• Contraception
• Hormone Therapy
• Lipid Disorders
• Thrombotic Disorders

Oral contraceptives (OCs) are the most commonly used form of birth control worldwide [Blackmore KM et al. BMC Womens Health 2011]. Estrogen and progestins have been used by millions of women as effective combined oral contraceptives (COCs). Their safety has been documented by years of follow-up, and serious adverse events that may be related to their use are rare in the young population that is exposed to these agents. Nonetheless, COCs are not risk-free. Regine Sitruk-Ware, MD, Center for Biomedical Research, Population Council, New York, New York, USA, discussed the risks, benefits, and strategic initiatives in the quest for safer and more effective OCs.

Although the balance between the benefits and liabilities of contraceptive steroids is generally positive, in particular when compared with the risks of pregnancy (especially in women with risk factors), cardiovascular (CV) and venous risks have been associated with surrogate markers, such as lipoprotein changes (eg, total cholesterol, total triglycerides, apolipoproteins, and very low low-density lipoprotein cholesterol) and coagulation factors (eg, factor VII, protein C, endogenous thrombin potential-based activated protein C resistance, and free protein S levels), that are induced by the synthetic steroids that are used in contraceptives. Thus, the dose of synthetic estrogen in ethinyl estradiol COC pills has been reduced to minimize the likelihood of ischemic stroke, myocardial infarction, and venous thromboembolism [Archer DF and Lasa IL. J Womens Health 2011].

Ethinyl estradiol (EE) exerts a stronger effect than natural estradiol (E2) on hepatic metabolism, including estrogen-dependent markers, such as liver proteins. EE's more powerful hepatic impact has been related to its 17α-ethinyl group, which prevents the inactivation of the molecule. Due to the strength of its activity, the administration of EE via a nonoral route does not prevent its impact on liver proteins [Sitruk-Ware R and Nath A. Rev Endocr Metab Disord 2011].

To circumvent the metabolic changes that are induced by EE, newer products that use more natural compounds, such as estradiol (E2) and estradiol valerate (E2V), have been introduced, as well as new formulations, including extended-cycle and continuous-use COC. They may offer improvements over their predecessors [Archer DF and Lasa IL. J Womens Health 2011].

Over the last 50 years, there has also been intense interest in the type of progestin that is used in COCs in an attempt to exploit novel properties and minimize adverse risks. The synthetic progestins that are used for contraception are structurally related either to testosterone (estranes and gonanes) or to progesterone (pregnanes and 19-norpregnanes).

Several new progestins that are closer to progesterone have been designed to bind more specifically to the progesterone receptor and to minimize side effects that are related to androgenic, estrogenic, or glucocorticoid receptor interactions. Dienogest, drospirenone, and the 19-norpregnanes (eg, Nestorone®, nomegestrol acetate, and trimegestone) have been combined with low-dose estrogen—EE, E2, or E2V. E2 and E2V induce fewer changes in coagulation markers than EE. However, the relevance to venous risk is not established. It is important, though, to note that the limited thrombotic risk that is observed with OC use is lower than risk during pregnancy

Risks and benefits of the newer progestins that are used in contraceptives depend upon molecular structure, the type and dose of estrogen that is used, and the route of administration. The lower impact of estradiol-based combinations on metabolic surrogate markers may result in an improved safety profile; but, only clinical outcomes are relevant to assess the risk, and large surveillance studies are warranted to confirm this hypothesis.

So far, the contraindications and warnings for use of current hormonal combinations also apply to the estradiol-based contraceptives.

• © 2011 MD Conference Express