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

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.