|Systematic (IUPAC) name|
|Bioavailability||in vitro 99% using 3H=R5020 / in vivo similar to progesterone|
|Biological half-life||16 to 18 hrs.|
|Excretion||urinary tract mainly|
|ATC code||G03 G03 (only combinations with estrogens)|
|Molecular mass||310.430 g/mol|
|(what is this?)|
- Melodene-15, Mirelle, and Minesse which contain 15 μg of ethinylestradiol and 60 μg of gestodene;
- Meliane, Sunya, Femodette, and Millinette 20/75 which contain 20 μg of ethinylestradiol and 75 μg of gestodene; and
- Gynera, Minulet, Femoden, Femodene, Katya and Millinette 30/75 which contain 30 μg of ethinylestradiol and 75 μg of gestodene.
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.
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.
Oral contraceptives almost invariably consist of a mixture of a progestational agent active by the oral route and a small amount of an estrogen. It was discovered quite early that, in contrast to the natural compounds, those lacking the 19 methyl group (19-nor) showed good oral activity; the availability of practical methods for total synthesis led to some emphasis on agents that possess an ethyl group at position 13 rather than the methyl of the natural steroids. Very widespread use of oral contraceptives led to the recognition of some side effects that were associated with the progestin component; there has thus been a trend to design drugs that could be administered in smaller quantity and a corresponding search for ever more potent progestins.
Birch reduction of the norgestrel intermediate 1 followed by hydrolysis of the enol ether gives the enone (2); oxidation of the alcohol at 17 leads to dione 3. Fermentation of that intermediate in the presence of the mold Penicillium raistrickii (ATCC® 10490™) serves to introduce a hydroxyl group at the 15 position (4). Ketal formation with neopentyl glycol affords the protected ketone which consists of a mixture of the Δ5 and Δ5,10 isomers; hindrance at position 17 ensures selective reaction at the 3 ketone. The hydroxyl is the converted to its mesylate (5). Treatment with sodium acetate leads to elimination of the mesylate and formation of the corresponding enone (6). Reaction of the ketone at 17 with ethynylmagnesium bromide introduces the requisite side chain. Removal of the ketal group by means of aqueous oxalic acid completes the synthesis of gestodene (8).
- Festin (2006). "Progestogens in combined oral contraceptives for contraception". The WHO Reproductive Health Library.
- Cerel-Suhl (1999). "Update on Oral Contraceptive Pills". American Family Physician 60 (7): 2073–2084.
- Lidegaard; et al. (2011). "Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses". BMJ 343: 1–15. doi:10.1136/bmj.d6423. PMC 3202015. PMID 22027398.
- Fried, J.; Bry, T. S.; 1968, U.S. Patent 3,374,226.
- DeWinter, M. S.; Siegman, C. M.; Szpilfogel, C. A.; Chem. Ind. (London) 1959, 905.