadotropin releasing hormone(GnRH)-analog with placebo, and with two additional arms given estrogen or testosterone on change on bone health in postmenopausal women with moderate-to-severe symptoms.
Read the detailed description
The hormonal changes occurring in perimenopause and menopause exert multiple effects on several organs and the accompanied symptoms can be very distressing and impair quality of life. Vasomotor symptoms (VMS) defined as hot flashes and sweating are the most frequent and bothersome symptoms of menopause and are experienced by up to 80% of women. Additionally, in the Western world, 66% of postmenopausal women are obese and 54% have osteoporosis. Along with obesity comes a wide variety of health issues such as type 2 diabetes, metabolic syndrome, and atherosclerosis, which can lead to cardiovascular disease. Osteoporosis is a huge economic cost for society, it impairs quality of life and vertebral and hip fractures are associated with increased mortality. Postmenopausal symptoms and complications take a large toll on both the physical and mental well-being of women and are a huge cost to society. Menopausal Hormonal Therapy (MHT) with estrogen and gestagen is used by many women as it alleviates symptoms and reduces the risk of osteoporosis and cardiovascular disease. However, due to the increased risk of breast cancer and venous thromboembolism, some women refuse MHT and there is an ongoing search for new treatments. The newly approved Veoza® (Fezolinetant) is also approved and on the marked, but only targets VMS and not menopausal complications, but can be a treatment option, if the woman can or will not have MHT.
Menopause is characterized by low circulating estrogen, but also by very high levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and these hormonal changes are linked with increased bone resorption and weight gain. Despite the high LH in menopause, LH pulses occur simultaneously with hot flashes also in postmenopausal women, and LH may be involved in the events. In a clinical study 10 postmenopausal women with severe VMS were given a GnRH antagonist cetrorelix 250 μg two times a day in 6 weeks. They found a significant decrease in VMS symptoms. Postmenopausal women experience a decline in core temperature, which we suggest is due to LH actions on brown and white fat cells leading to less heat generation, beta-oxidation, and more storing of fat. Furthermore, LH appears to be a rapid and potent inducer of renal calcium excretion, which induces a secondary and persistent increase in parathyroid hormone (PTH) that mobilizes calcium from the skeleton. The LH-induced calcium excretion occurs several hours before the subsequent changes in sex steroids, particularly estrogen, which indicates a direct effect of LH that can lead to increased bone resorption and eventually osteoporosis. This may be of great importance during the perimenopause/early phase of menopause, where the decrease in bone mineral density and increase in visceral adiposity is high concurrent with serum LH increasing dramatically, while serum estrogen is still not greatly reduced. The investigators propose to investigate if lowering LH using a gonadotropin releasing hormone (GnRH) analog against placebo can improve bone markers and secondarily reduce the frequency and severity of VMS in postmenopausal women with a direct comparison to estrogen - the gold standard treatment of women in menopause, and testosterone in the same RCT.
The main aim of the study is to show that by targeting LH the investigators can change bone markers and maybe even combat hot flashes and night sweats (VMS) in postmenopausal women. For important biological knowledge purpose, the investigators also investigate the 2 additional treatment arms with estradiol and testosterone to compare the effect against the current gold standard treatment option (estradiol) and to testosterone, which is a common supplement to postmenopausal women off-label. A study by Glaser et al. effectively documents that testosterone can improve most common post-menopausal symptoms.
Sample size calculation and statistics Previous studies have shown that CTX in postmenopausal women is usually between 0.44 ng/mL with a standard diviation on SD 0.2. The sample size is calculated based on a direct comparison between GnRH analog (pamorelin) and placebo on the primary outcome 'change in bone markers' (delta CTX between pamorelin and placebo), using a power of 80% and alpha of 0.05 leads to 44 participants in each group, and the investigators would be able to detect a change in CTX on 30 %. The calculations is based on only two arms, however for comparison reasons the investigators will include two extra arms with estradiol/testosterone and patients will be allocated 1:1:1:1 leading to a total sample size of 176 participants. Our design and analysis principles rely on the intent-to-treat (ITT) approach; the investigators strive to evaluate and include all randomized participants in the primary analysis, regardless of adherence to treatment assignment or protocol requirements.
