library.onepin.app/progesterone-cream Peptide Education Library
Education only, not medical advice 21+ Every dose is an example to finalize with a licensed provider

OnePin Peptide Library · Hormonal

Hormonal Hormone replacement therapy Prescription drug

Progesterone Cream

Bioidentical Progesterone · Topical Progesterone

Hormone replacement therapySteroid 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 (approximately 1/2 teaspoon of standard 2% cream)
Frequency
Daily
Timing
Anytime

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
Quick Start
Conservative start
50 mg (approximately 1/2 teaspoon of standard 2% cream) · Topical · Daily
Lowest starting point. Hold about a week to assess tolerance before stepping up.
50 mg (approximately 1/2 teaspoon of standard 2% cream)
Daily
Standard
Estrogen Dominance Balance
20-40 mg · Topical · Daily
human clinical trial · Leonetti et al. 1999 (Obstet Gynecol)
20-40 mg
Daily
01

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.

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.

02

What to expect

Early
Days 1–7

1-7 days: sleep improvement

03

Evidence

HumanModerate
AnimalPresent
In-vitroStrong
1999Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss · Leonetti HB et al, Obstetrics & Gynecology ↗peer reviewed
2000Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern, and plasma progesterone and salivary progesterone levels in postmenopausal women · Wren BG et al, Climacteric ↗peer reviewed
2003Transdermal progesterone and its effect on vasomotor symptoms, blood lipid levels, bone metabolic markers, moods, and quality of life for postmenopausal women · Wren BG et al, Menopause ↗peer reviewed
2005Transdermal progesterone cream as an alternative progestin in hormone therapy · Stanczyk FZ et al, Altern Therapies in Health and Medicine ↗review
04

Interactions & stacking

What's safe to combine, and what belongs in a separate pin.

Safe & synergistic

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.
05

Side effects & safety

Commonly reported

  • Drowsiness
  • Breast tenderness (early)
  • Mood changes
  • Dizziness

Less common & notes

  • Headache
  • Nausea
  • Application site irritation
  • Unscheduled bleeding
06

Pharmacokinetics

Illustrative plasma concentration · 24 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
Activity
~12-24 hours per dose

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

07

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.

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