Equilin
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| 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 | |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.006.809 |
| Chemical and physical data | |
| Formula | C18H20O2 |
| Molar mass | 268.356 g·mol−1 |
| 3D model (JSmol) | |
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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
[edit]Pharmacodynamics
[edit]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]
| Estrogen | HF | VE | UCa | FSH | LH | HDL-C | SHBG | CBG | AGT | 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 UCa. FSH = Suppression of FSH levels. LH = Suppression of LH 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
[edit]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
[edit]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
[edit]- ^ 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.