The investigators estimate to screen 250 to include 192 to be randomized and 176 to complete the study leaving 16 patients for dropout (9%). The design enables us to investigate multiple secondary outcomes where the primary comparison will be between GnRH analog treatment and placebo. The study is not powered to show significant differences between placebo and GnRH treatment for most secondary endpoints and should be considered as a pilot placebo-controlled intervention study for these outcomes. T-tests will be used for the primary endpoint, while Nonresponder imputation will be used for missing response data. Change in mean frequency and severity of VMS per 24 hours will be analyzed for each week using a mixed effect model for repeated measures, with change from baseline as the dependent variable and treatment group, visit, and smoking status as factors and baseline measurement as a covariate, as well as interaction of treatment by week and an interaction of baseline measurement by week.
Predefined subgroups: Efficacy in patients with detectable versus undetectable serum hCG, high versus low LH at baseline, low versus high BMI, low versus high BMD, low versus high fat %.
Ethics and side effects All patients will be informed of potential adverse effects, and that they can leave the trial at any point without any consequences. GnRH-analogs have been proven safe in numerous randomized clinical trials (RCT) and have for many years been involved in the treatment of several groups including children with precocious puberty, transgender hormone treatment, and as part of in vitro fertilization. MHT have been tested in previously large RCT, where an increased risk of breast cancer and thromboembolic events have been detected. It is estimated that the risk of breast cancer increases with 0.5 % after 5 years of hormonal treatment. It is therefore regarded safe for participant in this trial to be treated with estrogen in 8 weeks however women with increased risk of cancer or thromboembolic events will be excluded. All side effects will be closely monitored and reported. The study will be approved by the regional ethical committee, conducted in compliance with The Declaration of Helsinki, registered on clinicaltrial.gov, and monitored by the GCP unit of Copenhagen University Hospitals in compliance with International Conference on Harmonisation.
- Conditions
- Menopausal Osteoporosis, Bone Markers
- Being tested
- Triptorelin 11.25 mg, Sodium Chloride 0.9%, Estradiol (E2), Testosterone, Placebo gel
- Medical subject headings
- Osteoporosis, Postmenopausal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Triptorelin 11.25 mgDrug
Also called Pamorelin
Pamorelin 11.25 mg intramuscular injection once
Sodium Chloride 0.9%Drug
Also called Saline
Saline intramuscular injection once
Estradiol (E2)Drug
Also called Estreva
Estreva gel 1.5 mg daily
TestosteroneDrug
Also called Tostran
Tostran gel 10 mg every other day
Placebo gelDrug
Placebo gel every day or every other day
| Study group | Role | What they receive |
|---|---|---|
| GnRH analog | Active comparator | Pamorelin 11.25 mg intramuscular injection once + Daily placebo gel Receives: Drug: Triptorelin 11.25 mg; Drug: Placebo gel |
| Placebo | Placebo comparator | Saline intramuscular injection once + Daily placebo gel Receives: Drug: Sodium Chloride 0.9%; Drug: Placebo gel |
| Transdermal Estrogen | Active comparator | Saline intramuscular injection once + Estreva gel 1.5 mg daily Receives: Drug: Sodium Chloride 0.9%; Drug: Estradiol (E2) |
| Transdermal testosterone | Active comparator | Saline intramuscular injection once + Tostran gel 10 mg every other day + placebo gel every other day Receives: Drug: Sodium Chloride 0.9%; Drug: Testosterone; Drug: Placebo gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in bone remodeling from baseline to week 8.
Change in bone remodeling defined by change in bone marker (ΔCTX) from baseline to week 8.
The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between:
- GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order:
- Combined analysis of all 4 arms of the RCT
- GnRH analog and estradiol
- GnRH analog and testosterone
- Estradiol and placebo
- Testosterone and placebo
- Estradiol and testosterone
Measured: From baseline to week 8
Change in bone remodeling from baseline to week 8.
Change in bone remodeling defined by change in bone marker (ΔP1NP) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: From baseline to week 8
Change in bone remodeling from baseline to week 8
Change in bone remodeling defined by change in bone marker-ratios (ΔCTX/ΔP1NP, and ΔBBI) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: From baseline to week 8
Secondary outcomes (38)
Change in serum levels of Hypothalamic-Pituitary-Adrenal (HPA) axis from baseline to week 8
Change in serum levels of Hypothalamic-Pituitary-Adrenal (HPA) axis from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 8
Change in serum levels of Hypothalamic-Pituitary-Gonadal (HPG) axis from baseline to week 8
Change in serum levels of Hypothalamic-Pituitary-Gonadal (HPG) axis from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 8
Change in serum levels of Hypothalamic-Pituitary-Thyroid (HPT) axis from baseline to week 8
Change in serum levels of Hypothalamic-Pituitary-Thyroid (HPT) axis from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 8
Change in quality of life evaluated with MENQOL-1 from baseline to week 8
Change in quality of life evaluated with The Menopause-specific Quality of Life (MENQOL) Questionnaire from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. MENQOL is ranging from 0 (asymptomatic woman) to 232 (extremely bothered).
