Update on the management of endometriosis-associated pain in France
Hervé Fernandez1, Aubert Agostini2, Hortense Baffet3
1AP-HP, Gynecology and Obstetrics Department, Bicetre Hospital, GHU Sud, 78 avenue du Général Leclerc, Le Kremlin Bicetre F-94276, France; Paris Saclay University, 63 rue Gabriel Péri, Le Kremlin Bicetre F-94276, France; Centre of research in epidemiology and population health (CESP), UMR1018, Inserm, Paris Saclay University, Hôpital Paul Brousse, 16 avenue Paul Vaillant Couturier, Villejuif F-94816, France.
Abstract:
The French National College of Obstetricians and Gynecologists (CNGOF) published guidelines for managing endometriosis-associated pain in 2018. Given the development of new pharmacological therapies and a review that was published in 2021, most national and international guidelines now suggest a new therapeutic approach. In addition, a novel validated screening method based on patient questionnaires and analysis of 109-miRNA saliva signatures, which combines biomarkers and artificial intelligence, opens up new avenues for overcoming diagnostic challenges in patients with pelvic pain and for avoiding laparoscopic surgery when sonography and MRI are not conclusive. Dienogest (DNG) 2 mg has been a reimbursable healthcare expense in France since 2020, and, according to recent studies, it is at least as effective as combined hormonal contraception (CHC) and can be used as an alternative to CHC for first-line treatment of endometriosis-associated pain. Since 2018, the literature concerning the use of DNG has grown considerably, and the French guidelines should be modified accordingly. The levonorgestrel intrauterine system (LNG IUS) and other available progestins per os, including DNG, or the subcutaneous implant, can be offered as first-line therapy, gonadotropin-releasing hormone (GnRH) agonists with add-back therapy (ABT) as second-line therapy. Oral GnRH antagonists are promising new medical treatments for women with endometriosis-associated pain. They competitively bind to GnRH receptors in the anterior pituitary, preventing native GnRH from binding to GnRH receptors and from stimulating the secretion of luteinizing hormone and follicle-stimulating hormone. Consequently, estradiol and progesterone production is reduced. Oral GnRH antagonists will soon be on the market in France. Given their mode of action, their efficacy is comparable to that of GnRH agonists, with the advantage of oral administration and rapid action with no flare-up effect. Combination therapy with ABT is likely to allow long-term treatment with minimal impact on bone mass. GnRH antagonists with ABT may thus be offered as second-line treatment as an alternative to GnRH agonists with ABT. This article presents an update on the management of endometriosis-associated pain in women who do not have an immediate desire for pregnancy.
Insights
New guidelines for endometriosis pain management are needed due to emerging therapies like dienogest (DNG) and oral GnRH antagonists. These treatments offer effective alternatives for pain relief, potentially improving diagnosis and treatment strategies.
Area of Science:
- Reproductive Medicine and Endocrinology
- Gynecologic Surgery and Pain Management
- Biomarkers and Artificial Intelligence in Diagnostics
Background:
- Current French guidelines for endometriosis-associated pain management, published in 2018 by the CNGOF, require updating.
- Recent advancements include new pharmacological therapies and a 2021 review advocating for revised therapeutic approaches.
- Novel diagnostic methods combining patient questionnaires, salivary miRNA signatures, biomarkers, and AI show promise for pelvic pain diagnosis.
Purpose of the Study:
- To provide an updated overview of endometriosis-associated pain management strategies for women not seeking immediate pregnancy.
- To discuss the evolving role of pharmacological treatments, including dienogest and GnRH antagonists, in clinical practice.
- To highlight advancements in diagnostic screening for endometriosis-associated pelvic pain.
Main Methods:
- Review of recent literature on pharmacological treatments for endometriosis-associated pain.
- Analysis of new diagnostic approaches utilizing biomarkers, AI, and patient-reported outcomes.
- Comparison of efficacy and administration routes for various therapeutic options, including dienogest, LNG IUS, GnRH agonists, and oral GnRH antagonists.
Main Results:
- Dienogest (2 mg) is as effective as combined hormonal contraception (CHC) and recommended as a first-line treatment alternative.
- Levonorgestrel intrauterine system (LNG IUS), other oral progestins, and subcutaneous implants are also viable first-line options.
- Gonadotropin-releasing hormone (GnRH) agonists with add-back therapy (ABT) are second-line treatments; oral GnRH antagonists offer similar efficacy with oral administration and no flare-up effect, also suitable for second-line therapy with ABT.
Conclusions:
- French guidelines for endometriosis pain management require updating to reflect the efficacy of dienogest and the potential of oral GnRH antagonists.
- A multi-modal approach integrating novel diagnostic tools and diverse pharmacological options can improve patient outcomes.
- Oral GnRH antagonists with ABT represent a promising, convenient, and effective second-line treatment for endometriosis-associated pain.
