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

Inclusion criteria

• Females
• 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 (an average of ≥ 28 episodes during a consecutive 2-week period with symptom severity sufficient to have prompted the participant to seek therapeutic treatment).
• Hot flashes must be present for \>30 days prior to study entry.
• Willingness to self-inject drug
• Provided informed consent to be part of the study.
• 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

• Current or recent use (past 4 weeks) treatment with menopausal hormone therapy.
• Any current, recent use (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 or recent use (past 4 weeks) treatment for menopausal symptoms with cognitive behavioral therapy and/or hypnosis.
• Current or recent use (past 4 weeks) of fezolinetant or elinzanetant.
• 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 was 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.
• 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
• Current or recent (within 3 months) use of chronic systemic glucocorticoid therapy for over 2 weeks within the past 3 months.
• Female who is pregnant, breastfeeding, or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
• 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.