Estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone

EB/EDE/TEBH
Combination of
Estradiol benzoateEstrogen
Estradiol dienanthateEstrogen
Testosterone enanthate benzilic acid hydrazoneAndrogen; Anabolic steroid
Clinical data
Trade namesClimacteron, Lactimex, Lactostat, Amenose
Other namesEB/EDE/TEBH
Routes of
administration		Intramuscular injection
Identifiers
CAS Number
PubChem CID

Estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone (EB/EDE/TEBH), sold under the brand names Climacteron, Lactimex, Lactostat, and Amenose, is an injectable combination medication of estradiol benzoate (EB), an estrogen, estradiol dienanthate (EDE), an estrogen, and testosterone enanthate benzilic acid hydrazone (TEBH), an androgen/anabolic steroid, which is used in menopausal hormone therapy for peri- and postmenopausal women and to suppress lactation in postpartum women. Clinical studies have assessed this formulation.

Climacteron and Amenose contained 1.0 mg EB, 7.5 mg EDE, and 150 mg TEBH (69 mg free testosterone) and was used to treat menopausal symptoms. They were administered by intramuscular injection typically once every 6 weeks but with a range of every 4 to 8 weeks or less frequently. Climacteron was marketed in Canada in 1961 but was withdrawn in this country in October 2005 due to risk of endometrial hyperplasia and cancer from unopposed estrogen exposure (i.e., no concomitant progestogen) as well as induction of supraphysiological testosterone levels.

Lactimex and Lactostat contained 6 mg EB, 15 mg EDE, and 300 mg TEBH in 2 mL of corn oil and were used to suppress lactation. They were administered as a single intramuscular injection after childbirth or during breastfeeding. They were previously available in Germany and Canada.

Estradiol and testosterone levels following a single intramuscular injection of EB/EDE/TEBH versus 10 mg estradiol valerate have been studied over 28 days.

Androgen replacement therapy formulations and dosages used in women
RouteMedicationMajor brand namesFormDosage
OralTestosterone undecanoateAndriol, JatenzoCapsule40–80 mg 1x/1–2 days
MethyltestosteroneMetandren, EstratestTablet0.5–10 mg/day
FluoxymesteroneHalotestinTablet1–2.5 mg 1x/1–2 days
NormethandroneaGinecosideTablet5 mg/day
TiboloneLivialTablet1.25–2.5 mg/day
Prasterone (DHEA)b–Tablet10–100 mg/day
SublingualMethyltestosteroneMetandrenTablet0.25 mg/day
TransdermalTestosteroneIntrinsaPatch150–300 μg/day
AndroGelGel, cream1–10 mg/day
VaginalPrasterone (DHEA)IntrarosaInsert6.5 mg/day
InjectionTestosterone propionateaTestovironOil solution25 mg 1x/1–2 weeks
Testosterone enanthateDelatestryl, Primodian DepotOil solution25–100 mg 1x/4–6 weeks
Testosterone cypionateDepo-Testosterone, Depo-TestadiolOil solution25–100 mg 1x/4–6 weeks
Testosterone isobutyrateaFemandren M, FolivirinAqueous suspension25–50 mg 1x/4–6 weeks
Mixed testosterone estersClimacteronaOil solution150 mg 1x/4–8 weeks
Omnadren, SustanonOil solution50–100 mg 1x/4–6 weeks
Nandrolone decanoateDeca-DurabolinOil solution25–50 mg 1x/6–12 weeks
Prasterone enanthateaGynodian DepotOil solution200 mg 1x/4–6 weeks
ImplantTestosteroneTestopelPellet50–100 mg 1x/3–6 months
Notes: Premenopausal women produce about 230 ± 70 μg testosterone per day (6.4 ± 2.0 mg testosterone per 4 weeks), with a range of 130 to 330 μg per day (3.6–9.2 mg per 4 weeks). Footnotes: a = Mostly discontinued or unavailable. b = Over-the-counter. Sources: See template.
Potencies and durations of natural estrogens by intramuscular injection
EstrogenFormDose (mg)Duration by dose (mg)
EPDCICD
EstradiolAq. soln.?–<1 d
Oil soln.40–60–1–2 ≈ 1–2 d
Aq. susp.?3.50.5–2 ≈ 2–7 d; 3.5 ≈ >5 d
Microsph.?–1 ≈ 30 d
Estradiol benzoateOil 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 dipropionateOil soln.25–30–5 ≈ 5–8 d
Estradiol valerateOil soln.20–3055 ≈ 7–8 d; 10 ≈ 10–14 d;
40 ≈ 14–21 d; 100 ≈ 21–28 d
Estradiol benz. butyrateOil soln.?1010 ≈ 21 d
Estradiol cypionateOil soln.20–30–5 ≈ 11–14 d
Aq. susp.?55 ≈ 14–24 d
Estradiol enanthateOil soln.?5–1010 ≈ 20–30 d
Estradiol dienanthateOil soln.?–7.5 ≈ >40 d
Estradiol undecylateOil soln.?–10–20 ≈ 40–60 d;
25–50 ≈ 60–120 d
Polyestradiol phosphateAq. soln.40–60–40 ≈ 30 d; 80 ≈ 60 d;
160 ≈ 120 d
EstroneOil soln.?–1–2 ≈ 2–3 d
Aq. susp.?–0.1–2 ≈ 2–7 d
EstriolOil soln.?–1–2 ≈ 1–4 d
Polyestriol phosphateAq. soln.?–50 ≈ 30 d; 80 ≈ 60 d
Notes and sources
Notes: All aqueous suspensions are of microcrystalline particle size. Estradiol production during the menstrual cycle is 30–640 µg/d (6.4–8.6 mg total per month or cycle). The vaginal epithelium maturation dosage of estradiol benzoate or estradiol valerate has been reported as 5 to 7 mg/week. An effective ovulation-inhibiting dose of estradiol undecylate is 20–30 mg/month. Sources: See template.

