Another method of administering testosterone is through transdermal absorption. Testosterone is available as a transdermal delivery system (TDS) in various concentrations for topical application. Testosterone is purchased in raw form (testosterone base) by compounding pharmacies and drug manufactures to be used to create various testosterone products. A specific concentration of testosterone base is then added to a transdermal delivery system either in the form of an alcohol-based gel or transdermal cream. A patient can apply a measured amount of the gel or cream to the skin where a small amount of the hormone penetrates through the skin, absorbing into circulation. When applied on a daily basis, topical testosterone provides 24-hour duration of action, which naturally mimics the rise and fall of testosterone throughout the day.

Types of transdermal delivery systems

Transdermal delivery systems are self-contained dosage forms that, when applied to unbroken skin, are designed to deliver the drug(s) through the skin to systemic circulation. TDS works by diffusion. The drug diffuses from the carrier through the skin into general circulation. Transdermal testosterone products are available in different types of TDS. The most common types of delivery systems used for hormones are in the form of a gel, lotion, cream, or patch. Although each type of delivery system has a different appearance and texture, all of them are designed to deliver the highest concentration of active ingredient deep into the dermis. There are transdermal creams and gels that are also designed to deliver multiple active ingredients at one time. A compounded hormone combination cream is an example of a multi-drug transdermal delivery system (ie. Testosterone 10%+DHEA 10% topical cream). Compounding pharmacies have the ability to compound testosterone using different delivery systems depending on which one is best for the patient. Manufactured brand-name transdermal testosterone products are available only as either a gel or transdermal patch.

Common transdermal testosterone delivery systems

Compounding pharmacies usually carry a variety of TDS bases that can be used to make a transdermal hormone. Many pharmacies manufacture their own TDS formulas and even make improvements to existing base formulas available at the pharmacy supplier. Here is a list of common TDS bases used in transdermal hormone products including testosterone.

Lipoderm®- Transdermal cream base that is designed to deliver multiple medications or hormones through the skin.

HRT Cream base-An oil-in-water emulsion developed for use as a topical or vaginal delivery system in Hormone Replacement Therapy. Primarily used for women, this versatile base can also be used for men. It's highly absorbent and is specially designed with an emollient to help soften skin. Alternatively, this base can be used in a wide variety of other medicated topical applications.

Versabase®- Cosmetic transdermal cream base that is designed to deliver fast absorption of medication. Due to its moisturizing effects on the skin, Versabase ® can be used for both cosmetic and pharmaceutical application.

Hydro-Alcohol Gel-Alcohol is used to solubilize the skin to allow for diffusion of the hormone. Hydro-alcohol gels dry faster than transdermal creams, but can also cause drying of the skin and irritation at the site of application.

All types of TDS listed are available at compounding pharmacies.

Transdermal Testosterone Absorption

Absorption can vary between individuals who apply transdermal testosterone to the skin. The standard measurement of predicted absorption used by compounding pharmacists is at 10%. Roughly 10% of the total dosage of topically applied hormone will penetrate the skin. This means that for every 100mg of testosterone applied only 10mg will actually be absorbed through the skin. Depending on the individual sometimes less is absorbed, therefore it is important to follow up with laboratory testing so that the testosterone dose might be titrated to maximize transdermal absorption.

Men require a daily supply of 7mg-10mg of testosterone to achieve a physiological level in the upper-quartile and to reverse the symptoms of hypogonadism. Using compounded transdermal testosterone appears to be more effective than brand name (manufactured) transdermal testosterone products (Androgel, Testim, etc) for a few reasons. Higher concentrations of testosterone can be achieved in a compounded transdermal. Common strengths found in compounded topical testosterone products range between 5%-20% testosterone. 5% equals a 50mg/ml concentration of testosterone; 7% equals 70mg/ml; 10% equals 100mg/ml; etc. The highest concentration available for most transdermal hormone creams and gels is 20%, or 200mg/ml. More than 20% concentration may result in poor distribution of the testosterone, ‘clumping’ of the ingredients, and reduced absorption of the medication. Most male patients respond best to dosages between 5%-20% applied topically to reach 5mg-10mg absorption. Another reason compounded transdermal testosterone might more effective is due to the ability to provide patients a transdermal delivery system that works best for them. For example, cream based delivery systems apply better to skin in sensitive areas, such as the scrotum or inner thighs. Using an alcohol based gel in these areas can irritate the skin, therefore using a compounded cream is preferred. Some patients who do not experience skin irritation may like the consistency and faster rate of absorption found in gels. Compounding pharmacies can compound either a gel or cream depending on what the prescription calls for. If the type of delivery system is not specified on the prescription, the pharmacy will usually default to either a cream or gel base.

