Dr Mahmoud Abdel-Aleem

Assistant Professor of Obstetrics and Gynecology

Endometriosis

Non-surgical Interventions

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

Why this subject

(I) Definitely A hot topic

Publications Growth Rate

Registered trials

80 Ongoing Clinical Trials

Sampson 1921

II The Basics are

Changing

38 differences

between the

endometrium and

the endometrial

tissue of

endometriosis

51 basic science

articles

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

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

Why this subject

(I) Definitely A hot topic

Publications Growth Rate

Registered trials

80 Ongoing Clinical Trials

Sampson 1921

II The Basics are

Changing

38 differences

between the

endometrium and

the endometrial

tissue of

endometriosis

51 basic science

articles

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

Why this subject

(I) Definitely A hot topic

Publications Growth Rate

Registered trials

80 Ongoing Clinical Trials

Sampson 1921

II The Basics are

Changing

38 differences

between the

endometrium and

the endometrial

tissue of

endometriosis

51 basic science

articles

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

(I) Definitely A hot topic

Publications Growth Rate

Registered trials

80 Ongoing Clinical Trials

Sampson 1921

II The Basics are

Changing

38 differences

between the

endometrium and

the endometrial

tissue of

endometriosis

51 basic science

articles

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

Publications Growth Rate

Registered trials

80 Ongoing Clinical Trials

Sampson 1921

II The Basics are

Changing

38 differences

between the

endometrium and

the endometrial

tissue of

endometriosis

51 basic science

articles

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

Registered trials

80 Ongoing Clinical Trials

Sampson 1921

II The Basics are

Changing

38 differences

between the

endometrium and

the endometrial

tissue of

endometriosis

51 basic science

articles

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

80 Ongoing Clinical Trials

Sampson 1921

II The Basics are

Changing

38 differences

between the

endometrium and

the endometrial

tissue of

endometriosis

51 basic science

articles

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

Sampson 1921

II The Basics are

Changing

38 differences

between the

endometrium and

the endometrial

tissue of

endometriosis

51 basic science

articles

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

38 differences

between the

endometrium and

the endometrial

tissue of

endometriosis

51 basic science

articles

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

III New insights into

pathogenesis

The newly discovered biomarkers opened the way

for newer and medical interventions for this

mysterious disease

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

IV Different forms of the

disease

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

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

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

(V) A Changing Paradigm

SURGERY MEDICAL

TREATMENT

ldquoEndometriosis is best viewed primarily as a medical disease withsurgical back-up Individuals with chronic superficial orpresumed disease should be treated medically reserving surgeryfor those having large endometriomas or palpable disease thatfails to respond to treatment ASRM_2014

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

Why Changing Paradigm

Current thinkingDeep-rooted thinking

bull Preservation of OR is a

priority

bull Removal of lesions is a

priority

bull It is an inflammatory

syndrome

bull It is just a gynecological

lesion

bull Richness of databull Paucity of data

bull Recurrence means

persistent offending

factor

bull Recurrence means

incomplete 1ry surgery

bull ART is nowadays safer

and more effective

bull ART wasnrsquot that safe

effective

bull Endometriosis is the

nemesis of the eggs

bull No effect on the ovary

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

The nemesis of eggs

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

(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 40ndash45 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

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

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 ratesEvidence on harms was scanty but GnRH analogues

danazol and depot progestagens were associated with

higher rates than other interventions

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

The concept of ldquoMe-toordquo 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

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

The elephant in the room

Many studies

Poor quality

ldquoWith 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 articlesrdquo

Koninckx PR1 Batt RE Hummelshoj L McVeigh E Ussia A Yeh JJ Minim

Invasive Gynecol 2010

Clinical Recommendations

ESHRE 2013

ACOG

COCHRANE REVIEWS

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

Medical Treatment for

endometriosisndashassociated 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

surgery1- COCs (continuous) 2- MPA 3-

GnRH agonists 4- Danazol

First line

1 NSAIDs

2 CoCs (cyclic)

Peritoneal

disease

Lesions lt3cm

Medical Treatment for

endometriosisndashassociated

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

Established medications

GnRH agonists Leuprolide

Common (in gt60 of patients) hot flashes

Less common (in 20ndash60 of patients) headache insomnia memory disorder substantial temporary loss of bone mineral density (if used for le6 mo)

Infrequent (2ndash19 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 (lt2 of patients) vaginal hemorrhage allergic reaction

