les progestatifs de l`endométriose - Meeting-com

PRISE EN CHARGE ACTUALISEE
DES ENDOMETRIOSES SEVERES
Daniel RAUDRANT
Université Lyon 1
Centre Hospitalier Lyon Sud
Service de chirurgie gynécologique et oncologique - Obstétrique
Xxème symposium de l’ASRCC – Avril 2012
Le travail m’a été facilité par le 11 ème congrès
mondial sur l’endométriose en septembre 2011
à Montpellier
The WES 2011 Montpellier consensus on the
management of endometriosis
D’après Hervé DECHAUD
CHU Montpellier
Faculté de Médecine Montpellier
1 - LE TRAITEMENT
DES KYSTES OVARIENS
OVARIAN ENDOMETRIOMAS :
ISSUES RELATED TO TREATMENT
• Recent studies have demonstrated damage to the ovarian
reserve
– Methodology to assess this includes:
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Day 2 FSH and E2
AFC
Response to gonadotrophins in IVF
AMH
Somigliani 2006
Chang 2010
Benaglia 2010
Hirokawa 2011
IMPACT OF MODALITY ON TREATMENT OF
OVARIAN ENDOMETRIOMA
– Laparoscopic excision of pseudocyst versus drainage and
electrocoagulation of pseudocyst
• Excision
– Reduced rate of recurrence (OR 0.41; 95% CI 0.18 – 0.93)
– Reduced rate of reoperation (OR 0.21; 95% CI 0.05 – 0.79)
– Reduced rate of dysmenorrhea (OR 0.15; 95% CI 0.06 – 0.38)
– Reduced rate of dyspareunia (OR 0.08; 95% CI 0.01 – 0.51)
– Reduce rate of non-menstrual pelvic pain (OR 0.10; 95% CI
0.02 – 0.56)
Chapron C, et al.; Human Reprod Update 2002; 8: 591-597
Vercellini P, et al.; Am J Obstet Gynecol 2003; 188: 606-610
Hart RJ, et al.; Cochrane Database Syst Rev 2005; 5: CD004992
REDUCING RISKS
• Care with surgical technique:
– Excision is preferred method
– Care with identification of planes
– Minimize diathermy and conserve all ovarian tissue possible
• Recent small randomized clinical trial – shows potential less reduction in ovarian
reserve when suturing is used for haemostasis – AFC outcome measure (Coric 2011)
• Combined technique – excisional surgery and also ablative surgery for 10 – 20% of
endometrioma wall next to hilus (Donnez 2010)
– AMH excellent marker
• Group should consider recommendation of routine AMH testing pre and 3
months post endometrioma surgery
• Group should consider egg freezing prior to recurrent endometrioma surgery
in young patient with low AMH not trying to conceive
OVARIAN ENDOMETRIOMAS :
CONSENSUS STATEMENT PROPOSAL
• Evidence of moderate to high grade exists to recommend
excisional surgery for endometriomas 4 cm or more to
improve fertility
• Appropriate skill and training is required for safe and
complete excision
• It is important to minimize ovarian damage and further
studies are required to ascertain if suturing for haemostasis
is superior
• Surgeons should consider measurements of ovarian reserve
pre and post operative to help counsel patients
2 - LES ENDOMETRIOSES SOUS
PERITONEALES PROFONDES AVEC
ATTEINTE COLO RECTALE ET
STERILITE : CHIRURGIE OU IVF
CONSERVATIVE SURGERY FOR PELVIC
PAIN DUE TO ENDOMETRIOSIS
Effect of surgery for deep infiltrating disease:
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Incomplete resection negatively impacts success
- Radical interventions increase risk of major
complications, such as ureteral and rectal injuries
Fedele L, et al.; Am J Obstet Gynecol 2004; 191: 1539-1542
Ford J, et al.; BJOG 2004; 111: 353-356
CONSERVATIVE SURGERY FOR PELVIC
PAIN DUE TO ENDOMETRIOSIS
Effect of surgery for deep infiltrating disease:
More than 30 case series published in English peer reviewed journals since 2000
evaluating radical conservative surgery for rectovaginal endometriosis causing pain
•Deficiencies of studies which preclude the ability to make recommendations
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Most studies observational, or retrospective and non comparative
Numbers in studies generally small
Disease extent including depth of penetration often not well described
Surgical access inconsistent
Proportion of women undergoing colorectal surgery highly variable; i.e. aggressive vs.
