What is the dosing for cyclic progestins (progestin), such as norethindrone or medroxyprogesterone, for a woman of reproductive age with menorrhagia?

Cyclic Progestin Dosing for Menorrhagia

For women with menorrhagia, cyclic progestins are NOT recommended as first-line therapy because they are significantly inferior to other medical treatments in reducing menstrual blood loss, but if used, the standard regimen is medroxyprogesterone acetate 5-10 mg daily for 5-10 days starting on day 16 or 21 of the menstrual cycle. 1

FDA-Approved Dosing for Abnormal Uterine Bleeding

The FDA label for medroxyprogesterone acetate specifies the following regimen for abnormal uterine bleeding due to hormonal imbalance 1:

• Starting day: Day 16 or 21 of the menstrual cycle
• Dose: 5-10 mg daily (10 mg preferred for optimal secretory transformation)
• Duration: 5-10 days (10 days preferred)
• Expected outcome: Progestin withdrawal bleeding occurs within 3-7 days after discontinuing therapy 1

For patients with recurrent episodes, planned menstrual cycling with medroxyprogesterone acetate may be beneficial 1.

Alternative Progestin: Norethindrone

Norethindrone can be used in similar regimens 2, 3:

• Dose: 5 mg daily
• Duration: 7-10 days during luteal phase (day 15-19 or day 16-26)
• Efficacy: Comparable to medroxyprogesterone acetate but still inferior to other medical therapies 2

Critical Evidence on Effectiveness

Short-cycle progestins (luteal phase only) are significantly less effective than alternative treatments 2, 3:

• Inferior to tranexamic acid: Mean difference in menstrual blood loss reduction of 37.29 mL favoring tranexamic acid 2
• Inferior to levonorgestrel-IUS: The LNG-IUS reduces bleeding far more effectively with higher patient satisfaction (OR 5.19) 2, 4
• Inferior to danazol: Though danazol is no longer commonly used due to adverse effects 2

Long-cycle progestins (day 5-26) are also inferior to LNG-IUS, tranexamic acid, and ormeloxifene 2.

Why Cyclic Progestins Underperform

The evidence demonstrates that cyclic progestins during the luteal phase fail to adequately reduce menstrual blood loss in women with ovulatory menorrhagia 2, 3. This is because these women already produce adequate progesterone during their luteal phase, making supplemental progestin ineffective 5, 6.

When Cyclic Progestins May Be Appropriate

Cyclic progestins are more suitable for 5:

• Anovulatory bleeding in adolescents or perimenopausal women
• Patients requiring contraception (consider combined oral contraceptives instead)
• Patients who have failed or cannot tolerate first-line therapies

Recommended First-Line Alternatives

Based on superior efficacy for menorrhagia 2, 4:

1. Levonorgestrel-IUS: Most effective option with highest satisfaction rates and lowest discontinuation (14.6% vs 28.9% for medical therapy) 4
2. Tranexamic acid: Significantly more effective than cyclic progestins 2
3. NSAIDs: More effective than luteal-phase progestins 3

Common Pitfalls to Avoid

• Do not prescribe cyclic progestins as first-line therapy for ovulatory menorrhagia—they are demonstrably inferior to other medical options 2, 3
• Do not use short courses (<10 days) as they provide suboptimal endometrial transformation 1
• Do not confuse treatment of menorrhagia with endometrial protection in hormone replacement therapy—these are different clinical scenarios with different dosing requirements 7, 8
• Ensure proper diagnosis: Rule out anatomical pathology, coagulopathies (especially von Willebrand disease), and determine if bleeding is ovulatory or anovulatory before selecting therapy 5