|Trade names||Noristerat, Norigest, others|
|Synonyms||NETE; NET-EN; Norethindrone enanthate; SH-393; 17α-Ethynyl-19-nortestosterone 17β-enanthate; 17α-Ethynylestra-4-en-17β-ol-3-one 17β-enanthate|
|AHFS/Drugs.com||International Drug Names|
|Drug class||Progestin, progestogen, progestogen ester|
|Chemical and physical data|
|Molar mass||410.598 g/mol|
|3D model (JSmol)|
Norethisterone enanthate (NETE), also known as norethindrone enanthate, is a form of progestogen-only injectable birth control. It may be used following childbirth, miscarriage, or abortion. The failure rate per year in preventing pregnancy is 2 per 100 women. Each dose lasts two months with up to two doses recommended.
Side effects include breast pain, headaches, depression, irregular menstrual periods, and pain at the site of injection. Use in those with liver disease is not recommended as is use during pregnancy due to risk of birth defects. Use appears to be okay during breastfeeding. It does not protect against sexually transmitted infections. NETE is an ester and prodrug of norethisterone, through which it works. It works as a method of birth control by stopping ovulation.
Norethisterone was patented in 1951 and came into medical use in 1957. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about 1.04 to 7.99 USD per 200 mg vial. It has been approved in more than 60 countries including the United Kingdom and some in Europe, Central America, and Africa. It is not available in the United States.
NETE is a prodrug of norethisterone in the body. Upon reaching circulation, it is rapidly converted into norethisterone by esterases. Hence, as a prodrug of norethisterone, NETE has essentially the same effects as norethisterone, acting as a potent progestogen with additional weak androgenic and estrogenic activity (the latter via its metabolite ethinylestradiol).
Similarly to oral norethisterone and norethisterone acetate, intramuscular NETE has been found to form ethinylestradiol as an active metabolite. With a single intramuscular injection of 200 mg NETE in premenopausal women, the mean maximum concentration of ethinylestradiol was 32% of that of a combined oral contraceptive containing 30 μg ethinylestradiol, the maximum equivalent oral dose of ethinylestradiol observed in the first few days of exposure was 20.3 μg/day, and the mean equivalent oral dose of ethinylestradiol over 8 weeks was 4.41 μg/day. As such, the exposure to ethinylestradiol was described as markedly lower than that of an oral contraceptive containing 30 μg ethinylestradiol. The estimated conversion rate of NETE into ethinylestradiol was 0.1%, which was much lower than that observed for oral norethisterone and norethisterone enanthate (0.2–1.0%), likely due to the lack of the first-pass through the liver with parenteral administration. In accordance with the low levels of ethinylestradiol produced, no increase rates of thromboembolism or hepatic adenoma have been observed in post-authorization data of intramuscular NETE, and the medication does not resemble combined oral contraceptives containing ethinylestradiol in its safety profile.
NETE, also known as norethinyltestosterone enanthate, as well as 17α-ethynyl-19-nortestosterone 17β-enanthate or 17α-ethynylestr-4-en-17β-ol-3-one 17β-enanthate, is a progestin, or synthetic progestogen, of the 19-nortestosterone group, and a synthetic estrane steroid. It is the C17β enanthate ester of norethisterone. NETE is a derivative of testosterone with an ethynyl group at the C17α position, the methyl group at the C19 position removed, and an enanthate ester attached at the C17β position. In addition to testosterone, it is a combined derivative of nandrolone (19-nortestosterone) and ethisterone (17α-ethynyltestosterone). Esters related to NETE include norethisterone acetate and levonorgestrel butanoate.
- "Noristerat 200mg, solution for intramuscular injection - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. Archived from the original on 31 December 2016. Retrieved 31 December 2016.
- J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 886–. ISBN 978-1-4757-2085-3. Archived from the original on 5 November 2017.
- Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 750. ISBN 978-3-88763-075-1. Archived from the original on 28 May 2013. Retrieved 30 May 2012.
- Committee on Contraceptive Development (U.S.) (1 January 1990). Luigi Mastroianni; Peter J. Donaldson; Thomas T. Kane, eds. Developing New Contraceptives: Obstacles and Opportunities. National Academies. pp. 38–. NAP:14119. Archived from the original on 5 November 2017.
- WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 370. ISBN 9789241547659. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
- Wu L, Janagam DR, Mandrell TD, Johnson JR, Lowe TL (2015). "Long-acting injectable hormonal dosage forms for contraception". Pharmaceutical Research. 32 (7): 2180–91. doi:10.1007/s11095-015-1686-2. PMID 25899076.
- Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 478. ISBN 9783527607495. Archived from the original on 2016-12-20.
- Vern L. Bullough (2001). Encyclopedia of Birth Control. ABC-CLIO. pp. 145–. ISBN 978-1-57607-181-6. Archived from the original on 2017-11-05.
- "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
- "Norethisterone". International Drug Price Indicator Guide. Retrieved 8 December 2016.
- Amy Whitaker; Melissa Gilliam (27 June 2014). Contraception for Adolescent and Young Adult Women. Springer. p. 96. ISBN 978-1-4614-6579-9. Archived from the original on 5 November 2017.
- Bagade O, Pawar V, Patel R, Patel B, Awasarkar V, Diwate S (2014). "Increasing use of long-acting reversible contraception: safe, reliable, and cost-effective birth control" (PDF). World J Pharm Pharm Sci. 3 (10): 364–392. ISSN 2278-4357.
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 417–. ISBN 978-92-832-1291-1. Archived from the original on 2017-11-05.
Norethisterone and its acetate and enanthate esters are progestogens that have weak estrogenic and androgenic properties.
- Friedrich C, Berse M, Klein S, Rohde B, Höchel J (March 2018). "In Vivo Formation of Ethinylestradiol After Intramuscular Administration of Norethisterone Enantate". J Clin Pharmacol. doi:10.1002/jcph.1079. PMID 29522253.
- Nieschlag E (2010). "Clinical trials in male hormonal contraception". Contraception. 82 (5): 457–70. doi:10.1016/j.contraception.2010.03.020. PMID 20933120.