Gestodene

Gestodene

Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	X
Routes of administration	Oral
ATC code	G03AA10 (WHO) G03AB06 (WHO) (only combinations with estrogens)
Legal status
Legal status	℞ (Prescription only)
Pharmacokinetic data
Bioavailability	87–99%
Biological half-life	12–14 hours
Excretion	Urine
Identifiers
IUPAC name (8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14-decahydrocyclopenta[a]phenanthren-3-one
Synonyms	SHB-331
CAS Number	60282-87-3 Y
PubChem (CID)	3033968
DrugBank	DB06730 Y
ChemSpider	2298532 Y
UNII	1664P6E6MI Y
KEGG	D04316 Y
ChEMBL	CHEMBL1213583 Y
ECHA InfoCard	100.056.478
Chemical and physical data
Formula	C21H26O2
Molar mass	310.430 g/mol
3D model (Jmol)	Interactive image
SMILES O=C4\C=C3/[C@@H]([C@H]2CC[C@]1([C@@H](/C=C\[C@]1(C#C)O)[C@@H]2CC3)CC)CC4
InChI InChI=1S/C21H26O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,10,12-13,16-19,23H,3,5-9,11H2,1H3/t16-,17+,18+,19-,20-,21-/m0/s1 Y Key:SIGSPDASOTUPFS-XUDSTZEESA-N Y

Gestodene (INN, USAN, BAN), also known as Δ¹⁵-norgestrel or 15-dehydronorgestrel, as well as 17α-ethynyl-18-methylestra-4,15-dien-17β-ol-3-one, is a steroidal progestin of the 19-nortestosterone group related to norgestrel and levonorgestrel that is used in combination with ethinylestradiol as a hormonal contraceptive. It is marketed in Europe but is not available in the United States.

Gestodene is androgenically neutral, meaning that contraceptive pills containing gestodene do not exhibit the androgenic side effects (e.g. acne, hirsutism, weight gain) often associated with second-generation contraceptive pills, such as those containing levonorgestrel.

The synthetic 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.

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.

Products containing gestodene include:

Women who take oral contraceptives containing gestodene are 5.6 times as likely to develop thromboembolism than women who do not take any contraceptive pill, and 1.6 times as likely to develop thromboembolism compared to women taking oral contraceptives containing levonorgestrel.

Gestodene is a potent progestogen, and also possesses weak androgenic, antimineralocorticoid, and glucocorticoid activity. It has relatively high affinity for the androgen receptor (AR), with twice that of levonorgestrel (which is known to be one of the more highly androgenic 19-nortestosterone derivatives). 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). In addition, no difference in acne incidence has been observed with oral contraceptives containing gestodene and oral contraceptives containing desogestrel. 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), and this action was substantially greater than that of desogestrel or levonorgestrel. Taken together, like desogestrel, gestodene appears to have a low potential for androgenic effects. 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. Gestodene binds to SHBG with relatively high affinity, and is 75% bound to the protein in circulation.