Combination birth control pill effective across multiple subgroups

Daily intake of the oral contraceptive pill that combines estetrol (E4) and drospirenone (DRSP) appears to be highly effective across subgroups defined by age, contraceptive history, and body mass index (BMI), according to pooled data from two pivotal phase III trials.

Over 1 year of E4/DRSP use, the Pearl Index (PI) across subgroups was 1.61 and 1.43 pregnancies per 100 women–years among those aged 16–25 and 26–35 years; 1.88 and 1.24 pregnancies per 100 women–years among initiators and switchers; and 1.44, 2.19, and 2.27 pregnancies per 100 women–years among those with BMI <25, 25–29.9, and ≥30 kg/m², respectively. [Contraception 2022;doi:10.1016/j.contraception.2022.07.009]

According to the investigators, when compliance was lower than 99 percent of expected pills, women had more than a fourfold higher risk of getting pregnant (hazard ratio [HR], 4.21, 95 percent confidence interval [CI], 2.04–8.66).

“Other than compliance, predictors of contraceptive failure were nonmodifiable,” they added.

Multivariable analysis in the primary efficacy group revealed prior gravidity (hazard ratio [HR], 3.61, 95 percent CI, 1.56–8.38), Black race (HR, 4.61, 95 percent CI, 1.97–10.80), and younger age (16–25 years; HR 2.37, 95 percent CI, 1.09–5.15) as independent nonmodifiable risk factors for conception.

“The lower PI with increasing age likely reflects decreasing fecundity and more consistent pill taking. [On the other hand], the association between Black race and efficacy likely reflects … underlying social issues that may include systemic racism within healthcare,” given that most Black participants in the pooled cohort were from the US (98 percent), the investigators pointed out. [CMAJ 2013;185:565-573; https://tinyurl.com/2lwht5br]

“Additional research is needed to better understand predictors of combined oral contraceptive failure,” they said.

The two recent phase III clinical trials that the present analysis was based on evaluated E4 15 mg plus DRSP 3 mg, one of which was conducted in the US/Canada and the other in Europe/Russia. Both trials reported high contraceptive efficacy, a predictable bleeding pattern, and a good safety and tolerability profile in daily users. [Contraception 2021;104:222-228; BJOG 2022;129:63-71]

The pooled population comprised 3,027 women, with 14.9 percent having a BMI ≥30 kg/m². The overall PI was low at 1.52 (95 percent CI, 1.04–2.16) pregnancies per 100 women–years. The same was true for the 13-cycle life-table pregnancy rate, which was 1.28 percent (95 percent CI, 0.83–1.73).

“The US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and Health Canada have all recently approved the first E4-based combined oral contraceptive. E4 is a naturally occurring estrogen produced by the human foetal liver during pregnancy and derived from plant sources for clinical use,” the investigators said.

“The E4/DRSP formulations represent the first pharmaceutical compound formulated with the natural estrogen E4 that has been approved for clinical use… Our results provide evidence of high contraceptive efficacy across a diverse group of users,” they added.