Norethisterone enanthate

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Norethisterone enanthate
Clinical data
Trade namesNoristerat, Norigest, others
Other namesNETE; NET-EN; Norethindrone enanthate; SH-393; 17α-Ethynyl-19-nortestosterone 17β-enanthate; 17α-Ethynylestra-4-en-17β-ol-3-one 17β-enanthate
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Intramuscular injection
Drug classProgestin, progestogen, progestogen ester
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
Identifiers
  • [(9S,10R,13S,14S,17R)-17-ethynyl-13-methyl-3-oxo-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] heptanoate
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.021.207 Edit this at Wikidata
Chemical and physical data
FormulaC27H38O3
Molar mass410.598 g/mol g·mol−1
3D model (JSmol)
  • CCCCCCC(=O)O[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@H]34)C)C#C
  • InChI=1S/C27H38O3/c1-4-6-7-8-9-25(29)30-27(5-2)17-15-24-23-12-10-19-18-20(28)11-13-21(19)22(23)14-16-26(24,27)3/h2,18,21-24H,4,6-17H2,1,3H3/t21-,22+,23+,24-,26-,27-/m0/s1
  • Key:APTGJECXMIKIET-WOSSHHRXSA-N
  (verify)

Norethisterone enanthate (NETE), also known as norethindrone enanthate, is a form of progestogen-only injectable birth control.[1][2][3] It may be used following childbirth, miscarriage, or abortion.[1] The failure rate per year in preventing pregnancy is 2 per 100 women.[4] Each dose lasts two months with up to two doses recommended.[5][1]

Side effects include breast pain, headaches, depression, irregular menstrual periods, and pain at the site of injection.[5] Use in those with liver disease is not recommended as is use during pregnancy due to risk of birth defects.[1] Use appears to be okay during breastfeeding.[1] It does not protect against sexually transmitted infections.[1] NETE is an ester and prodrug of norethisterone,[6] through which it works.[1] It works as a method of birth control by stopping ovulation.[1]

Norethisterone was patented in 1951 and came into medical use in 1957.[7][8] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[9] The wholesale cost in the developing world is about 1.04 to 7.99 USD per 200 mg vial.[10] It has been approved in more than 60 countries including the United Kingdom and some in Europe, Central America, and Africa.[4][11][12] It is not available in the United States.[11]

Medical uses

NETE is used on its own as a long-lasting progestogen-only injectable contraceptive in women.[5][1] It is administered via intramuscular injection once every two months.[5][1]

Side effects

See also: Norethisterone § Side effects, and Progestin § Side effects

Side effects of NETE may include breast pain, headaches, depression, irregular menstrual periods, and pain at the site of injection.[5] It can cause birth defects in the fetus if used during pregnancy.[1]

Pharmacology

See also: Norethisterone § Pharmacology, and Norethisterone § Pharmacokinetics
Norethisterone, the active metabolite of NETE.

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).[13]

Similarly to oral norethisterone and norethisterone acetate, intramuscular NETE has been found to form ethinylestradiol as an active metabolite.[14] 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.[14] As such, the exposure to ethinylestradiol was described as markedly lower than that of an oral contraceptive containing 30 μg ethinylestradiol.[14] 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.[14] 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.[14]

Chemistry

See also: List of progestogens, Progestogen ester, List of progestogen esters, and List of androgens/anabolic steroids

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.[2][3] It is the C17β enanthate ester of norethisterone.[2][3] 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.[2][3] In addition to testosterone, it is a combined derivative of nandrolone (19-nortestosterone) and ethisterone (17α-ethynyltestosterone).[2][3] Esters related to NETE include norethisterone acetate and levonorgestrel butanoate.[2][3]

History

NETE was introduced by Schering as Noristerat in 1957.[8] It was the first progestogen-only injectable contraceptive, preceding medroxyprogesterone acetate (Depo-Provera).[8]

Research

NETE has been studied for use as a potential male hormonal contraceptive in combination with testosterone in men.[15]

See also

References

  1. ^ a b c d e f g h i j k "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. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  2. ^ a b c d e f 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. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  3. ^ a b c d e f 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. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  4. ^ a b 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. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  5. ^ a b c d e WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 370. ISBN 9789241547659. Archived from the original (PDF) on 13 December 2016. Retrieved 8 December 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  6. ^ 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.
  7. ^ 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. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  8. ^ a b c 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. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  9. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived from the original (PDF) on 13 December 2016. Retrieved 8 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  10. ^ "Norethisterone". International Drug Price Indicator Guide. Retrieved 8 December 2016.
  11. ^ a b 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. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  12. ^ 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.
  13. ^ 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. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  14. ^ a b c d e 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.
  15. ^ Nieschlag E (2010). "Clinical trials in male hormonal contraception". Contraception. 82 (5): 457–70. doi:10.1016/j.contraception.2010.03.020. PMID 20933120.
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