Pharmaceuticals/Chemicals Human RCT evidence

Progesterone (Vaginal)

Vaginal P4

20.7 hours

Half-life

100–400 mg

Typical dose

Luteal phase (fertility); chronic or cyclic (HRT)

Cycle length

Vaginal micronized progesterone; bypasses much first-pass metabolism.

Key takeaways

Approved for luteal-phase support in fertility treatment; also used for endometrial protection.
Bypasses liver first-pass metabolism, so far less sedation than oral progesterone.
Uterine tissue levels exceed serum levels; blood tests understate the local effect.
~21-hour half-life supports once- or twice-daily dosing.

🚧 Expanded guide coming soon. This compound has PK data and a source — a full overview, mechanism, and dosing guide is pending editorial review.

Reported dosing protocols

Protocols reported in research literature and clinic/community use — informational context, not a dosing recommendation.

Use case	Dose	Route	Frequency	Duration
IVF luteal support (label)	90 mg gel (Crinone 8%)	Vaginal	Once daily	Through ~10–12 weeks if pregnancy occurs
Endometrial protection (off-label)	100–200 mg capsule	Vaginal	Once daily at bedtime	Cyclic or continuous

Pharmacokinetic summary

Model tier: Advanced (t½ + Cmax + Tmax + F)
Half-life: 20.7 hours
Cmax: 12.3 ng/mL
Tmax: 0.3 days
Bioavailability: 50%
Typical dose: 100–400 mg

Frequently asked questions

Vaginal vs oral progesterone — what changes?

The vaginal route avoids most first-pass liver metabolism, so it produces far less of the sedating metabolite allopregnanolone and delivers higher local uterine levels. Daytime drowsiness is much less common.

Why do serum levels look low on vaginal progesterone?

Progesterone passes directly to the uterus before entering general circulation, so endometrial concentrations run much higher than a blood draw shows. Low serum numbers on vaginal dosing are expected, not a sign of under-dosing.

Is vaginal progesterone as effective as injections for IVF?

For luteal-phase support, trials and meta-analyses generally show comparable pregnancy outcomes with better tolerability than daily intramuscular injections, which is why vaginal products dominate modern IVF practice.

References

Dovepress micronized P4
Pharmacokinetics of micronized progesterone (DDDT) — Entry's PK source; covers oral and vaginal capsule disposition.
DailyMed — Crinone prescribing information — Label dosing for IVF luteal support.

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