Inclusion Criteria:

• Master female athletes:

  • Age ≥45-75 years

  • Physically active (≥ 7 hrs of structured endurance exercise per week)

  • Ongoing engagement in competitive events

• Older inactive females:

  • Age ≥45-75 years

  • Physically inactive (< 150 min of moderate physical activity per week)

• Older females on MHT:

  • Systemic estrogen therapy (same dose) for at least 9 months and initiated within 5 years of menopause including:

    • 17β-estradiol (oral; transdermal patch; or transdermal gel)

    • Oral conjugated estrogens

    • Ethinyl estradiol–containing combined hormonal contraceptives or similar preparations

    • Any progestogen used for endometrial protection (e.g., medroxyprogesterone acetate, norethindrone, norethindrone acetate, micronized progesterone, levonorgestrel intrauterine device)

Exclusion Criteria:

• Medical contraindications to exercise

• History of cardiovascular diseases

• Known ischemic heart disease

• Moderate or greater valvular heart disease or history of prior valve intervention

• Known structural heart disease (i.e., cardiomyopathy, current or history of heart failure)

• New cardiovascular symptoms with ongoing/incomplete cardiac workup

• Current smoker or previous heavy smoker (>15 pack years) who quit less than 12 months prior to enrollment

• Current musculoskeletal injuries

• Allergies to lidocaine

• Body-mass index ≥30 kg·m^-2 

• Pacemaker or implanted cardiac defibrillator

• Currently pregnant, breastfeeding or has been pregnant in the past year

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 03/23/2026. Questions regarding updates should be directed to the study team contact.