Progesterone Therapy Days 15-28 for Heavy Menstrual Bleeding
Oral progesterone administered from days 15-28 of the menstrual cycle (luteal phase) is NOT effective for heavy menstrual bleeding and should not be used—this regimen offers no advantage over other medical therapies and is significantly less effective than alternatives like tranexamic acid, the levonorgestrel-releasing IUD, or even NSAIDs. 1, 2
Why Luteal Phase Progesterone Fails
The evidence consistently demonstrates that progesterone given during the luteal phase (days 15-28 or days 19-26) performs poorly:
- Significantly inferior to tranexamic acid for reducing menstrual blood loss 1, 2
- Significantly inferior to the levonorgestrel IUD (LNG-IUS), which reduces bleeding by 71-95% compared to minimal effect with luteal progesterone 3, 4, 1
- Significantly inferior to danazol for bleeding reduction 1, 2
- Strong trend toward inferiority compared to NSAIDs 1
This regimen was designed based on a misunderstanding of the pathophysiology—most women with heavy menstrual bleeding have ovulatory cycles with normal progesterone production, so adding more progesterone during the luteal phase when levels are already adequate provides no benefit 2.
What Actually Works: Evidence-Based Alternatives
First-Line: Levonorgestrel IUD (20 μg/day)
The LNG-IUS is the most effective medical treatment for heavy menstrual bleeding, with efficacy comparable to endometrial ablation 3, 4:
- Reduces menstrual blood loss by 71-95% 3, 4
- Works primarily at the endometrial level with minimal systemic absorption 3
- More effective than oral progesterone by a wide margin (MD 66.91 mL reduction, 95% CI 42.61-91.20) 5
- Higher long-term acceptability and continuation rates compared to oral medications 5
- More cost-effective than surgical options over 2-10 years 5
Common side effects include intermenstrual bleeding (especially first 3-6 months), breast tenderness, and ovarian cysts 5, but overall satisfaction remains high.
Second-Line: Extended Progesterone Regimen (Days 5-26)
If the LNG-IUS is contraindicated or refused, oral progesterone for 21 days per cycle (days 5-26) is significantly more effective than luteal phase dosing 4, 6, 2:
- Produces meaningful reduction in menstrual blood loss 1, 2
- Typical dosing: norethisterone 5 mg three times daily for 21 days 1
- Less acceptable to patients than LNG-IUS due to daily pill burden 1, 5
- May be useful for short-term management while awaiting definitive treatment 2
Third-Line: Non-Hormonal Options
For women who cannot or will not use hormonal therapy:
- Tranexamic acid during menstruation (5-7 days) is highly effective 3, 4
- NSAIDs (5-7 days during bleeding) reduce blood loss 3, 4
- Avoid these in women with cardiovascular disease or thrombotic risk due to MI and thrombosis associations 3
Critical Evaluation Steps Before Treatment
Before attributing bleeding to hormonal causes, rule out 4, 7:
- Pregnancy (β-hCG test mandatory in all reproductive-age women) 3, 7
- Structural causes: Perform transvaginal ultrasound with Doppler to identify polyps, fibroids, adenomyosis, or malignancy 7
- Coagulopathy, thyroid dysfunction, hyperprolactinemia: Check TSH, prolactin, and consider coagulation studies if indicated 7
- Endometrial pathology: Endometrial biopsy if age >45 years, risk factors for hyperplasia/cancer, or failed medical therapy 6
Urgent evaluation required if bleeding saturates a large pad/tampon hourly for ≥4 hours 3, 7.
Common Pitfalls to Avoid
- Do not prescribe luteal phase progesterone (days 15-28) expecting meaningful bleeding reduction—the evidence shows it doesn't work 1, 2
- Do not use NSAIDs or tranexamic acid in women with cardiovascular disease or on antiplatelet therapy due to thrombotic risk 3
- Do not assume hormonal cause without imaging—structural lesions are present in 20% of cases and require different management 7
- Do not continue ineffective treatment—if bleeding persists after 3 months of appropriate medical therapy, proceed to hysteroscopy or consider surgical options 6