evidence based deep insight into medical treatment of endometriosis

1. Dr. Mahmoud Abdel-Aleem
Assistant Professor of Obstetrics and Gynecology
Endometriosis
Non-surgical Interventions

2. Case study ?
A healthy 25-year-old woman presents with worsening
dysmenorrhea, pain of recent onset in the LLQ
quadrant, and dyspareunia. She has regular menstrual
cycles, and her last menstrual period was 3 weeks
before presentation.

3. Why this subject ?

4. (I) Definitely A hot topic

5. Publications Growth Rate

6. Registered trials !!!

7. 80 Ongoing Clinical Trials

8. Sampson, 1921
II. The Basics are
Changing

9. 38 differences
between the
endometrium and
the endometrial
tissue of
endometriosis.
51 basic science
articles

10. III. New insights into
pathogenesis
The newly discovered biomarkers opened the way
for newer and medical interventions for this

12. IV. Different forms of the
disease

15. Endometriotic
nodules implant
inside the ovary.
It may then
extend to the
fallopian tubes or
the bowel
Endometriotic
nodules migrate
and implant
anywhere on the
peritoneal
surface.

16. (V) A Changing Paradigm
SURGERY MEDICAL
TREATMENT
“Endometriosis is best viewed primarily as a medical disease with
surgical back-up. Individuals with chronic superficial or
presumed disease should be treated medically, reserving surgery
for those having large endometriomas or palpable disease that
fails to respond to treatment, ASRM_2014

17. Why Changing Paradigm !!!
Current thinkingDeep-rooted thinking
• Preservation of OR is a
priority.
• Removal of lesions is a
priority.
• It is an inflammatory
syndrome
• It is just a gynecological
lesion
• Richness of data• Paucity of data
• Recurrence means
persistent offending
factor
• Recurrence means
incomplete 1ry surgery
• ART is nowadays safer
and more effective
• ART wasn’t that safe,
effective
• Endometriosis is the
nemesis of the eggs
• No effect on the ovary

18. The nemesis of eggs

19. (VI) Assessment of medical Rx: ASRM
2014.
 Assessing the success of medical treatment for
endometriosis is difficult.
 RCTs comparing different agents are confounded by
the side effects associated with the medications.
 Placebo effects in the range of 40%–45% have been
reported
 Some drugs result in hypoestrogenic effects that
interfere with efforts to perform a blinded study.
 No good quality studies have compared directly
medical versus surgical treatment of endometriosis.

20. Cochrane of the Cochrane(s)
 For women with pain: GnRH-a, (LNG-IUD) and
danazol are beneficial interventions.
 The evidence on NSAIDs is inconclusive.
 There was no evidence of benefit with post-
surgical medical treatment.
 There is no evidence that medical treatment
improves clinical pregnancy rates.
 In women with endometriosis undergoing ART, 3
months of treatment with GnRH agonist improved
pregnancy rates.
Evidence on harms was scanty, but GnRH analogues,
danazol and depot progestagens were associated with
higher rates than other interventions.

21. The concept of “Me-too” drugs
 Me-too drug: A drug that is structurally very
similar to already known drugs, with only minor
differences. The term "me-too" carries a negative
connotation. However, me-too products may
create competition and drive prices down.
 There is a Deluge= ‫طوفان‬of drugs that might help
patients with endometriosis.

22. The elephant in the room
 Many studies.
 Poor quality.
“With the steadily increasing volume
of endometriosis articles, and titles and abstracts
readily available online, there is a growing risk that
references are cited without the full articles having
been read by the author(s) or by referees. Too often
the titles and statements in abstracts are not
supported by data in the published articles”.
Koninckx PR1, Batt RE, Hummelshoj L, McVeigh E, Ussia A, Yeh J.J Minim
Invasive Gynecol. 2010

23. Clinical Recommendations
ESHRE, 2013
ACOG
COCHRANE REVIEWS

24. Principles of care
 Look for the main presentation of your patient.
 Ovarian reserve should be assessed before
intervention.
 If fertility is a strong issue, surgical treatment is
the first line treatment.
 Endometriosis surgery should be avoided in
women with diminished ovarian reserve who
should be offered art straightaway.
 Art is a strong option in recurrent cases and
cases with poor ovarian reserve.

25. Medical Treatment for
endometriosis–associated Pain
Third line
1. MIRENA
2. GnRH
agonists
3. AIs
4. Danazol
Failed line
2
Second line
1. CoCs
(continuous)
2. MPA
More
advanced
disease.
Adjunctive medical therapy after conservative
surgery
1- COCs (continuous) 2- MPA 3-
GnRH agonists 4- Danazol
First line
1. NSAIDs
2. CoCs (cyclic)
Peritoneal
disease.
Lesions <3cm.

26. Medical Treatment for
endometriosis–associated
infertility
Third line
1. MIRENA
2. GnRH
agonists
3. AIs
4. Danazol
Failed line
2
Second line
1. CoCs
(continuous)
2. MPA
More
advanced
disease.
NONESuper-ovulation AND IUI
IVF.

27. Established medications

28. GnRH agonists: Leuprolide
 Common (in >60% of patients): hot
flashes
 Less common (in 20–60% of patients):
headache, insomnia, memory disorder,
substantial temporary loss of bone
mineral density (if used for ≤6 mo)
 Infrequent (2–19% of patients):
substantial and persistent loss of bone
mineral density, anxiety, dizziness,
asthenia, depression, vaginal dryness,
dyspareunia, weight change, arthralgias,
myalgias, alopecia, peripheral edema,
breast tenderness, irritability and fatigue,
decreased skin elasticity, decreased
libido, nausea, altered bowel function,
irregular vaginal bleeding
 Rare (<2% of patients): vaginal
hemorrhage, allergic reaction

29. Progestins
ESHRE 2013: use progestagens
MPA, dienogest, CA, norethisterone
acetate or danazol or anti-
progestagens to reduce
endometriosis-associated pain
GRADE A
ESHRE 2013 recommends that
clinicians should consider NSAIDs
or other analgesics to reduce
endometriosis-associated pain.
GPP

30. Dienogest (Visanne)
 A progestin that combines the properties of
both 19-nortestosterone derivatives and
progesterone derivatives.
 Mainly peripheral mode of action.

31. Dienogest (Visanne)
 A progestogen with No estrogenic / androgenic /
mineralocorticoid effect
 Better safety profile.
 Comparable efficacy.
 Duration of use: 24 months study.
 Easy intake.
 Free of pain after 3 months of use.
 Growth of lesions is reduced by is use (Anti-
inflammatory and anti-angiogenic).
 High oral bioavailability >90%
 Irregular spotting is the main side effect

32. The tricky point !!

33. Comparable efficacy.

35.  Prolonged medical treatment without a
positive diagnosis of endometriosis
 Medical therapy as an alibi for incomplete
surgery.
 Unawareness of the anabolic side effects of
progestagen only therapy.
 Unawareness of the important placebo effect
for any type of medical therapy

36. Take Home Message

37. Pelvic pain

38. Infertility