Ethinyl estradiol
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| Non-proprietary name | Ethinylestradiol ( INN ) | |||||||||||||||||||||
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| Molecular formula | C 20 H 24 O 2 | |||||||||||||||||||||
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white to slightly yellowish white crystalline powder |
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| Molar mass | 296,40 g · mol -1 | |||||||||||||||||||||
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almost insoluble in water, readily soluble in various organic solvents |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||||||||
Ethinylestradiol is a synthetic drug from the group of estrogens . It is a derivative of the naturally occurring estradiol with an increased estrogenic effect and is mainly used for contraception .
Pharmacological properties
Like estradiol, ethinylestradiol acts as an agonist on the estrogen receptors found inside the cell . The additional ethynyl group at C-17 influences the pharmacokinetic properties in particular : Compared to estradiol, ethynylestradiol is subject to a significantly reduced first-pass effect in the liver, resulting in a significantly increased oral bioavailability .
Clinical information
Application areas (indications)
Ethinylestradiol is mainly used for contraception and, together with a progestin, serves as a typical ingredient in combined oral contraceptives ( birth control pills ). Other areas of application are hormone replacement therapy , palliative treatment for prostate cancer and various menstrual disorders such as primary and secondary amenorrhea .
dosage
With a typical birth control pill, the daily administered ethinylestradiol dose is now 20 to 35 micrograms. In the 1960s, dosages of 50 to 100 micrograms were still common.
Contraindications (contraindications)
Preparations containing ethinylestradiol should not be used in the following illnesses - acute or a history - (selection):
- Liver diseases , especially liver tumors
- Estrogen-dependent tumors of the uterus and mammary gland
- difficult-to-treat hypertriglyceridemia
- Pancreatitis
- Thromboembolic diseases
- unexplained vaginal bleeding
- Arterial hypertension (high blood pressure) that is difficult to control
- Diabetes mellitus with vascular changes
- Migraines with focal neurological symptoms
Use during pregnancy and breastfeeding
There is no indication for the use of ethinylestradiol during pregnancy . During breastfeeding , it should be noted that ethinylestradiol can pass into breast milk and also reduce its formation.
Drug interactions
Due to its pharmacokinetic properties, ethinylestradiol is subject to a variety of drug interactions . The first to be mentioned here are interactions with enzyme inducers of the cytochrome P450 enzyme system. Ethinylestradiol is v. a. Metabolized by CYP3A4 in the liver. Various drugs for the treatment of epilepsy ( anticonvulsants ) such as barbiturates , carbamazepine , phenytoin or primidone , but also the anti-infective rifampicin or the herbal antidepressant St. John's wort increase the expression of this enzyme, thus increasing the metabolism of ethinylestradiol, and reducing it - when used as part of the contraceptive pill - the contraceptive effect.
Ethinylestradiol is partially subject to an enterohepatic cycle . Conjugates with glucuronic acid or sulfate enter the intestine with the bile. There they are partly split by the intestinal flora, the unbound ethinylestradiol can be reabsorbed and act longer. When taking contraceptive pills with tetracyclines and various penicillins at the same time , decreased ethinylestradiol plasma levels have been observed. It is unclear whether this is actually due to an impairment of the enterohepatic circulation.
Adverse effects (side effects)
The most common side effects after taking ethinylestradiol (in oral contraceptives) include chest pain and sensitivity, weight changes, acne , mood changes, and vaginitis . Occasionally there will be changes in appetite, abdominal cramps, or a rash. By observing the contraindications, the occurrence of the most serious side effects such as thromboembolism and cancers of the liver, cervix and mammary gland should be minimized.
Other Information
Chemical information
Ethinylestradiol can be synthesized by introducing an ethinyl group in the 17-position of estrone . The 3-methyl ether of ethinylestradiol, mestranol , is another synthetic estrogen that is rarely used.
