Estradiol

Estradiol is the primary female sex hormone. For healthspan, systemic hormone replacement therapy (HRT) in post-menopausal women aims to restore youthful physiological levels, which has been shown to preserve bone mineral density, improve cardiovascular markers, and support cognitive function. Its use is primarily focused on mitigating the broad systemic effects of menopause-related hormonal decline.

Verdict

A foundational healthspan intervention for post-menopausal women under medical supervision.

Protocol

• Oral: 1-2 mg daily.
• Transdermal Patch: 0.025 to 0.1 mg/day applied once or twice weekly.
• Topical Gel: 0.5 to 1.0 mg applied daily.
• Must be co-administered with progesterone in women with an intact uterus.

Flags

• Unopposed estrogen (without progesterone) increases risk of endometrial cancer in women with a uterus.
• Increased risk of venous thromboembolism (VTE) and stroke, particularly with oral formulations.
• May increase risk of certain breast cancers, a topic of ongoing research and debate.
• Contraindicated in individuals with a history of breast cancer, VTE, or certain liver diseases.
• Transdermal routes (patches, gels) avoid first-pass liver metabolism and carry a lower risk of blood clots compared to oral estradiol.