In mPTEN+/- mice, estriol treatments resulted in a 187.54% gain in the relative ratio of uterine wet weight to body weight; estriol also increases the ratio to 176.88% in wild-type mice. Estriol treatment (20 mg/kg ip), in vivo, sensitizes Kupffer cells to LPS via mechanisms dependent on an increase in CD14 by elevated portal blood endotoxin caused by increased gut permeability in rats; while one-half of the rats given estriol intraperitoneally 24 hours before an injection of a sublethal dose of LPS (5 mg/kg) died within 24 hours.

Absorption, Distribution and Excretion
Estriol is readily absorbed after vaginal administration. Peak serum estriol concentrations are typically observed within 2 hours of vaginal administration and remain elevated for up to 6 hours. Systemic bioavailability after vaginal administration is superior to oral administration. In women with senile vaginal epithelial atrophy, intravaginal administration of 1 mg estriol achieves serum levels similar to those of oral administration of 10 mg estriol. Following intravaginal application of Gynest cream, plasma estriol levels increase approximately 50-fold from <90 pmol/L (26 pg/mL) within several hours. Eight to 10 hours after administration, estriol levels remain above 90 pmol/L (26 pg/mL) in 50% of women. Estriol circulates in the bloodstream, with approximately 14% existing in free form, 8% bound to sex hormone-binding globulin (SHBG), and the remainder bound to albumin. Over 95% of estriol is excreted in the urine, primarily as glucuronide.

---

Metabolism/Metabolites
The main metabolites of estriol include 16-α-glucuronide, 3-glucuronide, 3-sulfate, and 3-sulfate 16-α-glucuronide.
Estrogen metabolic pathways include oxidative metabolism (primarily hydroxylation) and conjugation metabolism, the latter including glucuronidation, sulfonation, and/or O-methylation. Estradiol is converted to estrone by 17β-hydroxysteroid dehydrogenase; the resulting estrone is further metabolized to 16α-hydroxyestradiol, which is then converted to estriol.
Estriol is a common metabolite of estrone and estradiol-17β in animals and humans. In the human body, estriol is 2-hydroxylated and excreted in the form of conjugated and unconjugated 2-hydroxyestriol.

Toxicity Summary
Estriol levels can be used to assess the overall health of the fetus. The fetal adrenal cortex produces dehydroepiandrosterone sulfate (DHEA-S), which the placenta converts into estriol. Abnormally low levels of unbound estriol in the pregnant woman may indicate a problem with fetal development. This drug interacts with target cell receptors. When estrogen receptors bind to their ligands, they enter the target cell nucleus, regulating gene transcription and generating messenger RNA (mRNA). The mRNA interacts with ribosomes to produce specific proteins that express the effects of estriol on target cells. Estrogen increases the synthesis of sex hormone-binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins in the liver and inhibits the secretion of follicle-stimulating hormone (FSH) from the anterior pituitary gland. Toxicity Data
Oral (LD50): Acute: >2000 mg/kg [Rat].

Mol Cell Endocrinol.2010 May 14;320(1-2):162-70;Lab Invest.2006 Mar;86(3):286-96.

Therapeutic Uses
Estriol is indicated for hormone replacement therapy in postmenopausal women for atrophic vaginitis and vaginal atrophy. Estriol is indicated for the treatment of vulvar itching and dyspareunia associated with vaginal epithelial atrophy. Drug Warnings Gynest cream is not suitable for use during pregnancy. If pregnancy occurs while using Gynest cream, treatment should be discontinued immediately. Gynest cream contains peanut oil and is contraindicated in patients with known peanut allergies. Because peanut allergy may be associated with soy allergy, patients with soy allergies should also avoid using Gynest cream. A detailed personal and family medical history should be obtained before starting or restarting hormone replacement therapy. Physical examinations (including pelvic and breast examinations) should follow this guideline, along with contraindications and warnings. Regular follow-up examinations are recommended during treatment; the frequency and method of follow-up should be determined on a case-by-case basis. Women should be informed which changes in their breasts need to be reported to their doctor or nurse. Examinations, including mammograms, should be performed according to currently accepted screening methods and adjusted based on individual clinical needs. Long-term use of systemic estrogen alone increases the risk of endometrial hyperplasia and cancer. The safety of long-term or repeated use of topical vaginal estrogen on the endometrium is uncertain. Therefore, if repeated treatment is required, a follow-up examination should be conducted at least annually, with particular attention paid to any symptoms of endometrial hyperplasia or cancer. For more complete data on drug warnings regarding estriol (40 total), please visit the HSDB records page.

---

Pharmacodynamics
Estriol (also known as estriol) is one of the three main estrogens produced by the human body. It is only produced in large quantities by the placenta during pregnancy. Researchers at the UCLA Geffen School of Medicine found that estriol significantly reduced symptoms in pregnant women with multiple sclerosis (MS).

C18H24O3

288.39

288.172

50-27-1

Estriol (Standard);50-27-1;Estriol-d3;79037-36-8;Estriol-d2;53866-32-3;Estriol-d;55727-98-5;Estriol-13C3;1255639-56-5;Estriol-d3-1;2687960-79-6

5756

White to off-white solid powder

1.3±0.1 g/cm3

469.0±45.0 °C at 760 mmHg

280-282 °C(lit.)

220.8±23.3 °C

0.0±1.2 mmHg at 25°C

1.624

2.94

3

3

0

21

411

6

C[C@]12CC[C@H]3[C@H]([C@@H]1C[C@H]([C@@H]2O)O)CCC4=C3C=CC(=C4)O

PROQIPRRNZUXQM-ZXXIGWHRSA-N

InChI=1S/C18H24O3/c1-18-7-6-13-12-5-3-11(19)8-10(12)2-4-14(13)15(18)9-16(20)17(18)21/h3,5,8,13-17,19-21H,2,4,6-7,9H2,1H3/t13-,14-,15+,16-,17+,18+/m1/s1

(8R,9S,13S,14S,16R,17R)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,16,17-triol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 5% DMSO +95%Corn oil: 10 mg/mL

---

 (Please use freshly prepared in vivo formulations for optimal results.)