Ethinyl estradiol (EE) is a synthetic estrogen derivative used alongside progestins in a large majority of combined oral contraceptives for better cycle control and to help prevent ovulation.
Abbreviation
EE
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Names
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CASRN
57-63-6
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PubChem CID
5991
ECHA InfoCard
IUPHAR/BPS
7071
DrugBank Accession Number
DB00977
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UNII
423D2T571U
KEGG Entry Number
D00554
Wikipedia Entry Name
Ethinylestradiol
ChEBI ID
CHEBI:4903
ChemSpider ID
5770
PDB
Ethinyl Estradiol
NIST
Ethinyl Estradiol
ATC Code(s)
Molecular Formula
C20H24O2
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Molecular Weight
296.403 g/mol
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Appearance
White or slightly yellowish-white, crystalline powder
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Melting Point
180-186 °C (if polymorphic modification: 142-146 °C)
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Solubility
BP: practically insoluble in water.
PubChem: 11.3 mg/L water at 27 °C.
PubChem, BP:
1 part in 6 of ethanol, 1 in 4 of ether, 1 in 5 of acetone, 1 in 4 of dioxane, and 1 in 20 of chloroform. Soluble in vegetable oils, and in solutions of fixed alkali hydroxides (e.g. NaOH, KOH)
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logP
3.67
Specific Optical Rotation
Pubchem/Toxnet:
[3.5°] at 24° C/D (c = 2 in dioxane); [-29.5°] at 24° C/D (c = 2 in pyridine)
USP: -28° to -29.5°, 50 mg/mL in colorless pyridine from a freshly opened container
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Vapor Pressure
1.95x10-9 mm Hg at 25° C (est)
Henry's Law Constant
7.94x10-12 atm-cu m/mol at 25° C (est.)
Polymorphism
Yes
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Storage Conditions
Protect from light
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GHS Hazard Code(s)
Class | Category | Code | Description |
---|---|---|---|
Acute Oral Toxicity | 4 | H302 | Harmful if swallowed |
Carcinogenicity | 1B | H350 | May cause cancer |
Carcinogenicity | 2 | H351 | Suspected of causing cancer if inhaled |
Reproductive Toxicity | 1A | H360 | May damage fertility or the unborn child |
Reproductive Toxicity, Effects On or Via Lactation | H362 | May cause harm to breast-fed children | |
Specific Target Organ Toxicity, Repeated Exposure | 1 | H372 | Causes damage to organs through prolonged or repeated exposure |
Side Effects
Adverse effects attributed to estrogenic and metabolic effects. Water and sodium retention, which may lead to weight gain, edema, and tender breast enlargement. Changes in libido and withdrawal vaginal bleeding. Liver function impairment, jaundice, and gallstones may occur. Headache, depression, dizziness, glucose intolerance, and a sensitivity to contact lenses have been reported. Nausea, vomiting and break through vaginal bleeding are not uncommon. Dermatological effects include chloasma, melasma, rashes, and urticaria. Erytheme multiforme and erytheme nodosum occur. Hypertension and thromoboembolic disease are reported.
Ortho Evra adverse effects: breast symptoms, headache, application site reaction, nausea, upper respiratory infection, menstrual cramps, abdominal pain.
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Carcinogenicity
There is sufficient evidence in humans for the carcinogenicity of post-menopausal estrogen therapy.
Mutagenicity
Not found to be mutagenic in the Ames Salmonella/microsome direct plate incorporation protocol.
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Genotoxicity
Not found to be genotoxic in human lymphocyte assay in vitro and mouse bone marrow micronucleus test in vivo.
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LD50
TDLo
human women: 0.21 mg/kg/21 days
TD50
rat, hepatic tumor: 0.2 mg/kg/day
MRTD
0.0005 mg/kg/day
Estrogen Receptor Activity
Agonist
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Bioavailability
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Elimination Half-Life (t1/2)
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Serum Protein Binding
97% bound. Mainly to serum albumin. No binding to SHBG, but induces SHBG synthesis.
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Metabolism
Metabolized by CYP3A4, CYP2C9, UGT
Excretion
Primarily in urine with sulfate and glucuronide conjugates. Some fecal excretion. Very small amounts excreted in milk.
Tmax
2-3 h
Enzyme Interactions
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Indications
For treatment of moderate to severe vasomotor symptoms associated with menopause, female hypogonadism, prostatic carcinoma-palliative therapy of advanced disease, breast cancer, as an oral contraceptive, and as emergency contraceptive.
Contributes to metabolism only to a small extent. Can be converted to methoxy EE by catechol O-methyltransferase.
Major metabolite. Formed by CYP3A4. Can be converted to the methoxy EE by catechol O-methyltransferase.