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| Clinical data | |
|---|---|
| Trade names | Lutagan, Secrosteron, others |
| Other names | Dimethindrone; 6α,21-Dimethylethisterone; 6α,21-Dimethyl-17α-ethynyltestosterone; 17α-Ethynyl-6α,21-dimethylandrost-4-en-17β-ol-3-one; 6α,21-Dimethyl-17β-hydroxy-17α-pregn-4-en-20-yn-3-one |
| Routes of administration | By mouth |
| Drug class | Progestogen;Progestin |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| UNII | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.001.106 |
| Chemical and physical data | |
| Formula | C23H32O2 |
| Molar mass | 340.507 g·mol−1 |
| 3D model (JSmol) | |
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Dimethisterone, formerly sold under the brand namesLutagan andSecrosteron among others, is aprogestin medication which was used inbirth control pills and in the treatment ofgynecological disorders but is now no longer available.[1][2][3][4] It was used both alone and in combination with anestrogen.[1][5] It is takenby mouth.[6]
Side effects of dimethisterone are similar to those of other progestins. When used in combination with high doses of an estrogen, an increased risk ofendometrial cancer can occur.[7] Dimethisterone is a progestin, or asyntheticprogestogen, and hence is anagonist of theprogesterone receptor, thebiological target of progestogens likeprogesterone.[8][9][10] It has someantimineralocorticoid activity and no other importanthormonal activity.[8][9][10]
Dimethisterone was first described and was introduced for medical use in 1959.[1][8] It started being used in birth control pills in 1965.[5] However, due to its lowpotency and consequent inability to prevent the increased risk of endometrial cancer with estrogens, dimethisterone was soon discontinued for such purposes.[7]
Dimethisterone was used alone in the treatment ofgynecological disorders and in combination withethinylestradiol inbirth control pills.[7][11]
Side effects of dimethisterone are similar to those of other progestins.[citation needed]
Dimethisterone was derived from modification of ethisterone via introduction ofmethyl groups at the C6α and C21 positions.[12][13] Relative to ethisterone, it is 12 times as potentorally as aprogestogen in animals (Clauberg test),[8][13] and, unlike ethisterone,[14] is a pure progestogen with noandrogenic (orestrogenic) activity in animals even at very high doses (although some weakantimineralocorticoid activity was observed at high doses in animals).[8][9][10] However, in spite of its improved potency over ethisterone, it is a weak progestogen relative to most other progestins,[3] in fact one of the weakest known.[2]
Dimethisterone, also known as 6α,21-dimethylethisterone or as 6α,21-dimethyl-17α-ethynyltestosterone, as well as 17α-ethynyl-6α,21-dimethylandrost-4-en-17β-ol-3-one or as 6α,21-dimethyl-17β-hydroxy-17α-pregn-4-en-20-yn-3-one, is asyntheticandrostanesteroid and aderivative oftestosterone.[1]
Chemical syntheses of dimethisterone have been published.[15]
Dimethisterone was developed by theBritishpharmaceutical companyBritish Drug Houses (which subsequently merged withMerck KGaA) and was first reported in the medical literature in 1959,[1][8] with introduction for medical use under the brand name Secrosteron following in the same year.[13][16] It was introduced in theUnited States as anoral contraceptive in combination with high doses ofethinylestradiol under the brand name Oracon (25 mg dimethisterone, 100 μg ethinylestradiol) in 1965.[5] Due to the fact that it contains a weak progestogen in combination with a large dose of a potentestrogen, this preparation was eventually found to be associated with a substantially increased risk ofendometrial cancer in women, and is now no longer marketed.[7]
The improved potency of dimethisterone due to 6α-methylation reportedly served as the basis for thesynthesis ofmedroxyprogesterone acetate.[13] Whereashydroxyprogesterone acetate (the 6α-demethylatedanalogue of medroxyprogesterone acetate) is around twice as potent as ethisterone orally,[17] medroxyprogesterone acetate shows 10 to 25 times the potency of ethisterone.[13]
Dimethisterone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name, andBANTooltip British Approved Name.[1]
Dimethisterone was marketed alone under the brand names Lutagan and Secrosteron and in combination withethinylestradiol under the brand names Oracon, Ovin, Secrodyl, Secrovin, and Tova.[1][5][18]
Studies have shown that women who used Oracon, a sequential preparation that employed dimethisterone (weak progestogen) with a large dose of a potent estrogen (ethinyl estradiol), had substantially elevated risks of uterine cancer (6,21). The risk associated with the use of other sequential oral contraceptives remains unclear, mainly because these drugs are no longer marketed.
Secrosteron (dimethisterone) is an orally active purely progestational agent twelve times as potent as ethisterone.
At The British Drug Houses, Ltd., V. Petrow and his group decided that substitution at the 6 position should help to strengthen the progesterone molecule. They prepared a series of 6α and 6β derivatives and, finding enhancement with 6α-methyl, proceeded to modify ethisterone and finally produced 6α,21-dimethylethisterone, which proved to have twelve times the oral activity of ethisterone. This latter product is marketed by British Drug Houses under the name of Secrosteron.
{{cite book}}:|journal= ignored (help)Secrosteron a new oral progestational substance British Drug Houses (South Africa) (Pty.) Ltd., announce the introduction of Secrosteron, a new fundamental discovery from the Research Laboratories of the British Drug Houses Ltd., London.
It is the purpose of this paper to introduce and describe a new steroid for oral administration, 17-a-hydroxyprogesterone acetate*, and to compare it with the most widely used oral substance with progestational properties, 20,21-anhydro-17-/3-hydroxyprogesterone. * Prodox, Upjohn Co., Kalamazoo, Michigan [...] It was found that 17-a-hydroxyprogesterone acetate has a progestational activity which is at least twice that of anhydrohydroxyprogesterone.