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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.[1][2][3][4][5][6][7] Clinical studies have assessed this formulation.[8][9][10][11][12][13][14][15][16][17][18][19][1]

Climacteron contained 1.0 mg EB, 7.5 mg EDE, and 150 mg TEBH (69 mg free testosterone) and was used to treat menopausal symptoms.[20][17] It was administered by intramuscular injection once every 4 to 8 weeks or less frequently.[20] The medication was marketed in Canada in 1961 but was withdrawn in this country in October 2005 due to risk of endometrial hyperplasia and cancer from unopposed estrogen exposure (i.e., no concomitant progestogen) as well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.[1][21][22]

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.[2][3][23][24] They were administered as a single intramuscular injection after childbirth or during breastfeeding.[2] They were previously available in Germany and Canada.[2][24]

Estradiol and testosterone levels following a single intramuscular injection of EB/EDE/TEBH versus 10 mg estradiol valerate have been studied over 28 days.[14][16]

Androgen replacement therapy formulations and dosages used in women

Route Medication Major brand names Form Dosage
Oral Testosterone undecanoate Andriol, Jatenzo Capsule 40–80 mg 1x/1–2 days
Methyltestosterone Metandren, Estratest Tablet 0.5–10 mg/day
Fluoxymesterone Halotestin Tablet 1–2.5 mg 1x/1–2 days
Normethandronea Ginecoside Tablet 5 mg/day
Tibolone Livial Tablet 1.25–2.5 mg/day
Prasterone (DHEA)b Tablet 10–100 mg/day
Sublingual Methyltestosterone Metandren Tablet 0.25 mg/day
Transdermal Testosterone Intrinsa Patch 150–300 μg/day
AndroGel Gel, cream 1–10 mg/day
Vaginal Prasterone (DHEA) Intrarosa Insert 6.5 mg/day
Injection Testosterone propionatea Testoviron Oil solution 25 mg 1x/1–2 weeks
Testosterone enanthate Delatestryl, Primodian Depot Oil solution 25–100 mg 1x/4–6 weeks
Testosterone cypionate Depo-Testosterone, Depo-Testadiol Oil solution 25–100 mg 1x/4–6 weeks
Testosterone isobutyratea Femandren M, Folivirin Aqueous suspension 25–50 mg 1x/4–6 weeks
Mixed testosterone esters Climacterona Oil solution 150 mg 1x/4–8 weeks
Omnadren, Sustanon Oil solution 50–100 mg 1x/4–6 weeks
Nandrolone decanoate Deca-Durabolin Oil solution 25–50 mg 1x/6–12 weeks
Prasterone enanthatea Gynodian Depot Oil solution 200 mg 1x/4–6 weeks
Implant Testosterone Testopel Pellet 50–100 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

