Clearing Up Confusion in Endometriosis Care (Part 2)

Understanding Endometriosis Treatment Confusion

Endometriosis affects millions of women worldwide and is characterized by pain, irregular menstruation, and infertility. This article is Part 2 in a series on this topic. It summarizes and comments on the findings from a 2021 review that provided a detailed analysis of international endometriosis treatment guidelines available as of September 2020.

Although discrepancies between guidelines are common in many diseases, endometriosis is notable for the degree of variation. A 2018 review revealed that only about 7% of recommendations were comparable across international guidelines, and up to 28% of the recommendations were not supported by good research evidence. These gaps help explain the wide variation in doctors’ recommendations in clinical practice.

The most recent publication examined key guidance from organizations including the American College of Obstetricians and Gynecologists (ACOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), the European Society of Human Reproduction and Embryology (ESHRE), the Australian National Endometriosis Clinical and Scientific Trials (ACCESS), the Royal College of Obstetricians and Gynaecologists (RCOG), the French National College of Gynecologists and Obstetricians (CNGOF), the American Association of Gynecologic Laparoscopists (AAGL), and the German Society for Gynecology and Obstetrics (DGGG).

Across these guidelines, treatment considerations span non-hormonal pain management, hormonal therapies, surgical approaches, complementary and alternative options, infertility-related decisions, and emerging research. Many recommendations hinge on disease severity, patient goals such as fertility, and the skill and experience of the treating surgeon, particularly for deep infiltrating disease. While some therapies are broadly endorsed, others are limited by inconclusive evidence, side-effect profiles, or access and training requirements. The sections below synthesize the detailed guidance and points of agreement and disagreement.

Detailed Summary of Treatment Recommendations

Non-Hormonal Medical Pain Management

Nonsteroidal anti-inflammatory drugs (NSAIDs): Considered by all guidelines to be first-line therapy for dysmenorrhea and acyclic pelvic pain, but 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, although specific formulations and dosages vary across guidelines. There is little mention of compounded micronized progesterone, which is hard to study but may deserve consideration. The Levonorgestrel Intrauterine System (LNG-IUS) is particularly noted for localized progestin delivery, reduced systemic side effects, and effective pain control.
• Megace (Megestrol Acetate): A potent progestin recommended by several guidelines, though its use varies as a first-line versus second-line option. An additional benefit is less bone loss than that seen with GnRH agonist therapy.
• GnRH Agonists: Uniformly recommended across 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): Gaining attention for rapid onset of action and fewer side effects compared to agonists, though the evidence is not conclusive.
• Danazol and Gestrinone: Older treatments with androgenic effects and less common use 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): Emerging options being explored for targeted action and potential benefits.
• Aromatase Inhibitors: Considered in some cases, especially for pain unresponsive to other treatments. Most guidelines agree 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 endometriosis.

Surgical Approaches: Navigating the Complexities

• Laparoscopic Surgery: Endorsed for efficacy and reduced recovery time compared to laparotomy. The extent of surgery (complete versus partial removal of lesions) varies among guidelines, and studies are likely hampered by differing surgeon skill sets.
• Robotic Surgery: Highlighted by AAGL and others for benefits in complex cases, though cost and accessibility limit widespread use. Specialized training is required.
• Ablation vs. Excision: The choice remains contentious. Ablation is simpler, requires less technical skill, and applies to superficial lesions, but it may not be as effective long-term as excision, which more comprehensively removes visible disease. Surgeon skill is critical, and high variability may affect the ability to prove or disprove the effectiveness and safety of each method.
• Endometrioma: Cystectomy or excision of endometriomas is superior to drainage in terms of lower recurrence. Excision provides the opportunity for pathologic confirmation, which can be important when the presence of a tumor is unclear. When fertility is a major concern, the more atraumatic the surgical approach, the less the ovarian reserve is affected; surgeon expertise is critical.
• Deep Infiltrating Endometriosis: Highly specialized excisional surgeries are recommended because ablation does not work for these lesions. There is an even stronger emphasis on the surgeon’s expertise and patient selection. Some strongly believe that the best outcomes for advanced cases with highly distorted anatomy may rest with robotic surgery in the hands of a master surgeon.
• Hysterectomy: Considered a “definitive” or last-resort surgery, but it may be helpful for complete excision of endometriosis at any point. It also allows removal of co-existing pain-producing adenomyosis embedded in the uterine wall.
• LUNA (laparoscopic uterine nerve ablation) and PSN (presacral neurectomy): Multiple reviews suggest no benefit to LUNA but a possible benefit for PSN in selected cases. PSN is technically very challenging and treatment should be individualized. Studies on LUNA include a mix of ablation and excision, resulting in a lack of precision and potential confounding by surgeon skill level; a definitive conclusion may be elusive until better study methodologies are employed.

Complementary and Alternative Therapies: Exploring Additional Avenues

• Acupuncture and Electrotherapy (TENS): Mentioned as adjunct therapies in some guidelines, with encouraging results but a need for more research. These are low-risk options.
• Nutritional Supplements: Some guidelines suggest dietary changes and supplements might play a role in symptom management, including microbiome management for optimal estrogen metabolism. Large randomized studies are unlikely due to impractical size requirements, but personalized molecular medicine is prompting exploration of alternative methodologies to determine which diet and lifestyle approaches may be most effective.

Infertility and Endometriosis: A Delicate Balance

Surgical vs. Non-Surgical Approaches: The decision to pursue surgery in infertility cases is complex and depends on individual factors such as age, severity of endometriosis, and prior treatments. Reducing inflammation appears to benefit intrauterine implantation and gestation.

Emerging Treatments and Research

Future Directions: Ongoing research into immunotherapies, new hormonal agents, and gene or molecular therapy offers promising avenues for more personalized strategies.

Final Thoughts

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