In addition to their lack of affinity for the androgen receptor, norgestimate and norelgestromin have virtually no affinity for SHBG, and therefore do not displace testosterone from this carrier protein (although levonorgestrel does still bind with high affinity to SHBG and hence could increase free testosterone levels via occupation of SHBG). In accordance, clinical trials of norgestimate have observed minimal androgenic side effects in women treated with the medication. As an example, clinical studies have found that norgestimate does not appreciably inhibit the increase in SHBG levels produced by ethinylestradiol. This is of interest because estrogens increase and androgens decrease liver production of SHBG and by extension circulating levels of SHBG.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% and 15%. Based on these findings, the ratios of AR to PR binding are 219 for norgestimate and 48 for norelgestromin, whereas the ratios for progesterone, levonorgestrel, and gestodene are 93, 11, and 28, respectively. As such, norgestimate and norelgestromin would appear to have much lower androgenic potency than other 19-nortestosterone progestins. However, levonorgestrel is an important metabolite of both norgestimate and norelgestromin, and it may serve to increase their androgenic potency to some degree.When norgestimate is combined with ethinylestradiol, which is potently antiandrogenic, there are only antiandrogenic effects overall and the combination is suitable for treatment of hyperandrogenism.
Norgestimate 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. It is the C3 oxime and C17β acetate ester of levonorgestrel and is also known as levonorgestrel acetate oxime. A related compound is norethisterone acetate oxime (norethisterone-3-oxime 17β-acetate). History
Norgestimate was introduced as a component of combined oral contraceptives in 1986. Based on its year of introduction, norgestimate is sometimes described as a "third-generation" progestin. Norgestimate was approved in combination with estradiol for use in menopausal hormone therapy in 1999 in the United States, and a generic version of this preparation became available in this country in 2005. Society and culture
Generic names
Norgestimate is the generic name of the drug and its INN, USAN, USP, BAN, and DCF. It is also known by its developmental code name ORF-10131. Brand names
Norgestimate is marketed in combination with ethinylestradiol as a birth control pill under the brand names Amicette, Cilest, Cyclen, Edelsin, Effiprev, Estarylla, MonoNessa, Orlon, Ortho Tri-Cyclen, Ortho Tri-Cyclen Lo, Ortho-Cyclen, Pramino, Previfem, Sprintec, Triafemi, TriCilest, Tri-Cyclen, Tri-Cyclen LO, Tridette, Tri-Estarylla, Tri-Linyah, TriNessa, Tri-Previfem, and Tri-Sprintec. It is marketed in combination with estradiol for menopausal hormone therapy under the brand name Prefest only. Availability
Norgestimate in combination with ethinylestradiol is marketed widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, South Africa, Latin America, and Asia. It is not listed as being marketed in Australia, New Zealand, Japan, South Korea, China, India, or certain other countries.