Estradiol valerate/dienogest: in oral contraception.

Estradiol valerate/dienogest is an oral contraceptive for women that combines the natural estrogen estradiol with the 19-nortestosterone derivative dienogest in a four-phasic formulation. Estradiol valerate/dienogest demonstrated contraceptive efficacy in a large (n = 1377), noncomparative, multicentre study in women aged 18-50 years, with 13 pregnancies over 1797.5 women-years of exposure generating an unadjusted Pearl Index (PI) of 0.73 (upper limit of 95% CI 1.24) [primary endpoint]. Six of the pregnancies were attributed to method failure, resulting in an adjusted PI, based on 1786.5 women-years of exposure, of 0.34 (upper limit of 95% CI 0.73). In a double-blind study in 798 women aged 18-50 years, estradiol valerate/dienogest and ethinylestradiol/levonorgestrel demonstrated an acceptable bleeding pattern and level of cycle control, according to several co-primary endpoints. As reported in the UK manufacturer's summary of product characteristics, the unadjusted PI for women aged 18-35 years or 18-50 years in a pooled analysis of clinical studies was 1.01 (upper limit of 95% CI 1.59) and 0.79 (upper limit of 95% CI 1.23). This pooled analysis of three studies excluded those pregnancies occurring within 14 days of the cessation of therapy. Estradiol valerate/dienogest was generally well tolerated in this population, with the nature of adverse events generally similar across the studies and between estradiol valerate/dienogest and ethinylestradiol/levonorgestrel.