Endometriosis Guidelines: A Closer Look at a Potential Source of Confusion in Treatment (Part 2)

Understanding Endometriosis Treatment Confusion

Endometriosis affects millions of women worldwide, presenting with pain, irregular menstruation, and infertility. To shed light on the most effective treatment methods, this article is Part 2 in our series on this topic.  It summarizes and comments on the findings from a recent 2021 review which provided a detailed analysis of various endometriosis treatment global guidelines as of September 2020. 

There are often some discrepancies between guidelines for any disease.  However, for endometriosis, a prior review in 2018 revealed that only about 7% of recommendations were comparable between international guidelines.  Up to 28% of the recommendations were not supported by good research evidence at all.  This helps explain why there is such a wide variation between doctors’ recommendations in clinical practice.  

Key Guidelines reviewed in the most recent publication were:

• American College of Obstetricians and Gynecologists (ACOG)–reviewed in our last post, which you can read HERE
• Society of Obstetricians and Gynaecologists of Canada (SOGC)
• European Society of Human Reproduction and Embryology (ESHRE)
• Australian National Endometriosis Clinical and Scientific Trials (ACCESS)
• Royal College of Obstetricians and Gynaecologists (RCOG)
• French National College of Gynecologists and Obstetricians (CNGOF)
• American Association of Gynecologic Laparoscopists (AAGL)
• German Society for Gynecology and Obstetrics (DGGG)

Summary Review of Treatment Recommendations

• Non-Hormonal Medical Pain Management
  • Nonsteroidal anti-inflammatory drugs (NSAIDs): While this is considered by all guidelines to be first-line therapy for dysmenorrhea and acyclic pelvic pain, it is not specific for endometriosis.  A diagnosis and targeted therapy is more prudent since a large review showed no difference in effectiveness between NSAIDs and placebo. 
    
• Hormonal Treatment Options:
  • Progestins and Combined Oral Contraceptives (COCs): Widely recommended for initial pain management. Specific formulations and dosages vary across guidelines. Of interest, there is little mention of compounded micronized progesterone which is hard to study but may deserve a place in the conversation. The Levonorgestrel Intrauterine System (LNG-IUS) is particularly noted for its localized progestin delivery, reducing systemic side effects and effectively managing pain.
  • Megace (Megestrol Acetate): A potent progestin recommended by several guidelines but varies as a first-line vs second-line option. The additional benefit is less bone loss than that seen with GnRH agonist therapy.  
  • GnRH Agonists: Uniformly recommended in all guidelines for severe symptoms after first-line therapy; potential side effects, which can be long-lasting, include decreased bone density and menopausal-like symptoms.  Add-back low-dose estrogen therapy can reduce symptoms. Most guidelines, and the FDA, recommend durations of 6 months or less.  
  • Emerging Hormonal Therapies: GnRH antagonists are gaining attention for their rapid onset of action and fewer side effects compared to agonists. The evidence is not conclusive. 
  • Danazol and Gestrinone: Older treatments with androgenic effects, are less commonly used today due to side effects. Gestrinone is not currently available in the United States. 
  • Selective Estrogen Receptor Modulators (SERMs) and Selective Progesterone Receptor Modulators (SPRMs) are emerging options being explored for their targeted action and potential benefits.
  • Aromatase Inhibitors: Considered in some cases, especially for pain unresponsive to other treatments.  Most guidelines agree that this is a possible second-line option, but the evidence is not conclusive.  A possible niche for effective use may be in post-menopausal patients who have endo. 
    
