What is the relationship between trauma and adenomyosis, and how should patients with a history of trauma and adenomyosis be managed?

Relationship Between Trauma and Adenomyosis

Chronic tissue microtrauma at the endometrial-myometrial junctional zone (EMJZ) is the mechanistic link between trauma and adenomyosis, with myofibroblasts serving as microscopic evidence of this ongoing injury. 1

Pathophysiologic Mechanism

The relationship between trauma and adenomyosis operates through a specific biomechanical pathway:

• Uterine hyperperistalsis causes chronic tissue microtrauma at the EMJZ, creating microdehiscences in the myometrium that facilitate translocation of basal endometrial fragments into the myometrial layer 1

• Myofibroblasts are significantly more abundant at the EMJZ in adenomyosis uteri (expressing alpha smooth muscle actin and collagen I), serving as ultrastructural and microscopic evidence of chronic tissue trauma 1

• This trauma-induced metaplasia is mediated by TGF-β1 and connective tissue growth factor (CTGF), leading to the development of adenomyotic lesions within the myometrium 1

• The myofibroblasts are of non-myometrial origin (lacking desmin immunolabeling), confirming they represent a metaplastic response to injury rather than smooth muscle proliferation 1

Clinical Implications for Management

First-Line Medical Therapy

Initiate levonorgestrel-releasing intrauterine device (LNG-IUD 20 μg/d) as first-line therapy, which reduces menstrual blood loss by 71-95% through local hormone delivery and provides superior symptom control compared to combined oral contraceptives 2

The LNG-IUD is preferred because:

• It has a local mechanism of action with lower systemic hormone exposure 2
• It demonstrates efficacy comparable to endometrial ablation 2
• It provides long-term symptom control with minimal user intervention required 2

Hierarchical Treatment Algorithm

When LNG-IUD is insufficient or contraindicated:

1. Combined oral contraceptives reduce painful and heavy menstrual bleeding, though less effectively than LNG-IUD 2

2. Oral GnRH antagonists (elagolix, linzagolix, relugolix) provide highly effective control of heavy menstrual bleeding with 18-30% reduction in lesion volume, but must be combined with low-dose estrogen and progestin add-back therapy to mitigate hypoestrogenic effects 2

3. Nonhormonal options for patients unable to use hormones:

   • Tranexamic acid provides significant reduction in menstrual blood loss 2
   • NSAIDs reduce bleeding symptoms but should be avoided in cardiovascular disease 2

Interventional Options

Uterine artery embolization (UAE) provides short-term symptom improvement in 94% and long-term improvement in 85% of patients, with symptom control maintained up to 7 years 2

Endometrial ablation offers greater long-term efficacy than oral medical treatment while reducing pregnancy risk 2

Definitive Surgical Management

Hysterectomy provides definitive resolution with patient satisfaction rates up to 90% and should be recommended when medical and interventional therapies fail 2

Critical Pitfalls and Caveats

• No medical therapy eradicates adenomyotic lesions—all treatments provide only temporary symptom relief with rapid recurrence after discontinuation 2

• Medical therapies will not treat bulk symptoms associated with enlarged uterus or mass effect 2

• The chronic microtrauma mechanism suggests that conditions causing uterine hyperperistalsis may perpetuate disease, though this has not been directly studied in intervention trials 1

• Adenomyosis frequently coexists with endometriosis and uterine fibroids, increasing diagnostic complexity and requiring comprehensive evaluation 3

• Diagnosis remains challenging as histopathologic confirmation traditionally required hysterectomy, though transvaginal ultrasound and MRI now enable preoperative diagnosis 3, 4