The effectiveness of quick starting oral contraception containing nomegestrol acetate and 17-β estradiol on ovulation inhibition: A randomized controlled trial

Abstract

To determine the effectiveness of quick starting combined oral contraception (COC) contain 2.5 mg nomegestrol acetate and 1.5 mg estradiol (NOMAC/E2) comparing with 0.075 mg gestodene and 0.02 mg ethinyl estradiol (GS/EE) on ovarian ovulation inhibition rate, we conducted a non-inferiority randomized controlled trial involving 69 healthy female volunteers aged 18-40 years who had normal menstrual history and were randomized at a 2:1 ratio to take one pack of COC containing either NOMAC/E2 (study group) or GS/EE (control group) starting on menstrual cycle Day7-9. The ovarian activity was assessed by using Hoogland and Skouby grading. Forty-six and 23 participants were randomized to NOMAC/E2 and GS/EE groups, respectively. Baseline characteristics were similar between groups. No significant difference was observed between the study and control groups for ovulation inhibition rate (93.4% vs. 95.6%, risk difference:-2.2%, 95% CI:-13.1, 8.8), ovarian quiescence rate (91.2% vs. 91.2%, P = 1.000), persistent cyst rate (2.2% vs. 4.4%, P = 1.000), and ovulation rate (6.6% vs. 4.4%, P = 1.000). Quick starting COC during day7-9 of menstrual cycle can inhibit ovulation for more than 90%. The quick starting NOMAC/E2 is non-inferior to GS/EE for preventing ovulation and suppressing follicular growth.

A randomized single-blind non-inferiority trial of delayed start with drospirenone-only and ethinyl estradiol-gestodene pills for ovulation inhibition

“…We compared 4 mg DRSP-only pills with ultra-low-dose COCs for ovulation inhibition, starting treatment on days 7–9 of the menstrual cycle. This timing reflects common delays in real-world contraceptive use, and the choice of ultra-low-dose COCs aligns with current trends in reducing hormone levels while maintaining effectiveness, and is supported by recent studies on delayed COCs initiation 20 , 21 , 27 , 28 . We set a 20% non-inferiority margin in ovulation inhibition compared to the active control, based on existing evidence 20 .…”

“…This timing reflects common delays in real-world contraceptive use, and the choice of ultra-low-dose COCs aligns with current trends in reducing hormone levels while maintaining effectiveness, and is supported by recent studies on delayed COCs initiation 20 , 21 , 27 , 28 . We set a 20% non-inferiority margin in ovulation inhibition compared to the active control, based on existing evidence 20 . Additionally, we evaluated the onset of changes in cervical mucus permeability, crucial for POPs recommendations.…”

“…Each packet included 21 active tablets and seven placebo tablets. The ultralow dose EE/GS was chosen as a control due to its proven efficacy in delay starting approaches from a prior study and its widespread use in Thailand 20 . The participants were instructed to take the study medication at night before bed, and note the time of tablet ingestion, bleeding, and bothersome adverse effects in their paper diaries.…”

“…The primary outcome was ovulation inhibition, as defined by the Hoogland and Skouby score, as shown in Fig. S1 20 , 33 . Secondary outcomes were the time required to achieve unfavorable mucus after treatment initiation and adverse events.…”

“…In this approach, while 7 days of additional contraception are recommended for COCs based on their mechanism of ovulation inhibition, only 2 days of additional contraception with POPs are recommended considering cervical mucus blockage, the primary mechanism of action of traditional POPs 9 , 16 . Despite these recommendations, few clinical studies have demonstrated the efficacy of OCPs in delayed-starting cycles, particularly for ovulation inhibition and follicular activity 15 , 20 – 26 .…”