Return of chronic pelvic pain from endometriosis after raloxifene treatment: a randomized controlled trial

Abstract

Objective: To evaluate whether 6 months of raloxifene was effective in treatment of chronic pelvic pain in women with endometriosis.

Methods: Women with chronic pelvic pain and no endometriosis treatment for 6 months underwent laparoscopy for excision of all lesions. Those with biopsy-proven endometriosis were randomly allocated to raloxifene (180 mg) or placebo daily. A second laparoscopy was performed at 2 years, or earlier, if pain returned. Return of pain was defined as 2 months of pain equal to or more severe than that at study entry. Menstrual cycles and adverse events were recorded. The log rank test was used to compare the time to return of pain by drug group. Analyses were done as intent-to-treat.

Results: A total of 127 of 158 women underwent surgery. Of these, 93 had biopsy-confirmed endometriosis and were randomly assigned to study treatment. Menstrual cycle length, pelvic pain severity, quality of life, bone mineral density, and adverse events did not differ between treatment groups. The Data Safety Monitoring Committee terminated the study early when the raloxifene group experienced pain (P=.03) and had second surgery (P=.016) significantly sooner than the placebo group. Interestingly, biopsy-proven endometriosis was not associated with return of pain (P=.6).

Conclusion: Raloxifene significantly shortened the time to return of chronic pelvic pain. Because recurrence of endometriosis lesions did not correlate with return of pain, other factors are implicated in pelvic pain.

Clinical trial registration: ClinicalTrials.gov, www.cliicaltrials.gov, NCT00001848

Level of evidence: I.

Figures

Fig. 1. Flowchart of patients in the study

Stratton. Chronic Pelvic Pain and Raloxifene Treatment. Obstet Gynecol 2008.

Fig. 2. Time to return of pain

Stratton. Chronic Pelvic Pain and Raloxifene Treatment. Obstet Gynecol 2008.

Fig. 3

Nonmenstrual pelvic pain, dysmenorrhea, and dyspareunia. Nonmenstrual pain is depicted in panels A and B, dysmenorrhea in panels C and D, and dyspareunia in panels E and F. Subjective rating for pain from pain questionnaires is depicted in the top panels and verbal rating on a scale from 0 to 10 in the bottom panels. In panels B, D, and F, raloxifene participants are indicated by a solid circle and solid line; placebo participants are indicated by a solid square and dotted line. The number of women responding regarding nonmenstrual pain and dysmenorrhea at baseline, 3, 6, 9, and 12 months for questions was 46, 36, 32, 23, and 19 women taking raloxifene and 45, 36, 36, 28, and 23 women taking placebo, respectively. The number of women responding regarding dyspareunia at baseline, 3, 6, 9, and 12 months were 25, 15, 14, 4, and 9 women taking raloxifene and 25, 13, 18, 7, and 18 taking placebo, respectively. * Subjective rating for nonmenstrual pelvic pain, dysmenorrhea, and dyspareunia were defined as follows: Nonmenstrual pain was mild if it was occasional, moderate if it occurred most of the time, and severe if it was daily. Dysmenorrhea was considered minimal if participants were able to work, but reported reduced efficiency; moderate if participants were in bed or could not work part of 1 day; or severe if participants were in bed more than 1 day or incapacitated. Dyspareunia was defined as mild if discomfort could be tolerated during intercourse, moderate if intercourse was interrupted by pain, or severe if intercourse was avoided because of pain. † Both nonmenstrual pain and dysmenorrhea significantly improved after surgery, but returned to baseline levels by 9 and 12 months in the raloxifene and placebo groups, respectively. Dyspareunia also significantly decreased in severity, returning to baseline levels after 6 and 9 months in the raloxifene and placebo groups, respectively. Treatment groups did not differ at any time point in pain severity and debility by pain type. R, raloxifene group; P, placebo group. Stratton. Chronic Pelvic Pain and Raloxifene Treatment. Obstet Gynecol 2008.