Available transdermal delivery systems for testosterone

Common brand name testosterone products on the market include AndroGel® from AbbVie and Testim® from Endo Pharmaceuticals. AndroGel® is a very expensive, low dose 1% (10mg/ml), testosterone product on the market since July 2000, which provides a safe, alcohol based gel containing testosterone in low physiologic doses. Due to the low concentration, larger amounts are required for adequate testosterone replacement in men. Testim®, released in 2004, seems to have slightly better absorption rate than AndroGel, making it more efficient, but it also has a low concentration of testosterone (1%) therefore the increased absorption rate may not provide significant elevation of total testosterone. Patients have also reported a slight musky odor after applying Testim®. Clinical trials have also proven that testosterone patch called Androderm®, developed by Watson pharmaceuticals in 1985, is another safe form of testosterone replacement. Androderm® is available in two strengths, as either a 2mg or 4mg transdermal patch. Due to the low strength, two patches are often needed to adequately restore testosterone. Patients who use testosterone patches have reported negative experiences including problems with the patch falling off, often when they are physically active. Patients have also reported skin irritation including a rash at the site where the patch is applied. Testosterone is also available at compounding pharmacies who specialize in hormone preparations. Compounding pharmacies have the ability customize topically applied testosterone into different strengths and combinations using a variety of transdermal delivery systems (Lipoderm, HRT, Versabase, alcohol gel). Compounding pharmacies can be used to prescribe a higher concentrated transdermal testosterone which will allow enough of the hormone to be absorbed to maintain a good physiologic level of total testosterone. In addition, testosterone can be compounded using a custom delivery system which will result in minimal skin reactions. Lipoderm, Versabase, and HRT base are delivery systems that can provide maximum bio-availability and penetration of active ingredients while minimizing skin irritation that can occur with alcohol-based gels or transdermal patches.

The higher-dose compounded testosterone creams containing 5% to 20% testosterone have been available by physician’s prescription from any compounding pharmacy specializing in hormone preparations. The cost for compounded testosterone creams are far less expensive than 1% AndroGel® Likewise, cheaper generic alternatives to can be compounded by many pharmacists. A low dose dihydrotestosterone, DHT gel, labeled Andactrim™, also from Solvay, has been available in Europe for almost a decade. Doctors who specialize in bio-identical hormone replacement therapy have been using cream and gel delivery of female hormones for decades.

Compounded testosterone creams create more physiologic testosterone levels, skin reactions are minimal and short-term discontinuation of therapy is possible due to the longer half-life of up to 25 hours. Scrotal application is also convenient and discrete while theoretically producing more DHT than when applied to other locations on the body.

Transdermal containers

There are different containers that can be used to dispense transdermal hormones. Dispensing syringes of various sizes are commonly used for hormone gels and creams. The hormone is dispensed by depressing the plunger until a measured dose releases from the syringe. Plastic or glass jars can also be used to store medicated transdermal gels and creams. The jar may come with a measuring spoon or the patient can use their finger to apply an estimated amount of hormone. Another common dispensing container is called “Topi-Click”, which looks like a deodorant container. The patient twists the dial at the bottom of the container to dispense a measured dose of transdermal hormone out of the opening at the top. 1 twist (click) of the dial equals 1/4ml of medication. Other containers might be available depending on the pharmacy. If the prescription does not request a specific type of container, then the compounding pharmacy will usually default to one of the more commonly used containers.

For more information of Topical Transdermal Delivery Systems go to: http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/transdermalStimArticle.pdf

Transdermal Testosterone Compounded transdermal testosterone cream in a Topi-Click container
Published in Defy Medical Blog

During the last year we have had an increase in reports from men stating that they are running out of their testosterone cypionate injections before the refill date. This article will hopefully help mitigate this problem. Lets first rule out those who over-draw the testosterone into the syringe, of course we must pay attention to detail when it comes to lining up the syringe plunger with the dosage line. If we are not paying attention, or have not been instructed properly, over drawing just a small amount of testosterone at each injection can result in running out of the medication prior to your refill date. There are other factors which can cause loss of testosterone as you inject regularly. If you notice at the base of your needle, where you attach the needle to the syringe, there is empty space which can trap the testosterone even after depressing the plunger completely. There always seems to be that little bit of medication that will not leave the needle space. In addition to the testosterone being trapped in the needle, there is also a small amount left behind on the internal syringe walls. This type of loss is unavoidable when using a 3ml or syringe with larger surface area for the medication to 'stick' to'. Over the course of administering ten to twenty injections using a 10ml multi-dosed bottle that little bit of lost testosterone adds up.

One of the reasons I believe we have noticed the rise in reports of men running out early during the past year is the result of increased regulations regarding the prescribing and dispensing of testosterone. It is a controlled substance which was previously overlooked by most regulators, and patients had the convenience of refilling earlier than due. I remember being able to refill 3 weeks early on a 10ml bottle. Now, with the regulations, it is 3 days to one week prior to being due depending on the pharmacy. This means we now have to be mindful of our dosage and injection technique.

