What factors influence the absorption of topical hormone creams?

Factors Affecting Absorption of Hormone Creams

The absorption of topical hormone creams is primarily determined by application site (abdomen absorbs fastest, followed by arms, thighs, and buttocks), formulation type (ointments provide more consistent absorption than creams or solutions), skin temperature and blood flow, and the specific physicochemical properties of the hormone molecule itself. 1

Application Site and Regional Variation

• The abdomen demonstrates the fastest rate of hormone absorption, followed by the arms, thighs, and buttocks in descending order. 1

• Application site selection significantly impacts absorption variability—rotating within one anatomical area (e.g., systematically within the abdomen) rather than switching between different body regions reduces day-to-day absorption variability. 1

• Transdermal testosterone preparations applied to different sites show this regional variation clearly, with recommendations to apply to skin of the back, abdomen, upper thighs, and upper arms depending on the specific product. 1

Formulation Type and Vehicle Effects

• Ointments provide even distribution across the treated area and more consistent absorption compared to creams and solutions, which spread unevenly with lower doses at the periphery due to rapid water/alcohol evaporation. 2

• The vehicle/formulation is one of the most clinically pertinent factors affecting percutaneous absorption, with microemulsion formulations significantly enhancing both stratum corneum flux and transport rate for multiple hormones including testosterone and hydrocortisone. 3, 4

• Transdermal hormone gels (like AndroGel, Testim) require application to specific sites and carry risk of transfer to partners or children through skin-to-skin contact, whereas ointments and patches do not pose this transference risk. 1

• The original testosterone formulation in olive oil showed approximately 40% absorption, while newer microemulsion formulations yield 10% higher bioavailability with more consistent pharmacokinetics. 1

Skin Temperature and Blood Flow

• Exercise and increased skin temperature (from sunbathing or hot water exposure) significantly increase absorption rates by enhancing blood flow to the skin. 1

• Increased skin surface temperature directly correlates with enhanced hormone absorption—this is why insulin absorption increases with heat exposure, and the same principle applies to topical hormones. 1

Skin Condition and Integrity

• Areas of lipohypertrophy or damaged skin show altered (usually slower) absorption patterns. 1

• Skin hydration status, pH, and the presence of trauma or skin diseases all modify percutaneous absorption of hormones. 3

• The stratum corneum serves as the major barrier to chemical transfer through the skin, and its integrity is crucial for predictable absorption. 5

Timing Relative to Meals

• For oral hormone preparations that undergo first-pass metabolism, timing matters—but for transdermal preparations, preprandial application may increase absorption compared to postprandial application based on pharmacokinetic studies with microemulsion formulations. 1

Dose and Application Technique

• The concentration of hormone in the vehicle, surface area of application, duration of exposure, and frequency of application all affect total systemic absorption. 3

• Rubbing or massaging the application site can enhance penetration, though this is not always desirable depending on the therapeutic goal. 3

• Inadequate quantities lead to under-application—for reference, adults typically require 15-30g per 2 weeks for face/neck areas, 30-60g for both arms, and 100g for trunk when using topical preparations. 6, 7

Systemic Absorption Considerations

• Vaginal hormone creams demonstrate rapid, efficient, and sustained systemic absorption—resulting in sustained high estrogen levels in the systemic circulation, not just local effects. 8

• This systemic absorption from vaginal application is clinically significant and can be dangerous when systemic estrogen is contraindicated. 8

Physicochemical Properties of the Hormone

• Molecular size, polarity, and lipophilicity of the specific hormone determine maximum epidermal flux—smaller, appropriately lipophilic molecules penetrate more effectively. 4

• The partition coefficient between the membrane and donor vehicle, along with the diffusion coefficient in the membrane, mathematically determines permeability. 1

Common Pitfalls to Avoid

• Avoid switching between different formulation types (gel to cream to ointment) as this creates unpredictable absorption patterns and potential therapeutic failures or toxicity. 1

• Do not apply hormone creams immediately after bathing in hot water or before exercise, as this dramatically increases absorption and may cause excessive systemic levels. 1

• Creams and solutions must be spread quickly to multiple sites to prevent uneven dosing from rapid evaporation, whereas ointments can be applied more slowly. 2

• For transdermal gels, failure to cover or wash the application site before skin-to-skin contact risks transferring hormones to partners or children. 1