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  • Title: Clinical experience with the recently developed progestogens.
    Author: Skouby SO, Petersen KR.
    Journal: Int J Fertil; 1991; 36 Suppl 1():32-7. PubMed ID: 1678379.
    Abstract:
    The third generation of combination estrogen/progestogen oral contraceptives (OCs) first became available in the early 1980s. The gonanes (e.g., norgestimate, desogestrel, and gestodene) are alternatives to the long-standing progestogens, norethindrone and norgestrel/levonorgestrel. While the newer compounds are related to levonorgestrel, their biochemical structure differs. All, however, are strongly progestogenic with respect to ovulation inhibition and are very selective in their affinity for endometrial progesterone receptors. At present, experience with the third-generation combined OCs is relatively limited, and extensive comparative data have yet to be accrued. Nevertheless, these ultra-low-dose compounds appear to be as efficacious as the traditional OCs, while their cycle control may be slightly superior. In addition, the incidence of minor side effects, such as nausea, weight gain, and mastalgia, compares favorably with that of the earlier OCs. In combination with estrogen, these new progestogens have revealed a neutral or possibly beneficial effect on lipid/lipoprotein metabolism. Thus, the newer progestogens do not appear to have adverse effects on the cardiovascular system and offer a range of noncontraceptive health benefits. A study using data from the United Kingdom (UK), Denmark, and Sweden and an ongoing study in the UK found a significant association between estrogen content of high dose combined oral contraceptives (OCs) and all thromboses except venous thrombosis of lower limb. In fact, the ongoing study and another study both found a distinct association between progestogen dose and arterial disease. These association prompted formulators to decrease OC estrogen and progestogen (norethindrone and levonorgestrel) content. These new formulations entered the market after 1975. The early 1980s witnessed the introduction of yet another generation of genane progestogens which were developed in hoped of reducing the incidence of thrombosis. Clinical trials found their contraceptive effectiveness to be comparable to those of the older demonstrated that their effect on associated incidence of bleeding is similar to the older OCs and falls over time. Moreover, even though the 3rd generation OCs have brought on the same side effects (weight gain, mastalgia, and nausea) as the others, the frequency has been at least, and often less, than the others. So far data have not implicated the 3rd generation OCs in impairing glucose tolerance. In addition, research has demonstrated that 3rd generation formulations cause a small increase in high density lipoprotein and either did not change or reduced low density lipoprotein and total cholesterol levels. Thus the new combined OCs do not promote atherosclerotic changes in lipid metabolism. Even though more research is needed, the data have indicated that physicians should continue to prescribe the 3rd generation OCs.
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