Management of Endometrial Hyperplasia with Stromal Reaction
Stromal reaction in endometrial hyperplasia does not fundamentally alter the standard management approach, which is determined primarily by the presence or absence of cytologic atypia, not stromal changes. 1
Understanding Stromal Reaction
Stromal reaction (areas of stromal decidualization, inflammation, or reactive changes) is a histologic finding that may accompany endometrial hyperplasia but does not independently define risk stratification or treatment decisions. 2 The critical determinant remains whether the hyperplasia shows cytologic atypia (now termed endometrial intraepithelial neoplasia/EIN). 1
Diagnostic Confirmation Required
Expert gynaecopathologist review is mandatory before initiating any treatment, as stromal changes can complicate histologic interpretation and misclassification could lead to undertreatment of atypical hyperplasia or occult carcinoma. 3, 1
Dilatation and curettage (D&C) is superior to pipelle biopsy for accurate grading when complex architectural patterns or stromal changes are present. 1
Pelvic MRI should be performed to exclude myometrial invasion if conservative management is being considered. 1
Treatment Algorithm Based on Atypia Status
For Complex Hyperplasia WITHOUT Atypia (with stromal reaction):
Oral progestins are the standard treatment: medroxyprogesterone acetate 400-600 mg/day or megestrol acetate 160-320 mg/day. 3, 1
Levonorgestrel-releasing intrauterine system is increasingly preferred as initial therapy, delivering high local progesterone concentrations directly to the endometrium with higher regression rates (65.8% durable complete response), lower recurrence rates, and fewer systemic adverse effects compared to oral progestins. 3, 4
Endometrial sampling every 3-6 months is required to monitor response. 1
Hysterectomy should be considered if there is failure to respond after 6-12 months, recurrent disease after initial regression, or patient preference when fertility is not desired. 3
For Atypical Hyperplasia/EIN (with stromal reaction):
Hysterectomy with bilateral salpingo-oophorectomy is the definitive treatment, as there is a 50% risk of concurrent endometrial cancer and high progression rates. 1, 5
In the landmark study by Kurman et al., 52% of atypical hyperplasias progressed to carcinoma without treatment, compared to only 2% of complex hyperplasia without atypia. 5
Fertility-sparing progestin therapy is only appropriate for highly selected patients who meet strict criteria: must be fully counseled that this is non-standard care, require referral to specialized centers, and need confirmation of diagnosis by expert gynaecopathologist. 6, 1
Complete response occurs in approximately 50% of patients with progestin therapy, but recurrence rates remain high at 35% even after initial response. 6, 1
Monitoring Protocol for Conservative Management
Endometrial sampling (biopsies or D&C) every 3-6 months during progestin treatment. 6, 1
Proceed to hysterectomy if: endometrial cancer is still present after 6 months of progestin therapy, documented progression occurs based on biopsy results, or after childbearing is complete. 6
Critical Contraindications to Progestin Therapy
- History of breast cancer, stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, or active smoking. 6, 1
Common Pitfalls to Avoid
Do not confuse DMPA injectable contraception with oral medroxyprogesterone acetate therapy - the dosing, pharmacokinetics, and endometrial effects are completely different, with therapeutic oral MPA requiring 400-600 mg daily for hyperplasia treatment. 3
Do not rely solely on stromal changes to guide management - the presence or absence of cytologic atypia is the primary determinant of cancer risk and treatment approach. 1, 5
Inadequate follow-up can result in missed progression - failure to perform endometrial sampling every 3-6 months may lead to undetected progression to carcinoma. 1