Esterified_Estrogens
Esterified estrogens
Pharmaceutical drug
Esterified estrogens (EEs), sold under the brand names Estratab and Menest among others, is an estrogen medication which is used hormone therapy for menopausal symptoms and low sex hormone levels in women, to treat breast cancer in both women and men, and to treat prostate cancer in men.[3][4][5][6][7] It is formulated alone or in combination with methyltestosterone.[3][4] It is taken by mouth.[1]
Estrone sulfate, the primary active component in esterified estrogens (constitutes about 75 to 85% of total content). | |
Equilin sulfate, the second most major active component in esterified estrogens (constitutes about 6 to 16% of total content). | |
| Combination of | |
|---|---|
| Sodium estrone sulfate | Estrogen |
| Sodium equilin sulfate | Estrogen |
| Clinical data | |
| Trade names | Estratab, Menest, others |
| Other names | Esterified oestrogens; EEs; Esterified equine estrogens; Esterified equine oestrogens; EEEs |
| Routes of administration | By mouth[1] |
| Drug class | Estrogen |
| ATC code |
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| Legal status | |
| Legal status | |
| Identifiers | |
| PubChem SID | |
| DrugBank | |
| UNII | |
Side effects of EEs include nausea, breast tension, edema, and breakthrough bleeding among others.[8] It is an estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol.[5][3][4] EEs are a prodrug mainly of estradiol and to a lesser extent of equilin.[5]
EEs were introduced for medical use by 1970.[9] They are available in only a few countries, such as Chile and the United States.[3] They have also been marketed in Argentina and Switzerland in the past.[3]
EEs are used in hormone therapy for menopausal symptoms, female hypogonadism, ovariectomy, and primary ovarian failure and in the treatment of breast cancer and prostate cancer.[4][10]
| Route/form | Estrogen | Low | Standard | High | |||
|---|---|---|---|---|---|---|---|
| Oral | Estradiol | 0.5–1 mg/day | 1–2 mg/day | 2–4 mg/day | |||
| Estradiol valerate | 0.5–1 mg/day | 1–2 mg/day | 2–4 mg/day | ||||
| Estradiol acetate | 0.45–0.9 mg/day | 0.9–1.8 mg/day | 1.8–3.6 mg/day | ||||
| Conjugated estrogens | 0.3–0.45 mg/day | 0.625 mg/day | 0.9–1.25 mg/day | ||||
| Esterified estrogens | 0.3–0.45 mg/day | 0.625 mg/day | 0.9–1.25 mg/day | ||||
| Estropipate | 0.75 mg/day | 1.5 mg/day | 3 mg/day | ||||
| Estriol | 1–2 mg/day | 2–4 mg/day | 4–8 mg/day | ||||
| Ethinylestradiola | 2.5–10 μg/day | 5–20 μg/day | – | ||||
| Nasal spray | Estradiol | 150 μg/day | 300 μg/day | 600 μg/day | |||
| Transdermal patch | Estradiol | 25 μg/dayb | 50 μg/dayb | 100 μg/dayb | |||
| Transdermal gel | Estradiol | 0.5 mg/day | 1–1.5 mg/day | 2–3 mg/day | |||
| Vaginal | Estradiol | 25 μg/day | – | – | |||
| Estriol | 30 μg/day | 0.5 mg 2x/week | 0.5 mg/day | ||||
| IMTooltip Intramuscular or SC injection | Estradiol valerate | – | – | 4 mg 1x/4 weeks | |||
| Estradiol cypionate | 1 mg 1x/3–4 weeks | 3 mg 1x/3–4 weeks | 5 mg 1x/3–4 weeks | ||||
| Estradiol benzoate | 0.5 mg 1x/week | 1 mg 1x/week | 1.5 mg 1x/week | ||||
| SC implant | Estradiol | 25 mg 1x/6 months | 50 mg 1x/6 months | 100 mg 1x/6 months | |||
| Footnotes: a = No longer used or recommended, due to health concerns. b = As a single patch applied once or twice per week (worn for 3–4 days or 7 days), depending on the formulation. Note: Dosages are not necessarily equivalent. Sources: See template. | |||||||
Available forms
EEs are available in the form of 0.3 mg, 0.625 mg, 1.25 mg, and 2.5 mg oral tablets.[11] Estratest is a combination formulation of 1.25 mg EEs with 2.5 mg methyltestosterone.[12]
EEs consist primarily of sodium estrone sulfate and sodium equilin sulfate, and are very similar to conjugated estrogens (CEEs, conjugated equine estrogens; brand name Premarin).[5][7][13][14] However, EEs and CEEs differ in the sources of their contents and in the percentages of their constituents; CEEs consist of approximately 53% sodium estrone sulfate and 25% sodium equilin sulfate, while EEs contain about 75 to 85% sodium estrone sulfate and 6 to 11% sodium equilin sulfate.[5][3][13][15][10] EEs have been found to produce similar serum levels of estrone and estradiol relative to CEEs, although with higher levels of estrone and lower levels of equilin.[5][16] One study found that the risk of venous thrombosis may be less with EEs relative to CEEs.[15][7]
