A large number of publications on oral contraceptives (OC) can be found in the medical literature. These reports deal not only with mode of action or efficacy of OCs but also with side effects. Adverse drug reactions (ADR) are not accepted nor acceptable from a population of young women free of disease who expect from their mode of contraception to be fully efficient and devoid from side effects. In most instances, side effects observed with OCs as well as their efficacy are related to the total dose of steroids contained in the combination, to the balance between the estrogen and the progestin content and to the specific characteristics of the molecules. Cardiovascular morbidity and mortality reported in OC users have been related firstly to the ethinylestradiol (EE) and as a first step, the estrogen dose has been reduced in the OCs synthesized in the 70s. Later on, cardiovascular risk has been correlated to lipid profile changes and progestins with androgenic properties have been made responsible for cardiovascular events reported in OC users. In order to minimize the incidence of ADRs and to induce beneficial changes in lipid patterns, new progestational molecules devoid of androgenic properties have been recently synthesized. Three compounds called << third generation >> progestins, derived from levonorgestrel are presently available in Europe. These three gonane progestins demonstrate affinity for the androgenic receptor, but when administered together with EE do not oppose the estrogenic effect observed on protein markers such as the Sex Hormone Binding Globulin (SHBG) or the High Density Lipoprotein (HDL). Although this later effect is considered to be beneficial, the decreased anti-estrogenic activity of the new progestins on anti-thrombin III, triglycerides and possibly target tissues may be questionable.
