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]
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]
Medical uses
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]
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]
Side effects
Pharmacology
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]
Relative oral potencies of estrogens
Estrogen
HF Tooltip Hot flashes
VE Tooltip Vaginal epithelium
UCa Tooltip Urinary calcium
FSH Tooltip Follicle-stimulating hormone
LH Tooltip Luteinizing hormone
HDL Tooltip High-density lipoprotein -
C Tooltip Cholesterol
SHBG Tooltip 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
hot flashes .
VE = Increased
proliferation of
vaginal epithelium .
UCa = Decrease in
UCa Tooltip urinary calcium .
FSH = Suppression of
FSH Tooltip follicle-stimulating hormone levels.
LH = Suppression of
LH Tooltip 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.
Chemistry
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
USP Tooltip 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]
See also
References
^
a
b 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 .
^
a
b
c
d
e
f
g
h
i 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 .
^
a
b
c
d
e
f
"Esterified estrogens" .
^
a
b
c
d
e
f Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric . 8 (Suppl 1): 3–63.
doi :
10.1080/13697130500148875 .
PMID
16112947 .
S2CID
24616324 .
^
a
b
c 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 .
^
a
b
c
d 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 .
^
a
b
Northwest Medicine . Vol. 69. Northwest Medical Pub. Association. 1970.
^
a
b 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 .
^
a
b 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 .
^
a
b 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.
Estrogens
ER Tooltip Estrogen receptor agonists
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Certain
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Esterified estrogens
Estetrol †
Estradiol
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estradiol acetate ,
estradiol benzoate ,
estradiol cypionate ,
estradiol enanthate ,
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ent -Estradiol
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ERA-63 (ORG-37663)
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RU-16117
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SERMs Tooltip Selective estrogen receptor modulators ) Antagonists
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Agonists Antagonists Unknown