Controversy
In February 2007, the consumer advocacy group Public Citizen released a petition requesting that the Food and Drug Administration ban oral contraceptives containing desogestrel in the United States, citing studies going as far back as 1995 that suggest the risk of dangerous blood clots is doubled for women on such pills in comparison to other oral contraceptives. In 2009, Public Citizen released a list of recommendations that included numerous alternative, second-generation birth control pills that women could take in place of oral contraceptives containing desogestrel. Most of those second-generation medications have been on the market longer and have been shown to be as effective in preventing unwanted pregnancy, but with a lower risk of blood clots. Medications cited specifically in the petition include Apri-28, Cyclessa, Desogen, Kariva, Mircette, Ortho-Cept, Reclipsen, Velivet, and some generic pills, all of which contain desogestrel in combination with ethinylestradiol. Medications containing desogestrel as the only active ingredient (as opposed to being used in conjunction with ethinylestradiol, like in combined oral contraceptives) do not show an increased thrombosis risk and are therefore safer than second-generation birth-control pills in regards to thrombosis. Research
Desogestrel has been studied extensively as an antigonadotropin for use in combination with testosterone as a hormonal contraceptive in men. Such combinations have been found to be effective in producing reversible azoospermia in most men and reversible azoospermia or severe oligozoospermia in almost all men. References
Further reading
Chez RA (1989). "Clinical aspects of three new progestogens: desogestrel, gestodene, and norgestimate". Am. J. Obstet. Gynecol. 160 (5 Pt 2): 1296–300. doi:10.1016/S0002-9378(89)80016-X.
Pharmacokinetics
The bioavailability of desogestrel has been found to range from 40 to 100%, with an average of 76%. This significant interindividual variability is comparable to that with norethisterone and levonorgestrel. Peak concentrations of etonogestrel occur about 1.5 hours after a dose while concentrations of desogestrel are very low and have disappeared by 3 hours after a dose. Steady-state levels of etonogestrel are achieved after about 8 to 10 days of daily administration. Accumulation of etonogestrel is thought to be related to progressive inhibition of 5α-reductase and cytochrome P450 monooxygenases (e.g., CYP3A4). The plasma protein binding of desogestrel is 99% and it is bound exclusively to albumin. Etonogestrel is bound 95 to 98% to plasma proteins. It is bound about 65 to 66% to albumin and 30 to 32% to SHBG, with 2 to 5% free in the circulation. While desogestrel is not bound to SHBG, etonogestrel has relatively high affinity for this plasma protein of 3 to 15% of that of dihydrotestosterone, although this is considerably less than that of the related progestins levonorgestrel and gestodene. Neither desogestrel nor etonogestrel are bound by corticosteroid-binding globulin.Desogestrel is a prodrug of etonogestrel (3-ketodesogestrel) and upon ingestion is rapidly and completely transformed into this metabolite in the intestines and liver. Hydroxylation of the C3 position of desogestrel catalyzed by cytochrome P450-dependent enzymes, with 3α-hydroxydesogestrel and 3β-hydroxydesogetrel as intermediates, followed by oxidation of the C3 hydroxyl group, is responsible for the transformation. A small percentage of desogestrel is metabolized into levonorgestrel, which involves the removal of the C11 methylene group.