Esterified estrogens

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Not to be confused with Estrogen ester or Conjugated estrogens.
Esterified estrogens
Sodium equilin sulfate
Estrogen
Clinical data
Trade namesEstratab, Menest, others
Other namesEsterified oestrogens; EEs; Esterified equine estrogens; Esterified equine oestrogens; EEEs
Routes of
administration		By mouth[1]
Drug classEstrogen
ATC code
  • None
Legal status
Legal status
Identifiers
PubChem SID
DrugBank
UNII

Esterified estrogens (EEs), sold under the brand names Estratab and Menest among others, is an

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]

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]

Medical uses

EEs are used in

primary ovarian failure and in the treatment of breast cancer and prostate cancer.[4][10]

Estrogen dosages for menopausal hormone therapy
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
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

Estratest is a combination formulation of 1.25 mg EEs with 2.5 mg methyltestosterone.[12]

Side effects

See also: Conjugated estrogens § Side effects, and Estrogen (medication) § Side effects

Pharmacology

See also: Pharmacodynamics of estradiol and Pharmacokinetics of estradiol

EEs consist primarily of

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]

Relative oral potencies of estrogens
Estrogen
HF
Tooltip 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
CBG
Tooltip Corticosteroid-binding globulin
AGT
Tooltip 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
liver proteins. Liver = Ratio of liver estrogenic effects to general/systemic estrogenic effects (hot flashes/gonadotropins
). Sources: See template.
Protein binding and metabolic clearance rates of estrogens
Compound
RBATooltip Relative binding affinity to
SHBG
Tooltip sex hormone-binding globulin (%)		 Bound to
SHBG (%)		 Bound to
albumin (%)		 Total
bound (%)
MCR
Tooltip 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.

Chemistry

See also: List of estrogens, Estrogen ester, and List of estrogen esters

EEs contain

synthetic, plant-derived estrogens and are manufactured from soybeans and yams.[6][7]

History

EEs were introduced for medical use by 1970.[9]

Society and culture

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

See also: List of estrogens available in the United States

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]

See also

References

  1. ^
    ISBN 978-1-4614-6268-2
    .
  2. FDA
    . Retrieved 22 Oct 2023.
  3. ^
    ISBN 978-0-85369-840-1
    .
  4. ^ a b c d e f "Esterified estrogens".
  5. ^
    S2CID 24616324
    .
  6. ^
    ISBN 978-0-312-67646-9
    .
  7. ^
    S2CID 23850792
    .
  8. ISBN 978-3-642-67570-6
    .
  9. ^ a b Northwest Medicine. Vol. 69. Northwest Medical Pub. Association. 1970.
  10. ^
    ISBN 978-1-4200-4744-8
    .
  11. ^ "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 30 March 2018.
  12. ISBN 978-1-59259-715-4
    .
  13. ^
    ISBN 978-1-4511-4847-3
    .
  14. ISBN 978-1-59486-927-3
    .
  15. ^
    PMID 15467060
    .
  16. PMID 16505258
    .
  17. ^ "Estrogens, Esterified (USP) - Searchable synonyms, formulas, resource links, and other chemical information". ChemIDplus. U.S. Library of Medicine. D042724000.
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