🌍 Introduction & Burden

• What is endometriosis? Endometrial-like tissue growing outside the uterus → chronic inflammatory disease.
• How common? Affects ~190 million women/AFAB worldwide (~10% during reproductive years).
• Impact 💸: Severe pain, infertility, fatigue. Average yearly patient costs ~$27,855, with US healthcare burden ~$22B.
• Diagnosis delay ⏳: Avg. 7 years, many see 3+ clinicians first. Lost work ~11 hrs/week (similar to diabetes or Crohn’s).

🔬 Definition, Symptoms & Types

• Subtypes of lesions:
  • Superficial peritoneal (80%) 🌱
  • Ovarian endometriomas ("chocolate cysts" 🍫)
  • Deep endometriosis (fibrotic, invasive)
  • Plus bladder, bowel, extra-abdominal, or post-surgical (iatrogenic).
• Symptoms:
  • Pelvic pain, dysmenorrhea, dyspareunia, dyschezia, dysuria 🚨
  • Infertility risk doubled
  • Fatigue & depression are common.
• Comorbidities: IBS, fibromyalgia, migraines, arthritis, bladder pain syndrome, autoimmune diseases, ↑ ovarian cancer risk (but absolute risk still low).

📊 Epidemiology

• Prevalence varies:
  • 15–71% in women with chronic pelvic pain
  • 9–68% in women with infertility
  • Adolescents with chronic pelvic pain: ~49%.
• Numbers likely undercount due to stigma, access barriers, and underdiagnosis.

🧬 Pathophysiology

• Genetics: 47–51% heritable. GWAS found 19 loci, mostly regulatory.
• Origins: Retrograde menstruation 🚺, stem cells (endometrial & bone marrow), immune and inflammatory dysfunction.
• Mechanisms:
  • Aberrant immune response (cytokines, reduced clearance of abnormal cells).
  • Progesterone resistance.
  • Neuroangiogenesis (new blood + nerve growth = chronic pain 🔥).
• Pain: Mixed type (nociceptive + neuropathic + nociplastic). Some patients develop central sensitization = persistent pain even after lesion removal.
• Infertility: Inflammation, ovarian dysfunction, adhesions, reduced oocyte quality.

🩺 Diagnosis & Monitoring

• Red flags 🚩: Pelvic pain, painful menses, painful sex, cyclic bowel/urinary issues, infertility + pain.
• Biomarkers: None reliable yet.
• Imaging: Ultrasound & MRI good for deep/ovarian disease; superficial disease harder.
• Gold standard: Laparoscopy 🔪 with histology confirmation.
• New concept: “Working diagnosis” = start treatment based on symptoms, don’t wait for surgery.

⚖️ Management

Pain Relief

• Surgery 🛠️:
  • Evidence weak for superficial lesions.
  • Ovarian cystectomy reduces recurrence but risks ovarian reserve.
  • Deep excision helps many but results vary.
  • Hysterectomy = last resort, not a cure.
  • Recurrence rates: 40–50% at 5 years.
• Drugs 💊:
  • NSAIDs: little evidence but widely used.
  • Hormones: contraceptives, progestogens, GnRH agonists/antagonists, aromatase inhibitors. All reduce pain, but symptoms recur after stopping.
  • Neuromodulators (gabapentin, antidepressants): weak evidence.
• Non-drug 🌱:
  • Physiotherapy, CBT, massage, diet (omega-3 PUFA shows some promise).
  • Multimodal & individualized approach recommended.

Fertility

• Medical suppression doesn’t help if pregnancy is desired.
• Surgery: May improve natural pregnancy chances (esp. superficial disease).
• ART (IVF/ICSI): Effective; surgery before IVF usually not needed except for pain.

🏥 Care Systems & Guidelines

• Specialist centers: Multidisciplinary (gynecology, urology, colorectal, pain management, psychology, physiotherapy).
• Guidelines: Vary, but most agree on contraceptives/progestogens as first line, laparoscopy as option for pain, ART for infertility.

🔮 Future & Emerging Approaches

• Diagnostics: MicroRNAs, metabolomics, novel imaging.
• Therapies: Repurposed drugs (e.g., dichloroacetate ⚗️), gut–brain axis, microbiome as targets.
• Research priorities:
  • Cause(s) of endometriosis
  • Non-invasive diagnostic test
  • Best fertility-preserving strategies
  • Non-surgical pain treatments
  • Psychological/fatigue management

📌 Conclusion

Endometriosis = chronic, multisystem, life-course disease. Key needs: earlier recognition, patient-centered care, multidisciplinary management, and more research into causes & personalized treatments.