conservative
Colorectal surgery varies (shaving, disk resection, low anterior resection)
Major intra and post operative complications vary – 0% to 13%
Follow up usually short
Dropouts not included
Use of medical treatment post operatively not reported
Surgical outcome is operator dependent
Publications bias (poor results may defer from publishing)
Heterogeneity of patient populations
Incorporation of dropouts
CONSERVATIVE SURGERY FOR PELVIC
PAIN DUE TO ENDOMETRIOSIS
Effect of surgery for deep infiltrating disease:
• 70 - 80% short term pain relief
• Success declined with time
– By one year many patients required analgesia or hormonal therapy
– 25% repeat surgery
Anaf V, et al.; JAAGL 2001; 8: 55-60
Thomassin I, et al.; Am J Obstet Gynecol 2004; 190: 1264-1271
Fleisch MC, et al.; Euro J Obstet Gynecol Reprod Biol 2005; 123: 224-229
Fedele L, et al.; Am J Obstet Gynecol 2004; 190: 1020-1024
Brouwer R, et al.; Anz J Surg 2007; 77: 562-571
Kristensen J et al.; Acta Obstet Gynecol Scand 2007; 86: 1467-1471
Mohr C, et al.; JSLS 2005; 9: 16-24
Mereu L et al.; JMIG 2007; 14: 463-469
CONSERVATIVE SURGERY FOR PELVIC
PAIN DUE TO ENDOMETRIOSIS
Effect of surgery for deep infiltrating disease:
Post operative complications:
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Urinary retention - most common
– Due to damage to parasympathetic plexus – bladder denervation
– Decreased risk with nerve sparing techniques
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Rectovaginal fistula – second most common
– Risk as high as 10%
– Lowered risk if rectal tumor not opened
– Hemoperitoneum, anastomotic leaks, ureteral fistula/uroperitoneum, bowel
perforation, pelvic abscess, temporary ileostomy, post-op bowel or ureteral stenosis
Volpi E, et al.; Surg Endosc 2004; 18: 109-112
Possover M, et al.; J Am Coll Surg 2005; 21: 913-917
Landi S, et al.; Hum Reprod 2006; 21: 774-781
Darai E, et al.; Am J Obstet Gynecol 2005; 192: 394-400
Dubernard G, et al.; Hum Reprod 2006; 21: 1243-1247
CONSERVATIVE SURGERY FOR PELVIC
PAIN DUE TO ENDOMETRIOSIS
Effect of surgery for deep infiltrating bowel disease
“The choice of the best surgical approach in the
management of deep infiltrating endometriosis of the
rectum (DIER) is the subject of a debate that is far from
being closed”
Roman H et al. Hum Reprod 2011; 26: 274-281
• Infertile patients with severe endometriosis including colorectal
disease should consider surgery as an alternative to IVF
• There are no RCT or meta-analyses to answer the question whether
the surgical excision of severe endometriosis will enhance
pregnancy rates
• However recent studies of better quality and larger numbers suggest
an improvement in pregnancy rates
• Surgery should only be undertaken with appropriate consent and
understanding of the risks
• Women should be given a full understanding of all available options
to help with conception
• Surgery for this major disease should be managed by the
appropriate multidisciplinary team
• Consensus:
– no benefit of medical therapy before or after
endometriosis surgery for infertility
• No evidence to recommend repeat surgery over IVF
• However should consider surgery if increasing pain, enlarging
endometrioma and no desire for IVF
• Surgery can be complex and appropriate consent needs to be
obtained
• Grade of evidence is low
• More studies required
• Surgery may play a role in patients who have failed IVF
treatment and endometriosis
• It may be inappropriate to continue with repeated IVF cycles
without considering surgery to excise the endometriosis
• Excision of endometriosis may enhance opportunity to conceive
spontaneously and even enhance IVF outcomes
• Level of evidence - low
3 - QUELLES TECHNIQUES ?
Voie coelioscopique et shaving
Voie vaginale
Voie coelioscopique et résection digestive
ENDOMETRIOSE CLOISON RECTO VAGINALE
QUELLES TECHNIQUES ?
Pr Michel CANIS : Voie coelioscopique et shaving
JOURNEES DANIEL DARGENT MAI 2011
ENDOMETRIOSE CLOISON RECTOVAGINALE QUELLES TECHNIQUES ?
Pr Daniel RAUDRANT : Voie vaginale
JOURNEES DANIEL DARGENT MAI 2011
ENDOMETRIOSE DIGESTIVE
QUELLES TECHNIQUES ?
Pr Pierre PANEL – Pr Patrick MADELENAT :
Voie coelioscopique et résection digestive
JOURNEES DANIEL DARGENT MAI 2011
4 - ENDOMETRIOSE ET DOULEURS
ENDOMETRIOSIS IN WOMEN
Symptoms:
Comorbidities or overlapping
Subfertility
pain syndromes:
Chronic pelvic pain:
Irritable bowel syndrome
Dysmenorrhea
Interstitial cystitis / painful
bladder
Dyspareunia
Migraines
Non-menstrual pain
Fibromyalgia
Dyschezia
Chronic fatigue syndrome
Dysuria
Pelvic visceral or
muscle pain
P. Stratton and K. Berkley, Hum Reprod Update, 2011
SURGICAL TREATMENT OF ENDOMETRIOSISRELATED CHRONIC PELVIC PAIN
Surgery based on oncologic principle to remove all lesions and restore normal
anatomy
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Surgical removal or destruction of lesions alleviates pain
– indicates lesions contribute to pain
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Severity of pain or duration of surgical effect does not correlate with extent of
disease
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Some lesions are more painful than others
– surgery benefits those with deeply infiltrating endometriosis
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Complete surgical removal does not relieve symptoms for at least a year in 50% of
patients
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In some patients whose pain is relieved, pain returns, without new lesions forming
P. Stratton and K. Berkley, Hum Reprod Update., 2010
HOW MIGHT ENDOMETRIOSIS BE ASSOCIATED
WITH PAIN?
