Continuous Progesterone Treatment for Endometrial Hyperplasia
Yes, continuous progestin-based therapy is effective for treating endometrial hyperplasia, achieving complete regression in approximately 50% of patients, with higher response rates in non-atypical hyperplasia (90-95%) compared to atypical hyperplasia. 1, 2
Evidence for Efficacy
Response Rates by Hyperplasia Type
Non-atypical (simple and complex) hyperplasia demonstrates significantly higher response rates to progestin therapy:
- Simple hyperplasia without atypia: 95% remission rate with progesterone treatment versus 75% with no therapy 3
- Complex hyperplasia without atypia: 89% remission rate with progesterone versus 35% with no therapy 3
- Overall complete response in non-atypical hyperplasia: 90.5% regression rate 4
Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) shows more modest results:
- Approximately 50% achieve durable complete response 1, 2
- Recurrence rates remain high at 35% even after initial response 1
Dose-Response Relationship
The evidence supports that 200 mg daily progesterone is the optimal dose for most patients:
- 100 mg daily: 81.8% remission for simple hyperplasia, 60% for complex hyperplasia 3
- 200 mg daily: 97.5% remission for simple hyperplasia, 92.4% for complex hyperplasia 3
- 300 mg daily: 100% remission for simple hyperplasia, 85.7% for complex hyperplasia 3
No statistically significant difference exists between 200 mg and 300 mg doses, making 200 mg the most cost-effective choice. 3
Treatment Regimens
Recommended Progestin Options
NCCN guidelines endorse three continuous progestin-based regimens:
For estrogen-induced hyperplasia specifically, medroxyprogesterone acetate 10 mg/day continuously for 6 weeks or cyclically for 3 months (2 weeks per month) achieves >90% reversal rates. 5
Monitoring Protocol
Close surveillance with endometrial sampling is mandatory:
- Perform endometrial biopsies or D&C every 3-6 months during treatment 1, 2
- More frequent sampling (every 3 months) is recommended for atypical hyperplasia 2
- If hyperplasia persists after 6-12 months of progestin therapy, proceed to hysterectomy 1
Critical Caveats and Contraindications
Absolute Contraindications to Progestin Therapy
Do not prescribe progestins in patients with: 1, 2
- History of breast cancer
- Prior stroke or myocardial infarction
- Active or history of pulmonary embolism or deep vein thrombosis
- Current smoking
- Peanut allergy (for progesterone capsules containing peanut oil) 6
Special Populations Requiring Different Management
Atypical hyperplasia/EIN patients desiring fertility preservation:
- Must be referred to specialized centers 2
- Require comprehensive counseling that this is non-standard treatment 1, 2
- Need pelvic MRI to exclude myometrial invasion before initiating conservative therapy 2
- After 6 months of failed hormonal therapy with persistent carcinoma, repeat pelvic MRI to exclude myoinvasion and nodal/ovarian metastasis 1
Lynch syndrome patients:
- Require annual surveillance with gynecological examination, transvaginal ultrasound, and endometrial biopsy starting at age 35 2
- Should discuss prophylactic hysterectomy and bilateral salpingo-oophorectomy at age 40 2
Common Pitfalls to Avoid
The most critical error is using progestin therapy for high-risk histologies:
- Never use fertility-sparing progestin therapy for high-grade endometrioid adenocarcinomas, uterine serous carcinoma, clear cell carcinoma, carcinosarcoma, or leiomyosarcoma 1
Inadequate follow-up leads to missed progression:
- Failure to perform endometrial sampling every 3-6 months can result in undetected progression to carcinoma 1
- After achieving complete response, recurrence occurs in 1.72% at 3 months and 6.1% at 6 months, necessitating continued surveillance 4
Definitive surgery should not be delayed indefinitely: