To assess the relationship of adherence and pregnancy in participants using an estetrol
and drospirenone combined oral contraceptive.
We pooled data from two parallel, multicenter, open-label, phase 3 trials (US/Canada
and Europe/Russia) that enrolled healthy participants aged 16–50 to receive estetrol
15 mg/drospirenone 3 mg in a 24/4 regimen for up to 13 cycles. We limited this efficacy
analysis to participants aged 16–35 at screening. Participants reported adherence
using paper diaries. We assessed the relationship between number of missed pills and
pregnancies in at-risk cycles (≥1 confirmed intercourse and no other contraceptive
use) and when pregnancies occurred during product use with test for trend and chi-square
analyses as appropriate.
Among 3,027 participants in this analysis, 31 on-treatment pregnancies occurred during
26,455 at-risk cycles of use for an overall Pearl Index of 1.52 (95% CI, 1.04–2.16).
Pregnancies occurred in 0.09%, 0.25%, 0.83%, and 1.6% of cycles in which participants
reported missing 0 (n=25,613 cycles), 1 (n=405 cycles), 2 (n=121 cycles) and >2 (n=314
cycles) active pills, respectively (p<0.0001). Pregnancy rates ranged from 0-0.21%
per cycle with no significant trend by cycle (p=0.45). About half (48.4%) of all pregnancies
occurred in the first four cycles, with pregnancies occurring in 0.17% of cycles vs.
0.08% during cycles 5–8 and 0.10% in cycles 9–13 (p=0.07).
Pregnancy occurs more frequently when combined oral contraceptive users report missing
pills and exceeds 1% only when >2 pills are missed. A 0.09% pregnancy risk among users
reporting no missed pills likely approximates a true method failure rate.