The Best Route to Hormone Replacement for Men and Women

So you and your physician have decided that the best thing for your health, your wellness, your sexuality, your cognition, your erections, your stamina or your menopausal symptoms is to initiate a course of hormone therapy.  

You have hopefully discussed the risks and benefits of therapy, and with a physical exam in conjunction with appropriate laboratory testing have chosen a dose of hormones that will be initiated.  This all seems pretty simple, and you leave the doctor’s office with a prescription in hand, or a call being made to your preferred Walgreens (although I would recommend that the call be made to the closest compounding pharmacy).  The salient question now is: have you been placed on an appropriate dose and delivery route of the hormone, and do you have a plan in place to monitor this medical regimen safely?

The safety of hormonal replacement for both men and women will be discussed in another post, as each merits a detailed look at the factors that contribute to the safe use of a medication, the current understanding of the risks and benefits, and the cultural implications and understanding.  Everything that we ingest, whether it is a drug, food or even simply water, has a toxic threshold, and as with all aspects of functional medicine, the trick lies in finding the correct balance for therapy.  Based on an individual’s needs, genetics and medical history, one dose or route of administration may not function across the board for all patients.  In spite of all of the technology, studies and testing available at our disposal, there is still an art to the practice of medicine.  Hormone replacement therapy is the artist’s studio.

To understand the potential considerations that should be made in the course of deciding your individual therapy, we first need to review a little biology, and to remind ourselves how substances enter our body.  Our largest organ is our skin, and a dermal approach is very effective for the transport of medications, nutrition and toxins into our circulation.  Typically substances that are aqueous, or water-like, generally do not penetrate well into our skin.  If that were the case we would all swell up like sponges in the rain.  Fats, on the other hand, found in creams, gels and lotions, are readily absorbed, and provide an excellent vehicle for the delivery of several medications to the human body.

So there is little debate that a lipid, or fat based substance is able to penetrate the skin.  Studies show that virtually the entire dose of a dermal hormone is able to gain access to our body.  Certainly there is variability between individuals, as some of us have thin and delicate skin, while others have thicker skin.  Our genetics unquestionably alter the absorptive rate between some groups, but in general it is fair to say that if a dose of a medication is placed on the skin of an average individual and left on the skin for a reasonable amount of time, the majority of the intended dose will make it in to the body.  

(Recall that this physical principal applies similarly to toxic substances as well, with heavy metals, polycyclic aromatic hydrocarbons, herbicides, and fungicides all having access past the protective layer of the skin.  And the list goes on.  At the time of this writing there are more than 54 million different kinds of chemicals that have been developed by humans on our planet.  You can bet that more than a couple are toxic, and can pass through our skin.  So I believe that it is very important to strongly consider what it is that we are putting on and in our skin.)  

Specific hormonal formulations will be discussed more fully in other writings, but this is a good time to review which hormones are delivered through the skin, and what advantages and disadvantages this route offers.  The hormones most commonly prescribed for female patients are estrogen, progesterone and testosterone.  These are all readily absorbed through the skin, and for this group of hormones the skin may be the best route.  Other formulations include the use of sublingual (under the tongue) troches and implanted pellets, which require a minor surgical procedure and generally provide between 4 and 6 months of hormone release.

In my practice I avoid the use of the troches, although they seem to be relatively popular in this part of the country.  There is ample literature to suggest that an oral dose of estrogen activates the liver, and increases the production of some of the clotting proteins.  This is likely the association that correlates the use of birth control pills with a greater risk of blood clots and strokes.  A troche is supposed to be held under the tongue, with the hormone absorbed through the gums.  But is it?  My concern is that a significant enough amount is swallowed to merit reconsidering the use of other, equally efficacious routes of administration.

I am similarly not a great fan of pellets, which effectively commit an individual, man or woman, to a set dose of hormones that lasts months.   If you get the hormone dosing wrong, you are committed to it until the hormone stores wear down and you speak to your provider about the next dose.  It also involves a fairly minor but not inconsequential surgical procedure to place the pellets, which in many cases cause scarring and the presence of a nodule or mass beneath the skin.

So my preference for administration of hormones for females is unquestionably through the use of dermal lotions, gels or creams.  This route of administration provides a steady, easily applied and reproducible dose of the hormone.  It can be readily modified and changed over a short period of time, and compounded to the exact specifications of the woman’s needs.  But let’s not forget that alternative dermal routes of administration exist as well for a female patient.  For the woman with genital symptoms, most commonly dryness or pain with intercourse, a vaginal administration of hormones does double duty- it provides whole body absorption of the drug along with a local effect of supporting and tonifying the vaginal tissues as well.

For my female patients I feel that the greatest safety, ease, adjustability is found through the use of dermally applied hormones.  However data published late 2014 in Menopause magazine by Dr. Zava, showed that for dermally applied hormones, the levels changed in different body fluid compartments.  This is to say that measured hormone levels, when applied dermally, are underrepresented  by a simple blood test.  A more accurate way of determining your actual levels of the hormone in the body are to perform testing through saliva or through newer testing known as bloodspot testing.   

For the most part, the rules surrounding hormone replacement for the male patient reflect the cautions and considerations outlined above.  The oral use of Testosterone is strongly contraindicated, and is associated with cancer of the liver.  The most physiological way to administer testosterone may be through injections, but this generally requires that the man self-administer a shot twice weekly.  The injected testosterone can be followed with standard blood testing, but too often prescribing doctors fail to ask the essential questions of how the hormone is being metabolized, and do not measure the essential testosterone metabolites of estrogen, estrone and DHT.  These metabolites are well associated with cancers and cardiovascular disease.  So why is your doctor not checking them of you are on hormone replacement?

Testosterone Replacement Therapy (TRT) applied through the skin is similarly well absorbed, and it is reasonable to assume that the majority of the dose of a drug will make it past the skin into the patient’s circulation.  While the Zava study only looked at the hormone progesterone, it is safe to say that dermal testosterone should be similarly followed with salivary or blood spot testing.  It is also reasonable to examine the dose of testosterone that is being used.  The typical male testis makes about 5-7 mg of the hormone daily.  The starting dose of commercially sold products such as Androgel is 50 mg- nearly 7 times the amount of the hormone produced physiologically!  The next interval dose for Androgel is 75, then 100 Mg!   Some recent studies have suggested that TRT increases cardiovascular disease in men, and while study design flaws severely limit the interpretation of these studies for clinical practice, this may simply reflect what happens when we overdose a drug from 7-15 times, and fail to properly monitor the levels.  Stay tuned, I will review these studies in greater depth in another post.

The bottom line is that a functionally trained physician is best suited to evaluate your hormonal needs, determine the best route of administration, and to follow the levels to provide a balanced, physiological and safe experience.  Does the decline in our hormones cause aging, or does aging promote a decline in hormone levels?  I think that both statements are true.  Given the opportunity, I would like to think that appropriately diagnosed, prescribed, and monitored hormonal regimens can minimize the effects of aging, help to balance our myriad biological functions, and to promote a longer and healthier life.