Measured: Baseline to week 8
Change in sexual function evaluated with female sexual function index from baseline to week 8
Change in sexual function evaluated with female sexual function index (FSFI) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. The FSFI use a 5-point Likert scale with higher scores indicating greater levels of sexual functioning on the respective item. The possible range is 2-36.
Measured: Baseline to week 8
Change in sexual function evaluated with female sexual distress scale-revised from baseline to week 8
Change in sexual function evaluated with female sexual distress scale-revised (FSDS-R) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. FSDS-R has a total score ranging from 0 to 52, with higher scores indicating more sexually related distress.
Measured: Baseline to week 8
Change in depressive symptoms evaluated by MDI from baseline to week 8
Change in depressive symptoms evaluated by Major Depression Inventory (MDI) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Total score between 0 (no depression) to 50 (maximum depressed).
Measured: Baseline to week 8
Change in depressive symptoms evaluated by CES-D from baseline to week 8
Description: Change in depressive symptoms evaluated by Center for Epidemiologic Studies Depression Scale (CES-D) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Possible range of scores is zero to 60, with the higher scores indicating the presence of more symptomatology.
Measured: Baseline to week 8
Change in anxiety symptoms evaluated by GAD-7 from baseline to week 8
Change in anxiety symptoms evaluated by General Anxiety Disorder-7 (GAD-7) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Scores ranges from 0 (No anxiety) to 21 (severe anxiety).
Measured: Baseline to week 8
Change in The Mean Patient-reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b) from baseline to week 8
Change in The Mean Patient-reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Scores ranges from 8-40. Higher scores indicate more severe sleep disturbance.
Measured: Baseline to week 8
Change in thyroid hormones from baseline to week 4 and 8
Change in thyroid hormones from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8.
Change in urine calcium from baseline to weeks 4 and 8
Change in urine calcium from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to weeks 4 and 8
Change in urine creatinine from baseline to weeks 4 and 8
Change in urine creatinine from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to weeks 4 and 8.
Change in urine phosphate from baseline to weeks 4 and 8
Change in urine phosphate from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to weeks 4 and 8
Change in urine magnesium from baseline to weeks 4 and 8
Change in urine magnesium from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to weeks 4 and 8
Change in urine sodium from baseline to weeks 4 and 8
Change in urine sodium from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to weeks 4 and 8
Change in urine cortisol and other hormones from baseline to weeks 4 and 8
Change in urine cortisol and other hormones from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to weeks 4 and 8.
Change in serum ionized calcium from baseline to week 4 and 8
Change in serum ionized calcium from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in serum calcium from baseline to week 4 and 8
Change in serum calcium from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in serum albumin from baseline to week 4 and 8
Change in serum albumin from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in serum PTH from baseline to week 4 and 8
Change in serum PTH from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in serum phosphate from baseline to week 4 and 8
Change in serum phosphate from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in serum vitamin D metabolites from baseline to week 4 and 8
Change in serum vitamin D metabolites from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in serum hCG from baseline to week 4 and 8
Change in serum hCG from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in thyroid hormone conversion (DIO2 activity) in fat cells determined by their conversion of T4 to T3 from baseline to week 8
Change in thyroid hormone conversion (DIO2 activity) in fat cells determined by their conversion of T4 to T3 from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 8
Change in adrenal hormones from baseline to week 4 and 8
Change in adrenal hormones from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in the mean frequency of moderate to severe VMS from Baseline to week 8
Change in the mean frequency of moderate to severe VMS from Baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Definition of moderate VMS: Moderate VMS is defined as a sensation of heat with sweating/dampness, but the woman is able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Definition of severe VMS: Severe VMS is defined as sensation of intense heat with sweating, caused disruption of activity. If at night
Measured: Baseline to week 8
Change in the mean frequency of moderate to severe VMS from Baseline to week 4
Change in the mean frequency of moderate to severe VMS from Baseline to week 4. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Definition of moderate VMS: Moderate VMS is defined as a sensation of heat with sweating/dampness, but the woman is able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Definition of severe VMS: Severe VMS is defined as sensation of intense heat with sweating, caused disruption of activity. If at night
Measured: Baseline to week 4
Change in the mean severity-score from Baseline to week 8
Change in the mean severity-score from Baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Definition of mean severity-score of VMS: Severity score of moderate to severe VMS per day was calculated as follows: ((number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3))/Total number of daily hot flashes.
