COMPASS - COpenhagen MenoPAuSe Study

NCT07254429 | Recruiting Phase 2 DMC

• 1 other identifier: 2025-522558-37-00
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Menopausal Osteoporosis; Bone Markers

Outcome Measures

Primary Outcomes (3)

• 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: 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

  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

  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

  From baseline to week 8

Secondary Outcomes (38)

• Change in serum levels of Hypothalamic-Pituitary-Adrenal (HPA) axis from baseline to week 8

  Baseline to week 8

• Change in serum levels of Hypothalamic-Pituitary-Gonadal (HPG) axis from baseline to week 8

  Baseline to week 8

• Change in serum levels of Hypothalamic-Pituitary-Thyroid (HPT) axis from baseline to week 8

  Baseline to week 8

• Change in quality of life evaluated with MENQOL-1 from baseline to week 8

  Baseline to week 8

• Change in sexual function evaluated with female sexual function index from baseline to week 8

  Baseline to week 8

Other Outcomes (18)

• Change in fasting insulin from baseline to week 8

  Baseline to week 8

• Change in HbA1C from baseline to week 8

  Baseline to week 8

• Change in HOMA-IR from baseline to week 8

  Baseline to week 8

Study Arms (4)

GnRH analog

ACTIVE COMPARATOR

Pamorelin 11.25 mg intramuscular injection once + Daily placebo gel

Drug: Triptorelin 11.25 mg; Drug: Placebo gel

Placebo

PLACEBO COMPARATOR

Saline intramuscular injection once + Daily placebo gel

Drug: Sodium Chloride 0.9%; Drug: Placebo gel

Transdermal Estrogen

ACTIVE COMPARATOR

Saline intramuscular injection once + Estreva gel 1.5 mg daily

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

Drug: Sodium Chloride 0.9%; Drug: Testosterone; Drug: Placebo gel

Interventions

Triptorelin 11.25 mg DRUG

Pamorelin 11.25 mg intramuscular injection once

Also known as: Pamorelin

GnRH analog

Sodium Chloride 0.9% DRUG

Saline intramuscular injection once

Also known as: Saline

Placebo; Transdermal Estrogen; Transdermal testosterone

Estradiol (E2) DRUG

Estreva gel 1.5 mg daily

Also known as: Estreva

Transdermal Estrogen

Testosterone DRUG

Tostran gel 10 mg every other day

Also known as: Tostran

Transdermal testosterone

Placebo gel DRUG

Placebo gel every day or every other day

GnRH analog; Placebo; Transdermal testosterone

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Martin Blomberg Jensen: lead

Study Sites (1)

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

Herlev, Denmark

RECRUITING

Related Publications (62)

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MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

Triptorelin Pamoate; Sodium Chloride; Estradiol; Testosterone

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Androstenols; Androstenes; Androstanes; Testosterone Congeners

Study Officials

• Martin Blomberg Jensen, D.M.Sc.

  Herlev Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Blomberg Jensen, D.M.Sc

CONTACT

+45 38 68 63 64; martin.blomberg.jensen@regionh.dk

Nadia Poulsen, MD

CONTACT

+45 38 68 63 64; nadia.nicholine.poulsen.02@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 30, 2025
• First Posted: November 28, 2025
• Study Start: October 2, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)