Promegestone

Overview

Promegestone, sold under the brand name Surgestone, is a progestin medication which is used in menopausal hormone therapy and in the treatment of gynecological disorders. It is taken by mouth.[1–4] WP

Side effects of promegestone include menstrual irregularities among others. Promegestone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has weak antiandrogenic, glucocorticoid, and antimineralocorticoid activity and no other important hormonal activity. The medication is largely a prodrug of trimegestone.[2][5][6][7] WP

Promegestone was first described in 1973 and was introduced for medical use in France in 1983. It has only been marketed in a few countries, including France, Portugal, Tunisia, and Argentina. In addition to its use as a medication, promegestone has been widely used in scientific research as a radioligand of the progesterone receptor.[1][4][8–12] WP

Uses, dosage and effects

Medical uses

Promegestone is used in menopausal hormone therapy and in the treatment of gynecological conditions caused by luteal insufficiency, including premenopausal disorders, dysmenorrhea and other menstrual disorders, and premenstrual syndrome. It has also been used to treat benign breast disorders such as mastalgia (breast pain). Promegestone tablets have a contraceptive effect and are used as a form of progestogen-only birth control, although it is not specifically licensed as such.[2][3][13][14] WP

Risks and side effects

Side effects

Side effects of promegestone include menstrual irregularities among others. It has no androgenic side effects.[1][3][5] WP

Pharmacology

Pharmacodynamics

Promegestone is a progestogen, or an agonist of the progesterone receptor. It has about 200% of the affinity of progesterone for the PR. The endometrial transformation dosage of promegestone is 10 mg per cycle and its ovulation-inhibiting dosage is 0.5 mg/day. Promegestone has weak glucocorticoid activity in addition to its progestogenic activity. Conversely, it has no androgenic, estrogenic, mineralocorticoid, or other hormonal activity. It appears to possess antiandrogenic activity. Its major metabolite trimegestone has weak antimineralocorticoid and antiandrogenic activity. In addition, promegestone has been found to possess some neurosteroid activity by acting as a non-competitive antagonist of the nicotinic acetylcholine receptor, similarly to progesterone.[2][3][6][7][12][15][16] WP

Pharmacokinetics

Following oral administration, peak serum levels of promegestone are reached after 1 to 2 hours. The medication is mainly bound to albumin; it does not bind to sex hormone-binding globulin, and binds only weakly to corticosteroid-binding globulin. The metabolism of promegestone is mainly via hydroxylation at the C21 position and at other positions. Progesterone is similarly hydroxylated at the C21 position, into 11-deoxycorticosterone (21-hydroxyprogesterone). However, the C9(10) double bond of promegestone greatly limits the A-ring reduction that progesterone undergoes, resulting in 21-hydroxylation being the main route of metabolism for promegestone. The medication is stereoselectively metabolized into trimegestone, the 21(S)-hydroxy metabolite, which is the main compound found in plasma; it circulates at levels approximately twice those of promegestone itself. In addition, trimegestone has more than three-fold higher affinity for the PR than does promegestone. As such, promegestone is largely a prodrug of trimegestone. A second metabolite, 21(R)-hydroxypromegestone, circulates at far lower concentrations (AUC (area-under-the-curve levels) ratio for the (S)- and (R)-isomers of about 21). The elimination half-life of trimegestone is 13.8 to 15.6 hours. Promegestone, trimegestone, and 21(R)-hydroxypromegestone are not excreted in urine, while 3% of a dose is recovered as the glucuronide and/or sulfate conjugate of trimegestone and 1% of a dose is recovered as the glucuronide and/or sulfate conjugate of 21(R)-hydroxypromegestone.[2][5][7][15][17][18][19] WP

History

History

Promegestone was first described in the literature in 1973 and was introduced for medical use in France in 1983. It was developed by Roussel Uclaf in France.[3][8][9][10] WP

Legal status

Generic names

Promegestone is the generic name of the drug and its INN (International Nonproprietary Name), while promégestone is its DCF (Dénomination Commune Française). It is also known by its developmental code name R-5020 or RU-5020.[4][8][11] WP

Brand names

Promegestone is marketed exclusively under the brand name Surgestone.[4][11] WP

Availability

Promegestone is or has been marketed in France, Portugal, Tunisia, and Argentina.[4][11] WP

