Contraception. 2015 Dec 16. pii: S0010-7824(15)30022-6.

Maintenance of ovulation inhibition with a new progestogen-only pill containing drospirenone after scheduled 24-h delays in pill intake

Duijkers IJ, Heger-Mahn D, Drouin D, Colli E and Skouby S


Objective: Traditional POPs have stringent daily timing and missed pill rules, that might affect contraceptive reliability. A new-generation oestrogen-free pill has been developed, containing 4mg drospirenone with a unique regimen of 24 active treatment days followed by 4 placebo tablets. A previous study showed that this new drospirenone-only pill effectively inhibited ovulation. Clinical efficacy, however, can be affected by compliance and delayed or forgotten pill intake often occurs in daily life. The aim of this study was to investigate if inhibition of ovulation was maintained after 4 scheduled 24-h delays in tablet intake.

Study design: One hundred thirty healthy women with proven ovulatory cycles were randomised and 127 were treated with the drospirenone-only pill during two cycles. In treatment group A (n=62) 24-h delays in tablet intake were scheduled on days 3, 6, 11 and 22 during cycle 2, and in treatment group B (n=65) during cycle 1, respectively. Ovulation was defined as disappearance or persistence of a large follicle and progesterone levels higher than 5ng/mL for at least 5 consecutive days.

Results: The overall ovulation rate was 0.8%, only one subject in group A fulfilled the ovulation criteria in cycle 2. Follicular diameters in the regular-intake and the delayed-intake cycles were similar.

Conclusions: Despite the 4-day hormone-free period and multiple intentional 24-h delays in tablet intake, ovulation inhibition was maintained. This property distinguishes this new-generation oestrogen-free pill from traditional POPs by allowing the same "safety window" or flexibility in intake as combined oral contraceptives without compromising contraceptive reliability.

Implications: Delayed or forgotten pill intake is very common. Ovulation inhibition by the new-generation oestrogen-free pill, containing 4mg drospirenone for 24days followed by a 4-day treatment-free period, was maintained despite four 24-h delays in tablet intake, so the impact of delayed intake on contraceptive reliability will be low.

Comment: POPs used to have the reputation of being less reliable than combination pills. One has to remember that it is the progestin in a combination pill that is responsible for the ovulation inhibition. It is good that there are now several estrogen-free pills available (both with drosperinone and with desogestrel) that are as effective as combination pills and even have a 24-hour "grace" period, when forgotten. Good news also for breastfeeding women. (HMV)