Progesterone Routes of Administration
Progesterone is available and used both orally and intravaginally, with each route having distinct pharmacokinetic properties and clinical applications. 1, 2
Oral Administration
Oral micronized progesterone is FDA-approved and widely available in capsule formulations containing 100 mg or 200 mg doses. 1 The oral route faces significant pharmacokinetic limitations:
- Oral progesterone undergoes extensive first-pass hepatic metabolism (>90%), resulting in poor bioavailability and requiring higher doses to achieve therapeutic effects. 3, 4
- Despite these limitations, oral micronized progesterone 200 mg daily for 12-14 days per cycle effectively protects the endometrium when combined with estrogen therapy in postmenopausal women. 5
- The extensive hepatic metabolism produces high levels of progesterone metabolites (particularly 5-α reduced forms) that cause sedation, dizziness, and drowsiness. 4
Intravaginal Administration
Vaginal progesterone represents a clinically effective alternative route with distinct advantages:
- Vaginal administration achieves preferential uterine uptake through direct vagina-to-uterus transport, producing higher endometrial tissue concentrations despite lower systemic progesterone levels compared to oral administration. 6, 3, 4
- Available formulations include 90 mg gels, 200 mg suppositories, and sustained-release preparations. 5
- The vaginal route avoids first-pass hepatic metabolism, resulting in fewer systemic side effects than oral progesterone or synthetic progestins. 3, 4
Clinical Context Matters
The choice between oral and vaginal routes depends on the clinical indication:
- For preterm birth prevention in singleton pregnancies with short cervical length (≤20 mm at 24 weeks), vaginal progesterone (90 mg gel or 200 mg suppository daily) is the evidence-based recommendation. 5
- For endometrial protection during hormone replacement therapy, both oral (200 mg daily for 12-14 days per cycle) and vaginal micronized progesterone are acceptable options, though vaginal administration may offer better tolerability. 5, 1
- For luteal phase support in assisted reproduction, vaginal progesterone is at least as effective as intramuscular injections and has become the preferred route. 3, 7
Important Caveat
Transdermal progesterone preparations lack sufficient evidence for endometrial protection and should not be used to oppose estrogen effects on the endometrium. 2 This route does not achieve adequate progestogenic effects even with low-dose estradiol therapy.