discussing new medical approach in management of endometriosis

1. Dr. Mahmoud Abdel-Aleem
Assistant Professor of Obstetrics and Gynecology
Endometriosis: A changing
Paradigm from surgical to
medical therapy

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. Definitely A hot topic
Endometriosis is still a
mysterious disease as regards
its etiology, pathogenesis, and
of sure its treatment.

5. Increasing Registered trials !!!

6. Many (80) Ongoing Clinical
Trials !

7. High Publications Growth Rate
!!!

8. Why should we think to change from surgical to
medical treatment ?
 Basics are changing and growing new insights into
pathogenesis do exist.
 Different behavior of the disease.
 Diverse locations of the lesions.
 Difficult surgery.
 Involvement of non-reproductive organs.
 Effect on ovarian reserve.
 Recurrence.

9. Sampson, 1921
I. The Basics are
Changing

10. 51 basic science
articles
38 differences between
the endometrium and
the endometrial tissue
of endometriosis.
Recepto
r study
Inflammator
y Markers
Histochemistry
Studies

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

13. 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.
III. Different forms of the disease

17. IV. 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

18. Why Changing Paradigm !!!
Current thinkingDeep-rooted thinking
• It is an inflammatory
syndrome
• It is just a gynecological
lesion
• Richness of data• Paucity of data
• Preservation of OR is a
priority.
• Removal of lesions is a
priority.
• 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

19. The nemesis of eggs

20. Clinical Recommendations
ESHRE, 2013
ACOG
COCHRANE REVIEWS

21. 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
 Side effects give the clue to the used drug in RCT
making assessment difficult.
 No good quality studies have compared directly
medical versus surgical treatment of endometriosis.

22. Principles of care
 Look for the main presentation of the
patient.
 Ovarian reserve should be assessed
before intervention.
 If fertility is a strong issue:
Surgical treatment is the first line
treatment unless diminished ovarian
reserve.
ART is a strong option in recurrent cases
and cases with poor ovarian reserve.

23. 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.

24. Medical Treatment for
endometriosis–associated
infertility
Second line
1. CoCs
(continuous)
2. MPA
More
advanced
disease.
NONESuper-ovulation AND IUI
IVF.

25. 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= ‫طوفان‬ of drugs that might help
patients with endometriosis.

26. 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

27. Finished trials: 1188-1023= 165

28. Established medications

29. 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

30. 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

31. Dienogest (Visanne)
 A progestin that combines the properties of
both 19-nortestosterone derivatives and
progesterone derivatives.
 Mainly peripheral mode of action.
 Effect: decidualization then atrophy of ectopic
endometrial tissue.

32. 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.

33. The tricky point !!

34. Comparable efficacy.

35. Medications Under Investigations

36. A long list
1- Angiogenesis inhibitors
2- Immunomodulators.
3- Aromatase inhibitors.
4- Progesterone receptor antagonists/selective
progesterone receptor modulators
5- Selective estrogen receptor modulators
6- Statins.
7- Valproic acid.
8- Phytoestrogens.
9- Melatonin. And /……….
On-label and off-label drug use in the treatment of endometriosis
Alexander M. Quaas, M.D., Ph.D., Elizabeth A. Weedin, D.O., and Karl R. Hansen, M.D., Ph.D.

38.  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