Estradiol dienantate

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Source: Wikipedia, the free encyclopedia.
Not to be confused with
Estradiol enanthate
.
Estradiol dienantate
Clinical data
Trade namesClimacteron, Amenose, Lactimex, Lactostat (all combinations)
Other namesEstradiol dienantate; EDE; EDEn; E2-EDN; Estradiol diheptanoate; Estra-1,3,5(10)-triene-3,17β-diol 3,17β-diheptanoate
Routes of
administration		Intramuscular injection
Drug classEstrogen; Estrogen ester
Identifiers
  • [(8R,9S,13S,14S,17S)-3-heptanoyloxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] heptanoate
JSmol)
  • CCCCCCC(=O)O[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=C3C=CC(=C4)OC(=O)CCCCCC)C
  • InChI=1S/C32H48O4/c1-4-6-8-10-12-30(33)35-24-15-17-25-23(22-24)14-16-27-26(25)20-21-32(3)28(27)18-19-29(32)36-31(34)13-11-9-7-5-2/h15,17,22,26-29H,4-14,16,18-21H2,1-3H3/t26-,27-,28+,29+,32+/m1/s1
  • Key:OVAHZPTYWMWNKO-CAHAWPIUSA-N

Estradiol dienanthate (EDE), sold under the brand names Climacteron among others, is a long-acting

testosterone enanthate benzilic acid hydrazone (TEBH), a long-acting androgen/anabolic steroid.[2][3][4] EDE has not been made available for medical use alone.[5] The medication, in combination with EB and TEBH, was given by injection into muscle once or at regular intervals, for instance once every 6 weeks.[6][7][8]

fluid retention.[9] EDE is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol.[10][11] It is an estrogen ester and a prodrug of estradiol in the body.[11][10] Because of this, it is considered to be a natural and bioidentical form of estrogen.[11]

EDE was first described by 1959.[12][13] It was previously available in Canada and Germany but was discontinued by 2005.[14][15][16] The medication is no longer available in any form.[5]

Medical uses

EDE, a long-acting estrogen, was used in combination with EB, a short-acting estrogen, and TEBH, a long-acting androgen/anabolic steroid, in

postpartum women.[6][8][7]

Available forms

See also: Estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone

EDE was available only in combination EB and TEBH.[17] The combination was available in two different dose forms, one for menopausal hormone therapy (brand names Climacteron, Amenose) and the other for lactation suppression (brand names Lactimex, Lactostat). Climacteron and Amenose contained 1.0 mg EB, 7.5 mg EDE, and 150 mg TEBH (69 mg free testosterone) and was given by repeated intramuscular injection at regular intervals.[6][18][8] Lactimex and Lactostat contained 6 mg EB, 15 mg EDE, and 300 mg TEBH in 2 mL of corn oil and was administered as a single intramuscular injection after childbirth or during breastfeeding.[7][19][20][21]

Pharmacology

Estradiol, the active form of EDE.

Pharmacodynamics

See also: Pharmacodynamics of estradiol

EDE is an

heptanoate (enanthate) esters. Because EDE is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.[11]