Endometriosis must be vascularized to survive
Blood vessels innervated by sensory and sympathetic nerves
Do nerves accompany blood vessels as they vascularize, sprouting
to innervate endometriosis?
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Yes, both a sensory and a sympathetic supply
Berkley et al, Science, 2005
PAIN SYNDROMES ASSOCIATED WITH
ENDOMETRIOSIS: SUMMARY
• For those undergoing surgery, recurrence of endometriosisrelated pain syndromes may be decreased by:
– Complete surgical resection of endometriosis lesions,
especially deep lesions that may be innervated
– Treating potential contributors to pelvic pain noted at surgery,
such as removing appendix, lysing adhesions
– Timing surgery during follicular phase or suppressing
reproductive tract events for weeks after surgery to decrease
risk of lesion recurrence
5 - LES TRAITEMENTS MEDICAUX
LES MOYENS MÉDICAUX
DE TRAITEMENT DE
L’ENDOMÉTRIOSE
LES ANALOGUES DE LH-RH
• Efficacité prouvée vs placebo et danazol
– Sur les douleurs
– Sur la régression des implants
• Durée maximale de traitement = 6 à 12 mois
• Effets secondaires
• Add back therapy immédiate ++
LES OESTROPROGESTATIFS
• Peu étudiés
• Efficaces sur la douleur par rapport au placebo (NP1)
Moore et al Cochrane 2000
• Première intention:
- en cas de symptômes sans lésions évidentes
- en cas de forme mineure
ACOG 2000, consensus d’expert
• Discontinu ou continu, en traitement prolongé (aménorrhée)
LES OESTROPROGESTATIFS PEUVENTILS PRÉVENIR L’APPARITION D’UNE
ENDOMÉTRIOSE ?
• Les utilisatrices actuelles d’oestroprogestatifs ont
moins de risque de diagnostic d’une endométriose
(OR = 0, 63)
• Les utilisatrices anciennes d’oestroprogestatifs ont
tendance à avoir plus d’endométriose (OR = 1,21 NS)
• Pourquoi ??
Vercellini P et al Hum Reprod Update 2011
LES OESTROPROGESTATIFS PEUVENTILS PRÉVENIR L’APPARITION D’UNE
ENDOMÉTRIOSE ?
• Pas de vraie prophylaxie des oestroprogestatifs en discontinu
• Les oestroprogestatifs améliorent les symptômes
• Les oestroprogestatifs sont davantage prescrits chez les adolescentes
avec dyménorrhée primaire, cad après le début de l’endométriose
• Le diagnostic d’endométriose est fait après l’arrêt des OP
LES PROGESTATIFS DE
L’ENDOMÉTRIOSE
• Doses anti-gonadotropes discontinu ou continu
• Efficacité prouvée sur les douleurs et la régression des
implants vs placebo et Danazol (NP1)
Prentice et al Cochrane 2000
• Problèmes :
– Progestatifs étudiés = non utilisés en France (MPA)
– Progestatifs utilisés en France = non étudiés
LES PROGESTATIFS RECOMMANDÉS
PAR L’AFFSSAPS
– Ac de chlormadinone: Lutéran® , 10mg/jour en TTT continu.
– Ac de nomégestrol (hors AMM): Lutényl® , 5mg, 1/j, 20j.
– Médrogestone: Colprone®, 5mg, 1-3/j, 20j.
– Promégestone (hors AMM): Surgestone ®, 0.5mg, 1/j, 20j.
– Ac de cyprotérone (hors AMM): Androcur® 50mg/j.
UN PROGESTATIF NOUVEAU-VENU DANS
L’ENDOMÉTRIOSE: LE DIENOGEST
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Dérivé de la nortestostérone
Forte activité progestative
Activité antiandrogénique
Administration orale
Visanne®
Moore et al Clin Drug Invest 1999
COMPARAISON
DIENOGEST VS ANALOGUES LH-RH
• Essai prospectif randomisé double aveugle
– 271 patientes endométriosiques
• Traitement pendant 24 semaines
• 128 = dienogest
• 125 = busereline nasale
• Critères d’évaluation =
– amélioration des douleurs
pelviennes, lombaires, à la défécation, dyspareunie, au TV
– tolérance
Harada et al Fertil Steril 2009
COMPARAISON
DIENOGEST VS ANALOGUES LH-RH
• Amélioration de tous les symptômes
• Pas de différence d’amélioration entre DNG et busereline
• Plus de spotting:
– dienogest 95 % versus busereline 67 %
• Moins de bouffées de chaleur:
– dienogest 50 % versus busereline 67 %
Harada et al Fertil Steril 2009
LES AUTRES TRAITEMENTS MÉDICAUX
• AINS:
– 1ère intention pour le TTT des douleurs et des
dysménorrhées de l’endométriose (accord professionnel)
• DIU au Lévonorgestrel
• Antalgiques de niveau 1 ou 2
Merci de votre attention