Mechanism of action of norgestrel 0.075 mg a progestogen-only pill. I. Effect on ovarian activity

Objective: To explore the effect on ovarian activity and ovulation of 28 days of correct daily use of a progestogen-only pill containing norgestrel 0.075 mg. Study design: We performed a prospective, randomized, crossover study at 2 US sites, recruiting healthy women of reproductive age to use norgestrel 0.075 mg daily for three 28-day treatment cycles. We monitored ovarian activity every 3 to 4 days with reproductive hormone measurements and ovarian ultrasonography. Participants recorded pill use in daily diaries. An adjudication committee independent of the research sites assessed ovarian activity using a modified Hoogland score combining hormone concentrations and follicle diameter and appearance (quiescence 1-3, ovarian activity without ovulation 4-5, and ovulatory/postovulatory 6-7). Results: We report here the findings of the initial 28-day treatment cycle in which 51 of 52 recruited participants provided data sufficient for analysis. Two thirds of subjects had no evidence of ovulation (34/51, 66.6%); eight of these (15.7%) had quiescent ovaries (follicle < 13 mm diameter) and 26 (51%) had follicular development (follicle > 13 mm diameter) without ovulation. Seventeen participants ovulated, of whom 12 (23.5%) had a normal, and 5 (9.8%) an abnormal luteal phase. Persistent ovarian follicles were common among women who had ovarian activity without ovulation, 17 of 26 participants (65.4%) had a large follicle which persisted beyond 28 days. Conclusion: During 28 days of exposure to a norgestrel 0.075 mg progestogen-only pill, most women had no evidence of ovulation. Implications: Ovulation inhibition and follicle growth disturbance are important in the mechanism of action of a progestogen-only pill containing norgestrel 0.075 mg. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )