Equilin

Equilin
Clinical data
Other names	Δ7-Estrone; 7-Dehydroestrone; Estra-1,3,5(10),7-tetraen-3-ol-17-one
Routes of; administration	By mouth
Drug class	Estrogen
Identifiers
	IUPAC name (9S,13S,14S)-3-hydroxy-13-methyl-9,11,12,14,15,16-hexahydro-6H-cyclopenta[a]phenanthren-17-one;
CAS Number	474-86-2 ;
PubChem CID	223368;
DrugBank	DB02187 ;
ChemSpider	193995 ;
UNII	08O86EX0J4;
KEGG	D04041 ;
ChEBI	CHEBI:42309 ;
ChEMBL	ChEMBL323533 ;
CompTox Dashboard (EPA)	DTXSID7047433 ;
ECHA InfoCard	100.006.809
Chemical and physical data
Formula	C18H20O2
Molar mass	268.356 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C3CC[C@H]4C/2=C/Cc1c(ccc(O)c1)[C@H]\2CC[C@]34C;
	InChI InChI=1S/C18H20O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3-5,10,14,16,19H,2,6-9H2,1H3/t14-,16+,18+/m1/s1 ; Key:WKRLQDKEXYKHJB-HFTRVMKXSA-N ;
	(verify)

Equilin is a naturally occurring estrogen sex hormone found in horses as well as a medication.^[1]^[2]^[3] It is one of the estrogens present in the estrogen combination drug preparations known as conjugated estrogens (CEEs; e.g. Premarin) and esterified estrogens (EEs; e.g. Estratab, Menest).^[2]^[3] CEEs is the most commonly used form of estrogen medications in hormone replacement therapy (HRT) for menopausal symptoms in the United States.^[3] Estrone sulfate is the major estrogen in CEEs (about 50%) while equilin sulfate is the second major estrogen in the formulation, present as about 25% of the total.^[2]^[3]

Pharmacology

Pharmacodynamics

Equilin is an estrogen, or an agonist of the estrogen receptors (ERs), the ERα and ERβ.^[2] In terms of relative binding affinity for the ERs, equilin has about 13% and 49% of that of estradiol for the ERα and ERβ, respectively.^[2] Analogously to the reversible transformation of estrone into estradiol by 17β-hydroxysteroid dehydrogenase, equilin can be converted into the more potent estrogen 17β-dihydroequilin in the body.^[2]^[3] This estrogen has about 113% and 108% of the relative binding affinities of estradiol for the ERα and ERβ, respectively.^[2]^[3] Equilin is present in CEEs in the form of equilin sulfate, which itself is inactive and acts as a prodrug of equilin via steroid sulfatase.^[2]^[3]

Similarly to synthetic estrogens like ethinylestradiol, equilin and CEEs have disproportionate effects in certain tissues such as the liver and uterus relative to bioidentical human estrogens like estradiol and estrone.^[2] Because of their disproportionate potency in the liver, equilin and CEEs have relatively increased effects on liver protein synthesis compared to estradiol.^[2]

A dosage of 0.25 mg/day equilin sulfate is equivalent to 0.625 mg/day CEEs in terms of relief from hot flashes.^[2] At a dosage of 0.625 mg/day equilin sulfate, the increases in circulating levels of sex hormone-binding globulin (SHBG), corticosteroid-binding globulin, and angiotensinogen were 1.5 to 8 times those observed with estrone sulfate.^[2] Equilin has about 42% of the relative potency of CEEs in the vagina and 80% of the relative potency of CEEs in the uterus, while its more active form, 17β-dihydroequilin, has about 83% of the relative potency of CEEs in the vagina and 200% of the relative potency of CEEs in the uterus.^[2]

Relative oral potencies of estrogens
Estrogen	HFTooltip Hot flashes	VETooltip Vaginal epithelium	UCaTooltip Urinary calcium	FSHTooltip Follicle-stimulating hormone	LHTooltip Luteinizing hormone	HDLTooltip High-density lipoprotein-CTooltip Cholesterol	SHBGTooltip Sex hormone-binding globulin	CBGTooltip Corticosteroid-binding globulin	AGTTooltip Angiotensinogen	Liver
Estradiol	1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
Estrone	?	?	?	0.3	0.3	?	?	?	?	?
Estriol	0.3	0.3	0.1	0.3	0.3	0.2	?	?	?	0.67
Estrone sulfate	?	0.9	0.9	0.8–0.9	0.9	0.5	0.9	0.5–0.7	1.4–1.5	0.56–1.7
Conjugated estrogens	1.2	1.5	2.0	1.1–1.3	1.0	1.5	3.0–3.2	1.3–1.5	5.0	1.3–4.5
Equilin sulfate	?	?	1.0	?	?	6.0	7.5	6.0	7.5	?
Ethinylestradiol	120	150	400	60–150	100	400	500–600	500–600	350	2.9–5.0
Diethylstilbestrol	?	?	?	2.9–3.4	?	?	26–28	25–37	20	5.7–7.5
Sources and footnotes Notes: Values are ratios, with estradiol as standard (i.e., 1.0). Abbreviations: HF = Clinical relief of hot flashes. VE = Increased proliferation of vaginal epithelium. UCa = Decrease in UCaTooltip urinary calcium. FSH = Suppression of FSHTooltip follicle-stimulating hormone levels. LH = Suppression of LHTooltip luteinizing hormone levels. HDL-C, SHBG, CBG, and AGT = Increase in the serum levels of these liver proteins. Liver = Ratio of liver estrogenic effects to general/systemic estrogenic effects (hot flashes/gonadotropins). Sources: See template.

Pharmacokinetics

Equilin has about 8% of the relative binding affinity of testosterone for SHBG, relative to 12% in the case of estrone.^[2] In terms of plasma protein binding, it is bound 26% to SHBG and 13% to albumin.^[2] The metabolic clearance rates of equilin and equilin sulfate are 2,640 L/day/m² and 175 L/day/m², respectively.^[2] In accordance, the biological half-life of equilin sulfate is substantially longer than that of equilin.^[2] Equilin is converted into 17β-dihydroequilin in the liver and in other tissues.^[2]^[3] Equilin and 17β-dihydroequilin can also be transformed into equilenin and 17β-dihydroequilenin.^[2]^[3] Equilin is excreted in the form of glucuronide conjugates.^[2]

Chemistry

Equilin, also known as δ⁷-estrone or as 7-dehydroestrone, as well as estra-1,3,5(10),7-tetraen-3-ol-17-one, is a naturally occurring estrane steroid and an analogue of estrone.^[2]^[3] In terms of chemical structure and pharmacology, equilin is to 17β-dihydroequilin (δ⁷-17β-estradiol) as estrone is to estradiol.^[2]^[3]

References

^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. p. 495. ISBN 978-1-4757-2085-3.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Bhavnani BR, Stanczyk FZ (July 2014). "Pharmacology of conjugated equine estrogens: efficacy, safety and mechanism of action". J. Steroid Biochem. Mol. Biol. 142: 16–29. doi:10.1016/j.jsbmb.2013.10.011. PMID 24176763. S2CID 1360563.

[Elks2014-1] J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. p. 495. ISBN 978-1-4757-2085-3.

[pmid16112947-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.

[pmid24176763-3] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Bhavnani BR, Stanczyk FZ (July 2014). "Pharmacology of conjugated equine estrogens: efficacy, safety and mechanism of action". J. Steroid Biochem. Mol. Biol. 142: 16–29. doi:10.1016/j.jsbmb.2013.10.011. PMID 24176763. S2CID 1360563.

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