Conversion from Transdermal Estradiol Patch to Estradiol Cypionate
There is no established dose equivalency between transdermal estradiol patches and intramuscular estradiol cypionate, and this conversion is not recommended in clinical practice. The available guidelines and evidence exclusively address transdermal and oral estradiol formulations without providing conversion protocols to injectable estradiol cypionate 1.
Why This Conversion Is Problematic
Transdermal estradiol patches are the preferred first-line therapy and should not be converted to estradiol cypionate unless there are compelling contraindications to transdermal delivery. The evidence strongly supports transdermal 17β-estradiol as superior to other routes of administration due to:
- Cardiovascular safety: Transdermal estradiol has a neutral effect on venous thromboembolism risk (OR 0.9), whereas oral estradiol significantly increases VTE risk (OR 4.2) 1
- Metabolic advantages: Transdermal administration avoids adverse hepatic effects including increased SHBG, renin substrate, and coagulation factors that occur with oral or potentially injectable estrogen 1
- Stable hormone levels: A 0.1 mg (100 mcg/day) transdermal patch maintains sustained premenopausal estradiol levels throughout the week, with mean plasma concentrations of approximately 49-66 pg/mL 2
Available Estradiol Formulations and Equivalencies
If transdermal therapy must be discontinued, the evidence-based alternatives are:
Oral Estradiol (Third-Line Option)
- A 0.1 mg (100 mcg/day) transdermal estradiol patch is approximately equivalent to 2 mg of oral micronized estradiol daily 1
- However, oral estradiol carries significantly higher cardiovascular and thrombotic risk (OR 4.2 for VTE) compared to transdermal routes 1
Alternative Transdermal Options
- Combined estradiol/progestin patches (e.g., 50 mcg estradiol + 7 mcg levonorgestrel daily) can be used continuously to avoid withdrawal bleeding 3, 1
- Vaginal estradiol gel at doses of 0.5-1 mg daily provides another transdermal option 3
Critical Endometrial Protection Requirement
Regardless of estradiol formulation or route, women with an intact uterus must receive progestin supplementation to prevent endometrial hyperplasia and cancer 1, 4:
- First choice: 200 mg oral or vaginal micronized progesterone daily for 12-14 days every 28 days 3, 1
- Alternative: 10 mg medroxyprogesterone acetate for 12-14 days monthly 3
Clinical Recommendation
Continue the 0.1 mg transdermal estradiol patch rather than converting to estradiol cypionate. If patch therapy is truly not feasible due to skin reactions or patient preference, switch to 2 mg oral micronized estradiol daily with appropriate progestin coverage 1. Estradiol cypionate injections lack the evidence base, dosing guidelines, and safety profile established for transdermal and oral formulations in hormone replacement therapy.