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

2. 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

3. 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.

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

5. 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

6. 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

7. Methods

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

9. 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 /-8.5 in the placebo. p<0.05

10. 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

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

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

13. 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

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

15. 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%)

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

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

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

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

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

21. Results

22. Results

23. 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

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

25. Methods Randomized double blind placebo controlled trial of 231 pts
Women ages endometriosis diagnosed surgically

26. 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 mg daily estrogen, D norethidrone acetate mg estrogen
Efficacy dysmenorrhea and pelvic pain
Bone mineral density of L1-L4 measured by x-ray absorptiometry

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

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

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

30. 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

31. 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

32. 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.

33. 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.