Measured: Baseline to week 8
Change in the mean severity-score from Baseline to week 4
Change in the mean severity-score from Baseline to week 4. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Definition of mean severity-score of VMS: Severity score of moderate to severe VMS per day was calculated as follows: ((number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3))/Total number of daily hot flashes.
Measured: Baseline to week 4
Change in VMS measured by the Greene Climacteric Scale (GCS) from baseline to week 8
Change in VMS measured using the questionnaire: The Greene Climacteric Scale (GCS) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Ranging from 0 (when every symptom is rated as "not at all") to a maximum of 63 (when every symptom is rated as "very often")
Measured: Baseline to week 8
Change in serum LH from baseline to weeks 4 and 8
Change in serum LH from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to weeks 4 and 8
Change in serum FSH from baseline to weeks 4 and 8
Change in serum FSH from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to weeks 4 and 8
Change in serum estradiol from baseline to week 4 and 8
Change in serum estradiol from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in serum SHGB from baseline to week 4 and 8
Change in serum SHGB from baseline to week 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Measured: Baseline to week 4 and 8
Change in physical strength tests from baseline to weeks 4 and 8.
Change in physical strength test measured by 30 second Sit-To-Stand-Test (STST) from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. Unit: number of stands/30 seconds.
Measured: Baseline to weeks 4 and 8.
Change in physical strength tests from baseline to weeks 4 and 8.
Change in physical strength test measured by Hand-grip strength (HGS) from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone. HGS will be evaluated using a digital hand-grip dynamometer measuring the absolute (kilograms-force) and relative (kilograms/weight in kilograms) grip strength
Measured: Baseline to weeks 4 and 8.
Change in androgens from baseline to weeks 4 and 8
Change in androgens including 11 oxygenated androgens measured by LCMS from baseline to weeks 4 and 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone.
Measured: Baseline to weeks 4 and 8.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2025
- Study start2 Oct 2025
- Primary completionDec 2027 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (62)Papers the sponsor has linked to this study.
- Other trials for Menopausal OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 192 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Martin Blomberg Jensen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Martin Blomberg Jensen, Copenhagen University Hospital at Herlev
- Investigators
- Martin Blomberg Jensen, D.M.Sc., Principal investigator, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07254429
- Sponsor's protocol ID
- 2025-522558-37-00
- Other IDs
- 2025-522558-37-00, 2025
- Acronym
- COMPASS
- Status last verified
- Feb 2026
- First submitted
- 30 Sep 2025
- Last updated
- 2 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rosen HN, Moses AC, Garber J, Iloputaife ID, Ross DS, Lee SL, Greenspan SL. Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int. 2000 Feb;66(2):100-3. doi: 10.1007/pl00005830.
PubMed 10652955Langdahl B, Chung YS, Plebanski R, Czerwinski E, Dokoupilova E, Supronik J, Rosa J, Mydlak A, Rowinska-Osuch A, Baek KH, Urboniene A, Mordaka R, Ahn S, Rho YH, Ban J, Eastell R. Proposed Denosumab Biosimilar SB16 vs Reference Denosumab in Postmenopausal Osteoporosis: Phase 3 Results Up to Month 12. J Clin Endocrinol Metab. 2025 May 19;110(6):e1951-e1958. doi: 10.1210/clinem/dgae611.
PubMed 39243386Kline GA, Holmes DT. Bone turnover markers for assessment of anti-resorptive effect in clinical practice: A good idea meets the problem of measurement uncertainty. Clin Biochem. 2023 Jun;116:100-104. doi: 10.1016/j.clinbiochem.2023.04.007. Epub 2023 Apr 19.
PubMed 37084998Brown JP, Don-Wauchope A, Douville P, Albert C, Vasikaran SD. Current use of bone turnover markers in the management of osteoporosis. Clin Biochem. 2022 Nov-Dec;109-110:1-10. doi: 10.1016/j.clinbiochem.2022.09.002. Epub 2022 Sep 9.
PubMed 36096182Migliorini F, Maffulli N, Spiezia F, Peretti GM, Tingart M, Giorgino R. Potential of biomarkers during pharmacological therapy setting for postmenopausal osteoporosis: a systematic review. J Orthop Surg Res. 2021 May 31;16(1):351. doi: 10.1186/s13018-021-02497-0.
