Estradiol dienantate explained

Estradiol dienanthate (EDE), sold under the brand names Climacteron among others, is a long-acting estrogen medication which was previously used in menopausal hormone therapy for women and to suppress lactation in women.[1] [2] [3] [4] It was formulated in combination with estradiol benzoate (EB), a short-acting estrogen, and testosterone enanthate benzilic acid hydrazone (TEBH), a long-acting androgen/anabolic steroid. 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]

Side effects of EDE include breast tenderness, breast enlargement, nausea, headache, and fluid retention.[7] EDE is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol.[8] It is an estrogen ester and a prodrug of estradiol in the body. Because of this, it is considered to be a natural and bioidentical form of estrogen.[9]

EDE was first described by 1959.[10] [11] It was previously available in Canada and Germany but was discontinued by 2005.[12] [13] [14] The medication is no longer available in any form.

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 menopausal hormone therapy in perimenopausal, postmenopausal, hypogonadal, and oophorectomized women, as well as for suppression of lactation in postpartum women.

Available forms

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

EDE was available only in combination EB and TEBH. 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] [15] [16] 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.[17] [18] [19] [20]

Pharmacology

Pharmacodynamics

See also: Pharmacodynamics of estradiol.

EDE is an estradiol ester, or a prodrug of estradiol. As such, it is an estrogen, or an agonist of the estrogen receptors. EDE is of about 82% higher molecular weight than estradiol due to the presence of its C3 and C17β heptanoate (enanthate) esters. Because EDE is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.

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.

Chemistry

See also: Estrogen ester.

EDE is a synthetic estrane steroid and the C3 and C17β heptanoate (enanthate) diester of estradiol. It is also known as estradiol 3,17β-heptanoate or as estra-1,3,5(10)-triene-3,17β-diol 3,17β-diheptanoate. EDE is structurally related to estradiol enanthate (estradiol 17β-heptanoate), which has a single heptanoate ester rather than two.

History

EDE was first described and introduced for medical use by 1959.

Society and culture

Brand names

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

Availability

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

See also

Notes and References

  1. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 898.
  2. Book: Ginsburg ES . Seifer DB, Kennard EA . Menopause . 1999 . 18 . 209–219 . 10.1007/978-1-59259-246-3_13 . Androgen Replacement in Postmenopausal Women . 978-1-61737-129-5.
  3. Greenblatt RB, Barfield WE, Jungck EC . The treatment of the menopause . Canadian Medical Association Journal . 86 . 3 . 113–114 . January 1962 . 13901504 . 1848811 .
  4. Book: Leondires MP, Segars JH, Walsh BW . The Use of Antiestrogens in the Postmenopausal Woman . https://books.google.com/books?id=t0zMBgAAQBAJ&pg=PT183 . Menopause: Endocrinology and Management . Springer Science & Business Media . 27 July 1999 . Seifer DB, Kennard EA . 183– . 978-1-59259-246-3 . 10.1007/978-1-59259-246-3_12.
  5. Web site: Estradiol: Uses, Dosage & Side Effects . Drugs.com .
  6. Web site: Climacteron Drug Information, Professional. Drugs.com. 2 June 2019. 2 June 2019. https://web.archive.org/web/20190602054345/https://www.drugs.com/mmx/climacteron.html. dead.
  7. Book: Ghosh AK . Mayo Clinic Internal Medicine Board Review. 23 September 2010. OUP USA. 978-0-19-975569-1. 222–.
  8. Kuhl H . Pharmacology of estrogens and progestogens: influence of different routes of administration . Climacteric . 8 . 3–63 . August 2005 . Suppl 1 . 16112947 . 10.1080/13697130500148875 . 24616324 .
  9. Book: Oettel M, Schillinger E . Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. 6 December 2012. Springer Science & Business Media. 978-3-642-60107-1. 261. 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..
  10. Book: Vademecum International. 1959. J. Morgan Jones Publications.. 121–122.
  11. Kelly MJ, Primrose T . Evaluation of a new preparation for the suppression of lactation . Canadian Medical Association Journal . 83 . 24 . 1240–1242 . December 1960 . 13752392 . 1938994 .
  12. Al-Imari L, Wolfman WL . The safety of testosterone therapy in women . Journal of Obstetrics and Gynaecology Canada . 34 . 9 . 859–865 . September 2012 . 22971455 . 10.1016/S1701-2163(16)35385-3 .
  13. Lexchin . Joel . Drug safety and Health Canada . 2010 . International Journal of Risk & Safety in Medicine . 22 . 1 . 41–53 . 10.3233/JRS-2010-0490 .
  14. Web site: Discontinuation of CLIMACTERON® Injection (estradiol dienanthate ⁄ estradiol benzoate and testosterone enanthate benzilic acid hydrazone injection in corn oil) . Sandoz . Health Canada . 23 November 2005 . https://web.archive.org/web/20130111212103/http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisories-avis/prof/2005/climacteron_hpc-cps-eng.pdf. 2 June 2019. 2013-01-11.
  15. Sherwin BB . Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women . Psychoneuroendocrinology . 13 . 4 . 345–357 . 1988 . 3067252 . 10.1016/0306-4530(88)90060-1 . 24695692 .
  16. Book: Bundesverband der Pharmazeutischen Industrie (Germany). Rote Liste: Verzeichnis pharmazeutischer Spezialpräparate. 1974. Editio Cantor. 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..
  17. Book: Geburtshilfe und Frauenheilkunde: Ergebnisse der Forschung für die Praxis. 1969. Georg Thieme Verlag.. 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..
  18. Book: Zentralblatt für Gynäkologie. 1971. J. A. Barth. 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. [...].
  19. Book: Vorherr H . The Breast: Morphology, Physiology, and Lactation. 2 December 2012. Elsevier Science. 978-0-323-15726-1. 201–.
  20. Book: Compendium of Pharmaceuticals and Specialties. 1983. Canadian Pharmaceutical Association. 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..
  21. Web site: MDX Pharmaceutical Knowledge . Merative US L.P. .

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