COMPASS: Copenhagen Menopause Project testing hormone and LH‑blocking treatments

Copenhagen Menopause Study (COMPASS): A Randomized Clinical Trial

This 8-week randomized study will test whether blocking LH, or giving estrogen or testosterone, helps bone health and menopausal symptoms in women aged 40–65 with frequent hot flashes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 192 (estimated)
• Ages: 40 Years to 65 Years
• Sex: Female
• Sponsor: Copenhagen University Hospital at Herlev (Academic / other)
• Locations: 1 site (Herlev)
• Trial ID: NCT07254429 on ClinicalTrials.gov

What this trial studies

This single-center, single-blinded Phase 2 randomized trial at Copenhagen University Hospital Herlev compares four parallel arms over 8 weeks: a GnRH analog (triptorelin), placebo, estradiol, and testosterone, with endpoints focused on bone markers and symptom changes. Eligible participants are women aged 40–65 with confirmed menopause and at least 14 moderate-to-severe vasomotor symptoms per week. The protocol excludes women with established osteoporosis, current or recent hormone therapy, prior cancer (except basal cell carcinoma), BRCA mutations, uncontrolled hyperthyroidism, or major psychiatric illness. Investigators will collect biochemical bone markers and clinical symptom data to compare short-term effects across the treatment arms.

Who should consider this trial

Good fit: Women aged >40 to ≤65 with confirmed menopause, BMI 18–35, at least 14 moderate-to-severe vasomotor symptoms per week, and willing/able to pause hormone therapies as required are the ideal candidates.

Not a fit: Women with diagnosed osteoporosis, current or recent hormone replacement therapy, active or prior cancer (other than basal cell carcinoma), known BRCA mutation, untreated hyperthyroidism, or major psychiatric disorders were excluded and are unlikely to benefit from or join this trial.

Why it matters

Potential benefit: If successful, this approach could offer a non‑estrogen option to protect bone and improve metabolic health and menopausal symptoms while avoiding some estrogen-related risks.

How similar studies have performed: Previous research links high LH to bone loss and metabolic problems and drugs like fezolinetant relieve hot flashes, but using LH blockade specifically to protect bone is a relatively novel approach with limited prior clinical trial evidence.

Eligibility criteria

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

Where this trial is running

Herlev

• Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital Herlev. — Herlev, Denmark (Recruiting)

Study contacts

• Principal investigator: Martin Blomberg Jensen, D.M.Sc. — Herlev Hospital
• Study coordinator: Martin Blomberg Jensen, D.M.Sc

Conditions Menopausal Osteoporosis; Bone Markers