Pregnancy less likely with combined estetrol, drospirenone oral contraceptive adherence

Key takeaways:

• Pregnancy rates were 0.09% when women reported taking all hormone pills vs. 1.6% when women reported missing more than two pills.
• No pregnancies occurred in cycles when missed-pill instructions were followed.

Pregnancy likelihood was higher when women using an estetrol and drospirenone combined oral contraceptive reported not taking all hormone-containing pills per 28-day cycle, according to a secondary analysis.

“Clinical trial authors will calculate perfect-use or method-failure to create a best estimate of efficacy, evaluating only those cycles in which all pill use instructions are followed and no medications are used that could affect combined oral contraceptive metabolism,” Mitchell D. Creinin, MD, professor in the department of obstetrics and gynecology and director of the Complex Family Planning Fellowship at the UC Davis Health System in Sacramento, California, and colleagues wrote. “No studies to date have assessed pregnancy risk on the basis of reported adherence alone to better understand the effects of missing pills.”

In this secondary analysis published in Obstetrics & Gynecology, researchers pooled data from two parallel, multicenter, phase 3 trials conducted in the U.S., Canada, Europe and Russia. All trials enrolled women aged 16 to 50 years to estetrol 15 mg and drospirenone 3 mg in a regimen of 24 hormonal tablets and four placebo tablets for up to 13 cycles. All 2,837 women reported pill intake, sexual intercourse and other contraceptive use in diaries.

Researchers evaluated the relationship between the number of pills not taken per cycle and pregnancy occurrence as well as when pregnancies occurred during product use.

Overall, 31 on-treatment pregnancies occurred during 26,455 at-risk cycles. Pregnancies occurred among 0.09% of cycles where women reported taking all hormone-containing pills, 0.25% of cycles where women reported not taking one pill, 0.83% of cycles where women reported not taking two pills and 1.6% of cycles where women reported not taking more than two pills (P < .001), the researchers reported.

There were no pregnancies in the 2,216 cycles when one or more hormone-containing pills were missed and missed-pill instructions were followed. In addition, all pregnancies related to missing hormone-containing pill doses occurred within the first three cycles, with pregnancy rates ranging from 0% to 0.21% per cycle with no significant trend.

“The cycle-based methodology presented in this report may give better insight into the true relationship between adherence and pregnancy risk and can be applied to both existing and future oral contraceptive studies,” the researchers wrote.