Hormonal Hormone replacement therapyFDA-approved medicinePrescription drug

Progesterone Cream

Bioidentical Progesterone · Topical Progesterone

Evidence: Approved label. Example dose: finalize with a provider. Not a fact-check stamp.

20-40 mg – 50 mg (approximately 1/2 teaspoon of standard 2% cream) Topical Daily

Steroid hormoneProgestogenTransdermal cream (topical route)

Transdermal bioidentical progesterone cream delivers progesterone through the skin, with the active metabolite allopregnanolone driving its characteristic GABAergic sedating effect. Cream-based (NOT a patch), typically applied daily to soft skin areas. Commonly compounded at 20, 50, or 100 mg per dose. In women with a uterus who are on systemic estrogen, progesterone is a non-optional adjunct to protect against endometrial hyperplasia. Evidence for transdermal progesterone's endometrial protection is weaker than oral micronized progesterone - discuss route with your prescriber.

Quick Start

Route

Topical

Start low

50 mg Topical

Frequency

Daily

Timing

Anytime

Starting dose. 50 mg — Approximately 1/2 teaspoon of standard 2% cream

Apply in the evening to inner thigh, forearm, or chest. Rotate sites daily to avoid receptor downregulation.

❋

Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.

Tiered Protocols · lowest first

Standard

Estrogen Dominance Balance

20-40 mg · Topical · Daily

human clinical trial · Leonetti et al. 1999 (Obstet Gynecol)

Apply to thin-skinned areas (inner wrists, neck). Promotes deep sleep via GABA receptor affinity.

20-40 mg

Daily

Conservative start

50 mg (approximately 1/2 teaspoon of standard 2% cream) · Topical · Daily

conservative starter

50 mg (approximately 1/2 teaspoon of standard 2% cream)

Daily

◆

How it works

Progesterone binds progesterone receptors (PR-A and PR-B) in uterine endometrium, breast, and CNS tissue. Its reduced metabolite allopregnanolone is a positive allosteric modulator of GABA-A receptors, producing anxiolytic and sedating effects - this is why evening dosing is preferred. Transdermal absorption varies widely between users and formulations (estimated 50-80% bioavailability), which is why transdermal progesterone's endometrial protection is considered less reliable than oral micronized progesterone.

What to expect

Early

Days 1–7

1-7 days: sleep improvement

Evidence

HumanModerate

AnimalPresent

In-vitroStrong

Each reference below was re-fetched from its PubMed record, and the quoted sentence was confirmed to appear in that abstract and to support the claim it sits under. Follow any of them to read the source.

Based on a systematic literature review on micronized progesterone for endometrial protection, an international expert panel's recommendations on MHT containing micronized progesterone are as follows: (1) oral micronized progesterone provides endometrial protection if applied sequentially for 12-14 days/month at 200 mg/day for up to 5 years; (2) vaginal micronized progesterone may provide endometrial protection if applied sequentially for at least 10 days/month at 4% (45 mg/day) or every other day at 100 mg/day for up to 3-5 years (off-label use); (3) transdermal micronized progesterone does not provide endometrial protection.

Based on a systematic literature review on micronized progesterone for endometrial protection, an international expert panel's recommendations on MHT containing micronized progesterone are as follows: (1) oral micronized progesterone provides endometrial protection if applied sequentially for 12-14 days/month at 200 mg/day for up to 5 years; (2) vaginal micronized progesterone may provide endometrial protection if applied sequentially for at least 10 days/month at 4% (45 mg/day) or every other day at 100 mg/day for up to 3-5 years (off-label use); (3) transdermal micronized progesterone does not provide endometrial protection.

The impact of micronized progesterone on the endometrium: a systematic review. Climacteric : the journal of the International Menopause Society · 2016 · PMID 27277331

Evidence scope. Systematic review/guideline synthesis in menopausal hormone therapy; directly relevant to transdermal progesterone's endometrial-protection limitation.

Claims we could not support

No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.

Dose/route: 50 mg (approximately 1/2 teaspoon of standard 2% cream) via Topical, Daily. No checked live PubMed abstract supported this complete molecule/formulation/route/dose/frequency combination.

Mechanism: Progesterone binds progesterone receptors (PR-A and PR-B) in uterine endometrium, breast, and CNS tissue. Its reduced metabolite allopregnanolone is a positive allosteric modulator of GABA-A receptors, producing anxiolyt. No checked live abstract supported this full mechanistic claim at the card's formulation/route without extrapolation.

Exact-regimen safety: Drowsiness. The verified safety row does not establish incidence or severity at every element of the card's exact regimen.

Interactions & stacking

Two different questions: what is documented about running these together, and what is documented about drawing them into the same syringe. A good pharmacological partner can still have to be pinned separately.

Documented together

DHEAUpstream precursor - monitor full hormone panel.

MelatoninBoth evening doses, complementary sleep support.

Estradiol Transdermal PatchStandard HRT pairing - endometrial protection is not optional in women with a uterus.

Climara (Estradiol Weekly Patch)Same HRT pairing.

Keep separate

Pregnenolone (high-dose)Pregnenolone converts to progesterone downstream - additive effect, adjust if combining.

Check any specific pair in the Stack & Interaction Checker, which answers both questions separately. Absence of a documented conflict is not evidence of safety.

Side effects & safety

Commonly reported

Drowsiness
Breast tenderness (early)
Mood changes
Dizziness

Less common & notes

Headache
Nausea
Application site irritation
Unscheduled bleeding

Pharmacokinetics

Illustrative plasma concentration · 3.3 h

Half-life

~5-20 minutes

(free progesterone plasma); allopregnanolone persists hours

Peak · Tmax

1-4 hours

Post-application

Elimination

12-24 hours

For most metabolites

Bioavailability

~50-80%

Transdermal (formulation-dependent)

Duration of action

~12-24 hours

Per dose

Clearance

Hepatic CYP3A4 to pregnanediol; renal excretion

Storage. Refrigerate compounded creams for best stability. Commercial creams stable at room temperature. Keep away from children and pets - skin contact can transfer hormone.

Regulatory status

Prescription-only when compounded. OTC progesterone creams (low-strength, bioidentical) are available but unregulated for content. FDA-approved oral micronized progesterone (Prometrium) is the preferred route for endometrial protection per most guidelines.

Put it to work

Calculate, log & track

Open Progesterone Cream straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.

Open Progesterone Cream in the app →

Go deeper

The guide & community

The complete Progesterone Cream walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.

Join the community ↗

Open in app Community