2014 Update on abnormal uterine bleeding

All women in the trial were started on continuous OCs (20 µg ethinyl estradiol with 100 µg levonorgestrel; Aviane) and then randomly assigned to receive one of the following for 84 days in addition to the OC:

• doxycycline 40 mg daily (controlled-release Oracea), a subantimicrobial dose
• placebo.

After 84 days, doxycycline was discontinued, and participants were observed for an additional 28 days on the OC regimen alone for the documentation of bleeding patterns.

General findings:

• The number of bleeding and spotting days decreased in both groups over the course of the study.
• During the first 84 days of the trial, bleeding and spotting occurred among a median of 11 and 17 women in the doxycycline and placebo groups, respectively, and bleeding alone (without spotting) occurred in a median 3 and 4 women in the doxycycline and placebo groups, respectively.
• During the 28-day observation period, bleeding and spotting occurred among a median of 0 and 6 women in the doxycycline and placebo groups, respectively. Bleeding alone (without spotting) was absent in both groups.
• Women in the doxycycline group were significantly less likely to report side effects such as headache, depressed mood, and abdominal cramping. However, they were more likely to prefer continuous OCs without doxycycline, compared with women receiving placebo (16.1% vs 10.7%).

WHAT THIS EVIDENCE MEANS FOR PRACTICE
This trial increases our insight into AUB associated with the use of progestins and suggests that concomitant doxycycline may reduce unscheduled bleeding and spotting in women using continuous combination OCs. The trial was of adequate sample size for the primary outcomes, lending credence to its findings, although longer-term data would be helpful.
I have included this trial for two reasons:
It offers useful information regarding the mechanisms and potential prevention or reduction of AUB-I in users of continuous combined estrogen-progestin contraception.
Doxycycline is one of the agents covered in a Cochrane review of high-quality research into AUB-I in women using progestin-only products, including injectables, implantables, intrauterine systems, and oral agents.4 Estrogens have been shown to have some value in reducing breakthrough bleeding associated with depot medroxyprogesterone acetate, and individual use of tranexamic acid or doxycycline has shown value in terminating an episode of breakthrough bleeding in women using progestin-only contraceptives.

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