Chemical compound
Norgestrienone
Trade names Ogyline, Planor, Miniplanor Other names RU-2010; A-301; 17α-Ethynyltrienolone; 17α-Ethynyltrenbolone; Δ9,11 -Norethisterone; 17α-Ethynylestra-4,9,11-trien-17β-ol-3-one
Routes of administration
By mouth
Drug class
Progestogen ;
Progestin ;
Androgen ;
Anabolic steroid
ATC code
(8S ,13S ,14S ,17R )-17-ethynyl-17-hydroxy-13-methyl-1,2,6,7,8,14,15,16-octahydrocyclopenta[a ]phenanthren-3-one
CAS Number
PubChem
CID
ChemSpider
UNII
KEGG
CompTox Dashboard (
EPA )
ECHA InfoCard
100.011.544
Formula C 20 H 22 O 2
Molar mass 294.394 g·mol−1 3D model (
JSmol )
O=C4\C=C3/C(=C2/C=C\[C@]1([C@@H](CC[C@]1(C#C)O)[C@@H]2CC3)C)CC4
InChI=1S/C20H22O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,8,10,12,17-18,22H,4-7,9,11H2,2H3/t17-,18+,19+,20+/m1/s1
Y Key:GVDMJXQHPUYPHP-FYQPLNBISA-N
Y
(verify)
Norgestrienone , sold under the brand names Ogyline , Planor , and Miniplanor , is a
progestin medication which has been used in
birth control pills , sometimes in combination with
ethinylestradiol .
[1]
[2]
[3]
[4]
[5] It was developed by
Roussel Uclaf and has been registered for use only in
France .
[4]
[5]
[6] Under the brand name Planor , it has been marketed in France as 2 mg norgestrienone and 50 μg ethinylestradiol tablets.
[7] It is taken
by mouth .
[5]
Norgestrienone is a progestin, or a
synthetic
progestogen , and hence is an
agonist of the
progesterone receptor , the
biological target of progestogens like
progesterone .
[8] It has some
androgenic activity.
[9]
[10]
[11]
[12]
Norgestrienone was first described in the literature in 1965.
[10] It is sometimes referred to as a "second-generation" progestin.
[13] Norgestrienone is no longer available.[
citation needed ]
Medical uses
Norgestrienone was used in
hormonal contraception to prevent
pregnancy .
[2]
[7] It has typically been used as an
oral contraceptive at a dosage of 2 mg/day in combination with
ethinylestradiol and 350 μ/day when used alone.
[5]
Side effects
Pharmacology
Pharmacodynamics
Norgestrienone has been found to possess similar
affinity for the
progesterone receptor and
androgen receptor ,
[8] and in accordance, has some
androgenic activity.
[9]
[10]
[11]
[12] The androgenic activity of norgestrienone is greater than that of other
19-nortestosterone derivatives due to the presence of the C9(11)
double bond , which enhances said activity.
[12] The ratio of
progestogenic to
androgenic activity appears to be much lower for norgestrienone that it is for other 19-nortestosterone progestins such as
norethisterone and
levonorgestrel .
[14]
[15]
[16]
[17]
Gestrinone , the 18-methyl
analogue of norgestrienone, has even greater androgenic activity than norgestrienone, as this modification increases androgenic activity similarly.
[12]
Relative affinities (%) of norgestrienone 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
Norethisterone
155–156
43–45
<0.1
2.7–2.8
0.2
?
?
Norgestrienone
63–65
70
<0.1
11
1.8
?
?
Levonorgestrel
170
84–87
<0.1
14
0.6–0.9
?
?
Gestrinone
75–76
83–85
<0.1, 3–10
77
3.2
?
?
Notes: 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:
[14]
[15]
[16]
[17]
Pharmacokinetics
The
metabolism of norgestrienone in humans has been studied.
[18]
Chemistry
Norgestrienone, also known as 17α-ethynyl-19-nor-δ9,11 -testosterone or as 17α-ethynylestra-4,9,11-trien-17β-ol-3-one, as well as δ9,11 -norethisterone or 17α-ethynyltrienolone (17α-ethynyltrenbolone), is a
synthetic
estrane
steroid and a
derivative of
testosterone and
19-nortestosterone .
[1]
[4]
[19] It is structurally related to the
anabolic steroid
trenbolone (19-nor-δ9,11 -testosterone; the non-17α-ethynylated
analogue of norgestrienone), the
progestogenic and
androgenic steroid
gestrinone (the 13β-
ethyl variant or 18-
methyl derivative of norgestrienone), and the anabolic steroid
tetrahydrogestrinone (the 18-methyl and 17α-ethyl variant of norgestrienone).
