Post-Operative GnRH Analogue Treatment After Conservative Surgery for Symptomatic Endometriosis Stage III–IV: A Randomized Controlled Trial

Symptomatic women with stage III to IV endometriosis today are most often managed by conservative laparoscopic surgery, but recurrences continue to occur. Roughly one in five patients will have further disease within 5 years after complete removal of endometriotic lesions. This study examined the effects of postoperative treatment with a gonadotropin-releasing hormone (GnRH) analog, leuprolide acetate depot (3.75 mg), for 3 months after surgery. Forty-four women aged 40 and younger with diagnosed stage III to IV endometriosis were randomly assigned to active treatment, and 45 others were managed expectantly. Treatment was administered by monthly intramuscular injections, and the women were followed for 6 to 36 months. Mean follow-up was 20 months for actively treated women and 19 months for those given placebo. All women assigned to GnRH analog treatment stopped menstruating, and most had menopausal symptoms. These side effects were, however, generally well tolerated; a single patient withdrew after 1 month. One third of 15 women who wanted a child and who received the GnRH analog became pregnant, as did 40% of 15 not treated, not a significant difference. About one fourth of each group had moderate to severe pelvic pain during follow-up, and there was no meaningful group difference in time to recurrent pain. Four women in each group had recurrent disease as evidenced by gynecologic examination and/or pelvic ultrasonography. Two women assigned to analog therapy had repeated surgery. These findings fail to support the routine use of GnRH analog treatment after laparoscopic removal of lesions in women with symptomatic stage III to IV endometriosis. Nevertheless, it is possible that such treatment, or other estrogen-lowering measures, may prove helpful in selected patients, especially those whose disease has not been completely removed.