Estrogen Form Major brand names EPD CIC-D Duration
Estradiol Oil solution 40–60 mg 1–2 mg ≈ 1–2 days
Aqueous suspension Aquadiol, Diogyn, Progynon, Mego-E ? 3.5 mg 0.5–2 mg ≈ 2–7 days; 3.5 mg ≈ >5 days
Microspheres Juvenum-E, Juvenum ? 1 mg ≈ 30 days
Estradiol benzoate Oil solution Progynon-B 25–35 mg 1.66 mg ≈ 2–3 days; 5 mg ≈ 3–6 days
Aqueous suspension Agofollin-Depot, Ovocyclin M 20 mg 10 mg ≈ 16–21 days
Emulsion Menformon-Emulsion, Di-Pro-Emulsion ? 10 mg ≈ 14–21 days
Estradiol dipropionate Oil solution Agofollin, Di-Ovocylin, Progynon DP 25–30 mg 5 mg ≈ 5–8 days
Estradiol valerate Oil solution Delestrogen, Progynon Depot, Mesigyna 20–30 mg 5 mg 5 mg ≈ 7–8 days; 10 mg ≈ 10–14 days;
40 mg ≈ 14–21 days; 100 mg ≈ 21–28 days
Estradiol benzoate butyrate Oil solution Redimen, Soluna, Unijab ? 10 mg 10 mg ≈ 21 days
Estradiol cypionate Oil solution Depo-Estradiol, Depofemin 20–30 mg 5 mg ≈ 11–14 days
Aqueous suspension Cyclofem, Lunelle ? 5 mg 5 mg ≈ 14–24 days
Estradiol enanthate Oil solution Perlutal, Topasel, Yectames ? 5–10 mg 10 mg ≈ 20–30 days
Estradiol dienanthate Oil solution Climacteron, Lactimex, Lactostat ? 7.5 mg ≈ >40 days
Estradiol undecylate Oil solution Delestrec, Progynon Depot 100 ? 10–20 mg ≈ 40–60 days;
25–50 mg ≈ 60–120 days
Polyestradiol phosphate Aqueous solution Estradurin 40–60 mg 40 mg ≈ 30 days; 80 mg ≈ 60 days;
160 mg ≈ 120 days
Estrone Oil solution Estrone, Kestrin, Theelin ? 1–2 mg ≈ 2–3 days
Aqueous suspension Estrone Aq. Susp., Kestrone, Theelin Aq. ? 0.1–2 mg ≈ 2–7 days
Estriol Oil solution ? 1–2 mg ≈ 1–4 days
Polyestriol phosphate Aqueous solution Gynäsan, Klimadurin, Triodurin ? 50 mg ≈ 30 days; 80 mg ≈ 60 days
Notes: All aqueous suspensions are of microcrystalline particle size. Estradiol production during the menstrual cycle is 30–640 µg/day (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. ^ a b c Al-Imari L, Wolfman WL (September 2012). "The safety of testosterone therapy in women". J Obstet Gynaecol Can. 34 (9): 859–865. doi:10.1016/S1701-2163(16)35385-3. PMID 22971455.
  2. ^ 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.
  3. ^ a b 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, Elizabeth S. (1999). "Androgen Replacement in Postmenopausal Women". In Seifer, David B.; Kennard, Elizabeth A. (eds.). Menopause. 18. pp. 209–219. doi:10.1007/978-1-59259-246-3_13. ISBN 978-1-61737-129-5.
  5. ^ Robert B. Greenblatt; William E. Barfield; Edwin C. Jungck (January 1962). "The treatment of the menopause". Can Med Assoc J. 86 (3): 113–4. PMC 1848811. PMID 13901504.
  6. ^ David B. Seifer (27 July 1999). 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. ^ Hans Hermann Julius Hager; Walther Kern; Paul Heinz List; Hermann Josef Roth (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". Can Med Assoc J. 83: 1240–2. PMC 1938994. PMID 13752392.
  9. ^ Schneider J, MacArthur JL, Patrick JW, Burton GV (August 1964). "The Suppression of Lactation: An Objective Study". Obstet Gynecol. 24 (2): 294–7. 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". Am. J. Obstet. Gynecol. 148 (5): 552–7. 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". Am. J. Obstet. Gynecol. 151 (2): 153–60. 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): 225–33. 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): 325–35. doi:10.1016/0306-4530(85)90009-5. PMID 3903822.
  14. ^ a b c d e Sherwin BB, Gelfand MM, Schucher R, Gabor J (February 1987). "Postmenopausal estrogen and androgen replacement and lipoprotein lipid concentrations". Am. J. Obstet. Gynecol. 156 (2): 414–9. doi:10.1016/0002-9378(87)90295-X. PMID 3826177.
  15. ^ a b c d Sherwin, Barbara B.; Gelfand, Morrie M. (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. ^ a b Sherwin BB (1988). "Affective changes with estrogen and androgen replacement therapy in surgically menopausal women". J Affect Disord. 14 (2): 177–87. doi:10.1016/0165-0327(88)90061-4. PMID 2966832.
  17. ^ a b Sherwin BB (1988). "Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women". Psychoneuroendocrinology. 13 (4): 345–57. doi:10.1016/0306-4530(88)90060-1. PMID 3067252.
  18. ^ Sherwin, Barbara B. (1994). "The Effect of Sex Steroids on Brain Mechanisms Relating to Mood and Sexuality". Comprehensive Management of Menopause. Clinical Perspectives in Obstetrics and Gynecology. pp. 327–333. doi:10.1007/978-1-4612-4330-4_31. ISBN 978-1-4612-8737-7. ISSN 0178-0328.
  19. ^ Sherwin, Barbara B (2002). "Randomized clinical trials of combined estrogen-androgen preparations: effects on sexual functioning". Fertility and Sterility. 77: 49–54. doi:10.1016/S0015-0282(02)03002-9. ISSN 0015-0282. PMID 12007902.
  20. ^ a b "Climacteron Drug Information, Professional". Drugs.com. Retrieved 2 June 2019.
  21. ^ Lexchin, Joel (2010). "Drug safety and Health Canada". International Journal of Risk & Safety in Medicine. 22 (1): 41–53. doi:10.3233/JRS-2010-0490.
  22. ^ "Wayback Machine" (PDF). web.archive.org. 11 January 2013. Retrieved 2 June 2019.
  23. ^ Helmuth Vorherr (2 December 2012). The Breast: Morphology, Physiology, and Lactation. Elsevier Science. pp. 201–. ISBN 978-0-323-15726-1.
  24. ^ a b 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.