Continuous Progesterone for Hyperplastic Endometrium: Shedding Not Required
Continuous daily progesterone for 30 days before ultrasound assessment is appropriate and does not require scheduled endometrial shedding, as the primary goal is endometrial suppression and regression of hyperplasia, not cyclical bleeding. 1
Rationale for Continuous Therapy
The concept of mandatory endometrial shedding during progesterone treatment is outdated and not supported by current evidence:
Continuous progestin-based therapy is the recommended approach for treating endometrial hyperplasia, with regimens including megestrol acetate, medroxyprogesterone acetate, or levonorgestrel intrauterine devices used continuously rather than cyclically. 2, 1
The mechanism of action relies on sustained endometrial suppression, not periodic shedding—progesterone works by opposing estrogen-driven proliferation and inducing secretory transformation or atrophy of hyperplastic endometrium. 3
More than 90% of endometrial hyperplasia can be reversed with continuous progestin therapy, with studies showing that continuous administration of medroxyprogesterone acetate (10 mg/day for 6 weeks continuously) is highly effective. 4
Evidence Supporting Continuous Use
The clinical data strongly favor continuous over cyclic administration:
Continuous combined treatment confers better endometrial protection than cyclic regimens, with the protective effect against hyperplasia and endometrial cancer being affected by regimen type, with continuous dosing providing superior results. 5
Natural progesterone at 200 mg daily shows 92-97% regression rates for both simple and complex hyperplasia without requiring scheduled withdrawal bleeding. 6
Treatment duration of 3-6 months is standard, with endometrial sampling performed every 3-6 months to assess response—your proposed 30-day continuous course before ultrasound fits well within this framework. 2, 1
Practical Treatment Algorithm
For your specific clinical scenario:
Start with continuous daily progesterone (200 mg orally at bedtime for endometrial protection, or 400 mg for amenorrhea treatment per FDA labeling). 7
Continue for 30 days without interruption before performing ultrasound assessment—this allows adequate time for endometrial response without the need for withdrawal bleeding. 1
Perform endometrial sampling at 3-6 months (not just ultrasound) to histologically confirm regression, as imaging alone is insufficient to assess treatment response. 2, 1
If hyperplasia persists after 6-12 months of continuous therapy, proceed to hysterectomy rather than continuing medical management. 1
Critical Monitoring Requirements
Close surveillance is mandatory regardless of bleeding pattern:
Endometrial biopsy or D&C every 3-6 months is required during treatment, with more frequent sampling for atypical hyperplasia—ultrasound alone is inadequate for monitoring. 2, 1
Pelvic MRI should be performed before initiating conservative management to exclude myometrial invasion, particularly if fertility preservation is desired. 1
Review by expert gynaecopathologist is essential to confirm diagnosis and classification before starting treatment. 1
Important Contraindications to Avoid
Screen carefully before initiating continuous progesterone:
Absolute contraindications include history of breast cancer, stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, and active smoking. 2, 1
Peanut allergy is a contraindication to many oral progesterone formulations that contain peanut oil. 7
High-risk histologies are not candidates for progesterone therapy—do not use for high-grade endometrioid adenocarcinomas, serous carcinoma, clear cell carcinoma, carcinosarcoma, or leiomyosarcoma. 1
Common Clinical Pitfall
The most significant error is assuming withdrawal bleeding is necessary or beneficial:
Scheduled shedding is not required for therapeutic effect—the antiproliferative action of progesterone occurs through continuous suppression, and forcing withdrawal bleeding may actually reduce compliance and therapeutic efficacy. 5, 3
Amenorrhea during treatment is acceptable and even desirable—absence of bleeding does not indicate treatment failure and may reflect optimal endometrial suppression. 2
Inadequate follow-up is more dangerous than absence of bleeding—failure to perform endometrial sampling every 3-6 months leads to undetected progression to carcinoma, regardless of bleeding pattern. 1