Efficacy and bleeding profile of a combined oral contraceptive containing oestradiol valerate/dienogest: a pooled analysis of three studies conducted in North America and Europe.

OBJECTIVE: To summarise all clinical data on the contraceptive efficacy and bleeding profile associated with an oestradiol valerate (E2V) and dienogest (DNG) [E2V/DNG] combined oral contraceptive (COC) derived from Phase III trials. METHODS: Pooled analysis of three large-scale multicentre trials conducted in healthy women who received oral E2V/DNG for 7 to 28 cycles (28-day cycles). RESULTS: A total of 2266 women were included in this analysis. Overall, 19 pregnancies occurred over 13 cycles during 880,950 days of relevant exposure (Pearl Index [PI] of 0.79; upper limit of the two-sided 95% confidence interval [CI]: 1.23). Ten pregnancies attributed to method failure came about during 871,091 days of relevant exposure (adjusted PI of 0.42; upper limit of the two-sided 95% CI: 0.77). In women aged 18 to 35 years (n = 1687), the corresponding PI and adjusted PI were 1.01 (upper limit of the two-sided 95% CI: 1.59) and 0.51 (upper limit of the two-sided 95% CI: 0.97), respectively. In the first 13 cycles of treatment, 76 to 81% of women experienced scheduled withdrawal bleeding, and 13 to 23% experienced intracyclic bleeding. CONCLUSIONS: E2V/DNG provides reliable contraceptive efficacy in women aged 18 to 50 years.

Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.

BACKGROUND: This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol. STUDY DESIGN: This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years. RESULTS: Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG. CONCLUSIONS: A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC.