What is the best type of estrogen to take?

Best Type of Estrogen for Hormone Replacement Therapy

Transdermal 17β-estradiol is the superior choice for estrogen replacement therapy, delivering physiologic estradiol levels while avoiding the cardiovascular and thrombotic risks associated with oral formulations. 1

Primary Recommendation: Transdermal 17β-Estradiol

The optimal regimen consists of transdermal 17β-estradiol patches delivering 50-100 mcg/day applied twice weekly, combined with oral micronized progesterone 200 mg daily for 12-14 days per month in women with an intact uterus. 1, 2

Why Transdermal is Superior

• Transdermal estradiol has a neutral effect on venous thromboembolism risk (OR 0.9), whereas oral estradiol significantly increases VTE risk (OR 4.2). 1
• Transdermal administration avoids first-pass hepatic metabolism, eliminating adverse hepatic effects including increased SHBG, renin substrate, and coagulation factors that occur with oral estrogen. 1, 3
• Blood pressure and metabolic profiles are more favorable with transdermal versus oral estradiol. 1
• Transdermal delivery maintains physiological estrone-to-estradiol ratios, mimicking natural ovarian hormone production. 4

Specific Formulation Options

Patches (Preferred)

• Start with 50 mcg/24-hour patches applied twice weekly (every 3-4 days) to clean, dry skin on the lower abdomen, buttocks, or upper outer arm, rotating sites to minimize irritation. 1
• If symptoms persist after 2-3 months, increase to 100 mcg/24-hour patches applied twice weekly. 1
• Maximum maintenance dosing typically reaches 100-200 mcg/day for optimal symptom control. 1
• Seven-day patches (Climara) are available and show sustained blood levels for the full 7 days with excellent adhesion, though twice-weekly patches remain standard. 4

Gels (Alternative)

• Transdermal estradiol gel 0.1% at doses of 0.87-2.6 g/day (delivering 0.0125-0.027 mg estradiol daily) effectively reduces vasomotor symptoms and vaginal atrophy. 5, 6
• The lowest effective dose of 0.87 g/day gel produces the fewest adverse events while maintaining efficacy. 6

Critical Endometrial Protection Requirement

Women with an intact uterus must receive progestin supplementation to prevent endometrial hyperplasia and cancer—this is non-negotiable. 1

Progestin Regimen Options

• First choice: Oral micronized progesterone 200 mg daily for 12-14 days every 28 days (sequential regimen). 1, 2
• Second choice: Medroxyprogesterone acetate 10 mg daily for 12-14 days monthly. 1, 2
• Third choice: Dydrogesterone 5-10 mg daily for 12-14 days monthly. 7
• Continuous combined option: Combined estradiol/levonorgestrel patches applied continuously to avoid withdrawal bleeding. 1

What NOT to Use

Never use ethinyl estradiol patches for hormone replacement therapy, as this synthetic estrogen carries significantly higher thrombotic risk than bioidentical 17β-estradiol. 1

Dose Equivalency for Context

• A 100 mcg/day transdermal estradiol patch is approximately equivalent to 2 mg oral micronized estradiol daily. 1
• However, transdermal delivery is strongly preferred despite this equivalency due to superior safety profile. 1

Monitoring and Follow-Up

• Once established on therapy, conduct annual clinical review paying particular attention to compliance. 7
• No routine monitoring tests are required but may be prompted by specific symptoms or concerns. 7

Common Pitfalls to Avoid

• Local skin irritation occurs in approximately 15% of women using transdermal patches but is rarely severe enough to discontinue therapy. 8
• Failing to add progestin in women with an intact uterus creates unacceptable endometrial cancer risk. 1
• Using oral estradiol when transdermal is available unnecessarily increases cardiovascular and thrombotic risk. 1