Dose of Medroxyprogesterone Acetate (MPA) for Endometrial Hyperplasia
For treating endometrial hyperplasia without atypia, use MPA 10 mg daily for 12-14 days per month in a cyclic regimen, or 2.5 mg daily for continuous therapy when combined with estrogen. For fertility-sparing treatment of atypical hyperplasia or early endometrial cancer, much higher doses of 400-600 mg/day are required 1.
Context-Specific Dosing
The appropriate MPA dose depends critically on the clinical indication:
For Endometrial Protection During Hormone Therapy
When MPA is used to protect the endometrium in women receiving estrogen replacement therapy, the established doses are 2:
- Cyclic regimen: 5 mg daily for 10-12 days per month
- Continuous regimen: 2.5 mg daily
These doses provide adequate endometrial protection and have Level 1 evidence supporting their efficacy. The 2021 guidelines for premature ovarian insufficiency confirm that sequential regimens require 10 mg of MPA for 12-14 days per month, while continuous regimens require a minimum of 2.5 mg daily 3.
For Treatment of Endometrial Hyperplasia Without Atypia
For therapeutic reversal of non-atypical endometrial hyperplasia, the dose is 10 mg daily administered cyclically 4. This regimen, given for 2 weeks of each month over 3-6 months, achieves regression rates exceeding 90% 4. Research comparing cyclic versus continuous 15 mg MPA showed no significant difference in regression rates (90% vs 82.5%), though cyclic administration was better tolerated 5.
Important caveat: Injectable Depo-Provera (medroxyprogesterone acetate) at one injection every 3 months demonstrated superior regression rates (91.8%) compared to oral norethisterone acetate (67.1%) for non-atypical hyperplasia 6, though this formulation is not typically first-line for this indication.
For Fertility-Sparing Treatment of Atypical Hyperplasia or Early Endometrial Cancer
This is an entirely different clinical scenario requiring dramatically higher doses. The 2016 ESMO-ESGO-ESTRO consensus guidelines explicitly recommend 1:
- MPA 400-600 mg/day for fertility-sparing therapy
- Treatment duration: minimum 6 months with endometrial assessment
- Alternative: Megestrol acetate 160-320 mg/day
These high doses achieve complete response rates of approximately 75% but carry recurrence rates of 30-40% 1. The 2023 NCCN guidelines confirm continuous progestin-based therapy with medroxyprogesterone as an option for highly selected patients with grade 1, stage IA disease 7.
Research demonstrates that repeated high-dose MPA therapy (400-600 mg/day) remains effective even for intrauterine recurrence, with complete response rates of 96-100% in retreatment scenarios 8, 9.
Dose-Response Relationship for Severe Hyperplasia
Historical data from 1986 established a dose-response gradient for adenomatous hyperplasia 10:
- Grade I severity: 50-100 mg/day
- Grade II severity: 100-150 mg/day
- Grade III severity: 150 mg/day
However, these intermediate doses are rarely used in contemporary practice, which has largely shifted to either low-dose endometrial protection (2.5-10 mg) or high-dose fertility-sparing therapy (400-600 mg).
Critical Distinctions
Do not confuse endometrial protection doses with therapeutic doses. The 2.5-10 mg range prevents hyperplasia development in women on estrogen therapy, while 400-600 mg is required to reverse established atypical hyperplasia or early cancer. Using inadequate doses for fertility-sparing treatment represents a treatment failure that could compromise oncologic outcomes.
The FDA label confirms that for endometrial or renal carcinoma, initial doses of 400-1000 mg per week are recommended, with maintenance potentially reduced to 400 mg per month 11. This parenteral dosing is distinct from oral fertility-sparing protocols.