PubMed 34059108Everts-Graber J, Reichenbach S, Ziswiler HR, Studer U, Lehmann T. A Single Infusion of Zoledronate in Postmenopausal Women Following Denosumab Discontinuation Results in Partial Conservation of Bone Mass Gains. J Bone Miner Res. 2020 Jul;35(7):1207-1215. doi: 10.1002/jbmr.3962. Epub 2020 Feb 11.
PubMed 31991007Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guanabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Zillikens MC. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone. 2017 Dec;105:11-17. doi: 10.1016/j.bone.2017.08.003. Epub 2017 Aug 5.
PubMed 28789921Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11.
PubMed 19671655Yu L, Buysse DJ, Germain A, Moul DE, Stover A, Dodds NE, Johnston KL, Pilkonis PA. Development of short forms from the PROMIS sleep disturbance and Sleep-Related Impairment item banks. Behav Sleep Med. 2011 Dec 28;10(1):6-24. doi: 10.1080/15402002.2012.636266.
PubMed 22250775Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
PubMed 16717171Greene JG. A factor analytic study of climacteric symptoms. J Psychosom Res. 1976;20(5):425-30. doi: 10.1016/0022-3999(76)90005-2. No abstract available.
PubMed 1003364Derogatis LR, Rosen R, Leiblum S, Burnett A, Heiman J. The Female Sexual Distress Scale (FSDS): initial validation of a standardized scale for assessment of sexually related personal distress in women. J Sex Marital Ther. 2002 Jul-Sep;28(4):317-30. doi: 10.1080/00926230290001448.
PubMed 12082670Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, Ferguson D, D'Agostino R Jr. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000 Apr-Jun;26(2):191-208. doi: 10.1080/009262300278597.
PubMed 10782451Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas. 1996 Jul;24(3):161-75. doi: 10.1016/s0378-5122(96)82006-8.
PubMed 8844630Radtke JV, Terhorst L, Cohen SM. The Menopause-Specific Quality of Life Questionnaire: psychometric evaluation among breast cancer survivors. Menopause. 2011 Mar;18(3):289-95. doi: 10.1097/gme.0b013e3181ef975a.
PubMed 20881889
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Copenhagen Menopause Study (COMPASS): A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07254429
- Acronym / sponsor ID
- COMPASS / 2025-522558-37-00
- Conditions
- Menopausal Osteoporosis, Bone Markers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 192 participants (estimated)
- Lead sponsor
- Martin Blomberg JensenUniversity, hospital or other
- Study start
- 2 Oct 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 28 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
During menopause, estrogen levels drop while the level of another hormone - LH (luteinizing hormone) substantially increases. This hormonal shift is linked to bone Loss and other complications. Estrogen therapy can help, but some women avoid it due to the increased risk of blood clots and cancer. This project will investigate whether blocking LH could offer a safe alternative to alleviate symptoms and complications of menopause since it is known from previous research that high LH levels contribute to both bone deterioration and metabolic issues. The goal is to explore new treatment options that can improve health and quality of life for women both during and after menopause. This randomized clinical trial is a single center, sponsor-investigator-initiated single-blinded 8 weeks clinical trial with four parallel groups comparing the effect of an gonadotropin releasing hormone(GnRH)-analog with placebo, and with two additional arms given estrogen or testosterone on change on bone health in postmenopausal women with moderate-to-severe symptoms.
Detailed description
The hormonal changes occurring in perimenopause and menopause exert multiple effects on several organs and the accompanied symptoms can be very distressing and impair quality of life. Vasomotor symptoms (VMS) defined as hot flashes and sweating are the most frequent and bothersome symptoms of menopause and are experienced by up to 80% of women. Additionally, in the Western world, 66% of postmenopausal women are obese and 54% have osteoporosis. Along with obesity comes a wide variety of health issues such as type 2 diabetes, metabolic syndrome, and atherosclerosis, which can lead to cardiovascular disease. Osteoporosis is a huge economic cost for society, it impairs quality of life and vertebral and hip fractures are associated with increased mortality. Postmenopausal symptoms and complications take a large toll on both the physical and mental well-being of women and are a huge cost to society. Menopausal Hormonal Therapy (MHT) with estrogen and gestagen is used by many women as it alleviates symptoms and reduces the risk of osteoporosis and cardiovascular disease. However, due to the increased risk of breast cancer and venous thromboembolism, some women refuse MHT and there is an ongoing search for new treatments. The newly approved Veoza® (Fezolinetant) is also approved and on the marked, but only targets VMS and not menopausal complications, but can be a treatment option, if the woman can or will not have MHT.