See also

References

  1. 1 2 3 Al-Imari L, Wolfman WL (September 2012). "The safety of testosterone therapy in women". Journal of Obstetrics and Gynaecology Canada. 34 (9): 859–865. doi:10.1016/S1701-2163(16)35385-3. PMID 22971455.
  2. 1 2 3 4 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.
  3. 1 2 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. [...]
  4. ↑ Ginsburg ES (1999). "Androgen Replacement in Postmenopausal Women". In Seifer DB, Kennard EA (eds.). Menopause. Contemporary Endocrinology. Vol. 18. Humana Press. pp. 209–219. doi:10.1007/978-1-59259-246-3_13. ISBN 978-1-61737-129-5.
  5. ↑ Greenblatt RB, Barfield WE, Jungck EC (January 1962). "The treatment of the menopause". Canadian Medical Association Journal. 86 (3): 113–114. PMC 1848811. PMID 13901504.
  6. ↑ Seifer DB (27 July 1999). Seifer DB, Kennard EA (eds.). Menopause: Endocrinology and Management. Springer Science & Business Media. pp. 183–. doi:10.1007/978-1-59259-246-3. ISBN 978-1-59259-246-3.
  7. ↑ Hager HH, Kern W, Heinz P, Roth HJ (29 July 2013). Hagers Handbuch der Pharmazeutischen Praxis: Für Apotheker, Arzneimittelhersteller, Ärzte und Medizinalbeamte: Wirkstoffgruppen II Chemikalien und Drogen (A-AL). Springer-Verlag. pp. 157–. ISBN 978-3-662-25655-8.
  8. ↑ Kelly MJ, Primrose T (December 1960). "Evaluation of a new preparation for the suppression of lactation". Canadian Medical Association Journal. 83 (24): 1240–1242. PMC 1938994. PMID 13752392.
  9. ↑ Schneider J, Macarthur JL, Patrick JW, Burton GV (August 1964). "The Suppression of Lactation: An Objective Study". Obstetrics and Gynecology. 24 (2): 294–297. PMID 14199544.
  10. ↑ Sherwin BB, Gelfand MM (March 1984). "Effects of parenteral administration of estrogen and androgen on plasma hormone levels and hot flushes in the surgical menopause". American Journal of Obstetrics and Gynecology. 148 (5): 552–557. doi:10.1016/0002-9378(84)90746-4. PMID 6367474.
  11. ↑ Sherwin BB, Gelfand MM (January 1985). "Differential symptom response to parenteral estrogen and/or androgen administration in the surgical menopause". American Journal of Obstetrics and Gynecology. 151 (2): 153–160. doi:10.1016/0002-9378(85)90001-8. PMID 3881960.
  12. ↑ Sherwin BB (September 1985). "Changes in sexual behavior as a function of plasma sex steroid levels in post-menopausal women". Maturitas. 7 (3): 225–233. doi:10.1016/0378-5122(85)90044-1. PMID 4079822.
  13. ↑ Sherwin BB, Gelfand MM (1985). "Sex steroids and affect in the surgical menopause: a double-blind, cross-over study". Psychoneuroendocrinology. 10 (3): 325–335. doi:10.1016/0306-4530(85)90009-5. PMID 3903822. S2CID 40861936.
  14. 1 2 3 4 5 Sherwin BB, Gelfand MM, Schucher R, Gabor J (February 1987). "Postmenopausal estrogen and androgen replacement and lipoprotein lipid concentrations". American Journal of Obstetrics and Gynecology. 156 (2): 414–419. doi:10.1016/0002-9378(87)90295-X. PMID 3826177.
  15. 1 2 3 4 Sherwin BB, Gelfand MM (1987). "Individual differences in mood with menopausal replacement therapy: possible role of sex hormone-binding globulin". Journal of Psychosomatic Obstetrics & Gynecology. 6 (2): 121–131. doi:10.3109/01674828709016773. ISSN 0167-482X.
  16. 1 2 Sherwin BB (1988). "Affective changes with estrogen and androgen replacement therapy in surgically menopausal women". Journal of Affective Disorders. 14 (2): 177–187. doi:10.1016/0165-0327(88)90061-4. PMID 2966832.
  17. 1 2 Sherwin BB (1988). "Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women". Psychoneuroendocrinology. 13 (4): 345–357. doi:10.1016/0306-4530(88)90060-1. PMID 3067252. S2CID 24695692.
  18. ↑ Sherwin BB (1994). "The Effect of Sex Steroids on Brain Mechanisms Relating to Mood and Sexuality". Comprehensive Management of Menopause. Clinical Perspectives in Obstetrics and Gynecology. Springer. pp. 327–333. doi:10.1007/978-1-4612-4330-4_31. ISBN 978-1-4612-8737-7. ISSN 0178-0328.
  19. ↑ Sherwin BB (April 2002). "Randomized clinical trials of combined estrogen-androgen preparations: effects on sexual functioning". Fertility and Sterility. 77 (Suppl 4): S49–S54. doi:10.1016/S0015-0282(02)03002-9. PMID 12007902.
  20. 1 2 "Climacteron Drug Information, Professional". Drugs.com. Archived from the original on 2 June 2019. Retrieved 2 June 2019.
  21. ↑ Bundesverband der Pharmazeutischen Industrie (Germany) (1974). Rote Liste: Verzeichnis pharmazeutischer Spezialpräparate. Editio Cantor. 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.
  22. ↑ Lexchin J (2010). "Drug safety and Health Canada". International Journal of Risk & Safety in Medicine. 22 (1): 41–53. doi:10.3233/JRS-2010-0490.
  23. ↑ "Discontinuation of CLIMACTERON® Injection (estradiol dienanthate ⁄ estradiol benzoate and testosterone enanthate benzilic acid hydrazone injection in corn oil)" (PDF). Sandoz Canada Inc. 23 November 2005. Archived from the original (PDF) on 2013-01-11. Retrieved 2 June 2019.
  24. ↑ Vorherr H (2 December 2012). The Breast: Morphology, Physiology, and Lactation. Elsevier Science. pp. 201–. ISBN 978-0-323-15726-1.
  25. 1 2 Compendium of Pharmaceuticals and Specialties. Canadian Pharmaceutical Association. 1983. 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.