|Trade names||Ortho-Cyclen, Ortho Tri-Cyclen, Previfem, Sprintec, Prefest, others|
|Synonyms||ORF-10131; Norgestrel acetate oxime; Norgestrel 17β-acetate 3-oxime; 17α-Ethynyl-18-methyl-19-nortestosterone 3-oxime 17β-acetate; 17α-Ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime 17β-acetate|
|AHFS/Drugs.com||Micromedex Detailed Consumer Information|
|Drug class||Progestogen; Progestogen ester|
|Biological half-life||12–30 hours|
|Chemical and physical data|
|Molar mass||369.497 g/mol|
|3D model (JSmol)|
|(what is this?)|
Norgestimate, sold under the brand names Ortho-Cyclen, Ortho Tri-Cyclen, Previfem, Sprintec, and Prefest among others, is a progestin that is used in combination with ethinylestradiol as an oral contraceptive and in combination with estradiol in menopausal hormone replacement therapy. It is a prodrug, mainly of norelgestromin, but also of levonorgestrel in small amounts.
Norgestimate, unlike related progestins such as levonorgestrel, shows high selectivity for the progesterone receptor (PR) and little androgenic activity. Moreover, norgestimate and its main active metabolite norelgestromin do not bind to or occupy sex hormone-binding globulin (SHBG). In accordance, clinical trials of norgestimate have observed minimal androgenic side effects.
The relative binding affinity of norgestimate and its metabolite norelgestromin for the rat prostatic androgen receptor (AR) are 0.3% and 1.3% of those of dihydrotestosterone (DHT), respectively, whereas the respective values for levonorgestrel and gestodene are 22.0% and 15.4%. Moreover, the ratios of AR to PR binding are 219 for norgestimate and 48 for its metabolite norelgestromin, whereas the ratios of progesterone, levonorgestrel, and gestodene are 93, 11, and 28, respectively.
Estrogens increase and androgens inhibit hepatic production of SHBG and by extension circulating SHBG levels. Clinical studies have found that norgestimate does not appreciably inhibit the increase in SHBG levels produced by ethinylestradiol, and this is in accordance with preclinical research and the notion that norgestimate is minimally androgenic. In addition, norgestimate and norelgestromin show virtually no affinity for SHBG, unlike levonorgestrel and gestodene (which have 87% and 202% of the relative binding affinity of testosterone for SHBG, respectively) but similarly to progesterone.
Norgestimate acts as a prodrug to norelgestromin (17β-deacetylnorgestimate or levonorgestrel 3-oxime), the primary active metabolite, and to a lesser extent to levonorgestrel (~22% of an administered dose; deacetylation of norgestimate occurs in the intestines and the liver), as well as to levonorgestrel 17β-acetate in very small quantities.
Norgestimate, also known as 17α-ethynyl-18-methyl-19-nortestosterone 3-oxime 17β-acetate or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one 3-oxime 17β-acetate, is a synthetic estrane steroid and a derivative of testosterone. It is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is a member of the gonane (18-methylestrane) subgroup of the 19-nortestosterone family of progestins. Norgestimate is the C3 oxime and C17β acetate ester of levonorgestrel and is also known as levonorgestrel acetate oxime.
Norgestimate was introduced in 1986.
Society and culture
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