Gestodene, sold under the brand names Femodene and Minulet among others, is a progestin medication which is used in birth control pills for women.[3][4] It is also used in menopausal hormone therapy.[5] The medication is available almost exclusively in combination with an estrogen.[6] It is taken by mouth.[4][7] Side effects of the combination of an estrogen and gestodene include menstrual irregularities, headaches, nausea, breast tenderness, mood changes, and others.[citation needed] Gestodene is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[8][9] It has weak androgenic activity, weak antimineralocorticoid activity, and weak glucocorticoid activity.[8][9] Gestodene was introduced for medical use, specifically in birth control pills, in 1987.[10] It was subsequently introduced for use in menopausal hormone therapy as well.[5][6] Gestodene is sometimes referred to as a "third-generation" progestin.[11] It is marketed in birth control pills widely throughout the world, whereas it is available for use in menopausal hormone therapy only a few countries.[6][5] Gestodene is not approved in the United States.[12][13] Gestodene is neutral in terms of androgenic activity, meaning that contraceptive pills containing gestodene do not exhibit the androgenic side effects (e.g., acne, hirsutism) sometimes associated with second-generation contraceptive pills such as those containing levonorgestrel.[14] The estrogen dosage in third-generation contraceptive pills (including those containing gestodene) is lower than that in second-generation oral contraceptives, reducing the likelihood of weight gain, breast tenderness, and migraine.[15] Third-generation oral contraceptives are also suitable for use in patients with diabetes or lipid disorders because they have minimal impact on blood glucose levels and the lipid profile.[16] Gestodene is also available in combination with estradiol for use in menopausal hormone therapy.[5][6] Contraceptive products containing gestodene include: Women who take oral contraceptives containing gestodene are 5.6 times as likely to develop venous thromboembolism than women who do not take any contraceptive pill, and 1.6 times as likely to develop venous thromboembolism compared to women taking oral contraceptives containing levonorgestrel.[18] Gestodene is a highly potent progestogen, and also possesses weak androgenic, antimineralocorticoid, and glucocorticoid activity.[7][8][9] Due to its progestogenic activity, it has antigonadotropic and functional antiestrogenic effects.[7] Gestodene is a progestogen, and hence is an agonist of the progesterone receptor.[7] Based on the dosage necessary to inhibit ovulation in women, gestodene is the most potent of all of the currently used oral contraceptive progestogens.[19][20][21] The oral dosage of gestodene required for ovulation inhibition is 30 or 40 μg per day.[20][22] This is about 10,000 times lower than the oral dosage of progesterone required to inhibit ovulation (300 mg/day).[9][23] A dosage of gestodene of 75 μg/day is used in contraceptives.[21] Gestodene has relatively high affinity for the androgen receptor (AR), with twice that of levonorgestrel (which is known to be one of the more androgenic 19-nortestosterone derivatives).[24] However, the ratio of progestogenic to androgenic effects of gestodene is distinctly higher than that of levonorgestrel, and the increase in sex hormone-binding globulin (SHBG) levels (a marker of androgenicity) produced by oral contraceptives containing gestodene is slightly less than that produced by oral contraceptives containing desogestrel (which is known to be one of the more weakly androgenic 19-nortestosterone derivatives).[24] In addition, no difference in acne incidence has been observed with oral contraceptives containing gestodene and oral contraceptives containing desogestrel.[25] Moreover, gestodene has been found to strongly inhibit 5α-reductase in vitro (14.5% and 45.9% inhibition at 0.1 μM and 1 μM, respectively),[7] and this action was substantially greater than that of desogestrel or levonorgestrel.[24] Taken together, like desogestrel, gestodene appears to have a low potential for androgenic effects.[24] Although gestodene does not bind to the estrogen receptor itself, the drug may have some estrogenic activity, and this would appear to be mediated by its weakly estrogenic metabolites 3β,5α-tetrahydrogestodene and to a lesser extent 3α,5α-tetrahydrogestodene.[26] In addition to the AR, gestodene has very high affinity for the mineralocorticoid receptor (MR), but only a relatively weak antimineralocorticoid effect that is comparable to that of progesterone.[24] Gestodene binds to SHBG with relatively high affinity, and is 75% bound to the protein in circulation.[9][24] The bioavailability of gestodene is 87 to 100%.[1][2] Unlike other third-generation progestins like desogestrel and norgestimate, gestodene is not a prodrug.[27] Its biological half-life is 12 to 14 hours.[1] Gestodene, also known as 17α-ethynyl-18-methyl-19-nor-δ15-testosterone, as well as 17α-ethynyl-18-methylestra-4,15-dien-17β-ol-3-one or 13β-ethyl-18,19-dinor-17α-pregna-4,15-dien-20-yn-17β-ol-3-one, is a synthetic estrane steroid and a derivative of testosterone.[3][6] 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.[28] Gestodene is almost identical to levonorgestrel in terms of chemical structure, differing only in having an additional double bond between the C15 and C16 positions, and for this reason is also known as δ15-norgestrel or as 15-dehydronorgestrel.[29][30] Gestodene was introduced for medical use, specifically in combination with ethinylestradiol as a combined oral contraceptive, in 1987.[10] It was introduced for use in menopausal hormone therapy in combination with estradiol in some countries such as in Europe and Latin America years later.[5][6] Gestodene is the generic name of the drug and its INN, USAN, BAN, and DCF.[3][4][6] It is also known by its developmental code name SHB-331.[3][6] Gestodene is marketed as a contraceptive in combination with ethinylestradiol under a variety of brand names including Femoden, Femodene, Femodette, Gynera, Harmonet, Lindynette, Logest, Meliane, Millinette, Minesse, Minulet, Mirelle, and Triadene as well as many others.[6] It is marketed for use in menopausal hormone therapy in combination with estradiol under the brand names Avaden, Avadene, and Convaden.[5][6] Gestodene is marketed in the United Kingdom, Ireland, elsewhere throughout Europe, South Africa, Australia, Latin America, Asia, and elsewhere in the world.[6] It is not listed as being marketed in the United States, Canada, New Zealand, Japan, South Korea, India, or certain other countries.[6] Gestodene is marketed for use specifically in menopausal hormone therapy only in a few countries, including Colombia, Ecuador, Mexico, Peru, and Portugal.[6]

Source:Wikipedia.org