Chemical compound
Methylestradiol
Trade names Ginecosid, Ginecoside, Mediol, Renodiol Other names NSC-52245; 17α-Methylestradiol; 17α-ME; 17α-Methylestra-1,3,5(10)-triene-3,17β-diol
Routes of administration
By mouth
[1]
Drug class
Estrogen
(8R ,9S ,13S ,14S ,17S )-13,17-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H -cyclopenta[a ]phenanthrene-3,17-diol
CAS Number
PubChem
CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard
100.005.572
Formula C 19 H 26 O 2
Molar mass 286.415 g·mol−1 3D model (
JSmol )
CC12CCC3C(C1CCC2(C)O)CCC4=C3C=CC(=C4)O
InChI=1S/C19H26O2/c1-18-9-7-15-14-6-4-13(20)11-12(14)3-5-16(15)17(18)8-10-19(18,2)21/h4,6,11,15-17,20-21H,3,5,7-10H2,1-2H3/t15-,16-,17+,18+,19+/m1/s1
Key:JXQJDYXWHSVOEF-GFEQUFNTSA-N
Methylestradiol , sold under the brand names Ginecosid , Ginecoside , Mediol , and Renodiol , is an
estrogen medication which is used in the treatment of
menopausal symptoms .
[2]
[3]
[4] It is formulated in combination with
normethandrone , a
progestin and
androgen /
anabolic steroid medication.
[3]
[4] Methylestradiol is taken
by mouth .
[1]
Side effects of methylestradiol include
nausea ,
breast tension ,
edema , and
breakthrough bleeding among others.
[5] It is an
estrogen , or an
agonist of the
estrogen receptors , the
biological target of estrogens like
estradiol .
[6]
Methylestradiol is or has been marketed in
Brazil ,
Venezuela , and
Indonesia .
[3] In addition to its use as a medication, methylestradiol has been studied for use as a
radiopharmaceutical for the
estrogen receptor .
[7]
Medical uses
Methylestradiol is used in combination with the progestin and androgen/anabolic steroid
normethandrone (methylestrenolone) in the treatment of
menopausal symptoms .
[3]
[4]
Available forms
Methylestradiol is marketed in combination with
normethandrone in the form of
oral
tablets containing 0.3 mg methylestradiol and 5 mg normethandrone.
[8]
[9]
Side effects
Side effects of methylestradiol include
nausea ,
breast tension ,
edema , and
breakthrough bleeding .
[5]
Pharmacology
Pharmacodynamics
Methylestradiol is an
estrogen , or an
agonist of the
estrogen receptor .
[6] It shows somewhat lower
affinity for the estrogen receptor than
estradiol or
ethinylestradiol .
[6]
Methylestradiol is an
active metabolite of the androgens/anabolic steroids
methyltestosterone (17α-methyltestosterone),
metandienone (17α-methyl-δ1 -testosterone), and
normethandrone (17α-methyl-19-nortestosterone), and is responsible for their
estrogenic
side effects , such as
gynecomastia and
fluid retention .
[10]
[11]
[12]
Relative affinities (%) of methylestradiol and related steroids
Compound
PR Tooltip Progesterone receptor
AR Tooltip Androgen receptor
ER Tooltip Estrogen receptor
GR Tooltip Glucocorticoid receptor
MR Tooltip Mineralocorticoid receptor
SHBG Tooltip Sex hormone-binding globulin
CBG Tooltip Corticosteroid binding globulin
Estradiol
2.6
7.9
100
0.6
0.13
8.7
<0.1
Ethinylestradiol
15–25
1–3
112
1–3
<1
?
?
Methylestradiol
3–10, 15–25
1–3
67
1–3
<1
?
?
Methyltestosterone
3
45, 100–125
?
1–5
?
5
?
Normethandrone
100
146
<0.1
1.5
0.6
?
?
Sources: Values are percentages (%). Reference
ligands (100%) were
progesterone for the
PR Tooltip progesterone receptor ,
testosterone for the
AR Tooltip androgen receptor ,
E2 for the
ER Tooltip estrogen receptor ,
DEXA Tooltip dexamethasone for the
GR Tooltip glucocorticoid receptor ,
aldosterone for the
MR Tooltip mineralocorticoid receptor ,
DHT Tooltip dihydrotestosterone for
SHBG Tooltip sex hormone-binding globulin , and
cortisol for
CBG Tooltip Corticosteroid-binding globulin . Sources:
[13]
[6]
[14]
[15]
Pharmacokinetics
Due to the presence of its C17α
methyl group , methylestradiol cannot be deactivated by
oxidation of the C17β
hydroxyl group , resulting in improved
metabolic stability and
potency relative to
estradiol .
[10] This is analogous to the case of
ethinylestradiol and its C17α
ethynyl group .
[10]
Chemistry
Methylestradiol, or 17α-methylestradiol (17α-ME), also known as 17α-methylestra-1,3,5(10)-triene-3,17β-diol, is a
synthetic
estrane
steroid and a
derivative of
estradiol .
