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| Clinical data | |
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| Trade names | Nestorone, others |
| Other names | SGA; SA; ST-1435; AC-6844; CS-0411; 16-Methylene-17α-acetoxy-19-norprogesterone; 16-Methylene-17α-acetoxy-19-norpregn-4-ene-3,20-dione |
| Routes of administration | Subcutaneousimplant,vaginal ring,transdermal patch[1] |
| Drug class | Progestogen;Progestin;Progestogen ester |
| ATC code |
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| Legal status | |
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| Pharmacokinetic data | |
| Bioavailability | Oral: 10%[1][2] |
| Protein binding | 95% (toalbumin and not toSHBGTooltip sex hormone-binding globulin[1][3][4] |
| Metabolism | Hydroxylation (CYP3A4),reduction (5α-reductase) |
| Eliminationhalf-life | Vaginal ring: 4.5 hours[4] Parenteral: 24–72 hours[5][6] Oral: 1–2 hours[1] |
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| Chemical and physical data | |
| Formula | C23H30O4 |
| Molar mass | 370.489 g·mol−1 |
| 3D model (JSmol) | |
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Segesterone acetate (SGA), sold under the brand nameNestorone among others, is aprogestin medication which is used inbirth control and in the treatment ofendometriosis.[1][7] It is available both alone and in combination with anestrogen assegesterone acetate/ethinylestradiol.[1][7] It is not effectiveby mouth and must be given by otherroutes, most typically as avaginal ring orimplant that is placed into fat.[1][8]
Side effects of segesterone acetate are similar to those of other progestins. Segesterone acetate is a progestin, or asyntheticprogestogen, and hence is anagonist of theprogesterone receptor, thebiological target of progestogens likeprogesterone.[1][3][9][10] It has someaffinity for theglucocorticoid receptor and has no other importanthormonal activity.[1][3][9][10]
Segesterone acetate was developed by thePopulation Council and was introduced for medical use by 2000.[7][11] It is under development in theUnited States andEurope as agel in combination withestradiol ortestosterone for use as a method of birth control in women and in men, respectively.[12][13][14][15] In August 2018, a first-of-its-kind one-yearcontraceptive vaginal ring containing segesterone acetate in combination withethinyl estradiol was approved in the United States.[4][16]
Segesterone acetate is used as ahormonal contraceptive and in the treatment ofendometriosis.[1][4][7]
Side effects of segesterone acetate are similar to those of other progestins.[citation needed]
Segesterone acetate acts primarily as a high-affinityagonist of theprogesterone receptor (272% of the affinity ofprogesterone and 136% of that ofpromegestone).[3] It does not bind significantly to theandrogen receptor,estrogen receptor, ormineralocorticoid receptor.[3][9] As such, segesterone acetate does not haveestrogenic,androgenic,antiandrogenic, orantimineralocorticoid activity.[5] However, segesterone acetate does have significant affinity for theglucocorticoid receptor (38% of that ofdexamethasone), but in spite of its relatively high affinity for the glucocorticoid receptor, it either does not have anyglucocorticoid effects or shows glucocorticoid effects only at exceptionally high doses in animals.[1][3][10] Segesterone acetate has noantiglucocorticoid activity in animals either.[10] Theovulation-inhibiting dosage ofparenteral segesterone acetate has been reported to be 150 μg per day, while theendometrial transformation dosage has been reported to be 600 μg per cycle.[5] Segesterone acetate hasantigonadotropic effects and functionalantiestrogenic effects via its progestogenic activity similarly to other progestogens.[3][5] In healthy young men, segesterone acetate alone at a dose of 2 to 3 mg/day as atransdermal gel (delivering 200–300 μg/day SGA) for 2 weeks suppressed testosterone levels from ~581 ng/dL to ~276 ng/dL (–52%).[17]
