RECRUITINGPhase 2INTERVENTIONAL

COMPASS - COpenhagen MenoPAuSe Study

Copenhagen Menopause Study (COMPASS): A Randomized Clinical Trial

About This 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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 - 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 Should NOT Join This Trial: - 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 - 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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 * 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 Exclusion Criteria: * 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 * 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

Treatments Being Tested

DRUG

Triptorelin 11.25 mg

Pamorelin 11.25 mg intramuscular injection once

DRUG

Sodium Chloride 0.9%

Saline intramuscular injection once

DRUG

Estradiol (E2)

Estreva gel 1.5 mg daily

DRUG

Testosterone

Tostran gel 10 mg every other day

DRUG

Placebo gel

Placebo gel every day or every other day

Locations (1)

Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital Herlev.

Herlev, Denmark