Potencies and durations of natural estrogens by intramuscular injection
Estrogen Form Dose (mg) Duration by dose (mg)
EPD CICD
Estradiol Aq. soln. ? – <1 d
Oil soln. 40–60 – 1–2 ≈ 1–2 d
Aq. susp. ? 3.5 0.5–2 ≈ 2–7 d; 3.5 ≈ >5 d
Microsph. ? – 1 ≈ 30 d
Estradiol benzoate Oil soln. 25–35 – 1.66 ≈ 2–3 d; 5 ≈ 3–6 d
Aq. susp. 20 – 10 ≈ 16–21 d
Emulsion ? – 10 ≈ 14–21 d
Estradiol dipropionate Oil soln. 25–30 – 5 ≈ 5–8 d
Estradiol valerate Oil soln. 20–30 5 5 ≈ 7–8 d; 10 ≈ 10–14 d;
40 ≈ 14–21 d; 100 ≈ 21–28 d
Estradiol benz. butyrate Oil soln. ? 10 10 ≈ 21 d
Estradiol cypionate Oil soln. 20–30 – 5 ≈ 11–14 d
Aq. susp. ? 5 5 ≈ 14–24 d
Estradiol enanthate
 Oil soln. ? 5–10 10 ≈ 20–30 d
Estradiol dienanthate Oil soln. ? – 7.5 ≈ >40 d
Estradiol undecylate Oil soln. ? – 10–20 ≈ 40–60 d;
25–50 ≈ 60–120 d
Polyestradiol phosphate Aq. soln. 40–60 – 40 ≈ 30 d; 80 ≈ 60 d;
160 ≈ 120 d
Estrone Oil soln. ? – 1–2 ≈ 2–3 d
Aq. susp. ? – 0.1–2 ≈ 2–7 d
Estriol Oil soln. ? – 1–2 ≈ 1–4 d
Polyestriol phosphate Aq. soln. ? – 50 ≈ 30 d; 80 ≈ 60 d
Notes and sources
Notes: All
ovulation-inhibiting dose of estradiol undecylate
is 20–30 mg/month. Sources: See template.
Hormone levels with estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone by intramuscular injection
  • Estradiol and testosterone levels after an intramuscular injection of 1 mg estradiol benzoate, 7.5 mg estradiol dienanthate, and 150 mg testosterone enanthate benzilic acid hydrazone in oil (brand name Climacteron) in ovariectomized women.[22] Assays were performed using immunoassays.[22] Source was Sherwin (1987).[22]
    Estradiol and testosterone levels after an intramuscular injection of 1 mg
    testosterone enanthate benzilic acid hydrazone in oil (brand name Climacteron) in ovariectomized women.[22] Assays were performed using immunoassays.[22] Source was Sherwin (1987).[22]
  • Estradiol levels after an intramuscular injection of 10 mg estradiol valerate in oil or Climacteron (1 mg estradiol benzoate, 7.5 mg estradiol dienanthate in oil) in ovariectomized women.[23][24] Assays were performed using RIA.[23][24] Source was Sherwin et al. (1987).[23][24]
    Estradiol levels after an intramuscular injection of 10 mg estradiol valerate in oil or
    estradiol dienanthate in oil) in ovariectomized women.[23][24] Assays were performed using RIA.[23][24] Source was Sherwin et al. (1987).[23][24]

Pharmacokinetics

See also: Pharmacokinetics of estradiol and Estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone

Estradiol and testosterone levels following a single intramuscular injection of Climacteron (including 1 mg EB, 7.5 mg EDE, and 150 mg TEBH equivalent to 69 mg free testosterone) versus 10 mg estradiol valerate have been studied over 28 days.[23][24]

Potencies and durations of natural estrogens by intramuscular injection
Estrogen Form Dose (mg) Duration by dose (mg)
EPD CICD
Estradiol Aq. soln. ? – <1 d
Oil soln. 40–60 – 1–2 ≈ 1–2 d
Aq. susp. ? 3.5 0.5–2 ≈ 2–7 d; 3.5 ≈ >5 d
Microsph. ? – 1 ≈ 30 d
Estradiol benzoate Oil soln. 25–35 – 1.66 ≈ 2–3 d; 5 ≈ 3–6 d
Aq. susp. 20 – 10 ≈ 16–21 d
Emulsion ? – 10 ≈ 14–21 d
Estradiol dipropionate Oil soln. 25–30 – 5 ≈ 5–8 d
Estradiol valerate Oil soln. 20–30 5 5 ≈ 7–8 d; 10 ≈ 10–14 d;
40 ≈ 14–21 d; 100 ≈ 21–28 d
Estradiol benz. butyrate Oil soln. ? 10 10 ≈ 21 d
Estradiol cypionate Oil soln. 20–30 – 5 ≈ 11–14 d
Aq. susp. ? 5 5 ≈ 14–24 d
Estradiol enanthate
 Oil soln. ? 5–10 10 ≈ 20–30 d
Estradiol dienanthate Oil soln. ? – 7.5 ≈ >40 d
Estradiol undecylate Oil soln. ? – 10–20 ≈ 40–60 d;
25–50 ≈ 60–120 d
Polyestradiol phosphate Aq. soln. 40–60 – 40 ≈ 30 d; 80 ≈ 60 d;
160 ≈ 120 d
Estrone Oil soln. ? – 1–2 ≈ 2–3 d
Aq. susp. ? – 0.1–2 ≈ 2–7 d
Estriol Oil soln. ? – 1–2 ≈ 1–4 d
Polyestriol phosphate Aq. soln. ? – 50 ≈ 30 d; 80 ≈ 60 d
Notes and sources
Notes: All
ovulation-inhibiting dose of estradiol undecylate
is 20–30 mg/month. Sources: See template.

