The goal of this clinical trial is to learn if neurokinin-1/neurokinin-3 receptor antagonist elinzanetant improves blood vessel health in women with moderate to severe hot flashes. The main questions it aims to answer is does neurokinin-1/neurokinin-3 receptor antagonist elinzanetant improve blood vessel health?

Inclusion Criteria:

• Age 40-65 years

• Peri- and post-menopausal women (STRAW -1 to +1)

• Moderate or high vasmotor symptom burden

• Cardiometabolic disease (as evidenced by ≥ 2 of the following):

  • Obesity (body mass index ≥ 30 kg/m2)
  • Elevated waist circumference (≥ 88 cm)
  • Elevated triglycerides (≥ 150 mg/dL or drug treatment)
  • Reduced HDL-cholesterol (<50 mg/dL or drug treatment)
  • Elevated blood pressure (≥ 130 mmHg systolic blood pressure or ≥ 85 mmHg diastolic blood pressure, or drug treatment)
  • Elevated fasting glucose (≥ 100 mg/dL or drug treatment)

Exclusion Criteria:

• Inability to provide informed consent or comply with study protocol
• Major comorbidities: cancer, end-stage renal (eGFR <45 mL/min/1.73 m2), liver or lung disease
• Concomitant use of strong or moderate cytochrome P450 3A4 inhibitors
• Elevated liver function tests (ALT, AST, and/or total bilirubin ≥2x ULN)
• Undiagnosed uterine bleeding over past 6 months