Endocrine Abstracts (2011) 26 S14.2

New Pills

Regine Sitruk-Ware


Population Council and Rockefeller University, New york, USA.


The balance between the benefits and the risks of contraceptive steroids is generally positive in particular when comparing to the risks of pregnancy and especially in women with risk factors. Since recently the most common estrogen contained in the OCs remained ethinyl-estradiol although the doses used per tablet decreased dramatically in the most recent combinations. In parallel with the change in the progestin content from androgenic to non or anti-androgenic molecules, the estrogen have also been shifted recently to more natural compounds such as estradiol (E2) and estradiol valerate (E2V) with the objective of improving the safety of OCs.

Ethinyl-estradiol (EE) exerts a stronger effect that natural estradiol (E2) on hepatic metabolism including estrogen-dependent markers such as liver proteins. Current combined oral contraceptives (COC) affect a variety of hemostatic variables and estrogen-sensitive liver proteins, and these effects can be modulated by the associated progestin. In contrast, metabolism studies using the same surrogate markers as end-points indicate that the impact of estradiol-based novel COCs is similar or even lower than that of the second-generation COCs combining EE and an androgenic progestin such as Levonorgestrel.

Several new progestins have been designed to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor interactions. Dienogest (DNG), and drospirenone (DRSP) and the 19-norpregnanes including Nestorone (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG) have been combined with estrogen either EE or E2 or estradiol valerate (E2V).

The lower metabolic impact of novel estradiol-based oral contraceptives may result in an improved safety profile, but large surveillance studies are warranted to confirm this plausible hypothesis. So far, the contraindications and warnings for use of current COCs also apply to the estradiol-based COCs.

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