Norethisterone enanthate

Source: Wikipedia, the free encyclopedia.
Norethisterone enanthate
Progestin; 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
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

hormonal birth control which is used to prevent pregnancy in women.[1][2][3] It is used both as a form of progestogen-only injectable birth control and in combined injectable birth control formulations. It may be used following childbirth, miscarriage, or abortion.[1] The failure rate per year in preventing pregnancy for the progestogen-only formulation is 2 per 100 women.[4] Each dose of this form lasts two months with only up to two doses typically recommended.[5][1]

Side effects include

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 NETE came into medical use in 1957.[7][8] It is on the World Health Organization's List of Essential Medicines.[9] It has been approved by itself in more than 60 countries including the United Kingdom and some in Europe, Central America, and Africa, and in combination with estradiol valerate in at least 36 countries mainly in Latin America.[4][10][11][12] It is not available in the United States.[10]

Medical uses

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

Contraindications

See also:
Progestin § Contraindications

Side effects

See also:
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]

Overdose

See also:
Progestin § Overdose

Interactions

See also:
Progestin § Interactions

Pharmacology

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

Pharmacodynamics

NETE is a prodrug of norethisterone in the body.[13] 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).[14] NETA has some progestogenic activity of its own, but it is unclear if NETE does similarly.[13]

NETE is of about 38% higher

molecular weight than norethisterone due to the presence of its C17β enanthate ester.[2]

Relative affinities (%) of norethisterone, metabolites, and prodrugs
Compound Typea PRTooltip Progesterone receptor ARTooltip Androgen receptor ERTooltip Estrogen receptor GRTooltip Glucocorticoid receptor MRTooltip Mineralocorticoid receptor SHBGTooltip Sex hormone-binding globulin
CBG
Tooltip Corticosteroid binding globulin
Norethisterone – 67–75 15 0 0–1 0–3 16 0
5α-Dihydronorethisterone Metabolite 25 27 0 0 ? ? ?
3α,5α-Tetrahydronorethisterone Metabolite 1 0 0–1 0 ? ? ?
3α,5β-Tetrahydronorethisterone Metabolite ? 0 0 ? ? ? ?
3β,5α-Tetrahydronorethisterone Metabolite 1 0 0–8 0 ? ? ?
Ethinylestradiol Metabolite 15–25 1–3 112 1–3 0 0.18 0
Norethisterone acetate Prodrug 20 5 1 0 0 ? ?
Norethisterone enanthate Prodrug ? ? ? ? ? ? ?
Noretynodrel Prodrug 6 0 2 0 0 0 0
Etynodiol Prodrug 1 0 11–18 0 ? ? ?
Etynodiol diacetate Prodrug 1 0 0 0 0 ? ?
Lynestrenol Prodrug 1 1 3 0 0 ? ?
Notes: Values are percentages (%). Reference
CBGTooltip Corticosteroid-binding globulin. Footnotes: a = Active or inactive metabolite, prodrug
, or neither of norethisterone. Sources: See template.
Parenteral potencies and durations of progestogens[a][b]
Compound Form Dose for specific uses (mg)[c] DOA[d]
TFD[e] POICD[f] CICD[g]
Algestone acetophenide Oil soln. - – 75–150 14–32 d
Gestonorone caproate Oil soln. 25–50 – – 8–13 d
Hydroxyprogest. acetate[h] Aq. susp. 350 – – 9–16 d
Hydroxyprogest. caproate Oil soln. 250–500[i] – 250–500 5–21 d
Medroxyprog. acetate Aq. susp. 50–100 150 25 14–50+ d
Megestrol acetate Aq. susp. - – 25 >14 d
Norethisterone enanthate Oil soln. 100–200 200 50 11–52 d
Progesterone Oil soln. 200[i] – – 2–6 d
Aq. soln. ? – – 1–2 d
Aq. susp. 50–200 – – 7–14 d
Notes and sources:
  1. ^ Sources: [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]
  2. subcutaneous injection
    .
  3. OID
    Tooltip ovulation-inhibiting dose of OHPC is 250 to 500 mg/month.
  4. ^ Duration of action in days.
  5. ^ Usually given for 14 days.
  6. ^ Usually dosed every two to three months.
  7. ^ Usually dosed once monthly.
  8. ^ Never marketed or approved by this route.
  9. ^ a b In divided doses (2 × 125 or 250 mg for OHPC, 10 × 20 mg for P4).
estradiol valerate/norethisterone enanthate (5 mg/50 mg) (Mesigyna) in healthy young men.[34] Testosterone levels were maximally suppressed by about 94%, to ~30 ng/dL, when measured at day 7 post-injection.[34]

