Continuous Norethindrone Dosing
For continuous norethindrone therapy, the minimum effective dose is 1 mg daily of norethisterone (norethindrone) when used for endometrial protection with estrogen replacement, taken continuously without interruption. 1
Dosing by Clinical Indication
For Hormone Replacement Therapy (Endometrial Protection)
Continuous combined regimens require a minimum of 1 mg of oral norethisterone daily when administered with transdermal or oral estradiol. 1 This represents the lowest dose that provides adequate endometrial protection while avoiding withdrawal bleeding.
- Sequential regimens (if withdrawal bleeding is acceptable): 10 mg daily for 12-14 days every 28 days when combined with continuous estrogen 1
- Research demonstrates that even lower doses of norethindrone acetate (0.1 mg daily) can prevent endometrial hyperplasia when combined with 1 mg estradiol, though the 1 mg continuous dose remains the guideline-recommended minimum 2
Administration Protocol
Take one tablet daily at the same time every day, with continuous administration and no interruption between pill packs. 3 This FDA-approved dosing schedule applies to all continuous norethindrone regimens, whether used alone or in combination with estrogen.
Monitoring Requirements
Baseline Assessment
- Pregnancy status (Category X contraindication) 4
- Blood pressure measurement 4
- History of breast cancer (absolute contraindication) 4
Ongoing Surveillance
- Annual clinical review for stable patients, with more frequent monitoring during initial therapy 4
- Liver function tests should be monitored periodically, especially at doses ≥10 mg daily, with consideration of every 3-6 months initially, then annually if stable 4
- Blood pressure monitoring at each visit 4
Important Clinical Considerations
Norethindrone is listed as a second-choice progestin after micronized progesterone for hormone replacement therapy, particularly in young women with premature ovarian insufficiency. 1 Micronized progesterone carries lower cardiovascular and thrombotic risk compared to synthetic progestins.
- The 1 mg continuous dose effectively prevents endometrial hyperplasia while minimizing side effects 1
- Higher doses (2.5 mg daily) have been used for endometriosis treatment, though tolerability is lower than with alternative progestins 5
- Avoid interruptions in dosing to maintain stable hormone levels and prevent breakthrough bleeding 3
Common Pitfall to Avoid
Do not confuse norethindrone with norethindrone acetate—norethindrone acetate requires lower doses (0.1-0.5 mg daily) for endometrial protection due to higher potency, while norethindrone base requires the full 1 mg minimum dose. 1, 2