• Surgical Approaches: Navigating the Complexities
  • Laparoscopic Surgery: Endorsed for its efficacy and reduced recovery time, compared to big incision (laparotomy) surgery. However, the extent of surgery (complete vs. partial removal of lesions) varies among guidelines. Studies are likely hampered by different skill sets between participating surgeons.  
  • Robotic Surgery: AAGL and others highlight its benefits in complex cases, but its cost and accessibility limit widespread use. Specialized training is required. 
  • Ablation vs. Excision: The choice between these two methods remains a contentious topic, for some reason. Ablation is simpler and requires much less technical skill but is only applicable for treating superficial lesions.  It may not be as effective in the long term as excision, which is more comprehensive and accurate in terms of removing all of the visible disease.  Again, the skill base of surgeons is critical, and high variability in this regard may be affecting the ability to prove or disprove the effectiveness and safety of each.  
  • Endometrioma: Cystectomy or excision of endometriomas is superior to drainage in terms of lower recurrence.  Excision also provides the opportunity for pathologic confirmation, and this may be important where it is not clear whether or not there is also a tumor present.  Where fertility is a major concern, the more atraumatic the approach to surgery, the less ovarian reserve is affected, and this is another area where surgeon expertise is critical. 
  • Deep Infiltrating Endometriosis: Highly specialized excisional surgeries are recommended because ablation simply does not work with these lesions. There is an even stronger emphasis on the surgeon’s expertise and patient selection.  Intuitively, the best outcomes probably rest with selecting the best possible technology in a master surgeon’s hands.  Some strongly believe that this means robotic surgery for advanced cases with highly distorted anatomy. 
  • Hysterectomy:  This is considered a “definitive” or last resort surgery but may be helpful for complete excision of endo at any point.  It also allows the removal of any co-existing pain-producing adenomyosis, which is embedded in the wall of the uterus. 
  • LUNA (laparoscopic uterine nerve ablation) and PSN (presacral neurectomy):  Guidelines reflect multiple reviews that suggest no benefit to LUNA but a possible benefit for PSN in selected cases.  PSN is technically very challenging and treatment should be individualized.  As far as LUNA is concerned, studies include a mix of ablation and excision, which means a lack of precision in many of them and, again, surgeon skill level may be a factor.  Thus a definitive conclusion may be elusive until a better methodology to accurately study this is employed. 
    
• Complementary and Alternative Therapies: Exploring Additional Avenues
  • Acupuncture and Electrotherapy (TENS): Mentioned in some guidelines as adjunct therapies, with some encouraging results.  More research is needed to fully validate their effectiveness.  However, these are low-risk options. 
  • Nutritional Supplements: Some guidelines suggest that dietary changes and supplements might play a role in symptom management.  This includes microbiome management for optimal estrogen metabolism.  There will likely never be large randomized studies for any of these variables because they would have to be huge and thus impractical to conduct.  But in today’s emerging world of personalized molecular medicine, other study methodologies are being explored to determine which of these approaches to diet and lifestyle may be more effective than others. 
    
• Infertility and Endometriosis: A Delicate Balance
  • Surgical vs. Non-Surgical Approaches: The decision to opt for surgery in infertility cases is complex and depends on individual factors like age, severity of endometriosis, and previous treatments.  Reducing inflammation appears to be beneficial to effective intrauterine implantation and gestation. 
    
• Emerging Treatments and Research
  • Future Directions: Ongoing research into immunotherapies, new hormonal agents, and gene/molecular therapy offer promising avenues for more personalized treatment strategies. 

Endometriosis management is a highly dynamic field with evolving guidelines and currently very discrepant recommendations due to incomplete or low-quality scientific evidence. Understanding current options is crucial for women to make informed decisions about their health. Regular consultations with endometriosis experts, staying informed about new research, and considering a multi-disciplinary holistic approach to treatment can significantly improve quality of life.

Additional Reading:

• The Different Tests Used to Diagnose Endometriosis 
• Laparoscopy: A Common Treatment for Endometriosis

References:

1. Kalaitzopoulos, D. R., Samartzis, N., Kolovos, G. N., Mareti, E., Samartzis, E. P., Eberhard, M., Dinas, K., & Daniilidis, A. (2021). Treatment of endometriosis: a review with comparison of 8 guidelines. BMC Womens Health, 21(1), 397. https://doi.org/10.1186/s12905-021-01545-5 
2. Hirsch M, Begum MR, Paniz É, Barker C, Davis CJ, Duffy J. Diagnosis and management of endometriosis: a systematic review of international and national guidelines. BJOG. 2018;125(5):556–64.