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

Dienogest (Visanne)

A progestin that combines the properties of

both 19-nortestosterone derivatives and

progesterone derivatives

Mainly peripheral mode of action

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 gt90

Irregular spotting is the main side effect

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

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

Medical Treatment for

endometriosisndashassociated 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

surgery1- COCs (continuous) 2- MPA 3-

GnRH agonists 4- Danazol

First line

1 NSAIDs

2 CoCs (cyclic)

Peritoneal

disease

Lesions lt3cm

Medical Treatment for

endometriosisndashassociated

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

Established medications

GnRH agonists Leuprolide

Common (in gt60 of patients) hot flashes

Less common (in 20ndash60 of patients) headache insomnia memory disorder substantial temporary loss of bone mineral density (if used for le6 mo)

Infrequent (2ndash19 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 (lt2 of patients) vaginal hemorrhage allergic reaction

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

Dienogest (Visanne)

A progestin that combines the properties of

both 19-nortestosterone derivatives and

progesterone derivatives

Mainly peripheral mode of action

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 gt90

Irregular spotting is the main side effect

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

Medical Treatment for

endometriosisndashassociated 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

surgery1- COCs (continuous) 2- MPA 3-

GnRH agonists 4- Danazol

First line

1 NSAIDs

2 CoCs (cyclic)

Peritoneal

disease

Lesions lt3cm

Medical Treatment for

endometriosisndashassociated

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

Established medications

GnRH agonists Leuprolide

Common (in gt60 of patients) hot flashes

Less common (in 20ndash60 of patients) headache insomnia memory disorder substantial temporary loss of bone mineral density (if used for le6 mo)

Infrequent (2ndash19 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 (lt2 of patients) vaginal hemorrhage allergic reaction

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

Dienogest (Visanne)

A progestin that combines the properties of

both 19-nortestosterone derivatives and

progesterone derivatives

Mainly peripheral mode of action

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 gt90

Irregular spotting is the main side effect

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

Medical Treatment for

endometriosisndashassociated

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

Established medications

GnRH agonists Leuprolide

Common (in gt60 of patients) hot flashes

Less common (in 20ndash60 of patients) headache insomnia memory disorder substantial temporary loss of bone mineral density (if used for le6 mo)

Infrequent (2ndash19 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 (lt2 of patients) vaginal hemorrhage allergic reaction

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

Dienogest (Visanne)

A progestin that combines the properties of

both 19-nortestosterone derivatives and

progesterone derivatives

Mainly peripheral mode of action

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 gt90

Irregular spotting is the main side effect

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

Established medications

GnRH agonists Leuprolide

Common (in gt60 of patients) hot flashes

Less common (in 20ndash60 of patients) headache insomnia memory disorder substantial temporary loss of bone mineral density (if used for le6 mo)

Infrequent (2ndash19 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 (lt2 of patients) vaginal hemorrhage allergic reaction

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

Dienogest (Visanne)

A progestin that combines the properties of

both 19-nortestosterone derivatives and

progesterone derivatives

Mainly peripheral mode of action

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 gt90

Irregular spotting is the main side effect

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

GnRH agonists Leuprolide

Common (in gt60 of patients) hot flashes

Less common (in 20ndash60 of patients) headache insomnia memory disorder substantial temporary loss of bone mineral density (if used for le6 mo)

Infrequent (2ndash19 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 (lt2 of patients) vaginal hemorrhage allergic reaction

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

Dienogest (Visanne)

A progestin that combines the properties of

both 19-nortestosterone derivatives and

progesterone derivatives

Mainly peripheral mode of action

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 gt90

Irregular spotting is the main side effect

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

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

Dienogest (Visanne)

A progestin that combines the properties of

both 19-nortestosterone derivatives and

progesterone derivatives

Mainly peripheral mode of action

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 gt90

Irregular spotting is the main side effect

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

Dienogest (Visanne)

A progestin that combines the properties of

both 19-nortestosterone derivatives and

progesterone derivatives

Mainly peripheral mode of action

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 gt90

Irregular spotting is the main side effect

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

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 gt90

Irregular spotting is the main side effect

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

The tricky point

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

Comparable efficacy

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

Take Home Message

Pelvic pain

Infertility

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

Take Home Message

Pelvic pain

Infertility

Take Home Message

Pelvic pain

Infertility

Pelvic pain

Infertility

Infertility