Menopause is characterized by low circulating estrogen, but also by very high levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and these hormonal changes are linked with increased bone resorption and weight gain. Despite the high LH in menopause, LH pulses occur simultaneously with hot flashes also in postmenopausal women, and LH may be involved in the events. In a clinical study 10 postmenopausal women with severe VMS were given a GnRH antagonist cetrorelix 250 μg two times a day in 6 weeks. They found a significant decrease in VMS symptoms. Postmenopausal women experience a decline in core temperature, which we suggest is due to LH actions on brown and white fat cells leading to less heat generation, beta-oxidation, and more storing of fat. Furthermore, LH appears to be a rapid and potent inducer of renal calcium excretion, which induces a secondary and persistent increase in parathyroid hormone (PTH) that mobilizes calcium from the skeleton. The LH-induced calcium excretion occurs several hours before the subsequent changes in sex steroids, particularly estrogen, which indicates a direct effect of LH that can lead to increased bone resorption and eventually osteoporosis. This may be of great importance during the perimenopause/early phase of menopause, where the decrease in bone mineral density and increase in visceral adiposity is high concurrent with serum LH increasing dramatically, while serum estrogen is still not greatly reduced. The investigators propose to investigate if lowering LH using a gonadotropin releasing hormone (GnRH) analog against placebo can improve bone markers and secondarily reduce the frequency and severity of VMS in postmenopausal women with a direct comparison to estrogen - the gold standard treatment of women in menopause, and testosterone in the same RCT.
The main aim of the study is to show that by targeting LH the investigators can change bone markers and maybe even combat hot flashes and night sweats (VMS) in postmenopausal women. For important biological knowledge purpose, the investigators also investigate the 2 additional treatment arms with estradiol and testosterone to compare the effect against the current gold standard treatment option (estradiol) and to testosterone, which is a common supplement to postmenopausal women off-label. A study by Glaser et al. effectively documents that testosterone can improve most common post-menopausal symptoms.
Sample size calculation and statistics Previous studies have shown that CTX in postmenopausal women is usually between 0.44 ng/mL with a standard diviation on SD 0.2. The sample size is calculated based on a direct comparison between GnRH analog (pamorelin) and placebo on the primary outcome 'change in bone markers' (delta CTX between pamorelin and placebo), using a power of 80% and alpha of 0.05 leads to 44 participants in each group, and the investigators would be able to detect a change in CTX on 30 %. The calculations is based on only two arms, however for comparison reasons the investigators will include two extra arms with estradiol/testosterone and patients will be allocated 1:1:1:1 leading to a total sample size of 176 participants. Our design and analysis principles rely on the intent-to-treat (ITT) approach; the investigators strive to evaluate and include all randomized participants in the primary analysis, regardless of adherence to treatment assignment or protocol requirements.
The investigators estimate to screen 250 to include 192 to be randomized and 176 to complete the study leaving 16 patients for dropout (9%). The design enables us to investigate multiple secondary outcomes where the primary comparison will be between GnRH analog treatment and placebo. The study is not powered to show significant differences between placebo and GnRH treatment for most secondary endpoints and should be considered as a pilot placebo-controlled intervention study for these outcomes. T-tests will be used for the primary endpoint, while Nonresponder imputation will be used for missing response data. Change in mean frequency and severity of VMS per 24 hours will be analyzed for each week using a mixed effect model for repeated measures, with change from baseline as the dependent variable and treatment group, visit, and smoking status as factors and baseline measurement as a covariate, as well as interaction of treatment by week and an interaction of baseline measurement by week.
Predefined subgroups: Efficacy in patients with detectable versus undetectable serum hCG, high versus low LH at baseline, low versus high BMI, low versus high BMD, low versus high fat %.