[2]
[3] It is specifically the derivative of estradiol with a
methyl group at the C17α positions.
[2]
[3] Closely related steroids include
ethinylestradiol (17α-ethynylestradiol) and
ethylestradiol (17α-ethylestradiol).
[2] The C3
cyclopentyl
ether of methylestradiol has been studied and shows greater
oral
potency than methylestradiol in animals, similarly to
quinestrol (ethinylestradiol 3-cyclopentyl ether) and
quinestradol (estriol 3-cyclopentyl ether).
[16]
History
Methylestradiol was first marketed, alone as Follikosid and in combination with
methyltestosterone as Klimanosid, in 1955.
[17]
[18]
[19]
[20]
Society and culture
Generic names
Methylestradiol has not been assigned an
INN Tooltip International Nonproprietary Name or other formal name designations.
[2]
[3] Its
generic name in
English and
German is methylestradiol , in
French is méthylestradiol , and in
Spanish is metilestadiol .
[3] It is also known as 17α-methylestradiol .
[3]
Brand names
Methylestradiol is or has been marketed under the brand names Ginecosid, Ginecoside, Mediol, and Renodiol, all in combination with
normethandrone .
[3]
[2]
Availability
Methylestradiol is or has been marketed in
Brazil ,
Venezuela , and
Indonesia .
[3]
References
^
a
b Hegemann O (May 1959). "[Oral hormonal treatment with methylestrene-olone & methylestradiol as early pregnancy tests]". Die Medizinische (in German). 4 (21): 1032–1033.
PMID
13673847 .
^
a
b
c
d
e
f Elks J (14 November 2014).
The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . Springer. pp. 898–.
ISBN
978-1-4757-2085-3 .
^
a
b
c
d
e
f
g
h
i
j
k
"Methylestradiol" . Drugs.com . Retrieved 2 January 2016 .
^
a
b
c IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for Research on Cancer (2007).
Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy . World Health Organization. pp. 389–.
ISBN
978-92-832-1291-1 .
^
a
b Wittlinger H (1980). "Clinical Effects of Estrogens". Functional Morphologic Changes in Female Sex Organs Induced by Exogenous Hormones . pp. 67–71.
doi :
10.1007/978-3-642-67568-3_10 .
ISBN
978-3-642-67570-6 .
^
a
b
c
d Ojasoo T, Raynaud JP (November 1978).
"Unique steroid congeners for receptor studies" . Cancer Research . 38 (11 Pt 2): 4186–4198.
PMID
359134 .
^ Feenstra A, Vaalburg W, Nolten GM, Reiffers S, Talma AG, Wiegman T, et al. (June 1983). "Estrogen receptor binding radiopharmaceuticals: II. Tissue distribution of 17 alpha-methylestradiol in normal and tumor-bearing rats". Journal of Nuclear Medicine . 24 (6): 522–528.
PMID
6406650 .
^
Unlisted Drugs . Pharmaceutical Section, Special Libraries Association. 1982. Batynid. C. Each dragee contains: normethandrone, 5 mg.; and methylestradiol, 0.3 mg. E. (Formerly) Gynaekosid. M. Boehringer Biochemia, Florence. A. Estrogenic; Rx of secondary amenorrhea. R. Notiz Med Farm 32;295, Nov-Dec 81.
^ Akingba JB, Ayodeji EA (February 1966). "Amenorrhea as a leading symptom of choriocarcinoma". The Journal of Obstetrics and Gynaecology of the British Commonwealth . 73 (1): 153–155.
doi :
10.1111/j.1471-0528.1966.tb05137.x .
PMID
5948541 .
S2CID
38008851 .
^
a
b
c Thieme D, Hemmersbach P (18 December 2009).
Doping in Sports . Springer Science & Business Media. pp. 470–.
ISBN
978-3-540-79088-4 .
^ Llewellyn W (2011).
Anabolics . Molecular Nutrition Llc. pp. 533–.
ISBN
978-0-9828280-1-4 .
^ Friedl KE (1990). "Reappraisal of the health risks associated with the use of high doses of oral and injectable androgenic steroids". NIDA Research Monograph . 102 : 142–177.
PMID
1964199 .
^ Raynaud JP, Ojasoo T, Bouton MM, Philibert D (1979).
"Receptor Binding as a Tool in the Development of New Bioactive Steroids" . Drug Design . pp. 169–214.
doi :
10.1016/B978-0-12-060308-4.50010-X .
ISBN
9780120603084 .
^ Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen receptors". Journal of Steroid Biochemistry . 27 (1–3): 255–269.
doi :
10.1016/0022-4731(87)90317-7 .
PMID
3695484 .
^ Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, et al. (January 1980). "Steroid hormone receptors and pharmacology". Journal of Steroid Biochemistry . 12 : 143–157.
doi :
10.1016/0022-4731(80)90264-2 .
PMID
7421203 .
^ Falconi G, Rossi GL, Ercoli A (September 1970). James VH (ed.).