Chemistry

Formula

C22H30O2 PC

CAS number

34184-77-5 PC

Molar mass (g/mol)

326.5 PC

IUPAC name (computed by PubChem)

(8S,13S,14S,17S)-13,17-dimethyl-17-propanoyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one PC

SMILES

CCC(=O)[C@]1(CC[C@@H]2[C@@]1(CCC3=C4CCC(=O)C=C4CC[C@@H]23)C)C PC

InChIKey

QFFCYTLOTYIJMR-XMGTWHOFSA-N PC

PubChem CID

36709

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Raynaud JP, Ojasoo T. Promegestone, a new progestin. Journal de Gynécologie, Obstétrique et Biologie de la Reproduction. 1983. PMID 6366037
2. Journal / agency Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. August 2005. doi:10.1080/13697130500148875 · PMID 16112947
3. Other Allen RC. Annual Reports in Medicinal Chemistry. 11 September 1984
4. Other List of Progestins
5. Other Tulunay FC, Orme M. European Collaboration: Towards Drug Develo and Rational Drug Therapy: Proceedings of the Sixth Congress of the European Association for Clinical Pharmacology and Therapeutics Istanbul, June 24–28, 2003. 6 December 2012
6. Journal / agency Winneker RC, Bitran D, Zhang Z. The preclinical biology of a new potent and selective progestin: trimegestone. Steroids. November 2003. doi:10.1016/s0039-128x(03)00142-9 · PMID 14667983
7. Journal / agency Sitruk-Ware R, Bossemeyer R, Bouchard P. Preclinical and clinical properties of trimegestone: a potent and selective progestin. Gynecological Endocrinology. June 2007. doi:10.1080/09513590701267727 · PMID 17616854
8. Other Elks J. The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014
9. Journal / agency Philibert D, Raynaud JP. Progesterone binding in the immature mouse and rat uterus. Steroids. July 1973. doi:10.1016/0039-128x(73)90073-1 · PMID 4353432
10. Other William Andrew Publishing. Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. 22 October 2013
11. Other Index Nominum 2000: International Drug Directory. January 2000
12. Journal / agency Raynaud JP, Ojasoo T, Vaché V. Reproductive Processes and Contraception. 1981. doi:10.1007/978-1-4684-3824-6_7
13. Journal / agency Uzan S, Denis C, Pomi V, Varin C. Double-blind trial of promegestone (R 5020) and lynestrenol in the treatment of benign breast disease. European Journal of Obstetrics, Gynecology, and Reproductive Biology. February 1992. doi:10.1016/0028-2243(92)90177-z · PMID 1563574
14. Journal / agency Gourdy P, Bachelot A, Catteau-Jonard S, Chabbert-Buffet N, Christin-Maître S, Conard J, Fredenrich A, Gompel A, Lamiche-Lorenzini F, Moreau C, Plu-Bureau G, Vambergue A, Vergès B, Kerlan V. Hormonal contraception in women at risk of vascular and metabolic disorders: guidelines of the French Society of Endocrinology. Annales d'Endocrinologie. November 2012. doi:10.1016/j.ando.2012.09.001 · PMID 23078975
15. Journal / agency Kuhl H. Pharmacology of progestogens. Journal für Reproduktionsmedizin und Endokrinologie-Journal of Reproductive Medicine and Endocrinology. 2011
16. Journal / agency Blanton MP, Xie Y, Dangott LJ, Cohen JB. The steroid promegestone is a noncompetitive antagonist of the Torpedo nicotinic acetylcholine receptor that interacts with the lipid-protein interface. Molecular Pharmacology. February 1999. doi:10.1124/mol.55.2.269 · PMID 9927618
17. Journal / agency Chan DW, Slaunwhite WR. The binding of a synthetic progestin, R5020 to transcortin and serum albumin. The Journal of Clinical Endocrinology and Metabolism. May 1977. doi:10.1210/jcem-44-5-983 · PMID 858781
18. Other Litwack G. Biochemical Actions of Hormones. 2 December 2012
19. Other Carp HJ. Progestogens in Obstetrics and Gynecology. 9 April 2015

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