What is the maximum dose of norethindrone (Progestin) for Abnormal Uterine Bleeding (AUB)?

Maximum Dose of Norethindrone for Abnormal Uterine Bleeding

For acute abnormal uterine bleeding, norethindrone can be administered at 10-30 mg daily depending on bleeding severity, with cessation typically occurring within 46 hours, while for chronic management, the standard cyclic regimen is norethindrone acetate 5-10 mg daily for 10-14 days per month. 1, 2

Acute Bleeding Management

High-dose norethindrone (10-30 mg daily) is effective for acute severe uterine bleeding episodes in adolescents and adults, with the specific dose titrated based on:

• Severity of bleeding - heavier bleeding warrants higher doses within the 10-30 mg range 2
• Duration of bleeding episode - prolonged bleeding may require doses toward the upper end 2
• Patient weight - higher body weight may necessitate increased dosing 2

In a prospective study of 29 adolescents with severe AUB, doses ranging from 10-30 mg daily achieved bleeding cessation at a mean of 46.1 hours (range 8-120 hours) with minimal adverse effects 2. This high-dose approach is particularly valuable when rapid hemostasis is required, including cases necessitating blood transfusion 2.

Chronic/Recurrent Bleeding Management

For ongoing management of chronic abnormal uterine bleeding, the American College of Obstetricians and Gynecologists recommends cyclic oral progestin therapy with norethindrone acetate 5-10 mg daily for 10-14 days per month, which achieves an 87% reduction in menstrual blood loss. 1

Dosing Considerations by Clinical Context:

• Standard cyclic therapy: Norethindrone acetate 5-10 mg daily for 10-14 days each month for at least 3-6 months 1, 3
• Adolescents with anovulatory bleeding: Medroxyprogesterone acetate is often preferred, but norethindrone acetate 5-10 mg for 10 days monthly is an alternative 3
• Perimenopausal patients: Cyclic progestin with norethindrone acetate administered days 18-25 of a 25-day cycle 3

Important Safety Considerations

Progestins including norethindrone should not be used continuously for more than 6 months due to the risk of meningioma. 4 This is a critical safety limitation that must guide treatment duration.

Additional Caveats:

• High-dose norethindrone has a non-significant association with thromboembolic risk, making it relatively safer than combined oral contraceptives in high-risk patients 4
• For patients at high risk of venous thromboembolism (such as those with thrombocytopenia during chemotherapy), medroxyprogesterone acetate is preferred over norethindrone 4
• Endometrial sampling should be performed before initiating therapy in patients with risk factors for endometrial cancer 5

Practical Algorithm

1. Acute severe bleeding: Start norethindrone 10-30 mg daily (dose based on severity, duration, weight) until bleeding stops (typically 24-120 hours) 2

2. Transition to maintenance: After acute control, switch to cyclic norethindrone acetate 5-10 mg daily for 10-14 days per month 1

3. Duration limit: Do not exceed 6 months of continuous progestin therapy 4

4. If bleeding persists: Consider alternative therapies such as levonorgestrel-releasing IUD (71-95% reduction in blood loss), NSAIDs, or tranexamic acid 1, 6

The evidence strongly supports norethindrone's efficacy across a wide dose range (5-30 mg daily), with higher doses reserved for acute management and lower cyclic doses for chronic control, always respecting the 6-month maximum duration for continuous use.