OCs and Endometriosis

Abstract & Commentary

By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.

Synopsis: A low-dose oral contraceptive effectively treats dysmenorrhea associated with endometriosis.

Source: Harada T, et al. Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Fertil Steril. December 26, 2007, ePub.

Harada and colleagues from Japan conducted a double-blind, placebo-controlled, randomized multicenter trial of a low-dose oral contraceptive for the treatment of dysmenorrhea associated with endometriosis.1 The oral contraceptive, given for 3 out of 4 weeks for 4 cycles, consisted of 35 µg ethinyl estradiol and 1 mg norethindrone. One hundred patients were randomized to treatment, 3 were lost to follow-up, and 14 discontinued the study. Dysmenorrhea pain interestingly decreased in the placebo group, but the decrease in the OC group was about twice as great. The treatment group demonstrated a decrease in pelvic induration that did not achieve statistical significance. Only the OC group demonstrated a reduction in the size of ovarian endometriomas that were larger than 3 cm diameter at baseline.

Commentary

Progestational drugs have been used to treat the pain of endometriosis for a long time. In fact, norethindrone and norethynodrel were approved by the FDA for this purpose in 1957, 3 years before approval of the first oral contraceptive. By 1960, 500,000 women were using these agents, although it is unlikely that all had endometriosis or even dysmenorrhea. Therefore there is an enormous clinical history supporting the use of oral contraceptives for the treatment of endometriosis. Randomized trial data, however, have been lacking.

The Cochrane Collaboration meta-analysis in 2002 (CD002120) supported the use of OCs for the treatment of dysmenorrhea but emphasized that the supporting data were derived from very old studies of high-dose products. The current Japanese study, therefore, is valuable in that it is a placebo-controlled trial of dysmenorrhea associated with endometriosis and it provides data for a low-dose OC, confirming years of experience. It is worth noting that a randomized, placebo-controlled trial using a 20 µg estrogen OC has documented effective treatment of primary dysmenorrhea in adolescents.2

For years, many clinicians have believed that the daily use of an OC without a break is more effective for the treatment of endometriosis. Clinicians have also believed that monophasic products are superior to multiphasic products. Unfortunately, these two beliefs are derived from historical experience and reported in the literature as uncontrolled studies. But it is unlikely that randomized trials will address these two points, and until such studies are available, there is no valid reason to discount many years of clinical experience. In an Italian prospective study (but not a randomized trial), women experiencing recurrent dysmenorrhea associated with endometriosis while being treated with a cyclic OC regimen improved when switched to daily, continuous treatment with a 20 µg OC.3

Low-dose estrogen-progestin contraception is a good choice to treat pain associated with endometriosis. It is a less expensive option than GnRH analogues, side effects are not a major problem, and treatment can be maintained for long durations. This is also a good option to maintain suppression of endometriosis after surgical or GnRH analogue treatment; remember that treatments only suppress and don't cure or eliminate endometriosis. Another advantage of OC treatment is that endometriosis may be associated with a slight increase in ovarian cancer (as well as adenocarcinoma in endometriosis tissue), and the profound reduction in the risks of ovarian and endometrial cancer well-demonstrated in women without endometriosis is observed equally in women with endometriosis.4

References

  1. Harada T, et al. Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Fertil Steril. December 26, 2007, ePub.
  2. Davis AR, et al. Oral contraceptives for dysmenorrhea in adolescent girls: a randomized trial. Obstet Gynecol. 2005;106:97-104.
  3. Vercellini P, et al. Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen. Fertil Steril. 2003;80:560-563.
  4. Modugno F, et al. Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis. Am J Obstet Gynecol. 2004;191:733-740.