Norethindrone is superior to combined oral contraceptive pills in short-term delay of menses and onset of breakthrough bleeding: a randomized trial

Joshua Dean, Katherine J Kramer, Fauzia Akbary, Shaunte Wade, Maik Hüttemann, Jay M Berman, Maurice-Andre Recanati, Joshua Dean, Katherine J Kramer, Fauzia Akbary, Shaunte Wade, Maik Hüttemann, Jay M Berman, Maurice-Andre Recanati

Abstract

Background: To determine whether oral norethindrone acetate is superior to combined oral contraceptives (OCP) in delaying menstruation and preventing breakthrough bleeding when started late in the cycle.

Methods: This article comprises of a case control study followed by a pilot randomized controlled study. In the first study, four women who presented late in their cycle and desired avoiding vaginal bleeding within 10 days before a wedding were started on norethindrone 5 mg three times daily and compared to age matched controls started on OCPs. Subsequently, a randomized controlled pilot study (n = 50) comparing OCPs to norethindrone for the retiming of menses was conducted. Percentage of women reporting spotting were compared with level of statistical significance set at p < 0.05.

Results: Of the norethindrone treated group, only 2 women (8%) reported spotting compared with 10 women (43%) in the control group (p < 0.01). Norethindrone recipients experienced significant weight gain, which resolved after cessation of therapy and had heavier withdrawal bleed (p < 0.04) when compared to controls. Patient satisfaction was significantly higher in the norethindrone group, with 80% willing to choose this method again. Time to conceive was significantly shorter in the norethindrone group (p < 0.03).

Conclusions: Norethindrone, begun on or before cycle day 12, is superior for women who desire to avoid breakthrough bleeding and maintain fertility when compared to OCPs. It is an ideal approach in patients presenting late in their cycle and who desire delaying menses as well as in circumstances when even minute amounts of breakthrough bleeding cannot be tolerated.

Trial registration: Clinicaltrials.gov NCT03594604 , July 2018. Retrospectively registered.

Keywords: Menstruation delay; Norethindrone; Randomized controlled study; Vaginal bleeding.

Conflict of interest statement

None of the authors report any conflicts of interest.

Figures

Fig. 1
Fig. 1
Randomized control Study design and patient inclusion. Two patients were removed from the study for non-compliance
Fig. 2
Fig. 2
Questionnaire given to patients at the end of the study
Fig. 3
Fig. 3
Incidence of Vaginal Bleeding or Spotting on Therapy Comparison of patients treated with norethindrone 5 mg three times daily versus controls treated with combined oral contraceptive pills. Aggregate data from both studies shown. (n = 27, p < 0.002)

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