What is the typical dosage and administration of progesterone suppositories?

Progesterone Suppository Dosing and Administration

For preterm birth prevention in singleton pregnancies without prior spontaneous preterm birth but with short cervical length ≤20 mm at around 24 weeks, use vaginal progesterone 200 mg suppository daily from diagnosis until 36 weeks. 1

Evidence-Based Dosing by Clinical Indication

Preterm Birth Prevention

For singleton pregnancies with short cervical length (≤20 mm) discovered at 18-24 weeks:

• Vaginal progesterone 200 mg suppository administered daily 1
• Alternative: Vaginal progesterone 90 mg gel daily 1
• Start from diagnosis of short cervical length and continue until 36 weeks 1
• This reduces preterm birth <33 weeks (RR 0.54) and neonatal morbidity/mortality (RR 0.41) 1

For singleton pregnancies with prior spontaneous preterm birth:

• First-line: 17-alpha-hydroxyprogesterone caproate (17P) 250 mg IM weekly from 16-20 weeks until 36 weeks 1
• If cervical length shortens to <25 mm despite 17P, continue 17P (insufficient evidence to switch to vaginal progesterone) 1

Studies demonstrating efficacy of vaginal progesterone suppositories:

• 100 mg daily between 24-34 weeks reduced preterm birth <37 weeks (24% vs 50%, OR 3.11) and <34 weeks (5.4% vs 26.5%, OR 6.30) 1
• 90 mg gel daily from 18-23 weeks until 37 weeks significantly decreased preterm birth <32 weeks and NICU admissions 1

Hormone Replacement Therapy (Endometrial Protection)

For women with intact uterus receiving transdermal estradiol:

• Oral or vaginal micronized progesterone 200 mg daily for 12-14 days every 28 days in sequential regimen 2, 3
• This provides complete endometrial protection against estrogen-induced hyperplasia 2, 3
• Alternative: Medroxyprogesterone acetate 10 mg daily for 12-14 days per month 3

Pharmacokinetic Properties

Absorption characteristics of vaginal progesterone suppositories:

• Time to maximum concentration (Tmax): 2-6 hours, most commonly 4 hours 4, 5, 6
• Peak plasma concentrations: 7-10 ng/ml with 100 mg dose, 12 ng/ml with 200 mg dose 4, 5
• Elimination half-life: 9-16 hours depending on suppository base 4, 6
• Plasma levels are NOT dose-proportional (200 mg produces only 1.37× the AUC of 100 mg) 4

Key pharmacokinetic advantages:

• Avoids first-pass hepatic metabolism 5, 7, 6
• Achieves "uterine first-pass effect" with higher local endometrial concentrations 6
• Rapid absorption with high bioavailability 5, 7
• Repeated daily dosing does not cause accumulation 4

Administration Considerations

Route selection:

• Vaginal route is standard and most established 5, 7, 6
• Rectal administration 200 mg three times daily is equally effective alternative if vaginal route not tolerated 8
• Rectal route causes more constipation and flatulence; vaginal route causes more discharge 8

Critical Caveats

What does NOT work (avoid these errors):

• Progesterone has NO proven benefit in multiple gestations (twins, triplets) 1
• NO evidence of effectiveness for symptomatic preterm labor or PPROM 1
• NO benefit in singleton pregnancies without prior preterm birth AND normal cervical length 1
• Do NOT screen at gestational ages outside 18-24 weeks or use cervical length cutoffs >20 mm without evidence 1
• Do NOT substitute 17P for vaginal progesterone in the short cervix indication—they are NOT interchangeable 1

Safety profile:

• Well-tolerated with minimal side effects 7, 8, 6
• Oral micronized progesterone may cause mild transient drowsiness (take at bedtime) 7
• No adverse effects on hormonal, liver, or lipid profiles with continuous use 6
• No endometrial hyperplasia when used appropriately 6