Ethinyl Estradiol

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Ethinylestradiol Template:Pron-en, also ethinyl estradiol (EE), is a derivative of estradiol. Ethinyl estradiol is an orally bio-active estrogen used in almost all modern formulations of combined oral contraceptive pills (the Pill). It is one of the most commonly used medications. Most commonly sold as NuvaRing.

The first orally active synthetic steroidal estrogen, ethinylestradiol (17α-ethynylestradiol), the 17α-ethynyl analog of estradiol, was synthesized in 1938 by Hans Herloff Inhoffen and Walter Hohlweg at Schering AG in Berlin.<ref name="Inhoffen 1938">Inhoffen HH, Hohlweg W (February 11, 1938). "Neue per os-wirksame weibliche Keimdrüsenhormon-Derivate: 17-Aethinyl-oestradiol und Pregnen-in-on-3-ol-17 (New female glandular derivatives active per os: 17α-ethynyl-estradiol and pregnen-in-on-3-ol-17)". Naturwissenschaften 26 (6): 96. </ref><ref name="Maisel 1965">Template:Cite book</ref><ref name="Petrow 1970">Petrow V (1970). "The contraceptive progestagens". Chem Rev 70 (6): 713–26. doi:10.1021/cr60268a004. PMID 4098492. </ref><ref name="Sneader 2005">Template:Cite book</ref><ref name="Djerassi 2006">Djerassi C (2006). "Chemical birth of the pill". Am J Obstet Gynecol 194 (1): 290–8. doi:10.1016/j.ajog.2005.06.010. PMID 16389046. </ref>

Ethinylestradiol was approved by the FDA in the U.S. on June 25, 1943 and marketed by Schering as Estinyl.<ref name="Estinyl 1943">Template:Cite web search: Estinyl</ref> The FDA withdrew approval of Estinyl effective June 4, 2004 at the request of Schering, who had discontinued marketing Estinyl.<ref name="Estinyl 2004">FDA (May 5, 2004). "Schering Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications. Notice". Fed Regist 69 (87): 25124–30. </ref>

While estradiol is readily absorbed when taken orally, it is also quickly inactivated by the liver. Substitution at C17 of the estrane steroid with an ethinyl group proved to provide an estrogen that is much more resistant to degradation and paved the way for the development of oral contraceptives.

EE is absorbed in the small intestine and reaches a serum peak about 2 hours later. It undergoes extensive metabolism in the liver involving the cytochrome P450 3A4 isoenzyme. EE and its metabolites are in excreted with the bile. Due to the effect of enterohepatic circulation a second peak is seen several hours later. Individually, wide variations exist in the overall absorption process, and can be further modified by drugs (i.e. antibiotics) that affect the enterohepatic circulation or liver enzymes. In circulation EE is almost fully bound to plasma albumin. It is metabolized by hydroxylation of the aromatic ring and excreted in both, feces and urine, in part as glucuronide and sulfate conjugate.

EE is hormonally effective by activating the estrogen receptor and thus is an estrogen. It finds its most common use in the estrogen-progestin combination preparations of oral contraceptives. Over time, formulations have decreased the EE dose from as high as 100 μg to as low as 20 μg.

The same contraindications and precautions apply for EE as with other estrogen medications.

Estinyl was a preparation of EE alone that was used for the management of menopausal symptoms and female hypogonadism.<ref>RxList.com - Estinyl (ethinyl estradiol)</ref>

EE is released into the environment as a xenoestrogen from the urine and feces of people who take it as a medication.

