17β-Dihydroequilin

17β-Dihydroequilin
Clinical data
Other names	β-Dihydroequilin; Δ7-17β-Estradiol; 7-Dehydro-17β-estradiol; Estra-1,3,5(10),7-tetraen-3,17β-diol; NSC-12170
Routes of; administration	By mouth
Drug class	Estrogen
Identifiers
	IUPAC name (9S,13S,14S,17S)-13-Methyl-6,9,11,12,14,15,16,17-octahydrocyclopenta[a]phenanthrene-3,17-diol;
CAS Number	3563-27-7;
PubChem CID	11954027;
ChemSpider	10128322;
UNII	WXG88DST4R;
ChEBI	CHEBI:62851;
ChEMBL	ChEMBL121458;
CompTox Dashboard (EPA)	DTXSID40871892 ;
ECHA InfoCard	100.020.576
Chemical and physical data
Formula	C18H22O2
Molar mass	270.372 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@]12CC[C@H]3C(=CCC4=C3C=CC(=C4)O)[C@@H]1CC[C@@H]2O;
	InChI InChI=1S/C18H22O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3-5,10,14,16-17,19-20H,2,6-9H2,1H3/t14-,16+,17+,18+/m1/s1; Key:NLLMJANWPUQQTA-UBDQQSCGSA-N;

17β-Dihydroequilin is a naturally occurring estrogen sex hormone found in horses as well as a medication.^[1]^[2] As the C3 sulfate ester sodium salt, it is a minor constituent (1.7%) of conjugated estrogens (CEEs; brand name Premarin).^[1] However, as equilin, with equilin sulfate being a major component of CEEs, is transformed into 17β-dihydroequilin in the body, analogously to the conversion of estrone into estradiol, 17β-dihydroequilin is, along with estradiol, the most important estrogen responsible for the effects of CEEs.^[1]

Pharmacology

Pharmacodynamics

17β-Dihydroequilin is an estrogen, or an agonist of the estrogen receptors (ERs), the ERα and ERβ.^[1] In terms of relative binding affinity for the ERs, 17β-dihydroequilin has about 113% and 108% of that of estradiol for the ERα and ERβ, respectively.^[1] 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.^[1] Of the equine estrogens, it shows the highest estrogenic activity and greatest estrogenic potency.^[1]

Like CEEs as a whole, 17β-dihydroequilin has disproportionate effects in certain tissues such as the liver and uterus.^[1] Equilin, the second major component of conjugated estrogens after estrone, is reversibly transformed into 17β-dihydroequilin analogously to the transformation of estrone into estradiol.^[1] However, whereas the balance of mutual interconversion of estrone and estradiol is largely shifted in the direction of estrone, it is nearly equal in the case of equilin and 17β-dihydroequilin.^[1] As such, although 17β-dihydroequilin is only a minor constituent of CEEs, it is, along with estradiol, the most important estrogen relevant to the estrogenic activity of the medication.^[1]

v
t
e
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

17β-Dihydroequilin has about 30% of the relative binding affinity of testosterone for sex hormone-binding globulin (SHBG), relative to 50% for estradiol.^[1] The metabolic clearance rate of 17β-dihydroequilin is 1,250 L/day/m², relative to 580 L/day/m² for estradiol.^[1]

Chemistry

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

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o 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.
^ Fritz MA, Speroff L (28 March 2012). "Postmenopausal Hormone Therapy". Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 751–. ISBN 978-1-4511-4847-3.

[pmid16112947-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o 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.

[FritzSperoff2012-2] Fritz MA, Speroff L (28 March 2012). "Postmenopausal Hormone Therapy". Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 751–. ISBN 978-1-4511-4847-3.

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