Norethisterone acetate

Norethisterone acetate
Clinical data
Trade names Primolut-Nor, Aygestin, Gestakadin, Milligynon, Monogest, Norlutate, Primolut N, SH-420, Sovel, Styptin
AHFS/Drugs.com International Drug Names
MedlinePlus a604034
Routes of
administration		 Oral
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
Synonyms NETA; Norethindrone acetate; SH-420; 17α-Ethynyl-19-nortestosterone 17β-acetate; 17α-Ethynylestra-4-en-17β-ol-3-one 17β-acetate
CAS Number
PubChem CID
ChemSpider
ChEBI
ChEMBL
Chemical and physical data
Formula C22H28O3
Molar mass 340.456 g/mol
3D model (JSmol)
 NYesY (what is this?)  (verify)

Norethisterone acetate (abbreviated as NETA), or norethindrone acetate, sold under the brand name Primolut-Nor among others, is a progestin which is used in hormonal contraception, hormone replacement therapy, and to treat gynecological disorders.[1][2][3] It is taken by mouth. NETA is a prodrug of norethisterone.[4] In addition to its progestogenic activity, NETA also has weak androgenic and estrogenic activity.[5][6]

Medical uses

NETA is used as a hormonal contraceptive in combination with estrogen, in the treatment of gynecological disorders such as abnormal uterine bleeding, and as a component of hormone replacement therapy for menopause.[3]

Side effects

Pharmacology

NETA is a prodrug of norethisterone in the body.[4] Upon oral ingestion, it is rapidly converted into norethisterone by esterases during intestinal and first-pass hepatic metabolism.[7] Hence, as a prodrug of norethisterone, NETA has essentially the same effects, acting as a potent progestogen with additional weak androgenic and estrogenic activity (the latter via its metabolite ethinylestradiol).[5][6]

In terms of dosage equivalence, norethisterone and NETA are typically used at respective dosages of 0.35 mg/day and 0.6 mg/day as progestogen-only contraceptives, and at respective dosages of 0.5–1 mg/day and 1–1.5 mg/day in combination with ethinylestradiol in combined oral contraceptives.[6] Conversely, the two drugs have been used at about the same dosages in hormone replacement therapy for menopausal symptoms.[6] NETA is of slightly (12%) higher molecular weight than norethisterone due to the presence of its C17β acetate ester.[1]

Chemistry

NETA, also known as norethinyltestosterone acetate, as well as 17α-ethynyl-19-nortestosterone 17β-acetate or 17α-ethynylestra-4-en-17β-ol-3-one 17β-acetate, is a progestin, or synthetic progestogen, of the 19-nortestosterone group, and a synthetic estrane steroid.[1][2] It is the C17β acetate ester of norethisterone.[1][2] NETA is a derivative of testosterone with an ethynyl group at the C17α position, the methyl group at the C19 position removed, and an acetate ester attached at the C17β position.[1][2] In addition to testosterone, it is a combined derivative of nandrolone (19-nortestosterone) and ethisterone (17α-ethynyltestosterone).[1][2]

History

Schering AG filed for a patent for NETA in June 1957, and the patent was issued in December 1960.[8] The drug was first marketed, by Parke-Davis as Norlestrin in the United States, in March 1964.[8][9] This was a combination formulation of 2.5 mg NETA and 50 μg ethinylestradiol and was indicated as an oral contraceptive.[8][9] Other early brand names of NETA used in oral contraceptives included Minovlar and Anovlar.[8]

Society and culture

Generic names

Norethisterone acetate is the INN, BANM, and JAN of NETA while norethindrone acetate is its USAN and USP.[1][2][3]

Brand names

NETA is marketed under a variety of brand names throughout the world including Primolut-Nor (major), Aygestin (US), Gestakadin, Milligynon, Monogest, Norlutate (US, CA), Primolut N, SH-420 (UK), Sovel, and Styptin among others.[1][2][3]

Availability

United States

NETA is marketed in high-dose 5 mg oral tablets in the United States under the brand names Aygestin and Norlutate for the treatment of gynecological disorders.[10] In addition, it is available under a large number of brand names at much lower dosages (0.1 to 1 mg) in combination with estrogens such as ethinylestradiol and estradiol as a combined oral contraceptive and for use in hormone replacement therapy for menopausal symptoms.[10]

See also

References

  1. 1 2 3 4 5 6 7 8 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.
  2. 1 2 3 4 5 6 7 Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 750. ISBN 978-3-88763-075-1. Retrieved 30 May 2012.
  3. 1 2 3 4 http://www.drugs.com/ppa/norethindrone-acetate.html
  4. 1 2 Thomas L. Lemke; David A. Williams (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1316–. ISBN 978-0-7817-6879-5.
  5. 1 2 Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 Suppl 1: 3–63. PMID 16112947. doi:10.1080/13697130500148875.
  6. 1 2 3 4 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. Norethisterone and its acetate and enanthate esters are progestogens that have weak estrogenic and androgenic properties.
  7. ↑ Chwalisz K, Surrey E, Stanczyk FZ (2012). "The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis". Reprod Sci. 19 (6): 563–71. PMID 22457429. doi:10.1177/1933719112438061.
  8. 1 2 3 4 Lara Marks (2010). Sexual Chemistry: A History of the Contraceptive Pill. Yale University Press. pp. 73–. ISBN 978-0-300-16791-7.
  9. 1 2 Robert W. Blum (22 October 2013). Adolescent Health Care: Clinical Issues. Elsevier Science. pp. 216–. ISBN 978-1-4832-7738-7.
  10. 1 2 "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 6 December 2016.
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