Oral to Transdermal Estradiol Dose Equivalency
A 100 mcg/day transdermal estradiol patch (applied twice weekly) is approximately equivalent to 2 mg of oral micronized estradiol daily. 1
Standard Dose Conversion
The established equivalency is 100 mcg/day transdermal estradiol = 2 mg oral estradiol, as confirmed by multiple guideline societies including the American College of Obstetricians and Gynecologists and the Endocrine Society 1
This translates to a 50 mcg patch applied twice weekly (every 3-4 days), which delivers approximately 100 mcg/day over the application period 1
The dose range for maintenance therapy is typically 100-200 mcg/day transdermal (equivalent to 2-4 mg oral estradiol daily) for optimal symptom control 1
Pharmacokinetic Rationale
Transdermal delivery achieves steady-state estradiol concentrations of approximately 35 pg/ml with a 50 mcg/day patch, compared to average concentrations of 418 pg/ml (12-fold higher) with 2 mg oral estradiol 2
Despite lower serum levels, transdermal estradiol provides equivalent therapeutic efficacy to oral formulations for controlling menopausal symptoms because it avoids first-pass hepatic metabolism and maintains more physiologic estradiol-to-estrone ratios 1, 3
Oral estradiol produces large concentration fluctuations (fluctuation index = 3.68) with peak levels of 1084 pg/ml occurring within 1 hour of administration, whereas transdermal delivery maintains constant levels (fluctuation index = 0.65) 2
The estradiol/estrone ratio approximates 1:1 with transdermal delivery, mimicking premenopausal physiology, compared to excessive estrone elevation with oral administration 3
Critical Safety Advantages of Transdermal Route
Transdermal estradiol has a neutral effect on venous thromboembolism risk (OR 0.9), whereas oral estradiol significantly increases VTE risk (OR 4.2) 1, 4
Transdermal administration avoids adverse hepatic effects including increased sex hormone-binding globulin, coagulation factors, and renin substrate that occur with oral estrogen 1, 4
Blood pressure and metabolic profiles are more favorable with transdermal versus oral estradiol, particularly important in young women with premature ovarian insufficiency 1, 4
Endometrial Protection Requirement
Women with an intact uterus must receive progestin supplementation regardless of whether they use oral or transdermal estradiol to prevent endometrial hyperplasia and cancer 1
The recommended regimen is 100-200 mg oral micronized progesterone daily for 12-14 days every 28 days (sequential regimen) 1, 4
Alternative progestins include 10 mg medroxyprogesterone acetate for 12-14 days monthly, though micronized progesterone is preferred for its physiological profile 4