[edit] Melting Point

183 deg C EXP

[edit] log P

3.67 EXP

[edit] Water Solubility

11.3 mg/L 27 EXP

[edit] Vapor Pressure

2.67E-09 mm Hg 25 EST

[edit] Henry's Law Constant

7.94E-12 atm-m3/mole 25 EST

[edit] Atmospheric OH Rate Constant

|1.25E-10 cm3/molecule-sec 25 EST

[edit] Adverse Reactions / Side Effects

Abnormal growth filled with fluid or semisolid material; accidental injury; bladder pain; bloated full feeling; bloody or cloudy urine; body aches or pain; coating or white patches on tongue; congestion; cough producing mucus; decrease in amount of urine; difficult, burning, or painful urination; discouragement; dryness of throat; ear congestion or pain; excess air or gas in stomach or intestines; fear; feeling of warmth; feeling sad or empty; frequent urge to urinate; general feeling of discomfort or illness; headache, severe and throbbing; increased clear or white vaginal discharge; irritability; itching of the vaginal, rectal or genital areas; lack of appetite; lack or loss of strength; loss of interest or pleasure; mild dizziness; neck pain; nervousness; pain; pain during sexual intercourse; painful or difficult urination; pain or tenderness around eyes and cheekbones; passing gas; redness of the face, neck, arms and occasionally, upper chest; runny nose; skin irritation or redness where skin patch was worn; shivering; sleeplessness; sneezing; sore mouth or tongue; stuffy nose; sudden sweating; tender, swollen glands in neck; thick, white vaginal discharge with no odor or with a mild odor; tiredness; trouble concentrating; trouble sleeping; unable to sleep; voice changes

[edit] Medication Interactions

Ask your doctor before using any of these medicines with Ethinylestradiol:

   * Acetaminophen (e.g., Tylenol) (with long-term, high-dose use)
   * Amiodarone (e.g., Cordarone)
   * Anabolic steroids (Nandrolone [e.g., Anabolin], Oxandrolone [e.g., Anavar], Oxymetholone [e.g., Anadrol, Stanozolol [e.g., Winstrol])
   * Androgens (male hormones)
   * Anti-infectives by mouth or by injection (medicine for infection)
   * Antithyroid agents (medicine for overactive thyroid)
   * Carbamazepine (e.g., Tegretol)
   * Carmustine (e.g., BiCNU)
   * Chloroquine (e.g., Aralen)
   * Dantrolene (e.g., Dantrium)
   * Daunorubicin (e.g., Cerubidine)
   * Disulfiram (e.g., Antabuse)
   * Divalproex (e.g., Depakote)
   * Etretinate (e.g., Tegison)
   * Gold salts (medicine for arthritis)
   * Hydroxychloroquine (e.g., Plaquenil)
   * Isoniazid
   * Mercaptopurine (e.g., Purinethol)
   * Methotrexate (e.g., Mexate)
   * Methyldopa (e.g., Aldomet)
   * Naltrexone (e.g., Trexan) (with long-term, high-dose use)
   * Oral contraceptives (birth control pills) containing estrogen
   * Phenothiazines (Acetophenazine [e.g., Tindal], Chlorpromazine [e.g., Thorazine], Fluphenazine [e.g., Prolixin], Mesoridazine [e.g., Serentil], Perphenazine [e.g., Trilafon], Prochlorperazine [e.g., Compazine], Promazine [e.g., Sparine], Promethazine [e.g., Phenergan], Thioridazine [e.g., Mellaril], Trifluoperazine [e.g., Stelazine], Triflupromazine [e.g., Vesprin], Trimeprazine [e.g., Temaril])
   * Phenytoin (e.g., Dilantin)
   * Plicamycin (e.g., Mithracin)
   * Valproic acid (e.g., Depakene)— Use of these medicines with estrogens may increase the chance of problems occurring that affect the liver
   * Cyclosporine (e.g., Sandimmune)— Estrogens can prevent cyclosporine's removal from the body; this can lead to cyclosporine causing kidney or liver problems

[edit] Dosing

Depends on needs and age, see Consumer Information for more information.

[edit] Toxicity

[edit] See also

• Hormonal contraception
• Oral contraceptive formulations
• Diethylstilbestrol
• Esterified Estrogens
• Estradiol
• Estrone
• Estropipate
• Antineoplastic
• Osteoporosis prophylactic
• Ovarian hormone therapy
• Systemic Estrogen
• Birth Control

[edit] References

[edit] External links

• http://www.drugs.com/sfx/ethinyl-estradiol-side-effects.html
• http://www.drugs.com/cons/ethinyl-estradiol.html