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"Transdermal Delivery of Steroidal
Hormone Precursors"


Topical products have been used for centuries for treating local skin disorders, but using transdermal delivery systems (TDS) for systemic delivery of drugs, hormones, and even nutritional factors is relatively new and gaining rapidly in popularity. 

For example, look at widespread use of estrogen and testosterone patches. The administration of the steroid hormone precursors ptegnenolone (PREG) and DHEA, as well as the natural hormone progesterone, via the transdermal route has some important advantages over the oral delivery of these substances via standard capsules and pills.

Three primary factors must be considered in developing an effective system for transporting PREG, DHEA, and progesterone across the skin and into the general circulation:

        * The physiological, biochemical and biophysical properties of skin

        * The physicochemical properties of the hormones and the delivery system

        * The interactions between skin and the delivery system

Because the skin is the largest metabolizing  organ in the body - even larger than the liver - it’s important to realize that the skin is capable of metabolizing certain agents administered transdermally into inactive or potentially harmful metabolites. Even if you overcome this factor, you have to make sure that the agent has the capacity to permeate the skin. Plus, you need to know that the skin has the capacity to bind the agent to a point of saturation before distribution of the agent via the bloodstream can commence.

The effective transdermal application of PREG, DHEA, and progesterone hormones is possible because these prerequisites are all met:

        * These steroidal hormones are small, fat-soluble molecules that are easily absorbed across the skin where they can be stored in the fat tissues.

        * The hormones can reach a saturation level that is sufficiently high so that the fatty tissue diffuses them into the capillaries for uptake by the general blood circulation and transports them to
the target tissues.

        * During the transdermal delivery process, the skin does not inactivate these steroid hormones, nor does it produce harmful metabolites from them.


An excellent composition for transporting PREG, DHEA, and progesterone through the skin is an oil/water emulsion that contains components of the fatty tissue of the skin along with suitable permeation enhancers. The fatty tissue skin components include vitamin A, vitamin E, and cholesterol.

Permeation enhancers are substances that are especially compatible with steroid hormones, because they enhance the skin’s permeation of these hormones when they are administered at the same time. (Remember: the skin forms a protective barrier that must be penetrated.) Effective permeation enhancers include alcohol (such as ethanol and isopropanol), polyethylene glycols, fatty acid molecules with 10 to 20 carbon rings and certain, mono-, di-, or triglycerides of fatty acids.

Other possible ways of enhancing transdermal delivery include the use of liposomes and nanospheres. Liposomes are hollow spheres made from phospholipids (such as lecithin) that are up to 300 times smaller than skin cells. These liposomes are filled with agents (in our case PREC, DHEA, and/or progesterone) which gradually into the skin and gradually release.

Nanospheres are even smaller micro-reservoir particles. These porous polymers have a special structure permitting very high absorption and timed release of the agents into the skin. Because liposomes and nanospheres are timed release media, one must consider the rate of release and lag time of the agent for reaching skin saturation in order to diffuse into the capillaries and enter the blood stream.

A proper TDS for administering PREG, DHEA, and progesterone: can provide close to the same level of delivery of these steroid hormones as intravenous (IV) injection. IV injection is considered to be the perfect delivery system for this type of agent, but unfortunately, it requires medical supervision for best results.

By comparison, transdermally delivered steroidal precursors and hormones are up to 80%’ more bioavailable than equivalent dosages of orally administered steroid hormones. This has been proven by salivary hormone testing. In other words, oral delivery systems provide only a fraction of biological activity in comparison to the same dosage of steroid hormones administered from a TDS.

In practical terms, an oral dose of 25 mg DHEA might be equivalent to 5 mg transdermally. The significance of this is mostly economic - you don’t need to use as much of the hormone when you use the transdermal form. Some people, less concerned about the cost and more concerned about convenience, may still choose to take the oral forms.


Oral delivery systems of PREG, DHEA, and progesterone, in general, are less efficient for several reasons:

Individuals may have difficulties in absorbing these fat soluble substances.

Improperly formulated pills using the wrong binder agents and apsules using the wrong flow agents could impede the absorption of the steroids from the gut. After a hormone is absorbed from the gut, it is transported via the portal vein directly to the liver where much of it is metabolized and conjugated for excretion in the bile. This is called-first puss loss (or first-pass metabolism) through the liver.

If you add together the ingredient losses in each of the above-mentioned steps, you come to the conclusion that oral delivery is less cost effective than a TDS for administering PREC, DHEA, and progesterone. It should be added, however, that oral delivery of DHEA and PREG is more convenient for many people, especially given that morning usage is preferred. [With this Issue of Life enhancement, we are introducing a transdermal DHEA and PREG cream called DP-Transdermal


Reference:
1. Labrie C; Flamand M, Belangcr A, Labric F. High bioavailability of dehydroepiandrosterone administered percutaneously in the rat. J Endocrin 1996; 150 (Suppl): S107 - S118. ISSUE 31 LIFE enhancement MARCH 1997


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