Estriol Vaginal Preparations Are NOT FDA-Approved in the United States
Estriol vaginal preparations are not commercially available as FDA-approved products in the United States, though they can be obtained through compounding pharmacies. The FDA has only approved estradiol-based vaginal products (creams, tablets, and rings) for treatment of vaginal atrophy, not estriol formulations 1.
Available FDA-Approved Vaginal Estrogen Products in the US
The following estradiol-based vaginal preparations are FDA-approved and commercially available 1, 2:
- Estradiol vaginal tablets (e.g., Vagifem) - typically 10 μg estradiol
- Estradiol vaginal cream (e.g., Estrace) - 0.01% concentration
- Estradiol vaginal ring (e.g., Estring) - sustained-release formulation delivering estrogen over 3 months
- Conjugated estrogens vaginal cream (Premarin) - FDA-approved for moderate-to-severe dyspareunia
Estriol Availability Through Compounding
While not FDA-approved, estriol vaginal preparations can be obtained through compounding pharmacies in the US 3. Compounded preparations are not subject to the same rigorous FDA approval process and may have variable quality, potency, and consistency 3. The average cost of compounded estrogen products is approximately $42, representing significant savings compared to branded FDA-approved preparations ($82-138) 3.
Clinical Context: Why Estriol Is Discussed
Estriol is mentioned in clinical guidelines as potentially preferable for certain populations, particularly women on aromatase inhibitors for breast cancer, because estriol is a weaker estrogen that cannot be converted to estradiol 1, 4. However, this recommendation refers to products available in other countries (such as Ovestin in Europe), not FDA-approved US products 1.
Pharmacokinetic Evidence
Research demonstrates that 0.5-1 mg estriol applied vaginally produces plasma concentrations similar to 8-12 mg given orally, with peak levels of 0.5-0.6 nmol/L achieved 1-2 hours after application 5, 6. Vaginal administration circumvents first-pass hepatic metabolism, allowing more standardized dosing 6.
Important Clinical Caveat
If a patient specifically needs estriol-based therapy (such as breast cancer survivors on aromatase inhibitors), they would need to obtain it through a compounding pharmacy, understanding that this represents off-label, non-FDA-approved use 1, 3. For most patients with vaginal atrophy, FDA-approved low-dose estradiol vaginal preparations remain the standard of care with excellent efficacy and safety data 1, 2.