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Examining the Evidence


Q Which is better at stopping acute uterine bleeding—oral MPA or combination OCs?

December 2006 · Vol. 18, No. 12

<huc>A</huc> Both regimens appear to be effective and well-tolerated, but neither is as effective as the gold standard of high-dose, intravenous estrogen.

For the purposes of this study, acute uterine bleeding is excessive or prolonged bleeding that necessitates urgent or emergent intervention. As Munro and colleagues point out, it is a “substantial drain on health-care resources” because so many women with this complaint require hospitalization for surgical intervention. Among the options are dilation and curettage, endometrial ablation, uterine artery embolization, and hysterectomy, the definitive “cure.”

Expert Commentary

In the United States, acute menorrhagia affects at least 10% of the female population and requires immediate attention. Surgical management is generally reserved for the hemodynamically unstable patient, for those who fail medical management, and for those in whom medical management is contraindicated. The gold standard is high-dose, intravenous estrogen, which halts bleeding in 72% of women within 5 hours.

Although combination oral contraceptives (OCs) are frequently used for acute uterine bleeding, a 2000 Cochrane Review1 found only 1 randomized controlled trial comparing OCs with other medical therapies—and none with comparison with placebo. The Cochrane Review concluded there is not enough evidence to draw any conclusions about the efficacy of combined OCs for menorrhagia.

Until now, support for the use of combination OCs for this indication has been based primarily on textbooks and expert opinion, and we have very little information on the degree of patient satisfaction with the method.

Progesterone-dominant regimens are not as effective as estrogen

Munro and colleagues aimed to correct the paucity of data by treating women with acute menorrhagia with either combined high-dose OCs or high-dose medroxyprogesterone acetate (MPA). Unfortunately, both therapeutic regimens are progesterone-dominant. Estrogen is the gold standard because it stabilizes the endometrial lining by promoting rapid regrowth. Progesterone impedes the action of estrogen, making it less likely to be effective.

A placebo group was believed to be potentially unethical due to the outpatient nature of the study, but a better comparison could have been achieved with an estrogen-only arm.

Sample size fell far below initial projections

Another difficulty with this study is the level of enrollment (n=40), which was far below the number needed (n=400), based on the initial power analysis. Reasons given for the small sample include bias of the referring clinician and patient, and the refusal of many women to submit to randomization. It is difficult to draw significant conclusions based on such a small sample.

What this study reveals

Despite its shortcomings, this study does offer some new information. In the primary outcome of the study—avoidance of emergent surgery—both therapies appeared to be effective, with only 1 patient requiring an unscheduled surgical procedure during the 4 weeks of follow-up. At 2 weeks of follow-up, bleeding had stopped in 76% and 88% of the MPA- and OC-treated patients, respectively. Side effects were minimal in both groups.

Intravenous estrogen is still the gold standard

Although Munro and colleagues add to our understanding of treatments for acute uterine bleeding, estrogen remains the gold standard. Intravenous estrogen is indicated in the inpatient setting for up to 24 hours, followed by tapering to an oral regimen. High-dose oral estrogen is used in the outpatient setting until a significant reduction or cessation of bleeding occurs.

Progesterone therapy should be started in close sequence with estrogen to minimize the likelihood of heavy withdrawal bleeding.

REFERENCE

1. Iyer V, Farquhar C, Jepson R. Oral contraceptive pills for heavy menstrual bleeding. Cochrane Database Syst Rev. 2000;(2):CD000154.-

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