 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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| Identifiers | |
| PubChem SID | |
| DrugBank | |
| UNII | |
Esterified estrogens (EEs), sold under the brand namesEstratab andMenest among others, is anestrogen medication which is usedhormone therapy formenopausal symptoms andlow sex hormone levels in women, to treatbreast cancer in both women and men, and to treatprostate cancer in men.[2][3][4][5][6] It is formulated alone or in combination withmethyltestosterone.[2][3] It is takenby mouth.[1]
Side effects of EEs includenausea,breast tension,edema, andbreakthrough bleeding among others.[7] It is anestrogen, or anagonist of theestrogen receptors, thebiological target of estrogens likeestradiol.[4][2][3] EEs are aprodrug mainly ofestradiol and to a lesser extent ofequilin.[4]
EEs were introduced for medical use by 1970.[8] They are available in only a few countries, such asChile and theUnited States.[2] They have also been marketed inArgentina andSwitzerland in the past.[2]
EEs are used inhormone therapy formenopausal symptoms, femalehypogonadism,ovariectomy, andprimary ovarian failure and in the treatment ofbreast cancer andprostate cancer.[3][9]
| 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 orSC 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. | |||||||
EEs are available in the form of 0.3 mg, 0.625 mg, 1.25 mg, and 2.5 mgoraltablets.[10]Estratest is acombination formulation of 1.25 mg EEs with 2.5 mgmethyltestosterone.[11]
EEs consist primarily ofsodium estrone sulfate andsodium equilin sulfate, and are very similar toconjugated estrogens (CEEs, conjugatedequine estrogens; brand name Premarin).[4][6][12][13] 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% sodiumequilin sulfate, while EEs contain about 75 to 85% sodium estrone sulfate and 6 to 11% sodium equilin sulfate.[4][2][12][14][9] EEs have been found to produce similar serum levels ofestrone andestradiol relative to CEEs, although with higher levels of estrone and lower levels of equilin.[4][15] One study found that the risk ofvenous thrombosis may be less with EEs relative to CEEs.[14][6]
| 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 ofhot flashes.VE = Increasedproliferation ofvaginal epithelium.UCa = Decrease inUCaTooltip urinary calcium.FSH = Suppression ofFSHTooltip follicle-stimulating hormone levels.LH = Suppression ofLHTooltip luteinizing hormone levels.HDL-C,SHBG,CBG, andAGT = Increase in the serum levels of theseliver 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 forSHBG (%) is compared to 100% fortestosterone.Sources: See template. | |||||
EEs containsynthetic,plant-derived estrogens and are manufactured fromsoybeans andyams.[5][6]
EEs were introduced for medical use by 1970.[8]
Estrogens, esterified is thegeneric name of the drug and itsUSPTooltip United States Pharmacopeia.[16] It is also known asesterified estrogens.[3]
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 withmethyltestosterone, under the brand names Covaryx, Delitan, Eemt, Essian, Estratest, Feminova-T, Menogen, and Syntest.[2][5][3]
EEs are or have been marketed inArgentina,Chile,Switzerland, and theUnited States.[2] Both EEs and the combination of EEs andmethyltestosterone are listed as being marketed only in Chile and the United States as of present.[2]