Norgestrienone

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

Clinical data
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	G03AC07 (WHO)
Identifiers
IUPAC name (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	848-21-5 Y
PubChem CID	13313
ChemSpider	12749 Y
UNII	89386PYU9O
KEGG	D07220 Y
CompTox Dashboard (EPA)	DTXSID30878491
ECHA InfoCard	100.011.544
Chemical and physical data
Formula	C20H22O2
Molar mass	294.394 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C4\C=C3/C(=C2/C=C\[C@]1([C@@H](CC[C@]1(C#C)O)[C@@H]2CC3)C)CC4
InChI 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 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

See also: Progestin § 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	PRTooltip Progesterone receptor	ARTooltip Androgen receptor	ERTooltip Estrogen receptor	GRTooltip Glucocorticoid receptor	MRTooltip Mineralocorticoid receptor	SHBGTooltip Sex hormone-binding globulin	CBGTooltip 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 PRTooltip progesterone receptor, testosterone for the ARTooltip androgen receptor, E2 for the ERTooltip estrogen receptor, DEXATooltip dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, DHTTooltip dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip Corticosteroid-binding globulin. Sources: [14][15][16][17]

Pharmacokinetics

The metabolism of norgestrienone in humans has been studied.^[18]

Chemistry

See also: List of progestogens and List of androgens/anabolic steroids

Norgestrienone, also known as 17α-ethynyl-19-nor-δ^9,11-testosterone or as 17α-ethynylestra-4,9,11-trien-17β-ol-3-one, as well as δ^9,11-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-δ^9,11-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 INNTooltip 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

1. 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.
2. 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.
3. 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.
4. Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 751–. ISBN 978-3-88763-075-1.
5. 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.
6. McGuire JL (2000). Pharmaceuticals, 4 Volume Set. Wiley. p. 1580,1599. ISBN 978-3-527-29874-7.
7. 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.
8. 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.
9. Axelrod J (1 January 1982). Biochemical Actions of Hormones. Academic Press. ISBN 978-0-12-452809-3.
10. Lauritzen C, Studd JW (22 June 2005). Current Management of the Menopause. CRC Press. pp. 45–. ISBN 978-0-203-48612-2.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. Gomel V, Brill A (27 September 2010). Reconstructive and Reproductive Surgery in Gynecology. CRC Press. pp. 90–. ISBN 978-1-84184-757-3.
21. Lednicer D (4 March 2009). Strategies for Organic Drug Synthesis and Design. John Wiley & Sons. pp. 134–. ISBN 978-0-470-39959-0.
22. 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.