Environmental impact
As Frauke Hoffmann and Werner Kloas from the Leibniz Institute for Freshwater Ecology and Inland Fisheries have shown in animal experiments, even the smallest amounts (ng to µg / l ambient water ) of ethinylestradiol change the courtship behavior of African clawed frogs ( Xenopus laevis ) noticeably. The number of calls and clicks is significantly reduced, which also reduces the attractiveness of the males for the females. This also increases the risk of mating refusal. As ethinylestradiol is partly excreted in the urine, it ends up in wastewater in open water, where it can actually be found in the investigated concentrations. Ethinylestradiol could therefore make a contribution to the worldwide extinction of amphibians .
history
Ethinylestradiol was developed in 1938 by Hans Herloff Inhoffen and Walter Hohlweg at Schering AG in Berlin (today Bayer HealthCare Pharmaceuticals ).
Trade names
aida (D), Asumate (D), Balanca (D, A), Belara (D, A, CH), Bellgyn (A), Bellissima (D), Biviol (D), Chariva, Cilest (D, CH), Cileste (A), Clevia (D), Conceplan (D), Desmin (D), Diane (D, A, CH), Elleacnelle (CH), Eve (D), Evra (D, CH), Femigoa (D) , Femigyne (D), Femovan (D), Gabrielle (D), Gracial (A, CH), Gravistat (D), Harmonet (CH), Illina (D), Lamuna (D), Larissa Gynial (A), Leios (D), Leona (D), Levomin (D), Lovelle (D), madinette (D), Marvelon (D, A, CH), Maxim (D), Microgynon (D), Minisiston (D), Minulet ( D, A, CH), Miranova (D), Mirelle (A), Monahexal (D), MonoStep (D), Neo-Eunomin (D), NovaStep (D), Novial (D), NuvaRing (D, CH) , Ovysmen (A), Petibelle (D), Pramino (D), Selina mite Gynial (A), Swingo (D), Synphasec (D), Trigoa (D), TriNovum (D, A), Triquilar (D), Trisiston (D), Valette (D), Yasmin (D, A, CH), Yasminelle (D), Yaz (D)
Individual evidence
- ↑ European Pharmacopoeia. Addendum 2001 . Deutscher Apotheker Verlag, 2002, ISBN 3-7692-2768-9 .
- ↑ a b C. Hunnius (conception), HPT Ammon (ed.): Hunnius pharmaceutical dictionary. 9., rework. and exp. Edition. de Gruyter, Berlin / New York 2004, ISBN 3-11-017475-8 .
- ^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ, USA, 2006, ISBN 0-911910-00-X , p. 641.
- ↑ a b Data sheet 17α-Ethynylestradiol from Sigma-Aldrich , accessed on March 31, 2011 ( PDF ).
- ↑ a b L. L. Brunton, JS Lazo, K. Parker (Eds.): Goodman and Gilman's the Pharmacological Basis of Therapeutics. 11th edition, B&T Verlag, ISBN 978-0-07-142280-2 .
- ↑ a b c d e Red List Online . Retrieved August 2, 2008.
- ↑ Specialist information for an ethinylestradiol monopreparation (English). Retrieved December 3, 2013.
- ↑ a b c BfArM sample technical information for ethinylestradiol-levonorgestrel combination preparations. ( RTF ; 156 kB) Retrieved on August 13, 2008.
- ↑ IH Stockley (Ed.): Stockley's Drug interactions. 6th edition. Pharmaceutical Press, London / Grayslake, ISBN 0-85369-504-0 .
- ^ Axel Kleemann , Jürgen Engel, Bernd Kutscher, Dieter Reichert: Pharmaceutical Substances. 5th edition. Thieme-Verlag, Stuttgart 2009, ISBN 978-3-13-558405-8 , pp. 522-523; also online with biannual additions and updates.
- ↑ Frank Schubert: The active ingredient of birth control pills makes frogs flirt less. In: Spectrum of Science . Spectrum of Science Publishing Company , Heidelberg June 2012.
- ↑ bayerpharma.com: Milestones in the company's history ( Memento of the original from March 7, 2014 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice.
