What is the recommended dosage of estradiol (estrogen) tablets for a postmenopausal woman?

Estradiol Tablet Dosage for Postmenopausal Women

Start with oral estradiol 1-2 mg daily, using the lowest effective dose that controls symptoms, and always add progestin (micronized progesterone 200 mg at bedtime for 12-14 days per month) if the uterus is intact. 1

Standard Oral Dosing Regimen

The FDA-approved initial dosage range for oral estradiol tablets is 1-2 mg daily, adjusted to control presenting symptoms, with administration typically cyclic (3 weeks on, 1 week off). 1

• The minimal effective dose should be determined by titration after initiating therapy at 1-2 mg daily 1
• Treatment should be reevaluated every 3-6 months to determine if therapy is still necessary 1
• Lower doses (0.5-1 mg daily) have demonstrated effectiveness for vasomotor symptoms and bone loss prevention in research studies, though 1-2 mg remains the standard FDA-approved starting range 2, 3

Critical Progestin Requirements for Women with Intact Uterus

Women with an intact uterus must receive concurrent progestin supplementation to prevent endometrial cancer, which increases 10- to 30-fold with unopposed estrogen after 5+ years of use. 4, 1

• First-line progestin: Micronized progesterone 200 mg orally at bedtime for 12-14 days every 28 days (sequential regimen) 5, 6
• Alternative sequential options include medroxyprogesterone acetate 10 mg daily for 12-14 days per month or dydrogesterone 10 mg daily for 12-14 days per month 7, 5
• Continuous combined regimens (daily progestin) can be used to avoid withdrawal bleeding, requiring medroxyprogesterone acetate 2.5 mg daily or dydrogesterone 5 mg daily 7
• Adding progestin reduces endometrial cancer risk by approximately 90% compared to unopposed estrogen 4

Important Clinical Considerations

Transdermal estradiol patches (50 mcg/24-hour applied twice weekly) are strongly preferred over oral tablets due to superior cardiovascular and thrombotic safety profiles. 5, 6

• Oral estradiol increases VTE risk (OR 4.2) compared to transdermal estradiol (OR 0.9) due to hepatic first-pass metabolism 5
• If oral route is chosen due to patient preference or contraindications to patches, use the lowest effective dose (1-2 mg daily) 1
• Women without a uterus (post-hysterectomy) can use estrogen-alone therapy without progestin 1

Dose Titration Strategy

• Start at 1 mg daily for most postmenopausal women 1, 3
• If symptoms persist after 2-3 months, increase to 2 mg daily 1
• Attempt to taper or discontinue medication at 3-6 month intervals once symptoms are controlled 1
• The goal is the lowest effective dose for the shortest duration consistent with treatment goals 1

Common Pitfalls to Avoid

• Never prescribe oral estradiol alone to women with an intact uterus—this dramatically increases endometrial cancer risk (RR 2.3-9.5) 4
• Do not initiate HRT solely for chronic disease prevention (osteoporosis, cardiovascular disease) in asymptomatic women—this carries a Grade D recommendation against use 4
• Avoid starting doses higher than 2 mg daily, as this increases adverse events without additional benefit 1, 8
• Do not continue therapy indefinitely without periodic reassessment—breast cancer risk increases after 4-5 years of combined therapy 4

Absolute Contraindications

• Active or history of breast cancer 4
• Active or history of venous thromboembolism or stroke 4
• Active liver disease 4
• Coronary heart disease or myocardial infarction 4
• Antiphospholipid syndrome 4

Risk-Benefit Data for Informed Consent

For every 10,000 women taking combined estrogen-progestin for 1 year: 4

• 8 additional invasive breast cancers
• 8 additional strokes
• 8 additional pulmonary emboli
• 7 additional coronary heart disease events
• Balanced against: 75% reduction in vasomotor symptoms, 5 fewer hip fractures, 6 fewer colorectal cancers