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

Inclusion Criteria 1. Females 2. Age 46-60 years old. 3. BMI ≥30 kg/m2 or BMI ≥27 kg/m2 in the presence of adiposity-associated diseases (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease). 4. Presence of bothersome hot flashes (an average of ≥ 28 episodes during a consecutive 2-week period with symptom severity sufficient to have prompted the participant to seek therapeutic treatment). 5. Hot flashes must be present for \>30 days prior to study entry. 6. Willingness to self-inject drug 7. Provided informed consent to be part of the study. 8. Willingness and capability to follow an individualized hypocaloric diet designed to achieve an approximate energy deficit of 500 kcal/day relative to estimated total daily energy requirements. Daily energy requirements will be calculated using Harris-Benedict equation to estimate resting energy expenditure and multiplied by a sedentary physical activity factor of 1.2. Prescribed daily caloric intake will not be less than 1,000 kcal/day. Participants must also be willing to engage in at least 150 minutes per week of moderate-intensity or greater physical activity. Exclusion Criteria 1. Current or recent use (past 4 weeks) treatment with menopausal hormone therapy. 2. Any current, recent use (past 4 weeks), or planned use of: 1. Estrogen-containing contraceptive methods or menopausal hormone therapy (oral, transdermal, high dose vaginal ring, injection, pellets). 2. Vaginal estrogen. 3. Androgens. 4. Progestogens. 3. Current or recent use (past 4 weeks) treatment for menopausal symptoms with cognitive behavioral therapy and/or hypnosis. 4. Current or recent use (past 4 weeks) of fezolinetant or elinzanetant. 5. Menopause as a result of cancer treatments. 6. Impaired renal function (GFR ≤30 ml/min/1.73 m²). 7. Thyroid-stimulating hormone ≥7 with low free T4. 8. 10-year ASCVD risk \> 7.5%. 9. Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignancy, or uncontrolled psychiatric disease. 10. \>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). 11. Other obesity medication was used within the past 3 months. 12. History of bariatric surgery. Prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty performed \> 1 year before screening). 13. Past or intended endoscopic and/or device-based therapy or removal within last six months. 14. Use of weight gain-promoting medications (including tricyclic antidepressants, atypical antipsychotics, and mood stabilizers), unless the participant has been receiving the medication at a stable dose for ≥3 months prior to enrollment and has maintained a stable body weight during that time 15. Current or recent (within 3 months) use of chronic systemic glucocorticoid therapy for over 2 weeks within the past 3 months. 16. Female who is pregnant, breastfeeding, or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method. 17. 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. 18. 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. 19. Planned surgical procedures requiring general anesthesia or sedation during the study or within 2 weeks following the last dose of study drug.