What Is Estriol / Estradiol Vaginal?
It is a compounded vaginal preparation that combines two estrogens — estriol (weaker) and estradiol (stronger) — in the water-free Ellage® Anhydrous base. This estriol-plus-estradiol mix is often called "Biest." Prescribers use vaginal estrogens for local symptoms of the genitourinary syndrome of menopause (GSM). It is prepared by prescription for an individual patient.
How the Ingredients Work
Estradiol (E2) — the Potent Estrogen
Estradiol is the most active estrogen. In a Biest formulation, even though estriol makes up most of the amount (about 80%), estradiol accounts for most of the estrogen activity, having roughly 80 times the potency of estriol. Wikipedia
Estriol (E3) — the Weak Estrogen
Estriol is a low-potency estrogen that acts locally on vaginal tissue. Applied locally, low-dose vaginal estrogen treats vaginal atrophy/GSM and carries a very low risk of the serious effects associated with systemic estrogen. uspto
What Is It Used For?
Vaginal estrogen is used for GSM symptoms such as vaginal dryness, frequent UTIs, overactive bladder, and painful sex, but it does not help with hot flashes or night sweats. Selection and use are the prescriber's clinical decision. uspto
Is It FDA-Approved?
No. This compounded estriol-plus-estradiol (bi-est) combination is not FDA-approved. Estriol is not available as an FDA-approved product in the United States, although FDA-approved estradiol vaginal products — such as estradiol vaginal cream and suppositories — do exist. Compounding may be chosen when a prescriber wants a custom strength, ratio, or base. Wikipediauspto
What Should I Know About Compounded Hormones?
Compounded bioidentical hormones are not FDA-regulated for menopause and do not come with the standardized package insert and boxed-warning risk information that FDA-approved products carry, which can lead patients to assume they are safer or more "natural". In addition, the amount of estrogen absorbed from a compounded estradiol cream can differ from FDA-approved products, so accurate dosing and follow-up matter. Whether to use a compounded preparation is a decision between a patient and their prescriber. DiscreetKetamineScienceDirect
Safety Information
As a class, estrogens carry warnings, including boxed warnings on labeling. At the same time, low-dose vaginal estrogen shows minimal systemic absorption and a low risk of serious effects compared with systemic estrogen. Patient selection, dosing, and monitoring are the prescriber's responsibility.
Quality and Compliance — Hazardous Drug Handling
Because estrogens are handled as hazardous drugs, Mixwell prepares this preparation in a purpose-built lab that meets USP <795> standards for non-sterile compounding and USP <800> standards for hazardous drugs, including HD negative-pressure containment. It is dispensed only with a valid prescription for an individual patient. Mixwell is a non-sterile pharmacy and does not prepare sterile products or injectables. Compounded medications are not reviewed or approved by the FDA. Nothing here promises a specific result, and compounded preparations are not presented as superior to commercially available products.
References
- The NAMS 2020 GSM Position Statement Editorial Panel. The 2020 Genitourinary Syndrome of Menopause Position Statement of The North American Menopause Society. Menopause. 2020;27(9):976–992.
- Files JA, Ko MG, Pruthi S. Bioidentical Hormone Therapy. Mayo Clin Proc. 2011;86(7):673–680.
- Comparative estrogen exposure from compounded transdermal estradiol creams and FDA-approved transdermal estradiol gels and patches. Menopause. 2023.
- The 2022 Hormone Therapy Position Statement of The North American Menopause Society Advisory Panel. Menopause. 2022;29(7):767–794. doi:10.1097/GME.0000000000002028.
- Professional Compounding Centers of America (PCCA). Formulation science and compounding resources. https://www.pccarx.com/Blog/
