​Hormone Replacement Therapy — What’s the Best Route?

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 with 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 is now; 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 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 and lotions, are readily absorbed, and creams or gels provide an excellent vehicle for the administration 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.  This provides an excellent vehicle for the delivery of a medication.  In fact it is felt that virtually the entire dose of a dermal hormone is able to gain access to our body.   Certainly there is variability between individuals; some of us have thin and delicate skin, while others have thicker skin.  It is really largely due to our genetics and will unquestionable 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 lion’s share of the intended dose will make it in to the body. 
 
Recall that this physical principal applies similarly to toxic substances as well, with substances such as 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 our skin, the largest organ of the human body. 
 
While specific hormonal formulations will be discussed more fully in other writings, I feel that it is a good time to review which hormones are delivered through the skin, and what may be seen as both advantages and disadvantages to this route.  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 pellets, which require a minor surgical procedure and generally provide between 3 to 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.  But 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 a patient, whether a man or a woman, to a set dose of hormones that lasts months.   If you get the hormone dosing wrong, you’ve bought 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 can cause scarring and the presence of a nodule, or masses beneath the skin.  Finally , there is little evidence that the hormone released is done so in a stable and sustained fashion.  Based on a patient’s symptoms and experience, I get the sense that levels are higher in the beginning, then dropping as the implant loses its contents.
 
So my preference for administration of hormones to 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 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 (systemic) absorption of the drug along with a local effect of supporting and tonifying the vaginal tissues as well.
 
But what about using a hormone orally?  There is good data to show that hormones are absorbed both through the oral cavity, namely the mouth and gums, as well as through the GI tract.  Oral formulations of drugs such as oral contraceptives (birth control pills) have been in use for decades, and we are well accustomed to taking a medicine via an oral route.  For a medication such as testosterone, the response to an oral formulation should be uniformly “no”.  Oral testosterone has been associated with liver disease, and while an oral form of the hormone is available in Europe, this delivery method in the United States is verboten.  I suspect that this toxicity results from the hormone’s pass from the absorptive lining of the gut into the portal system of vessels, which then drains into the liver for processing and detoxification.  Testosterone administration should be performed either dermally, or ideally through intramuscular injection.
 
A similar condition exists for estrogen, and for the many “estrogen-like”  formulations that are marketed to the public as estrogen.  For the record, a hormone made from the urine of a pregnant horse is not estrogen, although it may have a biologic effect to activate and turn on an estrogen receptor.  Estrogen has a specific structure and molecular formula.  Be sure to ask for it by name.
 
Estrogen, when administered orally is similarly transported to the liver, where the hormone instructs the liver to up-regulate, or increase the production of several proteins.  Several of these proteins are involved in the clotting process, and in genetically predisposed individuals this additional protein production can promote the formation of a blood clot.  This can result in simply the nuisance of a superficial, painful clot; a more serious condition with a clotted vessel known as a deep vein thrombosis; or in a worse case scenario a terminal event with the passage of this clot to the lungs where it can block blood flow to the heart and brain- a  pulmonary embolism.
 
As with so many things in medicine, the devil is in the details.   I frequently see patients who have been started on a hormonal regimen with apparently little attention to correct dosing, metabolism and clearance of the hormone, or its best route of administration.  All of these factors contribute to the safety and efficacy of the medical intervention.  And most importantly, this should always be individualized.  If you are even in a clinic and the provider assigns you to a pre-printed assignment or dosing schedule you should run away.  There is no “one size fits all” for shoes, and certainly less so for the replacement of a something as unique to each of us as our hormones.
 
Find the right doc, the right medication, the right dose and the correct route of administration.  Attention to these details up front will serve your health and wellness long into your hormonal future.