Chronic Pelvic Pain Can Be Successfully Managed with GnRH Agonist Timi Tuamokumo, MSIII 3/16/05

Chronic Pelvic Pain Nonmenstrual pain with a duration of at least six months Below the umbilicus and is severe enough to cause functional disability or require treatment Includes: Endometriosis, Adenomyosis, PID, Somatization, IBS

Case A 24 YO female complains of pelvic pain a couple of days before her menses. She also complains of dyspareunia. PE is remarkable for uterosacral nodularity. You suspect endometriosis. After treating the patient with NSAIDs and OCPs, the patient has no relief. You wish to try a GnRH agonist, but first you want to know are GnRH agonist effective for endometriosis, not relieved by NSAIDs and OCPs.

Evaluate the safety and efficacy of Leupron depot in the treatment of endometriosis

Methods Randomized double blind placebo controlled trial of 63 pts Endometriosis confirmed by laparoscopy Must not have received treatment for endometriosis within three months of study

Methods Given IM Lupron (3.75mg) every four weeks, total 6 months Efficacy dysmenorrhea, pelvic pain, dyspareunia, and pelvic tenderness After 12 weeks if significant pain present considered failure

Methods

Results Statistically significant decrease in dysmenorrhea, pelvic pain, and pelvic tenderness after 6 months of treatment.

Results Only statistically significant adverse event reported was hot flushes 78% in Leuprolide pts 29 % in placebo p<0.05 Total cholesterol increased 16.9+/-5.4 mg/dl in Leuprolide group while decreased 4.9 +/-8.5 in the placebo. p<0.05

Discussion Leupron Depot effective in treating endometriosis w/o many adverse effects Strong study design We don’t know these patients would not have responded to NSAIDs or OCP’s

Evaluate Safety and Efficacy of Lueprolide Depot in women with clinically suspected endometriosis

Methods Randomized double blind placebo controlled trial of 100 pts Women ages 18-45 moderate to severe pelvic pain incompletely relieved by NSAID’s Exclusion endometriosis confirmed by laparoscopy, if had OCPs within 3 months of study

Methods Depot Leurolide (3.75mg) or Placebo given IM every four weeks, for 3 months Efficacy pelvic pain, dysmenorrhea, dyspareunia Laproscopy 2 weeks after to confirm endometriosis

Results Except for dyspareunia at week 4, at all weeks depot leuprolide had a statistically significant decrease in pain variables.

Results Endometriosis confirmed in 78% of women in Lupron group (90% CI 66,87%) Endometriosis confirmed in 87% of women in placebo group (90% CI 76, 94%)

Discussion Higher prevalence of endometriosis in placebo Supported by TAP, distributes depot leuprolide

Discussion Well designed study placebo controlled double blind randomized Improvement in dysmenorrhea, pelvic pain, dyspareunia in this cohort

Evaluate changes in pain during the stimulatory phase of GnRH agonist therapy

Methods Randomized double blind placebo controlled trial of 120 pts Women ages 18-40 w/ surgically diagnosed endometriosis Excluded if pts had treatment for endometriosis w/in 3 months of study

Methods Depot Leurolide (3.75mg) or Placebo given IM Efficacy pelvic pain, dysmenorrhea, dyspareunia; quality of life

Results

Results

Discussion Randomized double blind placebo controlled study Pain increase at 4 weeks not consistent w/ literature at 4-week interval Warn patients for about potential increase in pain during first month

Evaluate efficacy and safety of Leuprolide depot with three add-back regiments

Methods Randomized double blind placebo controlled trial of 231 pts Women ages 18-43 endometriosis diagnosed surgically

Methods All Groups Given Lupron (3.75mg monthly) + add back for 12 months A placebo, B: norethidrone acetate (5 daily mg) + placebo, C norethidrone acetate + 0.625 mg daily estrogen, D norethidrone acetate + 1.25 mg estrogen Efficacy dysmenorrhea and pelvic pain Bone mineral density of L1-L4 measured by x-ray absorptiometry

Results No significant differences were detected between groups in dysmenorrhea, pelvic pain, and pelvic tenderness.

Results Group A mean bone density declined 3.2+/11.8% No significant changes in groups B, C, and D.

Results Statistically significant increase in LDL for all 4 groups. Statistically significant increase in LDL/HDL ratio for the 3 add-back groups.

Discussion Well designed randomized double blind placebo-controlled multicenter trial Supported by TAP, distributes depot leuprolide Relief of pain, and preservation of bone mineral density

Chronic Pelvic Pain Can Be Successfully Managed with GnRH Agonist Recommendations Chronic Pelvic Pain Can Be Successfully Managed with GnRH Agonist A recommendation supported by Level I evidence

Future Studies Of women treated w/GnRH agonist for six months one third do not require further treatment. What is the fertility rate of those women compared to those who receive expectant management.

Case Revisited 24 YO girl with clinically suspected endometriosis, not relieved by NSAIDS and OCPs. Fortunately you have just attended a remarkable thesis presentation on GnRH agonist in endometriosis You start her on Depot Leuprolide (3.75mg IM) w/Norethidrone acetate (5 mg daily) and her pain resolved in one month.