Ethics and side effects All patients will be informed of potential adverse effects, and that they can leave the trial at any point without any consequences. GnRH-analogs have been proven safe in numerous randomized clinical trials (RCT) and have for many years been involved in the treatment of several groups including children with precocious puberty, transgender hormone treatment, and as part of in vitro fertilization. MHT have been tested in previously large RCT, where an increased risk of breast cancer and thromboembolic events have been detected. It is estimated that the risk of breast cancer increases with 0.5 % after 5 years of hormonal treatment. It is therefore regarded safe for participant in this trial to be treated with estrogen in 8 weeks however women with increased risk of cancer or thromboembolic events will be excluded. All side effects will be closely monitored and reported. The study will be approved by the regional ethical committee, conducted in compliance with The Declaration of Helsinki, registered on clinicaltrial.gov, and monitored by the GCP unit of Copenhagen University Hospitals in compliance with International Conference on Harmonisation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GnRH analog | Active comparator | Drug: Triptorelin 11.25 mg, Drug: Placebo gelPamorelin 11.25 mg intramuscular injection once + Daily placebo gel |
| Placebo | Placebo comparator | Drug: Sodium Chloride 0.9%, Drug: Placebo gelSaline intramuscular injection once + Daily placebo gel |
| Transdermal Estrogen | Active comparator | Drug: Sodium Chloride 0.9%, Drug: Estradiol (E2)Saline intramuscular injection once + Estreva gel 1.5 mg daily |
| Transdermal testosterone | Active comparator | Drug: Sodium Chloride 0.9%, Drug: Testosterone, Drug: Placebo gelSaline intramuscular injection once + Tostran gel 10 mg every other day + placebo gel every other day |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Women >40 years and ≤65 at screening visit
- A body mass index between 18-35
- Confirmed menopause
- Moderate to severe vasomotor symptoms (VMS)
Key exclusion criteria (21 listed)
- Current or previous hormone replacement therapy (HRT)
- Current or previous cancer diagnosis
- Known BRCA gene mutation
- Current hyperthyroid disease
- Osteoporosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Triptorelin 11.25 mgAlso: PamorelinPamorelin 11.25 mg intramuscular injection once | Drug | GnRH analog |
| Sodium Chloride 0.9%Also: SalineSaline intramuscular injection once | Drug | Placebo, Transdermal Estrogen, Transdermal testosterone |
| Estradiol (E2)Also: EstrevaEstreva gel 1.5 mg daily | Drug | Transdermal Estrogen |
| TestosteroneAlso: TostranTostran gel 10 mg every other day | Drug | Transdermal testosterone |
| Placebo gelPlacebo gel every day or every other day | Drug | GnRH analog, Placebo, Transdermal testosterone |
Primary outcome
Change in bone remodeling from baseline to week 8.
Time frame: From baseline to week 8
Change in bone remodeling defined by change in bone marker (ΔCTX) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1. GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2. Combined analysis of all 4 arms of the RCT 3. GnRH analog and estradiol 4. GnRH analog and testosterone 5. Estradiol and placebo 6. Testosterone and placebo 7. Estradiol and testosterone
Change in bone remodeling from baseline to week 8.
Time frame: From baseline to week 8
Change in bone remodeling defined by change in bone marker (ΔP1NP) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
Change in bone remodeling from baseline to week 8
Time frame: From baseline to week 8
Change in bone remodeling defined by change in bone marker-ratios (ΔCTX/ΔP1NP, and ΔBBI) from baseline to week 8. The following primary, secondary and exploratory endpoints will all be investigated as comparisons first and foremost between: 1) GnRH analog and placebo-group. After the first analysis between GnRH-analog group and placebo, the outcomes will be investigated between the groups in the following order: 2) Combined analysis of all 4 arms of the RCT 3) GnRH analog and estradiol 4) GnRH analog and testosterone 5) Estradiol and placebo 6) Testosterone and placebo 7) Estradiol and testosterone
38 secondary outcomes
Change in serum levels of Hypothalamic-Pituitary-Adrenal (HPA) axis from baseline to week 8
Time frame: Baseline to week 8
Change in serum levels of Hypothalamic-Pituitary-Gonadal (HPG) axis from baseline to week 8
Time frame: Baseline to week 8
Change in serum levels of Hypothalamic-Pituitary-Thyroid (HPT) axis from baseline to week 8
Time frame: Baseline to week 8
Change in quality of life evaluated with MENQOL-1 from baseline to week 8
Time frame: Baseline to week 8
Change in sexual function evaluated with female sexual function index from baseline to week 8
Time frame: Baseline to week 8
Change in sexual function evaluated with female sexual distress scale-revised from baseline to week 8
Time frame: Baseline to week 8
Change in depressive symptoms evaluated by MDI from baseline to week 8
Time frame: Baseline to week 8
Change in depressive symptoms evaluated by CES-D from baseline to week 8
Time frame: Baseline to week 8
Change in anxiety symptoms evaluated by GAD-7 from baseline to week 8
Time frame: Baseline to week 8
Change in The Mean Patient-reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b) from baseline to week 8
Time frame: Baseline to week 8
Change in thyroid hormones from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8.
