Gestodene was discovered in 1975 and was introduced for medical use, specifically in birth control pills, in 1987.[4][12] It was subsequently introduced for use in menopausal hormone therapy as well.[7][8] Gestodene is sometimes referred to as a "third-generation" progestin.[13] 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.[8][7] Gestodene is not approved in the
United States.[14][15]
Medical uses
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.[16]
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.[17]
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.[20]
Notes: Values are percentages (%). Reference
ligands (100%) were
promegestone for the
PRTooltip progesterone receptor,
metribolone for the
ARTooltip androgen receptor,
E2 for the
ERTooltip estrogen receptor,
DEXATooltip dexamethasone for the
GRTooltip glucocorticoid receptor,
aldosterone for the
MRTooltip mineralocorticoid receptor,
DHTTooltip dihydrotestosterone for
SHBGTooltip sex hormone-binding globulin, and
cortisol for
CBGTooltip Corticosteroid-binding globulin. Sources:[9]
Progestogenic activity
Gestodene is a
progestogen, and hence is an
agonist of the
progesterone receptor.[9] Based on the dosage necessary to inhibit
ovulation in women, gestodene is the most potent of all of the currently used oral contraceptive progestogens.[21][22][23] The oral dosage of gestodene required for ovulation inhibition is 30 or 40 μg per day.[22][24] This is about 10,000 times lower than the oral dosage of progesterone required to inhibit ovulation (300 mg/day).[11][9] A dosage of gestodene of 75 μg/day is used in contraceptives.[23]
Androgenic activity
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).[25] 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).[25] In addition, no difference in
acne incidence has been observed with oral contraceptives containing gestodene and oral contraceptives containing desogestrel.[26] Gestodene may also act to some extent as a
5α-reductase inhibitor.[9][25] Taken together, like desogestrel, gestodene appears to have a low potential for androgenic effects.[25]
Gestodene has very high affinity for the
mineralocorticoid receptor (MR), but has only a relatively weak antimineralocorticoid effect that is comparable to that of
progesterone.[25]
Other activities
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.[28]
Gestodene binds to SHBG with relatively high
affinity; it is 75% bound to the protein in circulation.[11][25]
Gestodene shows some
inhibition of
cytochrome P450enzymesin vitro, and has greater
potency in this action compared to other progestins (
IC50Tooltip half-maximal inhibitory concentration = 5.0 μM).[9][1] The medication also shows some inhibition of
5α-reductasein vitro (14.5% at 0.1 μM, 45.9% at 1.0 μM).[9] Like with cytochrome P450 inhibition, gestodene was more potent in this action compared to other progestins, including desogestrel and levonorgestrel.[9][25]
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
syntheticestranesteroid and a
derivative of
testosterone.[5][8] 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.[30] 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.[31][32]
Gestodene is the
generic name of the drug and its
INNTooltip International Nonproprietary Name,
USANTooltip United States Adopted Name,
BANTooltip British Approved Name, and
DCFTooltip Dénomination Commune Française.[5][6][8] It is also known by its developmental code name SHB-331.[5][8]
Brand names
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.[8] It is marketed for use in menopausal hormone therapy in combination with estradiol under the brand names Avaden, Avadene, and Convaden.[7][8]
^
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