Efficacy in Suppressing Ovulation and Safety of a Low dose Oral Contraceptive in a Continuous Regimen (84+7) With Continuous Ethinyl Estradiol Instead of a Hormone-Free Interval: An Evaluation of Ovulation Suppression and Ovarian Activity

Background: This study aimed to evaluate the efficacy of a low dose oral contraceptive in a continuous regimen (84+7) with continuous ethinyl estradiol (EE) instead of a hormone-free interval (HFI) (84 tablets containing 100 mcg levonorgestrel (LNG) + 20 mcg EE, and 7 tablets containing 10 mcg EE; MODELLE® LIBERA, Teva) in suppression of ovulation and ovarian activity.

Methods: A multicenter, open-label, single-treatment, Phase 3 study that evaluated 52 healthy non-pregnant females aged 18 through 35 years, of whom 47 (90%) participants completed the entire 91-day treatment. Evaluation of the efficacy of the formulation in suppressing ovulation was achieved by performing transvaginal ultrasound examinations and determining the serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone.

Results: Overall, 88% of the participants presented with a lack of ovarian activity during all three 28-day intervals corresponding to a standard cycle. Ovarian suppression was reported in 99% of all cycles. The serum levels of sex hormones corresponded to the predicted values with allowance for the relevant extended mode of administration of the combined oral contraceptives (COCs). During the post-therapeutic follow-up visit, the restoration of ovulation on the post-therapeutic follow-up visit (the 20th week of the study) was reported in 45 females (87%, 95% binomial CI: 74.2%, 94.4%), 13% did not return to ovulation.

Conclusions: The efficacy of the study drug in suppressing ovulation was confirmed by the absence of ovarian activity reported in the majority of the participants over the 91-day course of treatment. Ovarian activity was detected in 2 participants (grade 4 according to the Hoogland and Skouby scale, luteinized unruptured follicle), and in each, the relevant activity was observed during the 3rd interval within the 91-day cycle during the 7-day period when only low doses of EE were administered. The underlying basis of the ovarian activity observed during the 7-day EE-only period has not been fully elucidated. The results of the study demonstrate that a low dose oral contraceptive in a continuous regimen (84+7) with continuous EE instead of a hormone-free interval is safe and can be an additional contraceptive option for healthy women seeking decreased menstrual bleeding.

Trial registration: Grls.rosminzdrav.ru (RCT №37 (28.01.2014).

Keywords: Continuous regimen; Oral contraception; Low dose; Hormone-free interval; Modelle ® Libera; LoSeasonique