Treatment with doxycycline does not decrease unscheduled bleeding in continuous oral contraceptive users

Abstract

OBJECTIVE: Matrix metalloproteinases (MMPs) are known to play a role in uterine bleeding. The objective of this study was to determine whether doxycycline, an MMP inhibitor, will decrease unscheduled bleeding associated with initiation of a continuous oral contraceptive pill.DESIGN: This was a randomized, placebo controlled, double blind study that was conducted over four 28 day cycles (112 days of hormonally active pills).MATERIALS AND METHODS: All women took the same oral contraceptive (20mcg ethinyl estradiol/90mcg levonorgestrel) administered in a continuous fashion, without a placebo week. Women were randomized to doxycycline 100 mg orally twice a day for 5 days or placebo taken at the onset of each bleeding/spotting episode. After the first 84 days, bleeding was observed on the oral contraceptive alone for 28 days. The number of bleeding/spotting days for the first 84, last 28, and all 112 days of the trial were compared using a Mann Whitney U test. The length of bleeding and amenorrheic episodes was also compared. Our sample was calculated to detect a difference of 9 days over 84 days with 80% power and a significance of p=0.05.RESULTS: Administration of doxycycline at the time of bleeding did not result in a reduction in the median bleeding/spotting days in the first 84 days [doxycycline 18.0 (SD 19.3), placebo 12.0 (SD 18.4), p= 0.46], last 28 days [doxycycline 4.0 (SD 9.16), placebo 4.0 (SD 9.48), p=0.98] or all 112 days [doxycycline 24.0 (SD 27.38), placebo 17.0 (SD 26.3), p=0.47]. There was no difference in the median length of the longest bleeding/spotting episode [doxycycline 3.0 (SD 14.3), placebo 7.0 (SD 11.3), p=0.64)] or the longest amenorrheic episode [doxycycline 29.0 (SD 21.6), placebo 33.5 (SD 24.8), p = 0.16].CONCLUSIONS: Despite initial studies which suggested that doxycycline could treat unscheduled bleeding, this randomized trial shows that this MMP inhibitor does not decrease unscheduled bleeding associated with initiation of a continuous oral contraceptive. OBJECTIVE: Matrix metalloproteinases (MMPs) are known to play a role in uterine bleeding. The objective of this study was to determine whether doxycycline, an MMP inhibitor, will decrease unscheduled bleeding associated with initiation of a continuous oral contraceptive pill. DESIGN: This was a randomized, placebo controlled, double blind study that was conducted over four 28 day cycles (112 days of hormonally active pills). MATERIALS AND METHODS: All women took the same oral contraceptive (20mcg ethinyl estradiol/90mcg levonorgestrel) administered in a continuous fashion, without a placebo week. Women were randomized to doxycycline 100 mg orally twice a day for 5 days or placebo taken at the onset of each bleeding/spotting episode. After the first 84 days, bleeding was observed on the oral contraceptive alone for 28 days. The number of bleeding/spotting days for the first 84, last 28, and all 112 days of the trial were compared using a Mann Whitney U test. The length of bleeding and amenorrheic episodes was also compared. Our sample was calculated to detect a difference of 9 days over 84 days with 80% power and a significance of p=0.05. RESULTS: Administration of doxycycline at the time of bleeding did not result in a reduction in the median bleeding/spotting days in the first 84 days [doxycycline 18.0 (SD 19.3), placebo 12.0 (SD 18.4), p= 0.46], last 28 days [doxycycline 4.0 (SD 9.16), placebo 4.0 (SD 9.48), p=0.98] or all 112 days [doxycycline 24.0 (SD 27.38), placebo 17.0 (SD 26.3), p=0.47]. There was no difference in the median length of the longest bleeding/spotting episode [doxycycline 3.0 (SD 14.3), placebo 7.0 (SD 11.3), p=0.64)] or the longest amenorrheic episode [doxycycline 29.0 (SD 21.6), placebo 33.5 (SD 24.8), p = 0.16]. CONCLUSIONS: Despite initial studies which suggested that doxycycline could treat unscheduled bleeding, this randomized trial shows that this MMP inhibitor does not decrease unscheduled bleeding associated with initiation of a continuous oral contraceptive.