Tirzepatide for hot flashes and biological aging in postmenopausal women with obesity

The Effect of Tirzepatide on Menopausal Vasomotor Symptoms and Biological Aging in Post-menopausal Women With Obesity: A Pilot Study

This trial will test whether tirzepatide reduces bothersome hot flashes and improves measures of biological aging in postmenopausal women with obesity.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 46 Years to 60 Years
• Sex: Female
• Sponsor: Mayo Clinic (other)
• Locations: 1 site (Jacksonville, Florida)
• Trial ID: NCT07218445 on ClinicalTrials.gov

What this trial studies

Tirzepatide, a dual GLP-1/GIP agonist, will be compared with placebo in postmenopausal women aged 46–60 who have obesity and frequent bothersome hot flashes. Eligible participants will be randomized and will self-administer study drug while following a prescribed ~500 kcal/day hypocaloric diet, with scheduled clinic visits at Mayo Clinic in Florida. The study will track changes in vasomotor symptom frequency and severity and collect biomarkers related to biological aging, alongside safety and metabolic outcomes such as weight and cardiometabolic measures. Duration and dosing details are per the protocol and will be managed by the study team at the clinical site.

Who should consider this trial

Good fit: Ideal candidates are postmenopausal women aged 46–60 with BMI ≥30 (or ≥27 with adiposity-related conditions) who experience ≥28 bothersome hot flashes per week, can self-inject, and can follow a hypocaloric diet.

Not a fit: Women who do not meet the age, BMI, or hot-flash frequency criteria, who cannot self-inject or adhere to the diet, or who have contraindications to tirzepatide are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, tirzepatide could reduce hot flash frequency and severity and improve biological-aging markers while also delivering weight loss and metabolic benefits.

How similar studies have performed: GLP-1 and dual GLP-1/GIP agonists including tirzepatide have shown strong weight-loss and metabolic benefits in other trials, but applying tirzepatide specifically to menopausal hot flashes and biological aging is a novel approach with limited prior evidence.

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.

Where this trial is running

Jacksonville, Florida

• Mayo Clinic in Florida — Jacksonville, Florida, United States (RECRUITING)

Study contacts

• Principal investigator: Chrisandra Shufelt, MD — Mayo Clinic
• Study coordinator: Aubri Robbins, BHSc

Conditions: Obesity, Menopause Hot Flashes, Hot flashes, menopause, Tirzepatide, GLP