Change in urine calcium from baseline to weeks 4 and 8
Time frame: Baseline to weeks 4 and 8
Change in urine creatinine from baseline to weeks 4 and 8
Time frame: Baseline to weeks 4 and 8.
Change in urine phosphate from baseline to weeks 4 and 8
Time frame: Baseline to weeks 4 and 8
Change in urine magnesium from baseline to weeks 4 and 8
Time frame: Baseline to weeks 4 and 8
Change in urine sodium from baseline to weeks 4 and 8
Time frame: Baseline to weeks 4 and 8
Change in urine cortisol and other hormones from baseline to weeks 4 and 8
Time frame: Baseline to weeks 4 and 8.
Change in serum ionized calcium from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in serum calcium from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in serum albumin from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in serum PTH from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in serum phosphate from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in serum vitamin D metabolites from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in serum hCG from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in thyroid hormone conversion (DIO2 activity) in fat cells determined by their conversion of T4 to T3 from baseline to week 8
Time frame: Baseline to week 8
Change in adrenal hormones from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in the mean frequency of moderate to severe VMS from Baseline to week 8
Time frame: Baseline to week 8
Change in the mean frequency of moderate to severe VMS from Baseline to week 4
Time frame: Baseline to week 4
Change in the mean severity-score from Baseline to week 8
Time frame: Baseline to week 8
Change in the mean severity-score from Baseline to week 4
Time frame: Baseline to week 4
Change in VMS measured by the Greene Climacteric Scale (GCS) from baseline to week 8
Time frame: Baseline to week 8
Change in serum LH from baseline to weeks 4 and 8
Time frame: Baseline to weeks 4 and 8
Change in serum FSH from baseline to weeks 4 and 8
Time frame: Baseline to weeks 4 and 8
Change in serum estradiol from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in serum SHGB from baseline to week 4 and 8
Time frame: Baseline to week 4 and 8
Change in physical strength tests from baseline to weeks 4 and 8.
Time frame: Baseline to weeks 4 and 8.
Change in physical strength tests from baseline to weeks 4 and 8.
Time frame: Baseline to weeks 4 and 8.
Change in androgens from baseline to weeks 4 and 8
Time frame: Baseline to weeks 4 and 8.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2026.
- Background: PubMed 10652955Rosen HN, Moses AC, Garber J, Iloputaife ID, Ross DS, Lee SL, Greenspan SL. Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int. 2000 Feb;66(2):100-3. doi: 10.1007/pl00005830.
- Background: PubMed 39243386Langdahl B, Chung YS, Plebanski R, Czerwinski E, Dokoupilova E, Supronik J, Rosa J, Mydlak A, Rowinska-Osuch A, Baek KH, Urboniene A, Mordaka R, Ahn S, Rho YH, Ban J, Eastell R. Proposed Denosumab Biosimilar SB16 vs Reference Denosumab in Postmenopausal Osteoporosis: Phase 3 Results Up to Month 12. J Clin Endocrinol Metab. 2025 May 19;110(6):e1951-e1958. doi: 10.1210/clinem/dgae611.
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- Background: PubMed 34059108Migliorini F, Maffulli N, Spiezia F, Peretti GM, Tingart M, Giorgino R. Potential of biomarkers during pharmacological therapy setting for postmenopausal osteoporosis: a systematic review. J Orthop Surg Res. 2021 May 31;16(1):351. doi: 10.1186/s13018-021-02497-0.
- Background: PubMed 31991007Everts-Graber J, Reichenbach S, Ziswiler HR, Studer U, Lehmann T. A Single Infusion of Zoledronate in Postmenopausal Women Following Denosumab Discontinuation Results in Partial Conservation of Bone Mass Gains. J Bone Miner Res. 2020 Jul;35(7):1207-1215. doi: 10.1002/jbmr.3962. Epub 2020 Feb 11.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Martin Blomberg Jensen, D.M.Sc. principal investigator
Herlev Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Triptorelin 11.25 mg, Sodium Chloride 0.9% and Estradiol (E2) in people with Menopausal Osteoporosis and Bone Markers, run by Martin Blomberg Jensen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Martin Blomberg Jensen, D.M.Sc (+45 38 68 63 64, martin.blomberg.jensen@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in bone remodeling from baseline to week 8. (time frame: From baseline to week 8). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07254429, which also lists 62 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2026; AzTrials last refreshed its copy on 26 Oct 2026.