Quinestrol and other cyclopentyl ethers of estrogenic steroids: different rates of storage in body fat . Third International Congress on Hormonal Steroids, Hamburg. International Congress Series No. 210. Amsterdam, Excerpta Medica. pp. 218–219. Archived from
the original on 28 March 2018.
^ "Neue Spezialitäten". Klinische Wochenschrift . 33 (31–32): 773–774. 1955.
doi :
10.1007/BF01473523 .
ISSN
0023-2173 .
S2CID
1678069 .
^ Kahr H (8 March 2013).
Konservative Therapie der Frauenkrankheiten: Anzeigen, Grenzen und Methoden Einschliesslich der Rezeptur . Springer-Verlag. pp. 20–.
ISBN
978-3-7091-5694-0 .
^ Arends G, Zörnig H, Hager H, Frerichs G, Kern W (14 December 2013).
Hagers Handbuch der pharmazeutischen Praxis: Für Apotheker, Arzneimittelhersteller, Drogisten, Ärzte u. Medizinalbeamte . Springer-Verlag. pp. 1156–1157, 1164.
ISBN
978-3-662-36329-4 .
^ Helwig B (1956).
Moderne Arzneimittel: eine Spezialitätenkunde nach Indikationsgebieten für Ärzte und Apotheker . Wissenschaftliche Verlagsgesellschaft. p. 240.
Estrogens
ER Tooltip Estrogen receptor agonists
Steroidal:
Alfatradiol
Certain
androgens /
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testosterone esters ,
methyltestosterone ,
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Certain
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Clomestrone
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Estetrol †
Estradiol
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estradiol acetate ,
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estradiol undecylate ,
estradiol valerate ,
polyestradiol phosphate ,
estradiol ester mixtures (
Climacteron ))
Estramustine phosphate
Estriol
Estriol esters (e.g.,
estriol succinate ,
polyestriol phosphate )
Estrogenic substances
Estrone
Estrone esters
Ethinylestradiol #
Hydroxyestrone diacetate
Mestranol
Methylestradiol
Moxestrol
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Prasterone (dehydroepiandrosterone; DHEA)
Promestriene
Quinestradol
Quinestrol
Progonadotropins
Antiestrogens
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SERMs Tooltip selective estrogen receptor modulators /
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Aromatase inhibitors
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fluoxymesterone )
D2 receptor
antagonists (
prolactin releasers) (e.g.,
domperidone ,
metoclopramide ,
risperidone ,
haloperidol ,
chlorpromazine ,
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leuprorelin ,
goserelin )
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cetrorelix ,
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chlormadinone acetate ,
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Others
ER Tooltip Estrogen receptor
Agonists
Steroidal:
2-Hydroxyestradiol
2-Hydroxyestrone
3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol
3α-Androstanediol
3α,5α-Dihydrolevonorgestrel
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3α-Hydroxytibolone
3β-Hydroxytibolone
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4-Androstenediol
4-Androstenedione
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5-Androstenediol
7-Oxo-DHEA
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7α-Methylestradiol
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8,9-Dehydroestradiol
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8β-VE2
10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED)
11β-Chloromethylestradiol
11β-Methoxyestradiol
15α-Hydroxyestradiol
16-Ketoestradiol
16-Ketoestrone
16α-Fluoroestradiol
16α-Hydroxy-DHEA
16α-Hydroxyestrone
16α-Iodoestradiol
16α-LE2
16β-Hydroxyestrone
16β,17α-Epiestriol (16β-hydroxy-17α-estradiol)
17α-Estradiol (
alfatradiol )
17α-Dihydroequilenin
17α-Dihydroequilin
17α-Epiestriol (16α-hydroxy-17α-estradiol)
17α-Ethynyl-3α-androstanediol
17α-Ethynyl-3β-androstanediol
17β-Dihydroequilenin
17β-Dihydroequilin
17β-Methyl-17α-dihydroequilenin
Abiraterone
Abiraterone acetate
Alestramustine
Almestrone
Anabolic steroids (e.g.,
testosterone and
esters ,
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metandienone (methandrostenolone) ,
nandrolone and
esters , many others; via estrogenic metabolites)
Atrimustine
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Butolame
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Conjugated estriol
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DHEA-S
ent -Estradiol
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Epimestrol
Equilenin
Equilin
ERA-63 (ORG-37663)
Esterified estrogens
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Prodiame
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RU-16117
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Xenoestrogens:
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anethole ,
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dianethole ,
dianol ,
photoanethole )
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phlorizin (phloridzin) ,
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apigenin ,
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ECG ,
EGCG ,
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equol ,
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Lavender oil
Lignans (e.g.,
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enterolactone ,
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Metalloestrogens (e.g.,
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Phytosteroids (e.g.,
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digitalis ),
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Resorcylic acid lactones (e.g.,
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zearalenone ,
zeranol (α-zearalanol) ,
taleranol (teranol, β-zearalanol) )
Steroid -like (e.g.,
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SERMs Tooltip Selective estrogen receptor modulators ) Antagonists
Coregulator-binding modulators:
ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown