Disease relevance of DESOGESTREL

• BACKGROUND: Four studies published since December, 1995, reported that the incidence of venous thromboembolism (VTE) was higher in women who used oral contraceptives (OCs) containing the third-generation progestagens gestodene or desogestrel than in users of OCs containing second-generation progestagens [1].
• This phenomenon, designated as acquired APC resistance, is more pronounced in women using desogestrel-containing oral contraceptives than in women using levonorgestrel-containing preparations [2].
• It has been suggested that preparations containing the newer progestogens, Desogestrel and Gestodene, are not associated with any increase in risk of myocardial infarction, but there is not yet sufficient evidence to test this hypothesis [3].
• Long-term treatment of hirsutism: desogestrel compared with cyproterone acetate in oral contraceptives [4].
• The risk of development of deep vein thrombosis was also found to be 2 to 5 times greater with a low-estrogen, desogestrel-containing oral contraceptive than with second-generation monophasic and triphasic preparations [5].

High impact information on DESOGESTREL

• Given this caveat, odds ratios for ischaemic, haemorrhagic, and all strokes combined associated with use of oral contraceptives containing desogestrel or gestodene ("third generation") were found to be similar to those containing levonorgestrel in this study [6].
• With all second-generation OCs as the reference, the odds ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol and 1.18 (0.66-2.17) for the other third-generation progestagens [1].
• Compared with levonorgestrel, desogestrel-containing OCs significantly decreased protein S and increased activated protein C (APC) resistance in both groups [7].
• The four groups receiving hormone replacement therapy were given 2 mg estradiol valerate equivalents (E), either sequentially combined with 75 micrograms levonorgestrel (E/LNG), 10 mg medroxyprogesterone acetate (E/MPA), or 150 micrograms desogestrel (E/DG), or continuously combined with 1 mg cyproterone acetate (E/CPA) [8].
• Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel [9].

Chemical compound and disease context of DESOGESTREL

• CONCLUSION(S): Oral contraceptive pills containing low-dose ethinyl estradiol and desogestrel are effective in controlling hyperandrogenism and hirsutism and ameliorate the abnormal metabolic profile of women with hirsutism [10].
• Recent data indicate that users of third-generation oral contraceptives, those containing the new progestins desogestrel, gestodene, and norgestimate, have 2 to 3 times the risk of venous thromboembolism faced by users of second-generation oral contraceptives [5].
• Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men [11].
• AIMS: In October 1995 in response to the results of three studies, the Committee on the Safety of Medicines advised doctors and pharmacists that oral contraceptives containing desogestrel (DSG) and gestodene (GST) were associated with around a two-fold increase in the risk of thromboembolism compared with those containing other progestogens [12].
• The desogestrel-containing preparations Gracial and Marvelon, and possibly also the gestodene-containing preparation Gynera, have demonstrated a good efficacy in well-controlled studies in the treatment of mild to moderate acne and/or hirsutism [13].

Biological context of DESOGESTREL

• Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism [14].
• The effects of a synthetic oral progestogen, desogestrel (DSG), administered with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to targets compatible with effective male contraception [14].
• These data indicate that the OC-induced inhibition of endogenous fibrinolysis takes place in a factor XI-independent way and is more pronounced on desogestrel than on levonorgestrel-containing OC [15].
• After two cycles of use and a wash-out period of 2 menstrual cycles, the participants received the corresponding progestagen-only preparation containing 150 microg levonorgestrel or 150 microg desogestrel [16].
• Bone mineral density in young women with long-standing amenorrhea: limited effect of hormone replacement therapy with ethinylestradiol and desogestrel [17].

Anatomical context of DESOGESTREL

• This study measured whole blood platelet activation, serially, in women taking oral contraceptives containing 20 micrograms and 30 micrograms ethinyloestradiol combined with desogestrel [18].
• The most potent progestogens are gestodene and desogestrel, while the effect of dienogest and nomegestrol on endometrium and cervix is less, even though in a similar range [19].
• Initial studies using deuterated desogestrel confirmed that desogestrel is metabolised by human liver microsomes via 3alpha-hydroxy and 3beta-hydroxydesogestrel to 3-ketodesogestrel [20].
• Desogestrel was metabolised by microsomes from lymphoblasts containing cDNA-expressed CYP2C9 and CYP2C19 to 3alpha-hydroxydesogestrel with small amounts of 3beta-hydroxydesogestrel also being observed [20].
• 5. The results of this study indicate substantial first pass metabolism of desogestrel by the gut mucosa with evidence for the formation of the active metabolite [21].

Associations of DESOGESTREL with other chemical compounds

• The adjusted RR estimates from the cohort analysis were 1.9 (1.1-3.2) and 1.8 (1.0-3.2) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel [22].
• Both gestodene and desogestrel may moderately reduce SHBG levels and counteract the stimulating effect of ethinylestradiol on hepatic serum proteins, while dienogest and nomegestrol have no influence [19].
• Age-adjusted incidences were approximately twice as high for desogestrel- and norethisterone-containing COCs compared with levonorgestrel-containing COCs, although differences were not statistically significant [23].
• The role of CYP2C in the in vitro bioactivation of the contraceptive steroid desogestrel [20].
• OBJECTIVE: To assess the differences and similarities in efficacy, safety, and metabolic effects of oral contraceptives (OCs) containing the new progestins desogestrel, gestodene, and norgestimate [24].

Gene context of DESOGESTREL

• During the use of desogestrel-containing OC the plasma levels of alpha2-M, alpha1-antitrypsin, PCI and protein C significantly increased, whereas AT and protein S significantly decreased [25].
• TAFI (thrombin-activatable fibrinolysis inhibitor) levels increased on levonorgestrel, and even further increased on desogestrel [15].
• Women taking contraceptives with ethinyl estradiol and desogestrel or levonorgestrel had higher GH values, and the desogestrel group had lower IGF-1 values than women not taking contraceptives [26].
• In this study the effects of progesterone, with no significant androgen-receptor affinity are compared to desogestrel, a synthetic gestogen with relatively low affinity for the androgen receptor, on gonadotrophin secretion in normal men [27].
• Advantage of desogestrel containing pill in oral contraception: influence on blood lipids and LCAT activity [28].

Analytical, diagnostic and therapeutic context of DESOGESTREL

• One group was taking an oral contraceptive (150 microg desogestrel and 30 microg ethinyl estradiol); the other group (control) was not [29].
• We conclude that daily self-administered desogestrel with transdermal T is capable of suppressing the male reproductive axis, although the efficacy was less marked and less consistent than injectable regimens [30].
• We measured serum FSH and LH using a modified, highly sensitive immunofluorometric assay in samples obtained from three published studies using T enanthate (TE; 100 and 200 mg weekly) plus daily oral doses of cyproterone acetate (CPA; 5-100 mg), levonogestrel (LNG; 150-500 micro g), or desogestrel (DSG; 150-300 micro g) [31].
• Four epidemiologic studies showed a two-fold increase in risk of VTE with the use of OCs containing third-generation progestins (gestodene and desogestrel), relative to second-generations products (levonorgestrel) [32].
• A randomized cross-over study on the effects of levonorgestrel- and desogestrel-containing oral contraceptives on the anticoagulant pathways [25].

References