Promegestone

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Not to be confused with Progesterone (medication).
Promegestone
File:Promegestone.svg
Clinical data
Trade namesSurgestone
Other namesPMG; R-5020; RU-5020; 17α,21-Dimethyl-δ9-19-norprogesterone; 17α,21-Dimethyl-19-norpregna-4,9-diene-3,20-dione
Routes of
administration		By mouth[1]
Drug classProgestogen; Progestin
ATC code
Pharmacokinetic data
Protein bindingTo albumin[1]
MetabolismLiver (hydroxylation)[1][3]
Metabolites• Trimegestone
Elimination half-lifePromegestone: ?
Trimegestone: 13.8–15.6 hours[1][2]
Identifiers
  • (8S,13S,14S,17S)-13,17-dimethyl-17-propionyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
CompTox Dashboard (EPA)
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Chemical and physical data
FormulaC22H30O2
Molar mass326.480 g·mol−1
3D model (JSmol)
  • CCC(=O)[C@]1(CC[C@@H]2[C@@]1(CCC3=C4CCC(=O)C=C4CC[C@@H]23)C)C
  • InChI=1S/C22H30O2/c1-4-20(24)22(3)12-10-19-18-7-5-14-13-15(23)6-8-16(14)17(18)9-11-21(19,22)2/h13,18-19H,4-12H2,1-3H3/t18-,19+,21+,22-/m1/s1
  • Key:QFFCYTLOTYIJMR-XMGTWHOFSA-N

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.[4][1][5][6] It is taken by mouth.[1]

Side effects of promegestone include menstrual irregularities among others.[7] Promegestone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[1] It has weak antiandrogenic, glucocorticoid, and antimineralocorticoid activity and no other important hormonal activity.[1][8][2] The medication is largely a prodrug of trimegestone.[7][1]

Promegestone was first described in 1973 and was introduced for medical use in France in 1983.[9][10][11] It has only been marketed in a few countries, including France, Portugal, Tunisia, and Argentina.[6][12] In addition to its use as a medication, promegestone has been widely used in scientific research as a radioligand of the progesterone receptor.[4][13]

Medical uses

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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.[1][5] It has also been used to treat benign breast disorders such as mastalgia (breast pain).[14] 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.[15]

Side effects

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See also: Progestin § Side effects

Side effects of promegestone include menstrual irregularities among others.[7] It has no androgenic side effects.[4][5]

Pharmacology

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Pharmacodynamics

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File:Trimegestone.svg
Trimegestone (21(S)-hydroxyl-promegestone), the major active metabolite of promegestone.

Promegestone is a progestogen, or an agonist of the progesterone receptor.[1][3] It has about 200% of the affinity of progesterone for the PR.[1][3] The endometrial transformation dosage of promegestone is 10 mg per cycle and its ovulation-inhibiting dosage is 0.5 mg/day.[1][3] Promegestone has weak glucocorticoid activity in addition to its progestogenic activity.[1][3] Conversely, it has no androgenic, estrogenic, mineralocorticoid, or other hormonal activity.[1][3][5] It appears to possess antiandrogenic activity.[13] Its major metabolite trimegestone has weak antimineralocorticoid and antiandrogenic activity.[8][2] 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.[16]

Pharmacokinetics

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Following oral administration, peak serum levels of promegestone are reached after 1 to 2 hours.[1][3] The medication is mainly bound to albumin; it does not bind to sex hormone-binding globulin, and binds only weakly to corticosteroid-binding globulin.[1][3][17] The metabolism of promegestone is mainly via hydroxylation at the C21 position and at other positions.[1][3] Progesterone is similarly hydroxylated at the C21 position, into 11-deoxycorticosterone (21-hydroxyprogesterone).[18] 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.[18] 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.[7] In addition, trimegestone has more than three-fold higher affinity for the PR than does promegestone.[1] As such, promegestone is largely a prodrug of trimegestone.[7][19] A second metabolite, 21(R)-hydroxypromegestone, circulates at far lower concentrations (AUCTooltip area-under-the-curve levels ratio for the (S)- and (R)-isomers of about 21).[7] The elimination half-life of trimegestone is 13.8 to 15.6 hours.[1][2] 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.[7]

Chemistry

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See also: List of progestogens

Promegestone, also known as 17α,21-dimethyl-δ9-19-norprogesterone or as 17α,21-dimethyl-19-norpregna-4,9-diene-3,20-dione, is a synthetic norpregnane steroid and a derivative of progesterone.[9][12][11][1] It is specifically a combined derivative of 17α-methylprogesterone and 19-norprogesterone, or of 17α-methyl-19-norprogesterone.[9][11][1] Related derivatives of 17α-methyl-19-norprogesterone include demegestone and trimegestone.[9][12][1]

History

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Promegestone was first described in the literature in 1973 and was introduced for medical use in France in 1983.[9][10][11][5] It was developed by Roussel Uclaf in France.[5]

Society and culture

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Generic names

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Promegestone is the generic name of the drug and its INNTooltip International Nonproprietary Name, while promégestone is its DCFTooltip Dénomination Commune Française.[6][9][12] It is also known by its developmental code name R-5020 or RU-5020.[6][9][12]

Brand names

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Promegestone is marketed exclusively under the brand name Surgestone.[6][12]

Availability

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Promegestone is or has been marketed in France, Portugal, Tunisia, and Argentina.[6][12]

References

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Further reading

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  • Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  • Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
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