|Other names||PMG; R-5020; RU-5020; 17α,21-Dimethyl-δ9-19-norprogesterone; 17α,21-Dimethyl-19-norpregna-4,9-diene-3,20-dione|
|Drug class||Progestogen; Progestin|
|Protein binding||To albumin|
|Elimination half-life||Promegestone: ?|
Trimegestone: 13.8–15.6 hours
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||326.472 g/mol g·mol−1|
|3D model (JSmol)|
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.
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.
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.
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.
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.
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 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.
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. It is specifically a combined derivative of 17α-methylprogesterone and 19-norprogesterone, or of 17α-methyl-19-norprogesterone. Related derivatives of 17α-methyl-19-norprogesterone include demegestone and trimegestone.
Investigation of the Pharmacokinetics and Metabolism of Promegestone in Healthy Female Volunteers Following Single Oral Administration of 1 mg Promegestone I Gualano V., 1Geneteau A., I Chassard D., I Fordham P., 2Schatz B. I Aster-Cephac, 3/5, Rue Eugene Millon, 75015 Paris, France 2Laboratoire Aventis, 46 Quai De La Rapee, F-75601 Paris Cedex 12, France. A single 1 mg oral dose of promegestone (Surgestonee, 2x0.5 mg) was given to 12 healthy premenopausal women. The aims were to determine the concentrations of promegestone and its metabolites and their pharmacokinet-ic parameters. Blood and urine samples were followed until 96 hours post dose. To avoid any interference with natural hormones, promegestone was given between day 7 and 10 of the menstrual cycle. Clinical safety and tolerability were good. Most of the minor adverse events observed were estimated possibly linked to the study drug (menstrual disorders) because classically related to progestins therapy. In addition, no clinically relevant biological modifications were observed. There was a stereoselective metabolism of promegestone in favor of the 21S hydroxy-promegestone, the main circulating compound in plasma (AUC ratio 5/R of about 21). Levels of 21S hydroxy-promegestone are about twice greater than that of unchanged promegestone. The plasma levels of the second metabolite, i.e. 21 R hydroxy-promegestone are far below these of either promegestone and 21S hydroxy-promegestone. Promegestone, 215 hydroxy- and 21R hydroxy-promegestone are not excreted in urine. About 3% of the dose was recov-ered in urine as sulfo and/or glucuro-conjugate 21S hydroxy-promegestone and about 1% of the dose as sulfo and/or glucuro conjugate 21R hydroxy-promegestone.