By Monica Zatarski, PharmD, RPh
Topical application of bio-identical hormone therapy continues to gain more popularity with patients and practitioners as a convenient, practical, and effective means of administration. One reason for this increase in popularity, is that there are more risks evident with the oral administration of estrogen. In addition, studies continue to show that orally administered estrogen cannot achieve the biologic ratio of estriol to estradiol that normally exists (too much oral estrogen ends up being converted into the riskier estrone estrogen). Orally administered testosterone is absorbed readily. However, the majority of orally administered testosterone is rapidly converted to estrogen by the First Pass Effect in the liver. This is even a larger issue given the larger doses of testosterone given to men.
With the increased use of topical hormones, a thorough understanding of use is critical to ensure safe and clinically successful outcomes. Sex steroid hormones are low molecular weight, lipophilic molecules and therefore are good candidates for absorption across the skin. Conventional patches, creams and gels have all demonstrated good absorption and clinical outcomes with trans-dermal estradiol and testosterone.
Unique pharmacokinetics exist for topically administered hormones. An understanding of the delivery, metabolism, and storage of topically administered hormones is critical to obtaining symptom control at physiologic levels. One of the primary issues affecting the delivery of topically applied hormones is the vehicle base. When the hormones are applied to the skin they con concentrate in lipophilic tissues including subdermal adipose tissue and the skin cement. The lipophilic tissues tend to store the lipophilic hormones and release them slowly into the lymphatic system which in turn results in the hormone being slowly released into the blood stream where the hormone is then delivered to tissues throughout the body. The desired target for the hormone needs to be considered when selecting the base vehicle. Vehicles that contain penetration enhancers drive the hormone through the skin cement and into the blood stream quickly resulting in a quick response. However, since the hormone is being driven through the skin cement, the hormone will not depot, which results in the effect of the hormone being shorter acting. Therefore, hormones delivered in penetrating enhancing vehicles (which includes alcohol based gels) will require either more frequent application and/or higher amounts of hormones to achieve the effect achieved with a typical topical cream. Hormones delivered in a topical cream [without penetration enhancers] will result in more of the hormone being deposited into the lipophilic skin cement resulting in a longer depot effect. The main therapeutic difference with hormone being delivered via a topical cream is that the full therapeutic effect of the dose may not be experienced instantly.
Practitioners also need to consider that where the hormone is applied affects its delivery. Applying the cream over adipose tissue provides a depot effect and would opt for less frequent dosage, however the time to experience therapeutic effect may be delayed.
The volume of the dose applied is also important to consider. Application over a larger area of skin would result in more of a depot effect due to greater storage in the larger area of contacted skin. Applying too large of a volume is not convenient for patients; as well as applying large volumes of cream provides for a greater chance of transferring if not rubbed in well. A practical compromise would be to place the dose in a small volume of base (for example ¼ – ½ mL).
Topically applied hormones require the utilization of saliva or capillary blood for testing, as these are the only solutions that correlate well with the increase of hormones at the tissue receptor sites. Incorrect interpretation of serum testing can result in an overdose of topically applies hormones. An example of this is seen with the [commercial] testosterone use in men. It makes no sense that commercial topically delivered hormones correlate well with physiologic doses produced except for testosterone supplementation in males. A 25mg dose of testosterone represents a dose of testosterone 4-5x what a male would produce when young (in his 20’s). These large doses of testosterone have been determined to be necessary based on the interpretation of serum levels with topical application. Venous serum is a storage system in the body; taking away materials that the body does not need or want to the kidney or liver to be eliminated. Just like oxygen can not be measures in venous blood since it enters the body through the lungs and is delivered directly to the tissues, we can not measure topically applied hormones in the serum since they too are delivered directly to the tissues. Topically applied hormones found in venous serum are only indicative of excess dosing that the body in turn needs to clear. Excessive levels of hormones cause down regulation of tissue receptors for that hormone (called tachyphylaxis), which results in symptoms of hormone deficiency [due to the loss of hormone receptors]. This in turn leads to further dose increases in order to deliver the desired effect, resulting in increased risks associated with supra-physiologic dosing.
Hormones have very strong actions in the body and accurate dosing is critical. Hormone creams and gels should be dispensed in a container that provides easy and accurate delivery of dose. Jars should be avoided because of the possibility of contamination, degradation of the product, repeated exposure to air, and inaccurate precision in dosing.
Understanding the pharmacokinetics of topical administered hormones and the variance associated with base selection, volume, site of application and even packaging can affect the therapeutic outcome and can greatly increase the ability to achieve maximum efficacy with hormone therapy. By understanding how topically administered hormones work, a practitioner will be able to adjust application parameters in order to make a therapy more effective. Alleviating symptoms without having to increase a dose of hormones will help obtain the goal of utilizing bio-identical hormone therapy to resolve symptoms at the lowest physiological dose. If you need help with this speak with one of the pharmacists at MD Custom Rx today.