Chemistry

See also: Estrogen ester and List of estrogen esters § Estradiol esters

EDE is a

estradiol enanthate (estradiol 17β-heptanoate), which has a single heptanoate ester rather than two.[1]

Structural properties of selected estradiol esters
Estrogen Structure Ester(s) Relative
mol. weight		 Relative
E2 contentb		 log Pc
Position(s) Moiet(ies) Type Lengtha
Estradiol
– – – – 1.00 1.00 4.0
Estradiol acetate
C3
Ethanoic acid
 Straight-chain fatty acid 2 1.15 0.87 4.2
Estradiol benzoate
C3 Benzoic acid Aromatic fatty acid – (~4–5) 1.38 0.72 4.7
Estradiol dipropionate
C3, C17β
Propanoic acid
(×2)		 Straight-chain fatty acid 3 (×2) 1.41 0.71 4.9
Estradiol valerate
C17β
Pentanoic acid
 Straight-chain fatty acid 5 1.31 0.76 5.6–6.3
Estradiol benzoate butyrate
C3, C17β Benzoic acid, butyric acid Mixed fatty acid – (~6, 2) 1.64 0.61 6.3
Estradiol cypionate
C17β
Cyclopentylpropanoic acid
 Cyclic fatty acid – (~6) 1.46 0.69 6.9
Estradiol enanthate
C17β
Heptanoic acid
 Straight-chain fatty acid 7 1.41 0.71 6.7–7.3
Estradiol dienanthate
C3, C17β
Heptanoic acid
(×2)		 Straight-chain fatty acid 7 (×2) 1.82 0.55 8.1–10.4
Estradiol undecylate
C17β
Undecanoic acid
 Straight-chain fatty acid 11 1.62 0.62 9.2–9.8
Estradiol stearate
C17β
Octadecanoic acid
 Straight-chain fatty acid 18 1.98 0.51 12.2–12.4
Estradiol distearate
C3, C17β
Octadecanoic acid
(×2)		 Straight-chain fatty acid 18 (×2) 2.96 0.34 20.2
Estradiol sulfate
C3 Sulfuric acid Water-soluble conjugate – 1.29 0.77 0.3–3.8
Estradiol glucuronide
C17β Glucuronic acid Water-soluble conjugate – 1.65 0.61 2.1–2.7
Estramustine phosphated
C3, C17β Normustine, phosphoric acid Water-soluble conjugate – 1.91 0.52 2.9–5.0
Polyestradiol phosphatee
C3–C17β Phosphoric acid Water-soluble conjugate – 1.23f 0.81f 2.9g
Footnotes: a = Length of
hydrophobicity). Retrieved from PubChem, ChemSpider, and DrugBank. d = Also known as estradiol normustine phosphate. e = Polymer of estradiol phosphate (~13 repeat units
). f = Relative molecular weight or estradiol content per repeat unit. g = log P of repeat unit (i.e., estradiol phosphate). Sources: See individual articles.

History

EDE was first described and introduced for medical use by 1959.[12][13]

Society and culture

Brand names

EDE was marketed in combination with EB and TEBH under the brand names Climacteron, Amenose, Lactimex, and Lactostat.[17][8]

Availability

EDE is no longer available but was previously used in Canada, Germany and other countries.[5][17][7][21]

