(Estriol 80% / Estradiol 20%)
Available Dosage Strengths
0.5 mg/gm | 1 mg/gm | 1.25 mg/gm | 1.5 mg/gm | 2 mg/gm | 2.5 mg/gm | 3 mg/gm | 4 mg/gm | 5 mg/gm
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Estriol 1-4
Micronized estriol is a bioidentical form of estriol (E3)—one of the three naturally occurring estrogens in women (alongside estradiol and estrone). Estriol is the weakest estrogen, with a much lower receptor binding affinity and duration of action than estradiol (E2). Though the weakest estrogen, estriol shows potential for skin-rejuvenating properties such as restoring dermal thickness and elasticity. Estriol is most commonly used along with estradiol in postmenopausal women with estrogen-deficiency.
Estradiol 1,5-11
Micronized estradiol is a bioidentical form of 17β-estradiol, the primary estrogen produced by the ovaries in premenopausal women. It is used in a variety of hormone therapy (HT) regimens and can be considered one of the preferred estrogen formulations for menopausal women due to its bioidentical structure and favorable risk profile when appropriately prescribed. When applied topically and absorbed transdermally or implanted subcutaneously, micronized estradiol does not undergo first-pass metabolism through the liver, this leads to the favorable risk profile as the first pass-effect of estradiol causes the greatest increases in thromboembolic factors.
Most commonly, BIEST is compounded into a transdermal cream for more incremental dosing adjustments. A ratio between the Estriol/Estradiol must be included in any BIEST formulation; the most common ratios observed are 80/20 (80% estriol, 20% estradiol) and 50/50 (50% estriol, 50% estradiol). In addition to the ratio, a concentration must be defined typically as mg/gm (milligram per gram), for instance, BIEST 80/20 10mg/gm gives 8mg transdermal estriol and 2mg transdermal estradiol, in 1 gram of cream (within acceptable variance as allowed by the pharmacy not to exceed +/- 10%). Note: transdermal refers to being applied to the skin, as opposed to intravaginal application)
Estriol 1-4 acts by binding to estrogen receptors alpha (ERα) and beta (ERβ) in estrogen-responsive tissues, particularly the vaginal epithelium, bladder, urethra, and pelvic floor musculature.
Mechanisms and Effects:
– Can help restore vaginal epithelial thickness and improves cell maturation index
– Improves blood flow, elasticity, and lubrication of vaginal tissues
– Locally can improve thickening of dermal-epidermal junction, potentially improving skin firmness
– May exert cytoprotective and anti-inflammatory effects on urogenital tissues
Estradiol 1,5-11 binds estrogen receptors, which are widely distributed in reproductive tissues, the brain, bone, liver, and vasculature. Upon receptor binding, estradiol influences gene transcription, leading to a broad range of systemic and local effects:
– Endometrial stimulation: Promotes proliferation in the endometrial lining.
– Thermoregulatory effects: May relieve hot flashes by stabilizing hypothalamic activity.
– Bone preservation: May reduce osteoclast-mediated bone resorption, maintaining bone mineral density.
– Vaginal and urogenital health: Helps to maintain epithelial integrity, pH balance, and blood flow.
– Neuroprotection: Modulates neurotransmitter systems that affect mood, cognition, and sleep.
– Cardiovascular modulation: Promotes vasodilation and improves lipid profile, although the route of administration affects cardiovascular ris
Common1-11
Local side effects:
– Transient burning, itching, or discharge
– Spotting or light bleeding (usually resolves quickly)
– Increased vaginal secretions
– Breast tenderness
– Nausea
– Headache
– Bloating or fluid retention
– Breakthrough vaginal bleeding
– Mood swings
– Endometrial hyperplasia or cancer if unopposed by a progestogen in women with a uterus
Contraindications: 1-11
– Undiagnosed abnormal genital bleeding
– Active or history of estrogen-dependent cancer (e.g., breast, endometrial)
– Active or recent thromboembolic disorders (e.g., DVT, PE, stroke, heart attack)
– Active liver disease
– Known hypersensitivity to estradiol or formulation components
Precautions: 1-11
Use caution in women with:
– Controlled hypertension
– Migraine with aura
– Hypertriglyceridemia
– Diabetes mellitus
– History of gallbladder disease
– History of or active hormone-sensitive cancers
*Use with Progesterone:
For women with an intact uterus, progesterone in some form should be included with systemic estradiol therapy to prevent endometrial hyperplasia or carcinoma
Store in a cool, dry place, away from direct light and heat; Room temperature (20°C–25°C / 68°F–77°F) is ideal. Keep out of reach of children and pets.
1. Cynthia A. Stuenkel, Susan R. Davis, Anne Gompel, Mary Ann Lumsden, M. Hassan Murad, JoAnn V. Pinkerton, Richard J. Santen, Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 11, 1 November 2015, Pages 3975–4011, accessed July 2025 through: https://doi.org/10.1210/jc.2015-2236
2. North American Menopause Society (NAMS) Position Statement on Hormone Therapy (2022) Supports vaginal estrogen (including estriol) for GSM with minimal systemic risks; accessed July 2025 through: https://www.menopause.org/docs/default-source/professional/2022-nams-ht-position-statement.pdf
3. NIH DailyMed, Estriol; accessed July 2025 though: https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=estriol
4. Estriol: A Comprehensive Guide for Patients; accessed July 2025 through: https://clinicaltrials.eu/inn/estriol/
5. Rzepecki AK, Murase JE, Juran R, Fabi SG, McLellan BN. Estrogen-deficient skin: The role of topical therapy. Int J Womens Dermatol. 2019 Mar 15;5(2):85-90. Accessed July 2025; doi: 10.1016/j.ijwd.2019.01.001. PMID: 30997378; PMCID: PMC6451761
6. FDA Drug Label – Estradiol cream by Teva Pharmaceuticals accessed July 2025 through: https://fda.report/DailyMed/8cb31c7c-fba8-4201-833d-844ea1a8a4de
7. MedlinePlus Drug Information – Estradiol: https://medlineplus.gov/druginfo/meds/a605021.html
8. North American Menopause Society (NAMS) Position Statement (2022): “The 2022 Hormone Therapy Position Statement of The North American Menopause Society” https://www.menopause.org/docs/default-source/professional/2022-nams-ht-position-statement.pdf
9. Sobel TH, Shen W. Transdermal estrogen therapy in menopausal women at increased risk for thrombotic events: a scoping review. Menopause. 2022 Jan 14;29(4):483-490. doi: 10.1097/GME.0000000000001938. PMID: 35357370.
10. Canonico, M., Oger, E., Plu-Bureau, G., Conard, J., Meyer, G., Lévesque, H., … & Scarabin, P. Y. (2007). Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation, 115(7), 840-845.
11. Clinical Pharmacology estradiol clinical monograph accessed July 2025 through: https://www.clinicalkey.com/pharmacology/monograph/1330?n=Estradiol
This sheet is a summary. It may not cover all possible drug information about this product. Call your doctor for medical advice and/or about side effects. You may report side effects to the FDA at 1-800-FDA-1088. A Wells Pharmacy Network pharmacist will be happy to answer any questions. For consultation, please call 1-800-622-4510.
