The Effect of Tirzepatide on Menopausal Vasomotor Symptoms and Biological Aging in Post-menopausal Women With Obesity: A Pilot Study
Trial ID: NCT07218445
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: PHASE4
Start date: 2026-04
Completion date: 2027-09-18
Sponsor: Mayo Clinic
Conditions: Obesity; Menopause Hot Flashes
Interventions: Tirzepatide; Placebo
Locations: Mayo Clinic in Florida
Countries: United States
Enrollment: 40
Age range: 46 Years - 60 Years
Sex: FEMALE

Summary:
The purpose of this study is to determine the effect of tirzepatide on vasomotor symptoms and on measures of biological aging.

Eligibility criteria:
Inclusion Criteria

* Postmenopausal women defined as 12 months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels \> 40 mIU/ml, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
* Age 46-60 years old.
* BMI ≥30 kg/m2 or BMI ≥27 kg/m2 in the presence of adiposity-associated diseases (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease).
* Presence of bothersome hot flashes (≥ 28 episodes per week and of sufficient severity to prompt patients to seek therapeutic interventions).
* Hot flashes must be present for \>30 days prior to study entry.
* Ability to participate in all portions of the study, including willingness to self-inject drug
* Provided informed consent to be part of the study.
* Willingness and capability to follow a hypocaloric diet, consisting of an energy deficit of approximately 500 kcal/day compared to baseline total energy expenditure, and composed of 30% from fat, 20% from protein, and 50% of carbohydrate. In addition to performing at least 150 min/week of physical activity

Exclusion Criteria

* Current treatment with menopausal hormone therapy.
* Any current (past 4 weeks) or planned use of:

  * Estrogen-containing contraceptive methods or menopausal hormone therapy (oral, transdermal, high dose vaginal ring, injection, pellets).
  * Vaginal estrogen.
  * Androgens.
  * Progestogens.
* Current treatment for menopausal symptoms with cognitive behavioral therapy and/or hypnosis.
* Current use of fezolinetant.
* Menopause as a result of cancer treatments.
* Impaired renal function (GFR ≤30 ml/min/1.73 m²).
* Thyroid-stimulating hormone ≥7 with low free T4.
* 10-year ASCVD risk \> 7.5%.
* Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignancy, or uncontrolled psychiatric disease.
* \>5% change in weight during the 3 months prior to screening and, or eight fluctuation of ≥20 pounds within the past 6 months (self-report).
* Other obesity medication used within the past 3 months.
* History of bariatric surgery. Prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty performed \> 1 year before screening).
* Past or intended endoscopic and/or device-based therapy or removal within last six months.
* Current or recent (within 3 months) use of medications that may cause weight gain, including tricyclic antidepressants, atypical antipsychotics, and mood stabilizers.
* Current or recent (within 3 months) use of chronic systemic glucocorticoid therapy for over 2 weeks within the past 3 months.
* Contraindications to GLP-1 receptor agonist therapy as per Tirzepatide (Zepbound ®) label, including a personal or family history of medullary thyroid carcinoma; a history or diagnosis of multiple endocrine neoplasia syndrome type 2; known hypersensitivity to tirzepatide or any of its excipients.
* Currently enrolled in another clinical study involving an investigational product, or participated in one and received treatment (active or placebo) in the last 30 days.
* Planned surgical procedures requiring general anesthesia or sedation during the study or within 2 weeks following the last dose of study drug.

Outcomes:
Change in Vasomotor Symptoms Frequency; Change in Vasomotor Symptom Severity; Aging Biomarkers: Cellular Senescence Markers in Plasma; Difference between biological and chronological age