Clinical Review

UPDATE: CONTRACEPTION

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References

On average, 25% of women discontinue POPs because of changes in their menstrual cycle (TABLE 5).

PERSPECTIVE AND GUIDANCE FOR YOUR PRACTICE

The mechanism that results in irregular vaginal bleeding in women taking a POP is unclear; evidence suggests that incomplete suppression of ovulation and direct endometrial effects are possible. To the frustration of patients and clinicians, it isn’t possible to predict who will have irregular bleeding—i.e., there is no association between body weight, or age, and the risk of irregular bleeding. As with other progestin-only methods, irregular bleeding is the most common reason for discontinuing POPs.26 A Cochrane review of POPs is under way.27

Is unpredictable bleeding with progestin-only contraceptives treatable?

Bleeding and discontinuation rates associated with progestin-only contraceptives that are observed in clinical trials, especially rates used for FDA review and approval of a product, don’t always translate to real-life medicine. Typically, in such trials, no treatment for irregular or unacceptable bleeding patterns is permitted: If an effective treatment is available, overall acceptability and continuation of the contraceptive could, potentially, be boosted. This matter is most relevant with injectable, intrauterine, and implantable progestin-only methods.

Findings of one meta-analysis. A recent Cochrane review evaluated the literature until December 2006 on the treatment of vaginal bleeding irregularities induced by progestin-only contraceptives.28 Twenty-three randomized controlled trials, encompassing 2,674 subjects, were included. Seventy percent of the trials that were included were determined to reflect a low or moderate risk of bias.

Treatment with estrogen alone reduced the number of days of an ongoing bleeding episode among DMPA and levonorgestrel implant (Norplant) users. Treatment often led to individuals’ discontinuation in a study, however, because of gastrointestinal upset. Combined oral contraceptives can treat amenorrhea with success among DMPA users.

Antiprogestins such as mifepristone cause a reduction in bleeding among women using the levonorgestrel implant, but are not of benefit for ENG implant users.

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Last, use of NSAIDs to treat irregular bleeding has shown variable efficacy. Additional small studies cited in the Cochrane review suggest that the following treatments were more effective than placebo for terminating an episode of bleeding among women using progestin-only contraception: the antiprogestin mifepristone for DMPA and POP users; mifepristone plus an estrogen for ENG implant users; and doxycycline for ENG implant users.28

Overall, some women benefit from attempts at treatment. The authors of the Cochrane review caution that their findings do not support the routine clinical use of any of the regimens included in the trials, particularly for obtaining a long-term effect.28

Newer trials, different findings? A more recent double-blind, randomized trial, in which the subjects were 100 Thai women, showed that irregular bleeding with DMPA ceased completely in 88% of those treated with tranexamic acid, 250 mg QID for 5 days, compared with 8% of women in whom bleeding ceased after treatment with placebo.29

Another recent randomized trial found that mifepristone, combined with ethinyl estradiol or doxycycline, was significantly more effective than placebo in ending an episode of bleeding in ENG implant users. No improvement was seen, however, in subsequent bleeding patterns, and improvement with treatment, compared with placebo, amounted to a decrease of only about 2 days.30

Noticeably missing from the literature are large trials that evaluate the use of combined hormonal contraceptives for bleeding irregularities in women using long-acting progestin-only contraceptives. True, some women use these methods because of a contraindication to estrogen-containing methods, but, in reality, most women who use these methods do so because of their high efficacy and ease of use.

PERSPECTIVE AND GUIDANCE FOR YOUR PRACTICE

For women who use the ENG implant or LNG-IUS and have no contraindication to estrogen-containing contraceptives, we often provide a short (1 or 2 months) course of a combined hormonal contraceptive when they find bleeding irregularities bothersome.

Because the serum progestin level provided with these methods is extremely low, adding a low-dose combined oral contraceptive, contraceptive patch, or contraceptive vaginal ring is not that different than using any of the combined hormonal contraceptives. A woman will not become pregnant if she forgets to take the pill or the ring falls out because she still has the progestin-only method in place. And if the short course of a combined hormonal contraceptive helps her continue the more effective method, then the overall goal of avoiding unintended pregnancy is better accomplished.

Large trials to evaluate the use of combined hormonal methods in such circumstances would, of course, be of great benefit.

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