See also

References

  1. ^
    ISBN 978-1-4757-2085-3
    .
  2. ^
    ISBN 978-1-61737-129-5
    .
  3. ^
    PMID 13901504
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  4. ^
    ISBN 978-1-59259-246-3
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  5. ^ a b c "Estradiol: Uses, Dosage & Side Effects". Drugs.com.
  6. ^ a b c "Climacteron Drug Information, Professional". Drugs.com. Archived from the original on 2 June 2019. Retrieved 2 June 2019.
  7. ^ a b c d Geburtshilfe und Frauenheilkunde: Ergebnisse der Forschung für die Praxis. Georg Thieme Verlag. 1969. p. 387,390. [Kelly and Primose and Dodek found the following androgen-estrogen combination to be particularly effective and well-tolerated: 300 mg 3-benzilic acid hydrazone-testosterone-17-enanthate, 15 mg estradiol di-enanthate, 6 mg estradiol benzoate in 2 ml corn oil. This product is sold in Germany under the name Lactimex and has been clinically examined by us.] [...] Of 1200 postpartum patients one quarter stopped breast feeding for a variety of reasons and received an injection of Lactimex (Protina: Benzil acid hydrazon-testosteron-oenanthat 300 mg, Oestradiol-di-oenanthat 15 mg and Oestradiol-benzoate 6 mg in 1.0 ml of oil). In 76% of cases one injection was sufficient and the remaining 24% required a second injection. A second injection was required rarer if the first injection had been longer after delivery. A higher dosage of Lactimex was not necessary in cases with a preceding medical induction with intraveinous Oxytocin (Orasthin). Mothers who had been treated postpartum with methylergobasin did not as often require a second injection. No localized or generalized adverse reaction to the drug was noticed.
  8. ^
    ISBN 9783871930133
    . 49035 В Amenose® Rp Ampullen Zus.: 1 Amp. 1 ml enth.: Benzilsäurehydrazid-N-testosteron-hydrazon-17-oenanthat 150 mg, Oestradiol-di-oenanthat 7.5 mg. Oestradiolbenzoat 1 mg in öl-Lösg. Ind.: Androgen-Oestrogen-Gemisch. Gegen Ausfallserscheinungen im Klimakterium und nach Ovarektomie. Osteoporose. Kontraind.: A 90, О 5 Dos.: Durchschnittl. alle 6 Wochen 1 Amp. im. 1 Amp. I ml 6.75 3 Amp 17.40 AP.: 10 Amp.
  9. ISBN 978-0-19-975569-1
    .
  10. ^
    S2CID 24616324
    .
  11. ^
    ISBN 978-3-642-60107-1
    . Natural estrogens considered here include: [...] Esters of 17β-estradiol, such as estradiol valerate, estradiol benzoate and estradiol cypionate. Esterification aims at either better absorption after oral administration or a sustained release from the depot after intramuscular administration. During absorption, the esters are cleaved by endogenous esterases and the pharmacologically active 17β-estradiol is released; therefore, the esters are considered as natural estrogens.
  12. ^ a b Vademecum International. J. Morgan Jones Publications. 1959. pp. 121–122.
  13. ^
    PMID 13752392
    .
  14. PMID 22971455
    .
  15. doi:10.3233/JRS-2010-0490
    .
  16. ^ "Discontinuation of CLIMACTERON® Injection (estradiol dienanthate ⁄ estradiol benzoate and testosterone enanthate benzilic acid hydrazone injection in corn oil)" (PDF). Sandoz. Health Canada. 23 November 2005. Archived from the original (PDF) on 2013-01-11. Retrieved 2 June 2019.
  17. ^ a b c "MDX Pharmaceutical Knowledge". Merative US L.P.
  18. S2CID 24695692
    .
  19. ^ Zentralblatt für Gynäkologie. J. A. Barth. 1971. The preparation Lactimex (300 mg 3-benzyl hydrazone-testosterone-17-enanthate + 15 mg estradiol-dienanthate + 6 mg estradiol benzoate in 2 ml corn oil) was injected. [...]
  20. ISBN 978-0-323-15726-1
    .
  21. ^
    ISBN 978-0-919115-04-0
    . LACTOSTAT [...] Each 2 mL of injectable solution contains testosteorne enanthate benzilic acid hydrazone 300 mg, estradiol dienanthate 15 mg, estradiol benzoate 6 mg, benzyl alcohol 7.5% as preservative, benzyl benzoate 0.75 mg, corn oil q.s. Available in 2 mL ampuls, boxes of 25.
  22. ^
    ISSN 0167-482X
    .
  23. ^
    PMID 3826177
    .
  24. ^
    PMID 2966832
    .
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