Estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone

Not to be confused with Climacteric or Lactinex.

EB/EDE/TEBH

Combination of
Estradiol benzoate	Estrogen
Estradiol dienanthate	Estrogen
Testosterone enanthate benzilic acid hydrazone	Androgen; Anabolic steroid
Clinical data
Trade names	Climacteron, Lactimex, Lactostat, Amenose
Other names	EB/EDE/TEBH
Routes of administration	Intramuscular injection
Identifiers
CAS Number	8063-58-9
PubChem CID	9577491

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 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. ^{[20] [17] [21]} They were administered by intramuscular injection typically once every 6 weeks but with a range of every 4 to 8 weeks or less frequently. ^[20] Climacteron was marketed in Canada in 1961 but was withdrawn in this country in October 2005 due to risk of endometrial hyperplasia and cancer from unopposed estrogen exposure (i.e., no concomitant progestogen) as well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. ^{[1] [22] [23]}

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] [24] [25]} They were administered as a single intramuscular injection after childbirth or during breastfeeding. ^[2] They were previously available in Germany and Canada. ^{[2] [25]}

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]}

• v
• t
• e

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
	Normethandrone a	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 propionate a	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 isobutyrate a	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 enanthate a	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.

• v
• t
• e

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 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.

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. ^[15] Assays were performed using immunoassays. ^[15] Source was Sherwin (1987). ^[15]
• 
  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. ^[14] Assays were performed using RIA. ^[14] Source was Sherwin et al. (1987). ^[14]

See also

• List of combined sex-hormonal preparations

References

1. 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. 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. 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. 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. 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. 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. 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. "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. 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.