A single intramuscular injection of

estradiol valerate/norethisterone enanthate (5 mg/50 mg) (Mesigyna) has been found to strongly suppress testosterone levels in men.[34] Levels of testosterone decreased from ~503 ng/dL at baseline to ~30 ng/dL at the lowest point (–94%).[34]

Pharmacokinetics

Norethisterone and ethinylestradiol levels over 8 weeks after a single intramuscular injection of 200 mg NETE in premenopausal women.[35]

A single

body temperature in women.[36]

Similarly to oral norethisterone and

safety profile.[35]

Chemistry

See also:
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

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][37] In addition to testosterone, it is a combined derivative of nandrolone (19-nortestosterone) and ethisterone (17α-ethynyltestosterone).[2][37] Esters related to NETE include norethisterone acetate and levonorgestrel butanoate.[2][37]

History

NETE was introduced by Schering as Noristerat in 1957.[8] It was the second long-acting progestogen to be used clinically, after hydroxyprogesterone caproate.[38] The medication was the first progestogen-only injectable contraceptive, preceding medroxyprogesterone acetate (Depo-Provera).[8]

Society and culture

Generic names

Norethisterone enantate is the

INNMTooltip International Nonproprietary Name and BANMTooltip British Approved Name.[2][37][39][40][41] It is also spelled as norethisterone enanthate and is also known as norethindrone enanthate (the USANTooltip United States Adopted Name of norethisterone being norethindrone).[2][37][39][40][41] NETE is known by its former developmental code name SH-393 as well.[2][37][39][40][41]

Brand names

NETE has been marketed alone as a

combined injectable contraceptive under the brand names Chinese Injectable No. 3, Efectimes, Ginediol, Mesigyna, Mesilar, Meslart, Mesocept, Mesygest, Nofertyl, Nofertyl Lafrancol, Noregyna, Norestrin, Norifam, Norigynon, Nostidyn, Sexseg, and Solouna.[37][40][41][42]

Formulations and brand names of norethisterone and esters
Composition Dose Brand names Use
NET only Low (e.g., 0.35 mg) Multiple[a]
Progestogen-only oral contraceptive
NET or NETA only High (e.g., 5 mg, 10 mg) Multiple[b]
Gynecological disorders
and other uses
NETE only Injection (e.g., 200 mg) Multiple[c] Progestogen-only injectable contraceptive
NET or NETA with ethinylestradiol Low (e.g., 0.4 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg) Multiple[d]
Combined oral contraceptive
NET with mestranol Low (e.g., 1 mg, 2 mg) Multiple[e] Combined oral contraceptive
NETA with estradiol Low (e.g., 0.1 mg, 0.5 mg) Multiple[f]
Combined menopausal hormone therapy
NETE with estradiol valerate Injection (e.g., 50 mg) Multiple[g]
Combined injectable contraceptive
Abbreviations: NET = Norethisterone. NETA = Norethisterone acetate. NETE = Norethisterone enanthate.
Sources: [43][44] [37][45]
Notes:
  1. ^ Camila, Errin, Heather, Jencycla, Jolivette, Locilan, Micro-Novum, Micronovum, Micronor, Nor-QD, Nora, Noriday, Ortho Micronor
  2. ^ Aygestin, Lupaneta Pack (combination pack with leuprorelin), Norcolut, Norlutate, Primolut N, Primolut Nor, SH-420, Utovlan
  3. ^ Depocon, Doryxas, NET-EN, Noristerat, Norigest, Nur-Isterate
  4. ^ Aranelle, Balziva, Binovum, Brevicon, Brevinor, Briellyn, Cyclafem, Dasetta, Estrostep, Femcon, Generess, Gildagia, Gildess, Jinteli, Junel, Larin, Leena, Lo Loestrin, Lo Minastrin, Loestrin, Lolo, Lomedia, Microgestin, Minastrin, Modicon, Nelova, Norimin, Norinyl, Nortrel, Ortho, Ortho-Novum, Ovcon, Ovysmen, Philith, Primella, Select, Synphase, Synphasic, Tilia, Tri-Legest, Tri-Norinyl, Trinovum, Vyfemla, Wera, Wymzya, Zenchent, Zeosa
  5. ^ Norethin, Noriday, Norinyl, Norquen, Ortho-Novum, Sophia
  6. ^ Activella, Activelle, Alyacen, Cliane, Climagest, Climesse, Cliovelle, CombiPatch, Elleste Duet, Estalis, Estropause, Eviana, Evorel, Kliane, Kliofem, Kliogest, Kliovance, Mesigyna, Mesygest, Mimvey, Necon, Novofem, Nuvelle, Sequidot, Systen, Trisequens
  7. ^ Chinese Injectable No. 3, Efectimes, Ginediol, Mesigyna, Mesilar, Meslart, Mesocept, Mesygest, Nofertyl, Nofertyl Lafrancol, Noregyna, Norestrin, Norifam, Norigynon, Nostidyn, Sexseg, Solouna

