Oral contraceptives third-generation

Gestodene Gestodene (54), along with norgestimate and desogestrel, are the progestin components of the third-generation oral contraceptives (see Contraceptives). It may be crystallised from hexane/acetone (81) or ethyl acetate (82), and its crystal stmcture (83) and other spectral data have been reported (84). 

The Advisory Committee on NHS Drugs, when examining oral contraceptives as one of the classes involved in the second phase of the limited list exercise, formed a preliminary position that the more expensive third-generation oral contraceptives should be precluded from availability on NHS prescription on grounds of cost. The outcry from women s groups, family planning practitioners and the medical profession was such that these proposals were never implemented. 

And in another study it was found that users of oral contraceptives with second-generation progestogens have 30% greater increased risk of thrombotic diseases, a 260% greater increased risk of thrombotic deaths, and a 220% greater increased risk of post-thrombotic disability than users of oral contraceptives with third-generation progestogens (20). 

There are now reasons to doubt whether the third-generation oral contraceptives are indeed safer than their predecessors in respect to thromboembolism and substantial grounds for believing that they present greater risks. 

The laboratory findings therefore suggest that a greater thrombosis-inducing effect of the third-generation oral contraceptives can be explained and even anticipated on the basis of known mechanisms. Not all the relevant methods were available in the early years, but that relating to factor VII most certainly was. It is unfortunate, to say the least, that such work was either not performed or not properly interpreted. 

All in all, had a combination of hematological methods and field studies been initiated sufficiently soon, the increased risk of thromboembolism with the third-generation oral contraceptives could have been detected some years earlier, sufficient for society to take decisions on the benefit-to-harm balance of these drugs before so much needless injury was incurred. 

The third-generation oral contraceptives a judicial assessment... 

A 5-year case-control study involving all Danish hospitals has once more quantified the thromboembolic risks associated with oral contraceptives as a whole the risk with third-generation products was some 30% higher than with second-generation products (RR = 1.3 Cl = 1.0, 1.8) (123). However, data on cerebral thrombosis from the same study showed that with third-generation products the mean risk was some 40% lower than with second-generation products (RR = 0.6 Cl = 0.4, 0.9) (124). 

As has become clear since that time, these effects do not run parallel for all oral contraceptives the third-generation products, which contain either desogestrel or ges-todene, have rather different effects, the significance of which is unclear. 

Lipid changes seen with the most widely used combined oral contraceptives comprise an increase in low density lipoprotein and reductions in high density lipoprotein and cholesterol. The third-generation products have these effects to a much smaller extent, leading to claims that they would be less likely to have long-term adverse cardiovascular effects related to atherosclerosis. However, such a claim reflects an all too readily adopted belief that the lipid changes produced by the more traditional combined oral contraceptives are in this respect capable of causing this type of (primarily arterial) cardiovascular disease. This is of itself far from certain. 

Gris JC, Jamin C, Benifla JL, Quere I, Madelenat P, Mares P. APC resistance and third-generation oral contraceptives acquired resistance to activated protein C, oral contraceptives and the risk of thromboembolic disease. Hum Reprod 2001 16(l) 3-8. 

Rosing J, Tans G, Nicolaes GA, Thomassen MC, van Oerle R, van der Ploeg PM, Heijnen P, Hamulyak K, Hemker HC. Oral contraceptives and venous thrombosis different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. Br J Haematol 1997 97(l) 233-8. 

Jick H, Kaye JA, Vasilakis-Scaramozza C, Jick SS. Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995 cohort and case-control analysis. BMJ 2000 321(7270) 1190-5. 

Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Buller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995 346(8990) 1593-6. 

Kemmeren JM, Algra A, Grobbee DE. Third generation oral contraceptives and risk of venous thrombosis metaanalysis. BMJ 2001 323(7305) 131-4. 

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