Medroxyprogesterone for Abnormal Uterine Bleeding
Direct Recommendation
Medroxyprogesterone is a second-line option for abnormal uterine bleeding in reproductive-age women, reducing menstrual blood loss by only 20% in ovulatory women, whereas levonorgestrel-releasing intrauterine devices (LNG-IUD) should be first-line therapy, reducing blood loss by 71-95%. 1
Treatment Hierarchy
First-Line Therapy
- LNG-IUD is the most effective medical treatment and should be offered first, reducing menstrual blood loss by 71-95% compared to medroxyprogesterone's 20% reduction 1
- The American College of Obstetricians and Gynecologists specifically recommends LNG-IUD as first-line therapy for abnormal uterine bleeding 1
When to Use Medroxyprogesterone
For ovulatory dysfunction bleeding (anovulatory bleeding):
- Administer 10 mg daily for 10 days beginning on day 16 of the menstrual cycle to produce optimal secretory transformation of the endometrium 2
- Alternatively, give 5-10 mg daily for 5-10 days starting on the calculated 16th or 21st day of the cycle 2
- Progestin withdrawal bleeding typically occurs within 3-7 days after discontinuing therapy 2
For chronic management:
- A 10-day protocol (days 16-25 of the cycle) is more effective than a 15-day protocol (days 11-25), achieving better menstrual cycle regulation and AUB cessation with just 3 treatment cycles 3
- For adolescents with anovulatory bleeding, give medroxyprogesterone acetate orally once daily for 10 days each month for ≥3 months 4
Acute Bleeding Management
For acute, severe abnormal uterine bleeding requiring outpatient management:
- Administer depo-medroxyprogesterone acetate 150 mg intramuscularly combined with oral medroxyprogesterone acetate 20 mg every 8 hours for 3 days (9 doses total) 5
- This regimen stops bleeding in all patients within 5 days, with mean cessation time of 2.6 days 5
Critical Caveats
When NOT to Use Medroxyprogesterone
- Avoid in acute profuse bleeding unresponsive to progestin - high-dose estrogen is more effective for acute hemorrhagic episodes 4
- Do not use in women with known or suspected pregnancy, current or history of thromboembolism, undiagnosed vaginal bleeding, or liver disease 6
- The American Heart Association recommends avoiding estrogen therapy in anovulatory bleeding except for profuse bleeding unresponsive to progestin 1
Important Diagnostic Requirements
- Rule out pregnancy with β-hCG testing before initiating therapy 7
- Perform transvaginal ultrasound to exclude structural causes (polyps, fibroids, adenomyosis, malignancy) 7
- In women with risk factors for endometrial cancer (postmenopausal status, obesity, diabetes, unopposed estrogen exposure), perform endometrial sampling before attributing bleeding to hormonal imbalance 7, 2
When to Escalate Care
Urgent evaluation is required if:
- Bleeding saturates a large pad or tampon hourly for ≥4 hours 7, 6
- Bleeding persists after 2-3 treatment cycles - perform hysteroscopy to exclude focal lesions 1
Refer to gynecology if:
- Medical management fails 7
- Endometrial sampling shows hyperplasia or malignancy 7
- Postmenopausal bleeding with endometrial thickness ≥4 mm 7
Special Populations
Women on anticoagulation therapy:
- Strongly prefer LNG-IUD over oral medroxyprogesterone due to minimal systemic absorption and 71-95% reduction in bleeding 1, 6
- Approximately 70% of women on anticoagulation experience heavy menstrual bleeding 7
Women with cardiovascular disease:
- LNG-IUD is preferred due to minimal systemic absorption and reduced risk of MI/thrombosis 1
- Avoid NSAIDs and tranexamic acid in this population 7
Key Clinical Point
Medroxyprogesterone acetate is the only progestin with demonstrated full effectiveness in inducing secretory endometrium when used with full replacement estrogen doses 1, making it specifically useful for planned menstrual cycling in women with recurrent episodes of abnormal uterine bleeding 2. However, its modest 20% reduction in menstrual blood loss in ovulatory women makes it inferior to LNG-IUD for most clinical scenarios 1.