Approaches to the replacement of ethinylestradiol by natural 17β-estradiol in combined oral contraceptives

Hermann Hoffmann, C. Moore, Heiko Zimmermann, W. Elger, Sigfrid Schwarz, T Gräser, M. Öettel
In: Experimental and Toxicologic Pathology · 1998 · vol. 50(4-6) , pp. 458–464 · doi:10.1016/s0940-2993(98)80034-1 · PMID:9784023 · W2039968399
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This paper explores the feasibility of substituting ethinylestradiol with natural 17β-estradiol in combined oral contraceptives due to concerns about ethinylestradiol's safety profile.

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Abstract

The strong hepatic estrogenic actions of ethinylestradiol (EE) are very likely to be the cause of the cardiovascular morbidity related to the use of combined oral contraceptives (COCs). This survey presents results of EE replacement in COCs with natural 17beta-estradiol (E2) in the following stages: reduction of EE to daily doses of 0.01 mg and concomitant replacement with E2 (as valerate, EV), complete replacement of EE with E2 using a novel multiphasic combination containing EV and the progestin dienogest (DNG), and the use of natural E2 to develop estrogen sulfamates (J 995) showing sufficient dissociation of uterine from liver estrogenicity. Recent data from preclinical and clinical studies show that these approaches seem to be promising.

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