[1]
[4]
[20]
History
Norgestrienone was first described in the literature in 1965.
[10] It is sometimes referred to as a "second-generation" progestin based on its time of introduction.
[13]
Society and culture
Generic names
Norgestrienone is the
generic name of the drug and its
INN Tooltip International Nonproprietary Name .
[1]
[2]
[4] It is also known by its developmental code names RU-2010 and A-301 .
[1]
[2]
[4]
Brand names
Norgestrienone has been marketed under the brand names Ogyline, Planor, and Miniplanor.
[1]
[2]
[4]
Availability
Norgestrienone is no longer marketed and hence is no longer available in any country.[
citation needed ] It was previously used in
France .
[4] The medication was never marketed in the
United States .
[21]
Research
Norgestrienone has been studied for use in
male hormonal contraception .
[22]
References
^
a
b
c
d
e
f Elks J (14 November 2014).
The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . Springer. pp. 887–.
ISBN
978-1-4757-2085-3 .
^
a
b
c
d
e Morton IK, Hall JM (6 December 2012).
Concise Dictionary of Pharmacological Agents: Properties and Synonyms . Springer Science & Business Media. pp. 202–.
ISBN
978-94-011-4439-1 .
^ Diaz S, Pavez M, Quinteros E, Diaz J, Robertson DN, Croxatto HB (October 1978). "Clinical trial with subdermal implants containing norgestrienone". Contraception . 18 (4): 429–440.
doi :
10.1016/0010-7824(78)90027-6 .
PMID
720075 .
^
a
b
c
d
e
f
g
h
Index Nominum 2000: International Drug Directory . Taylor & Francis. January 2000. pp. 751–.
ISBN
978-3-88763-075-1 .
^
a
b
c
d Sweetman SC, ed. (2009).
"Sex hormones and their modulators" . Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2122.
ISBN
978-0-85369-840-1 . Norgestrienone is a progestogen structurally related to norethisterone that has been used as an oral contraceptive. Typical doses have been 2 mg daily with an oestrogen, and 350 micrograms daily when used alone.
^ McGuire JL (2000).
Pharmaceuticals, 4 Volume Set . Wiley. p. 1580,1599.
ISBN
978-3-527-29874-7 .
^
a
b 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. 455–.
ISBN
978-92-832-1291-1 .
^
a
b Loughney DA, Schwender CF (December 1992). "A comparison of progestin and androgen receptor binding using the CoMFA technique". Journal of Computer-Aided Molecular Design . 6 (6): 569–581.
Bibcode :
1992JCAMD...6..569L .
doi :
10.1007/bf00126215 .
PMID
1291626 .
S2CID
22004130 .
^
a
b Axelrod J (1 January 1982).
Biochemical Actions of Hormones . Academic Press.
ISBN
978-0-12-452809-3 .
^
a
b
c
d Lauritzen C, Studd JW (22 June 2005).
Current Management of the Menopause . CRC Press. pp. 45–.
ISBN
978-0-203-48612-2 .
^
a
b Di Giulio RT, Monosson E (6 December 2012).
Interconnections Between Human and Ecosystem Health . Springer Science & Business Media. pp. 60–.
ISBN
978-94-009-1523-7 .
^
a
b
c
d Rozenbaum H (March 1982). "Relationships between chemical structure and biological properties of progestogens". American Journal of Obstetrics and Gynecology . 142 (6 Pt 2): 719–724.
doi :
10.1016/S0002-9378(16)32477-2 .
PMID
7065053 .
^
a
b Weiss G (February 1999). "Risk of venous thromboembolism with third-generation oral contraceptives: A review". American Journal of Obstetrics and Gynecology . 180 (2 Pt 2): 295–301.
doi :
10.1016/S0002-9378(99)70721-0 .
PMID
9988833 .
^
a
b Delettré J, Mornon JP, Lepicard G, Ojasoo T, Raynaud JP (January 1980). "Steroid flexibility and receptor specificity". Journal of Steroid Biochemistry . 13 (1): 45–59.
doi :
10.1016/0022-4731(80)90112-0 .
PMID
7382482 .
^
a
b 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 .
^
a
b Ojasoo T, Raynaud JP, Doé JC (January 1994). "Affiliations among steroid receptors as revealed by multivariate analysis of steroid binding data". The Journal of Steroid Biochemistry and Molecular Biology . 48 (1): 31–46.
doi :
10.1016/0960-0760(94)90248-8 .
PMID
8136304 .
S2CID
21336380 .
^
a
b Raynaud J, Ojasoo T, Bouton M, Philibert D (1979).
