Estradiol hexahydrobenzoate

Last updated
Estradiol hexahydrobenzoate
Estradiol hexahydrobenzoate.svg
Clinical data
Trade names Benzo-Ginoestril A.P., BenzoGynoestryl Retard, Ginestryl-15-Depot, Menodin, Tardoginestryl
Other namesEHHB; Estradiol cyclohexanecarboxylate; ECHC; Oestradiol hexahydrobenzoate; Estradiol 17β-hexahydrobenzoate; Estradiol 17β-cyclohexanecarboxylate; Estradiol hexabenzoate
Routes of
administration 		Intramuscular injection
Drug class Estrogen; Estrogen ester
Identifiers
  • (3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl) cyclohexanecarboxylate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard 100.035.623 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C25H34O3
Molar mass 382.544 g·mol−1
3D model (JSmol)
  • CC12CCC3C(CCc4cc(O)ccc34)C1CCC2OC(=O)C5CCCCC5
  • InChI=1S/C25H34O3/c1-25-14-13-20-19-10-8-18(26)15-17(19)7-9-21(20)22(25)11-12-23(25)28-24(27)16-5-3-2-4-6-16/h8,10,15-16,20-23,26H,2-7,9,11-14H2,1H3
  • Key:IVRCALGRJCHPRV-UHFFFAOYSA-N

Estradiol hexahydrobenzoate (EHHB), sold under a number of brand names including Benzo-Ginoestril A.P., BenzoGynoestryl Retard, Ginestryl-15-Depot, Menodin, and Tardoginestryl, is an estrogen medication which was previously used for indications such as menopausal hormone therapy and gynecological disorders. [1] [2] [3] [4] [5] EHHB is given by injection into muscle at regular intervals, for instance once every few weeks. [3] [5] [6] [7]

Contents

Side effects of EHHB include breast tenderness, breast enlargement, nausea, headache, and fluid retention. [8] EHHB is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol. [9] [10] It is an estrogen ester and a prodrug of estradiol in the body. [10] [9] Because of this, it is considered to be a natural and bioidentical form of estrogen. [10]

EHHB was first described in 1956, [11] [12] and was introduced for medical use by 1957. [6] It was used in France. [6] The medication should not be confused with estradiol benzoate (EB), which has been marketed under similar brand names including Benzo-Ginestryl, Benzo-Ginoestril, and Benzo-Gynoestryl. [3] [6] [13]

Medical uses

EHHB was marketed in France in a 5 mg/mL oil solution in ampoules for intramuscular injection at regular intervals, for instance once every few weeks. [3] [5] [6] [7] Use of EHHB for feminizing hormone therapy in transgender women has been reported. [14] A combination of 3 mg EHHB, 75 mg hydroxyprogesterone caproate, and 100 mg testosterone hexahydrobenzoate in 2 mL oil solution provided in ampoules has been marketed under the brand name Trinestril AP in Brazil. [15] [16] [17] Its indications include menopausal hormone therapy and the treatment of functional uterine bleeding. [15] The combination is administered typically once per month by intramuscular injection. [15]

Pharmacology

Estradiol, the active form of EHHB. Estradiol.svg
Estradiol, the active form of EHHB.

Pharmacodynamics

EHHB is an estradiol ester, or a prodrug of estradiol. [10] [9] [18] As such, it is an estrogen, or an agonist of the estrogen receptors. [10] [9] EHHB is of about 40% higher molecular weight than estradiol due to the presence of its C17β cyclohexanecarboxylate ester. [1] Because EHHB is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen. [10]

Pharmacokinetics

A combination of EHHB and norgestrel as a combined injectable contraceptive reportedly has a duration of action of about 3 weeks. [19]

Chemistry

EHHB, also known as estradiol cyclohexanecarboxylate (ECHC) as well as estradiol 17β-hexahydrobenzoate or estradiol 17β-cyclohexanecarboxylate, is a synthetic estrane steroid and an estrogen ester. [1] [2] [3] [4] It is specifically the C17β cyclohexanecarboxylate (hexahydrobenzoate) ester of estradiol. [1] [2]

History

EHHB was first described and characterized in 1956. [11] [12] It was developed in France. [11] [12] The medication was introduced for medical use in France by 1957. [6] A publicized case report of a rapidly growing breast cancer tumor in a 53-year-old woman 10 days after initiation of therapy with 5 mg/month EHHB by intramuscular injection for hot flashes was published in 1962. [20] [21] [22] The woman died due to breast cancer 10 months after the diagnosis. [20] [22]

Society and culture

Generic names

Estradiol hexahydrobenzoate is the generic name of the drug and its INN Tooltip International Nonproprietary Name), while oestradiol hexahydrobenzoate is its BANM Tooltip British Approved Name. [1] [2] [3] [4] The medication is also known as estradiol cyclohexanecarboxylate (ECHC). [1] [2] [3] [4]

Brand names

EHHB has been marketed under the brand names Benzo-Ginoestril A.P., BenzoGynoestryl Retard, Ginestryl-15-Depot, Menodin, and Tardoginestryl. [1] [2] [3] [4] [5]

Availability

EHHB was previously marketed in France. [6]

Research

A combination of 5 mg EHHB in peanut oil solution and 25 mg norgestrel in aqueous suspension as a once-monthly combined injectable contraceptive was studied, but this formulation was ultimately never marketed. [23] [24] [25] [26] [27] [19]

Related Research Articles

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References

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  22. 1 2 Carcinogenesis Abstracts. National Cancer Institute. 1973. p. 900. A rapidly growing lump developed in a 53yr-old woman 1 wk after she had been given estradiol hexahydrobenzoate (5 mg/month) for hot flashes. The patient died of breast cancer 10 months later.
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