Bi-Est (Estriol 80% / Estradiol 20%)

Cream

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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Disclaimer: Images are for reference only; actual products may vary.

Product Overview

Estriol 1-4

Micronized estriol is a bioidentical form of estriol (E3), one of the three naturally occurring estrogens in women, along with estradiol and estrone. Estriol is considered the weakest estrogen, exhibiting significantly lower receptor binding affinity and a shorter duration of action compared to estradiol (E2). Despite its lower potency, estriol has demonstrated potential skin-related effects, including support for dermal thickness and elasticity. Estriol is most commonly used in combination with estradiol in postmenopausal women experiencing 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 utilized in various hormone therapy (HT) regimens and is often considered a preferred estrogen option for menopausal women due to its bioidentical composition and favorable risk profile when appropriately prescribed. When administered topically and absorbed transdermally or via subcutaneous implantation, micronized estradiol bypasses first-pass hepatic metabolism. This route of administration contributes to its favorable risk profile, as first-pass metabolism of estradiol is associated with greater increases in thromboembolic factors.

BIEST is most commonly compounded as a transdermal cream to allow for more precise and incremental dose adjustments. Any BIEST formulation must specify an estriol-to-estradiol ratio, with the most commonly used ratios being 80/20 (80% estriol and 20% estradiol) and 50/50 (50% estriol and 50% estradiol). In addition to the ratio, the concentration is typically defined in milligrams per gram (mg/g). For example, BIEST 80/20 10 mg/g provides 8 mg of transdermal estriol and 2 mg of transdermal estradiol per gram of cream, within acceptable pharmacy compounding variance not to exceed ±10%.

Note: Transdermal refers to application to the skin, as opposed to intravaginal administration.

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 risk.

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

WPPL operates as a 503A compounding pharmacy and prepares individualized prescription medications pursuant to provider direction. Compounded preparations are not reviewed, tested, or approved by the FDA.

This listing also includes commercially manufactured products for convenience; these items are not compounded by our pharmacy and are sold as provided by their manufacturers. Actual products in stock at time of dispensing may vary due to supply chain variability. Any statements regarding non-compounded products are manufacturer-supplied, have not been evaluated by the FDA, and are not intended to diagnose, treat, cure, or prevent any disease. WPPL does not verify or endorse any therapeutic claims made by manufacturers. Please refer to original labeling for complete product information.

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