"Receptor Binding as a Tool in the Development of New Bioactive Steroids" . Drug Design . Medicinal Chemistry: A Series of Monographs. Vol. 11. Academic Press. pp. 169–214.
doi :
10.1016/B978-0-12-060308-4.50010-X .
ISBN
9781483216102 .
^ Raynaud JP (1970).
"Metabolism of contraceptive steroids in man" . Excerpta Medica International Congress Series . 219 : 915–922. Archived from
the original on 29 March 2018.
^ Lavery JP, Sanfilippo JS (6 December 2012).
Pediatric and Adolescent Obstetrics and Gynecology . Springer Science & Business Media. pp. 236–.
ISBN
978-1-4612-5064-7 .
^ Gomel V, Brill A (27 September 2010).
Reconstructive and Reproductive Surgery in Gynecology . CRC Press. pp. 90–.
ISBN
978-1-84184-757-3 .
^ Lednicer D (4 March 2009).
Strategies for Organic Drug Synthesis and Design . John Wiley & Sons. pp. 134–.
ISBN
978-0-470-39959-0 .
^ Schearer SD (1978).
The use of progestins and androgens as a male contraceptive. Hormonal control of male fertility . DHEW Publication No.(NIH). (Report). pp. 78–1097. Archived from
the original on 29 March 2018.
Androgens (incl.
AAS Tooltip anabolic–androgenic steroid )
Antiandrogens
AR Tooltip Androgen receptor
antagonists
Steroidogenesis inhibitors
Antigonadotropins
D2 receptor
antagonists (
prolactin releasers ) (e.g.,
domperidone ,
metoclopramide ,
risperidone ,
haloperidol ,
chlorpromazine ,
sulpiride )
Estrogens (e.g.,
bifluranol ,
diethylstilbestrol ,
estradiol ,
estradiol esters ,
ethinylestradiol ,
ethinylestradiol sulfonate ,
paroxypropione )
GnRH agonists (e.g.,
leuprorelin )
GnRH antagonists (e.g.,
cetrorelix )
Progestogens (incl.,
chlormadinone acetate ,
cyproterone acetate ,
hydroxyprogesterone caproate ,
gestonorone caproate ,
medroxyprogesterone acetate ,
megestrol acetate )
Others
PR Tooltip Progesterone receptor
Agonists
Testosterone derivatives: Progestins:
6,6-Difluoronorethisterone
6,6-Difluoronorethisterone acetate
17α-Allyl-19-nortestosterone
Allylestrenol
Altrenogest
Chloroethynylnorgestrel
Cingestol
Danazol
Desogestrel
Dienogest
Ethinylandrostenediol
Ethisterone
Ethynerone
Etonogestrel
Etynodiol
Etynodiol diacetate
Gestodene
Gestrinone
Levonorgestrel
Levonorgestrel esters (e.g.,
levonorgestrel butanoate )
Lynestrenol
Lynestrenol phenylpropionate
Metynodiol
Metynodiol diacetate
Norelgestromin
Norethisterone (norethindrone)
Norethisterone esters (e.g.,
norethisterone acetate ,
norethisterone enanthate )
Noretynodrel
Norgesterone
Norgestimate
Norgestrel
Norgestrienone
Norvinisterone
Oxendolone
Quingestanol
Quingestanol acetate
Tibolone
Tigestol
Tosagestin ; Anabolic–androgenic steroids:
11β-Methyl-19-nortestosterone
11β-Methyl-19-nortestosterone dodecylcarbonate
19-Nor-5-androstenediol
19-Nor-5-androstenedione
19-Nordehydroepiandrosterone
Bolandiol
Bolandiol dipropionate
Bolandione
Dimethisterone
Dienedione
Dienolone
Dimethandrolone
Dimethandrolone buciclate
Dimethandrolone dodecylcarbonate
Dimethandrolone undecanoate
Dimethyldienolone
Dimethyltrienolone
Ethyldienolone
Ethylestrenol (ethylnandrol)
Methyldienolone
Metribolone (R-1881)
Methoxydienone (methoxygonadiene)
Mibolerone
Nandrolone
Nandrolone esters (e.g.,
nandrolone decanoate ,
nandrolone phenylpropionate )
Norethandrolone
Normethandrone (methylestrenolone, normethandrolone, normethisterone)
RU-2309
Tetrahydrogestrinone
Trenbolone (trienolone)
Trenbolone esters (e.g.,
trenbolone acetate ,
trenbolone enanthate )
Trendione
Trestolone
Trestolone acetate
Mixed (
SPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor (
PAQR Tooltip Progestin and adipoQ receptor )
AR Tooltip Androgen receptor
Agonists
SARMs Tooltip Selective androgen receptor modulator Antagonists
GPRC6A