Availability

NETE has been approved for use alone as a progestogen-only injectable contraceptive in more than 60 countries throughout the world including in Europe, Latin America, Asia, and Africa.[4][10][11] Specific countries in which NETE as a standalone medication is or has been available include Bangladesh, France, Germany, India, Italy, Malaysia, Mexico, the Philippines, Singapore, South Africa, Thailand, and the United Kingdom.[37][40][41][42]

NETE has been approved for use in combination with

St. Lucia, Turkey, Uruguay, Venezuela, and Zimbabwe.[40][41][42][14]

NETE is not available in any form in the United States.[10]

Research

NETE was studied by Schering for use as a progestogen-only injectable contraceptive at a dose of 25 mg once a month but produced poor cycle control with this regimen and was not marketed.[46]

NETE has been studied for use as a potential male hormonal contraceptive in combination with testosterone in men.[47]

See also

References

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  2. ^
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  3. ISBN 978-3-88763-075-1. Archived
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  4. ^
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  9. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
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    ISBN 978-1-4614-6579-9. Archived
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  11. ^
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  13. ^
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  15. ISBN 978-3-662-00942-0
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  16. ISBN 978-3-642-95583-9
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  17. ISBN 978-3-642-96158-8
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  18. ISBN 978-94-009-8195-9
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  19. ISBN 9783110006148
    . 17α-Hydroxyprogesterone caproate is a depot progestogen which is entirely free of side actions. The dose required to induce secretory changes in primed endometrium is about 250 mg. per menstrual cycle.
  20. ISBN 978-3-11-150424-7
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  21. OCLC 278011135
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  30. ^ Chu YH, Li Q, Zhao ZF (April 1986). "Pharmacokinetics of megestrol acetate in women receiving IM injection of estradiol-megestrol long-acting injectable contraceptive". The Chinese Journal of Clinical Pharmacology. The results showed that after injection the concentration of plasma MA increased rapidly. The meantime of peak plasma MA level was 3rd day, there was a linear relationship between log of plasma MA concentration and time (day) after administration in all subjects, elimination phase half-life t1/2β = 14.35 ± 9.1 days.
  31. ISBN 978-3-642-73790-9
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  34. ^ a b c d del Cisne Valle Alvarez D (11 May 2011). Efecto de una Dosis de 50 mg de Enantato de Noretisterona y 5 mg de Valerato de Estradiol en los Niveles de Testosterona Total en Hombres Mexicanos Sanos [Effect of a Dose of 50 mg of Norethisterone Enanthate and 5 mg of Estradiol Valerate on Total Testosterone Levels in Healthy Mexican Men] (MSc). National Polytechnic Institute of Mexico.
  35. ^
    S2CID 3813229
    .
  36. OCLC 278011135
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  37. ^
    ISBN 978-3-88763-075-1
    .
  38. PMID 13583829
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  39. ^
    ISBN 978-94-011-4439-1
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  41. ^
    ISBN 978-0-85369-840-1
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  42. ^ a b c "Micromedex Products: Please Login".
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  44. ^ "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Archived from the original on 16 November 2016. Retrieved 27 November 2016.
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  46. PMID 865726
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  47. PMID 20933120
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External links