Traitement médical de l’endométriose douloureuse sans infertilité, RPC Endométriose CNGOF-HAS

OBJECTIVE: To provide clinical practice guidelines for the management of painful endometriosis in women without infertility. METHODS: Systematic review of the literature literature since 2006, level of evidence rating, external proofreading and grading of the recommendation grade by an expert group according to HAS methodology. RESULTS: Combined hormonal contraceptives (COP) and the levonorgestrel-releasing intra-uterin system (LNG-IUS) are recommended as first-line hormonal therapies for the treatment of painful endometriosis (grade B). Second-line therapy relies on oral desogestrel microprogestative, etonogestrel-releasing implant, GnRH analogs (GnRHa) and dienogest (grade C). It is recommended to use add-back therapy containing estrogen in association with GnRHa (grade B). After endometriosis surgery, hormonal treatment relying on COP or LNG-IUS is recommended to prevent pain recurrence (grade B). COP is recommended to reduce the risk of endometrioma recurrence after surgery (grade B) but the prescription of GnRHa is not recommended (grade C). Continuous COP is recommended in case of dysmenorrhea (grade B). GnRHa is not recommended as first line endometriosis treatment for adolescent girl because of the risk of bone demineralization (grade B). The management of endometriosis-induced chronic pain requires an interdisciplinary evaluation. Physical therapies improving the quality of life such as yoga, relaxation or osteopathy can be proposed (expert agreement). Promising medical alternatives are currently under preclinical and clinical evaluation

Traitement médical de l’endométriose douloureuse chez l’adolescente, RPC Endométriose CNGOF-HAS

OBJECTIVE: To analyse the literature on the treatment of adolescent painful endometriosis. METHOD: This work is based on a Review of the literature between January 2006 and December 2017. The Medline (Pubmed) and Cochrane database were searched for meta-analyzes, randomized trials, literature reviews, controlled, not controlled and retrospective studies published on the subject. Studies concerning adolescent\u27s dysmenorrhea without endometriosis were excluded. RESULTS: Study quality is heterogeneous. Dienogest and GnRH agonists (GnRHa) are the only treatments specifically evaluated for the treatment of adolescent endometriosis. They reduce the pain associated with endometriosis. Combined oral contraceptives have not been studied in the context of endometriosis but they are effective on dysmenorrhea. Add back therapy, containing estrogens improves bone mineral density and quality of life for young women treated with GnRHa. CONCLUSION: Medical treatment of endometriosis in adolescent is associated with risks related to the young age. The therapeutic strategy should take into account the adverse effects of each treatment

Traitement médical de l’endométriose : prise en charge de la douleur et de l’évolution des lésions par traitement hormonal. RPC Endométriose CNGOF-HAS

The available literature, from 2006 to 2017, on hormonal treatment has been analysed as a contribution to the HAS-CNGOF task force for the treatment of endometriosis. Available data are heterogeneous and the general level of evidence is moderate. Hormonal treatment is usually offered as the primary option to women suffering from endometriosis. It cannot be used in women willing to conceive. In women who have not been operated, the first line of hormonal treatment includes combined oral contraceptives (COC) and the levonorgestrel-releasing intra uterine system (52mg LNG-IUS). As a second line, desogestrel progestin only pills, etonogestrel implants, GnRH analogs (GnRHa) with add back therapy and dienogest can be offered. Add back therapy should include estrogens to prevent bone loss and improve quality of life, it can be introduced before the third month of treatment to prevent side effects. The literature does not support preoperative hormonal treatment for the sole purpose of reducing complications or recurrence, or facilitating surgical procedures. After surgical treatment, hormonal treatment is recommended to prevent pain recurrence and improve quality of life. COCs or LNG IUS are recommended as a first line. To prevent recurrence of endometriomas COC is advised and maintained as long as tolerance is good in the absence of pregnancy plans. In case of dysmenorrhea, postoperative COC should be used in a continuous scheme. GnRHa are not recommended in the sole purpose of reducing endometrioma recurrence risk

From Fertilisation to Implantation in Mammalian Pregnancy-Modulation of Early Human Reproduction by the Endocannabinoid System.

There is an increasing recognition that the endocannabinoid system is the crucial cytokine-hormone system regulating early human pregnancy. The synchronous development of the fertilized embryo and the endometrium to ensure timely implantation has been shown to be one of the pivotal steps to successful implantation. This development is thought to be regulated by a finely balanced relationship between various components of the endocannabinoid system in the endometrium, the embryo and the Fallopian tube. In addition, this system has also been shown to be involved in the regulation of the development and maturation of the gametes prior to fertilization. In this review, we will examine the evidence from animal and human studies to support the role of the endocannabinoid system in gametogenesis, fertilization, implantation, early pregnancy maintenance, and in immunomodulation of pregnancy. We will discuss the role of the cannabinoid receptors and the enzymes involved in the synthesis and degradation of the key endocannabinoid ligands (e.g., anandamide and 2-arachinoylglycerol) in early reproduction

Place des nouveaux traitements médicaux dans l’endométriose douloureuse, RPC Endométriose CNGOF-HAS

OBJECTIVE: The objective of this work is to evaluate the place of new treatments in the management of endometriosis outside the context of infertility. METHODS: A review of the literature was conducted by consulting Medline data until July 2017. RESULTS: Dienogest is effective compared to placebo in short term (NP2) and long term (NP4) for the treatment of painful endometriosis. In comparison with GnRH agonists, dienogest is also effective in terms of decreased pain and improved quality of life in non-operated patients (NP2) as well as for recurrence of lesions and symptomatology postoperatively (NP2). Data on GnRH antagonists, selective progesterone receptor modulators as well as selective inhibitors (anti-TNF-α, matrix metalloprotease inhibitors, angiogenesis growth factor inhibitors) are insufficient to provide evidence of interest in clinical practice for the management of painful endometriosis (NP3). CONCLUSION: Dienogest is recommended as second-line therapy for the management of painful endometriosis (Grade B). Because of lack of evidence, aromatase inhibitors, elagolix, SERM, SPRM and anti-TNF-α are not recommended for the management of painful endometriosis (Grade C)

Obesity, inflammatory markers, and endometrial cancer risk: a prospective case–control study

Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case–control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03–2.41, Ptrend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08–2.54, Ptrend=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22–2.73, Ptrend=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10–20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu