Are there forms of progesterone available beyond oral administration?

Alternative Forms of Progesterone Beyond Oral Administration

Yes, there are several non-oral forms of progesterone available, with vaginal progesterone being the preferred alternative due to its superior bioavailability and reduced side effect profile compared to oral formulations. 1, 2

Available Non-Oral Progesterone Formulations

Vaginal Progesterone

• Vaginal micronized progesterone (100-200 mg) is the preferred non-oral form due to:
  • Better bioavailability through direct vagina-to-uterus transport 3
  • Fewer systemic side effects than oral progesterone 3
  • Available as gel, suppositories, and tablets 2
  • Recommended dosage: 400 mg daily for specific indications like short cervix 1

Injectable Progesterone

• 17-alpha-hydroxyprogesterone caproate (250 mg IM weekly) is recommended for women with history of spontaneous preterm birth 1
• Provides sustained release and avoids first-pass metabolism

Transdermal Progesterone

• Limited efficacy due to poor skin permeability 4
• Cannot deliver physiological doses comparable to corpus luteum production (up to 25 mg/day) 4
• Over-the-counter progesterone creams can produce significant drug exposure but with questionable standardization 5

Clinical Considerations for Progesterone Selection

Advantages of Non-Oral Routes

1. Vaginal administration:

   • Avoids first-pass hepatic metabolism 3
   • Produces endometrial changes similar to luteal phase despite lower systemic levels 3
   • Preferred for hormone replacement therapy and infertility treatment 2

2. Injectable progesterone:

   • Provides consistent hormone levels
   • Weekly administration improves compliance
   • Particularly useful for preterm birth prevention 1

When to Choose Non-Oral Progesterone

• Patients with liver dysfunction
• Those experiencing side effects from oral progesterone (dizziness, drowsiness) 3
• Women at cardiovascular risk 4
• Patients requiring luteal support during assisted reproduction 2
• Women with history of preterm birth 1

Dosing Considerations

For hormone replacement therapy:

• Vaginal micronized progesterone: 100-200 mg daily 1
• For adolescents with primary ovarian insufficiency: progesterone therapy should be initiated after at least 2 years of estrogen therapy 1

Common Pitfalls and Caveats

• Natural micronized progesterone has a more favorable cardiovascular risk profile compared to synthetic progestogens 6
• Transdermal progesterone creams may not provide consistent or adequate dosing despite significant absorption 5
• Oral progesterone undergoes >90% first-pass metabolism, leading to high levels of metabolites that can cause drowsiness 3
• When using vaginal progesterone, patients should be informed about potential discharge from the gel or suppository

The European Society for Human Reproduction and Embryology (ESHRE) recommends micronized progesterone among the preferred progestogens in hormone replacement therapy due to its safer pharmacological profile, particularly regarding cardiovascular and thrombotic risks 6.