What is the efficacy and dosing of Prometrium (progesterone) for the treatment of endometriosis?

Prometrium (Progesterone) for Endometriosis Treatment

Prometrium (oral micronized progesterone) has limited data supporting its use specifically for endometriosis, with progestins like medroxyprogesterone acetate (MPA) having more established efficacy at doses of 50-100 mg daily for endometriosis pain management. 1

Progestins in Endometriosis Management

Progestins are considered first-line treatment options for endometriosis according to multiple guidelines, with several advantages:

• Effective for pain relief in approximately 80% of patients with moderate to severe endometriosis 1
• Avoid hypo-estrogenic side effects that can be debilitating 2
• Can be used for long-term treatment across all endometriosis phenotypes 3

Specific Progestin Options and Dosing

1. Medroxyprogesterone acetate (MPA):

   • Dosage: 50 mg daily shown to be effective in clinical studies 1
   • Duration: Typically administered for at least 3-4 months
   • Efficacy: Reduces mean stage score of disease from 18.2 to 5.9 (p<0.005) 1
   • Mechanism: Induces pseudodecidualized reaction and atrophic changes in endometriotic implants while suppressing ovulation and reducing LH and estradiol levels 1

2. Other recommended progestins:

   • Norethindrone acetate
   • Depot medroxyprogesterone acetate (DMPA)
   • Dienogest 3

Prometrium (Oral Micronized Progesterone) Considerations

While the FDA label for Prometrium does not specifically mention endometriosis treatment 4, it may be considered based on the mechanism of action of progestins:

• Standard dosing for other indications:

  • 200 mg daily for 12 days in a 28-day cycle (for endometrial hyperplasia prevention) 4
  • 400 mg daily for 10 days (for secondary amenorrhea) 4

• Potential benefits:

  • More physiological option compared to synthetic progestins
  • May have fewer androgenic side effects

Treatment Algorithm for Endometriosis

1. First-line options:

   • Combined oral contraceptives (preferably continuous regimen)
   • Progestins (MPA 50 mg daily, norethindrone acetate, DMPA, or dienogest) 3

2. If first-line treatment fails (occurs in approximately 1/3 of patients due to progesterone resistance) 5:

   • GnRH agonists with add-back therapy
   • Consider laparoscopic removal of endometriotic lesions 3

3. For patients with completed childbearing and severe symptoms:

   • Consider hysterectomy with removal of endometriotic lesions 3

Monitoring and Follow-up

• Evaluate treatment response after 3-6 months
• Monitor for common side effects:
  • Amenorrhea (occurs in 75% of patients on MPA) 1
  • Breakthrough bleeding (20% of patients) 1
  • Weight gain
  • Mood changes

Important Considerations

• Progesterone resistance: Approximately one-third of women with endometriosis demonstrate resistance to progestin therapy, requiring alternative treatments 5

• Treatment duration: Long-term therapy is often necessary as symptoms frequently recur after treatment cessation, with 25-34% of patients experiencing recurrent pelvic pain within 12 months of discontinuing hormonal treatment 3

• Fertility concerns: For patients desiring pregnancy, treatment should be timed appropriately, as progestins inhibit ovulation during active treatment 1

Pitfalls to Avoid

• Delaying treatment escalation when first-line therapies fail
• Using GnRH agonists without add-back therapy
• Discontinuing hormonal therapy too early
• Using progestins alone in women with endometriosis who have undergone oophorectomy 3

For women with endometriosis who required oophorectomy, combined estrogen/progestogen therapy is recommended to treat vasomotor symptoms and may reduce the risk of disease reactivation 6.