les progestatifs de l`endométriose - Meeting-com
Transcription
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: • • • • 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: - 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 – – – – – – – – – – – – – – 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: • Urinary retention - most common – Due to damage to parasympathetic plexus – bladder denervation – Decreased risk with nerve sparing techniques • 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 • Surgical removal or destruction of lesions alleviates pain – indicates lesions contribute to pain • Severity of pain or duration of surgical effect does not correlate with extent of disease • Some lesions are more painful than others – surgery benefits those with deeply infiltrating endometriosis • Complete surgical removal does not relieve symptoms for at least a year in 50% of patients • 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? • 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 • • • • • 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