Segesterone acetate is only weakly activeorally, and is instead given as asubcutaneousimplant.[8] The oralbioavailability of segesterone acetate has been reported to be only 10%.[1][2] However, it has also been reported that the medication is more than 100-fold aspotent when delivered via subcutaneous implant relative to oral administration in rats.[1][3] It has been estimated that segesterone acetate administered at a dose of 2 to 3 mg/day in the form of atransdermal gel delivers approximately 200 to 300 μg/day segesterone acetate based on a transdermalbioavailability of about 10 to 12%.[17] Segesterone acetate isbound toalbumin.[1][3] It does not bind tosex hormone-binding globulin.[1][3]Segesterone, thedeacetylated form of segesterone acetate, is ametabolite of the medication.[18] Thebiological half-life ofparenteral segesterone acetate has been reported to be 24 to 72 hours.[5][6] One study specifically reported a biological half-life of 26.8 hours.[6] It has been reported that the biological half-life of segesterone acetate with oral administration is only 1 to 2 hours.[1] In contrast to all of the preceding however, the USFood and Drug Administration (FDA)label for Annovera, a one-year vaginal ring containing ethinylestradiol and segesterone acetate, lists a circulating half-life of segesterone acetate of 4.5 hours.[4]
Segesterone acetate, also known as 16-methylene-17α-acetoxy-19-norprogesterone or as 16-methylene-17α-acetoxy-19-norpregn-4-ene-3,20-dione, is asyntheticnorpregnanesteroid and aderivative ofprogesterone. It is a combined derivative of17α-hydroxyprogesterone and19-norprogesterone, or a derivative ofgestronol (17α-hydroxy-19-norprogesterone). The medication is the C17αacetateester ofsegesterone, which, in contrast, was never marketed.[18] Other 19-norprogesterone derivatives includedemegestone,gestonorone caproate (norhydroxyprogesterone caproate),nomegestrol acetate,promegestone, andtrimegestone.[3] Segesterone acetate is a derivative of16-methylene-17α-hydroxyprogesterone acetate, and is theanalogue ofmethenmadinone acetate without the C19methyl group or the C6double bond.[19] A derivative of segesterone acetate with even greater progestogenic potency in comparison to segesterone acetate is18-methylsegesterone acetate.[20][21][22]
Segesterone acetate was developed by thePopulation Council.[11] It has been marketed since at least 2000.[7]
Segesterone acetate is thegeneric name of the drug and itsUSANTooltip United States Adopted Name.[23][24] It is also known by its brand names Nestorone and Elcometrine,[25] as well as by its former developmental code namesST-1435,AC-6844, andCS-0411.[citation needed]
Segesterone acetate is marketed alone under the brand names Nestorone and Elcometrine and in combination withethinylestradiol assegesterone acetate/ethinylestradiol under the brand name Annovera among others.[4][7][26]
Segesterone acetate is available alone in several South American countries, including Brazil.[1] It is available in the United States and Canada as acontraceptive vaginal ring in combination withethinylestradiol.[4][26]
Acombination of segesterone acetate and theestrogenestradiol is under development in atransdermalgelformulation for use as acontraceptive in women by the Population Council in conjunction with Antares Pharma in the United States and Europe.[12][14] As of December 2017, it is inphase IIIclinical trials for this indication.[12] The medication has the tentative brand name NestraGel.[12] A combination of segesterone acetate and the estrogenethinylestradiol in avaginal ring formulation for use as a one-year contraceptive was developed by the Population Council in multiple regions includingLatin America, Europe, andAustralia.[27] It completed phase III clinical trials and[27] was approved in the United States in August 2018.[4][16]
A combination of segesterone acetate and theandrogentestosterone is under development as a transdermal gel formulation for use as a hormonal contraceptive in men by the Population Council.[13][15] As of December 2017, it is inphase II clinical studies for this purpose.[15][28] In a trial, 100 couples used segesterone/testosterone dermal gel as the sole contraception method, which resulted in no pregnancy. Side effects were described as mild, comprisingacne, weight gain and nocturnal sweating.[29]
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