| 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. | ||||||||||
| Compound | RBATooltip Relative binding affinity to SHBGTooltip sex hormone-binding globulin (%) | Bound to SHBG (%) | Bound to albumin (%) | Total bound (%) | MCRTooltip Metabolic clearance rate (L/day/m2) |
|---|---|---|---|---|---|
| 17β-Estradiol | 50 | 37 | 61 | 98 | 580 |
| Estrone | 12 | 16 | 80 | 96 | 1050 |
| Estriol | 0.3 | 1 | 91 | 92 | 1110 |
| Estrone sulfate | 0 | 0 | 99 | 99 | 80 |
| 17β-Dihydroequilin | 30 | ? | ? | ? | 1250 |
| Equilin | 8 | 26 | 13 | ? | 2640 |
| 17β-Dihydroequilin sulfate | 0 | ? | ? | ? | 375 |
| Equilin sulfate | 0 | ? | ? | ? | 175 |
| Δ8-Estrone | ? | ? | ? | ? | 1710 |
| Notes: RBA for SHBG (%) is compared to 100% for testosterone. Sources: See template. | |||||
EEs contain synthetic, plant-derived estrogens and are manufactured from soybeans and yams.[6][7]
EEs were introduced for medical use by 1970.[9]
Generic names
Estrogens, esterified is the generic name of the drug and its USPTooltip United States Pharmacopeia.[17] It is also known as esterified estrogens.[4]
Brand names
EEs are marketed under a variety of brand names including Amnestrogen, Estragyn, Estratab, Evex, Femibel, Femogen, Menest, Neo Estrone Tab, and Oestro-Feminal alone, and, in combination with methyltestosterone, under the brand names Covaryx, Delitan, Eemt, Essian, Estratest, Feminova-T, Menogen, and Syntest.[3][6][4]
Availability
EEs are or have been marketed in Argentina, Chile, Switzerland, and the United States.[3] Both EEs and the combination of EEs and methyltestosterone are listed as being marketed only in Chile and the United States as of present.[3]
- Sherif K (14 May 2013). Hormone Therapy: A Clinical Handbook. Springer Science & Business Media. pp. 120–. ISBN 978-1-4614-6268-2.
- "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2097. ISBN 978-0-85369-840-1.
- Weiner CP, Rope K (2 April 2013). The Complete Guide to Medications During Pregnancy and Breastfeeding: Everything You Need to Know to Make the Best Choices for You and Your Baby. St. Martin's Press. pp. 179–. ISBN 978-0-312-67646-9.
- Smith NL, Heckbert SR, Lemaitre RN, Reiner AP, Lumley T, Rosendaal FR, Psaty BM (December 2006). "Conjugated equine estrogen, esterified estrogen, prothrombotic variants, and the risk of venous thrombosis in postmenopausal women". Arteriosclerosis, Thrombosis, and Vascular Biology. 26 (12): 2807–2812. doi:10.1161/01.ATV.0000245792.62517.3b. PMID 16973976. S2CID 23850792.
- Wittlinger H (1980). "Clinical Effects of Estrogens". Functional Morphologic Changes in Female Sex Organs Induced by Exogenous Hormones. Springer. pp. 67–71. doi:10.1007/978-3-642-67568-3_10. ISBN 978-3-642-67570-6.
- Northwest Medicine. Vol. 69. Northwest Medical Pub. Association. 1970.
- Ebadi M (31 October 2007). Desk Reference of Clinical Pharmacology, Second Edition. CRC Press. pp. 249–. ISBN 978-1-4200-4744-8.
- "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 30 March 2018.
- Morley JE, van den Berg L (5 November 1999). Endocrinology of Aging. Springer Science & Business Media. pp. 172–. ISBN 978-1-59259-715-4.
- Fritz MA, Speroff L (28 March 2012). Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 752–. ISBN 978-1-4511-4847-3.
- Parker-Pope T (9 January 2007). The Hormone Decision: Untangle the Controversy, Understand Your Options, Make Your Own Choices. Rodale. pp. 157–. ISBN 978-1-59486-927-3.
- Smith NL, Heckbert SR, Lemaitre RN, Reiner AP, Lumley T, Weiss NS, et al. (October 2004). "Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis". JAMA. 292 (13): 1581–1587. doi:10.1001/jama.292.13.1581. hdl:1887/5083. PMID 15467060.
- Lemaitre RN, Weiss NS, Smith NL, Psaty BM, Lumley T, Larson EB, Heckbert SR (February 2006). "Esterified estrogen and conjugated equine estrogen and the risk of incident myocardial infarction and stroke". Archives of Internal Medicine. 166 (4): 399–404. doi:10.1001/archinte.166.4.399. PMID 16505258.
- "Estrogens, Esterified (USP) - Searchable synonyms, formulas, resource links, and other chemical information". ChemIDplus. U.S. Library of Medicine. D042724000.