What is the recommended dosing for progestin (e.g. norethindrone acetate, medroxyprogesterone acetate) therapy in a female patient of reproductive age with heavy vaginal bleeding, considering her medical history and potential contraindications?

Progestin Dosing for Heavy Vaginal Bleeding

For acute heavy vaginal bleeding in reproductive-age women, administer norethindrone acetate 5-10 mg orally three times daily (15-30 mg total daily dose) for 5-10 days to achieve rapid endometrial stabilization and hemostasis. 1, 2

Acute Management Regimens

High-Dose Progestin Protocol

• Norethindrone acetate 5-10 mg three times daily (total 15-30 mg/day) for 5-10 days is the standard acute treatment for heavy bleeding, producing secretory transformation of the endometrium and typically stopping bleeding within 24-48 hours 1, 2
• Medroxyprogesterone acetate 10-20 mg daily for 5-10 days is an alternative regimen with comparable efficacy, though norethindrone acetate offers superior cardiovascular and metabolic profiles 3, 4
• Progestin withdrawal bleeding typically occurs 3-7 days after discontinuation, which is expected and indicates successful endometrial stabilization 1

Recent High-Quality Evidence

• A 2025 randomized controlled trial (IMPLANET) demonstrated that norethindrone acetate 10 mg daily effectively stopped prolonged bleeding in 86.7% of patients within 7 days (versus 48.9% with placebo, P<.001), with a median of only 3 days of treatment needed 5
• This represents the most recent and highest-quality evidence supporting norethindrone acetate as first-line progestin therapy 5

Chronic/Recurrent Bleeding Management

Cyclic Progestin Regimens

• Norethindrone acetate 5-10 mg daily from cycle day 5-25 (21 days total) effectively reduces menstrual blood loss in ovulatory dysfunctional bleeding, with measured reductions from 110-113 mL to 71-76 mL 2
• Medroxyprogesterone acetate 10 mg daily for days 12-25 (14 days) is appropriate for anovulatory bleeding in adolescents and women not requiring contraception 3, 4
• For patients with recurrent episodes, planned menstrual cycling with these regimens prevents breakthrough bleeding 1

Adjunctive Therapy for Breakthrough Bleeding

• Adding norethindrone acetate 5 mg daily to existing progestin-only contraception significantly reduces breakthrough bleeding frequency at 2,4, and 6 weeks (P=0.019,0.002,0.002 respectively) without increasing side effects 6
• NSAIDs for 5-7 days can be added to any progestin regimen to acutely reduce blood flow 7, 4

Context-Specific Considerations

Contraceptive-Associated Bleeding

• For bleeding with LNG-IUD, implants, or DMPA: NSAIDs 5-7 days first-line, then consider hormonal treatment with combined oral contraceptives or estrogen 10-20 days if medically eligible 7
• For extended/continuous combined hormonal contraceptive users: implement a 3-4 day hormone-free interval (not during first 21 days, not more than once monthly) 7, 4

Important Caveats

• Always exclude pregnancy, infection, structural lesions, and coagulopathies (especially von Willebrand disease) before initiating progestin therapy, as these require different management 8, 3
• High-dose norethindrone (>15 mg daily) carries thrombotic risk; consider medroxyprogesterone acetate depot or levonorgestrel IUS in patients with elevated VTE risk 9
• Continuous norethindrone use should be limited to <6 months due to potential meningioma risk with prolonged high-dose exposure 9
• Norethindrone acetate does not prevent bleeding recurrence (median 5 days to recurrence versus 10.5 days with placebo), so transition to maintenance therapy is essential 5

Treatment Failure Protocol

• If bleeding persists after 30 days of progestin therapy (treatment failure rate 2.2% with norethindrone acetate versus 17.8% placebo), counsel on alternative methods including combined hormonal contraceptives, antifibrinolytics, or levonorgestrel IUS 7, 5
• Consider surgical options (endometrial ablation or hysterectomy) only after medical management failure in patients who have completed childbearing 3