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| Clinical data | |
|---|---|
| Trade names | Reteroid, Retroid, Retrone |
| Other names | Ro 4-8347; Triengestone; 1,6-Didehydro-6-chlororetroprogesterone; 6-Chloro-9β-10α-pregna-1,4,6-triene-3,20-dione |
| Routes of administration | By mouth |
| Drug class | Progestogen;Progestin |
| ATC code |
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| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Bioavailability | ≥41–46% (based on urinary excretion)[1] |
| Metabolism | Liver[2][3] |
| Metabolites | •20α-Dihydrotrengestone[1] |
| Eliminationhalf-life | • Trengestone: very short[1] •20α-DHTG: 8–14 hours[1] |
| Excretion | Urine: 41–46%[1] Feces: 30% (unchanged)[1] |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| UNII | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.023.617 |
| Chemical and physical data | |
| Formula | C21H25ClO2 |
| Molar mass | 344.88 g·mol−1 |
| 3D model (JSmol) | |
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Trengestone, sold under the brand namesReteroid,Retroid, andRetrone, is aprogestin medication which was formerly used to treatmenstrual disorders but is now no longer marketed.[4][5][6][7][8] It is takenby mouth.[9]
Side effects of trengestone includeheadache,fatigue, andbreast tenderness among others.[7] Trengestone is a progestin, or asyntheticprogestogen, and hence is anagonist of theprogesterone receptor, thebiological target of progestogens likeprogesterone.[7] It is notandrogenic orestrogenic.[7]
Trengestone was introduced for medical use in 1974.[5] It is no longer available.[8]
Trengestone was used in the treatment ofmenstrual disorders.[8] It has also been used toinduce ovulation, with about a 50% success rate on average.[7]
Side effects of trengestone includeheadache,fatigue, andbreast tenderness among others.[7] It is notandrogenic and does not causemasculinization.[7]
Trengestone is aprogestogen, or anagonist of theprogesterone receptor.[7] It is an atypical progestogen similarly todydrogesterone.[7] For instance, unlike other progestogens, trengestone and dydrogesterone do not increasebody temperature (i.e., have nohyperthermic effect).[7][10][11] In addition, whereas other progestogens areantigonadotropic and inhibitovulation, dydrogesterone is neither antigonadotropic norprogonadotropic and does not affect ovulation, and trengestone appears to be progonadotropic and can be used toinduce ovulation.[7][11][12] Similarly to dydrogesterone andprogesterone, trengestone has noandrogenic orestrogenic activity.[7][11]
Trengestone appears to be aprodrug of20α-dihydrotrengestone (20α-DHTG), as it is largelytransformed into this majormetabolite uponoral administration.[1][13] 20α-DHTG has potent progestogenic activity, with peak levels of this metabolite occurring at 2 to 4 hours following administration of trengestone and with abiological half-life of 8 to 14 hours.[1] Trengestone isexcreted 41 to 46% inurine and up to 30% unchanged infeces, suggesting that a significant portion of the medication is notabsorbed from thegastrointestinal tract.[1] Themetabolism andpharmacokinetics of trengestone have been reviewed.[2][3]
Trengestone, also known as 1,6-didehydro-6-chlororetroprogesterone or as 6-chloro-9β,10α-pregna-1,4,6-triene-3,20-dione, is asyntheticpregnanesteroid and aderivative ofprogesterone andretroprogesterone.[4][7][14] Retroprogesterone derivatives like trengestone areanalogues of progesterone in which thehydrogen atom at the 9th carbon has been switched from the α-position (below the plane) to the β-position (above the plane) and themethyl group at the 10th carbon has been switched from the β-position to the α-position.[7] This results in a "bent" configuration in which the plane of rings A and B is orientated at a 60° angle below the rings C and D.[11] Analogues of trengestone includedydrogesterone (6-dehydroretroprogesterone) andRo 6-3129 (16α-ethylthio-6-dehydroretroprogesterone).[4]
Trengestone wassynthesized in 1964 and was introduced for medical use byRoche in 1974.[4][5][6]
Trengestone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name.[4][6] It is also known by its former developmental code nameRo 4-8347.[4][6]
Trengestone was marketed under the brand names Reteroid, Retroid, and Retrone.[4]
Trengestone is no longer marketed and hence is no longer available in any country.[8]
Ro 4-8347 (21), a potent orally active progestagen, when given at the dose of 4 mg/day in the second half of the cycle, was found clinically useful in anovulatory women with decreased ovarian function.109
Fig. 17. Lack of hyperthermic effect of retroprogesterone derivative (Trengestone).
Trengestone, contrary to [dydrogesterone], not only does not inhibit ovarian activity while exerting a progestation effect, but it stimulates the former. One tablet per day is administered from the 5th [...] Both dydrogesterone and trengestone can inhibit ovulation in the rat and rabbit, but only the latter compound can do so in women — at doses far above the therapeutic range. Various clinical reports have suggested, on the basis of quite unrelated findings, that trengestone may, despite lack of inherent estrogenicity, somehow cause an indirect stimulation of the production of endogenous estrogens. Numerous investigators (Stamm et al., 1968; Dapunt and Windbichler, 1970) have satisfied themselves that the compound may stimulate ovulation in women with certain endocrinologic imbalances or deficiencies [...]