There is one thing being done by manufacturers and compounders to mitigate the loss. There is also something you can do to make your testosterone last the entire time up to your refill time.

At least one brand of testosterone cypionate and most compounded 10ml cypionates are actually overfilled to help compensate for the expected loss. Pfizer's Depot Testosterone is filled over 10ML. As of 2010, if I remember correctly, close to 10.8ml. The compounding pharmacies we use all fill the bottle to 11ml, which will help compensate the unavoidable loss. We had the opportunity to confirm this in a pharmacy setting in 2010 (APS Pharmacy, FL). During this test we also were able to observe the variations in the loss of medication between different syringes. Three commonly prescribed testosterone cypionate 200mg/ml 10ml bottles were selected, including Pfizer's Depot Testosterone, Watson's testosterone cypionate, and compounded testosterone cypionate. First, using a larger 12ml syringe we drew the entire contents of each bottle to confirm they were at least 10ml. A separate syringe was dedicated to each bottle to ensure accuracy. Next, using a new bottle of each testosterone cypionate and using ten individual 3ml syringes dedicated to each bottle, we drew 1ml into each 3ml syringe. This phase confirmed that each bottle lost an average of 1ml using ten 3ml syringes to draw 1ml versus using a 12ml syringe to draw the entire contents. You must be careful to accurately measure your dosage when injecting your testosterone using a 3ml syringe.

If you are having trouble drawing with a 3ml syringe, or if you are on a decimal dosage (such as 0.75ml), try using a 1ml Luerlock syringe. It looks similar to an "insulin" or tuberculin syringe but can be attached with any size/gauge needle. The 1ml Luerlock allows any standard needle to be secured onto the syringe. Two benefits to using a 1ml syringe: 1- You will draw your dose more accurately 2- There is less surface area on the internal syringe wall for the testosterone to adhere to when your weekly dosage is split into two injections using the 1ml Luerlock. I also find it easier to inject with proper technique when personally using a 1ml syringe.

2016 update:

I am currently working with another compounding pharmacy to perform testing including a similar test as mentioned in this article. I will post the details along with pictures/video when completed.

Jasen Bruce

Published in Defy Medical Blog
Tuesday, 14 October 2014 15:04

Different types of injectable testosterone

The most common forms of injectable testosterone in the US include Testosterone Cypionate, Testosterone Propionate, Testosterone Enanthate, or a combination of different ester types (ester blend). An 'ester' is basically a chain composed of Hydrogen, Carbon, and Oxygen atoms which are attached to the testosterone molecule which must be broken down creating a 'timed release" in the body once injected. Even though the testosterone molecule remains the same no matter the ester, each one can yield different results by the way they are metabolised in the body once injected. For testosterone replacement therapy the ester does not matter as much as the timing and frequency of injections. The ultimate goal should be to restore total testosterone to a good range, or 'optimal' range, with about 2%-4% free testosterone. You can acheive this using any ester if the injection is timed correctly. The problem with using blended esters instead of a single ester is that blends can cause testosterone levels to become unpredictable or too erratic for replacement therapy. Blended preparations using multiple testosterone esters look great on paper, and they can be easier for a compound pharmaceutical rep to sell, but they are not as easy to work with clinically. One reason a doctor might include more than one ester, for example a combination of propionate and cypionate, is to provide a more aggrssive release pattern "spike" in those men who sometimes feel better due to the way they metabolize testosterone once injected. Since everyone responds differently you want to make sure you are following up until response is established. I have tried every combination of ester available (and not available) and still prefer testosterone cypionate by itself as it is predictable for me.

Always remember that each of these forms is simply testosterone, the hormone molecule remains unchanged, and the only difference is the attached "ester" which determines the half-life within the body. 'Cypionate', 'enanthate', and 'propionate' are all esters.

Enanthate: This is metabolized in roughly 4-5 days. It can even remain in the body (in very small amounts) for 2 weeks. 100mg of Testosterone Enanthate yields ~73mg of actual testosterone, the rest is ester weight. Injections can be administered every 5 days. As we all know everyone is unique in their response to drugs but from what I have seen in my experience the approximate starting doses which may bring a patient within optimal ranges (650ng-1100ng) is 100mg-200mg IM every 5-7 days. Of course many factors come into play including the patient's baseline levels and biology.

Cypionate: This is metabolized in roughly 7-8 days. This is also considered a 'long-acting' testosterone. 100mg of Cypionate yields ~68mg of actual testosterone. A good starting dose would be similar to Enanthate, more commonly between 100mg-200mg IM every 7days.

Propionate: This is a faster acting ester which can peak in the blood within hours and metabolized over 3 days. Injections should be administered every 2-3 days. You must weigh the 'positives' with the 'negatives' before prescribing propionate. Since it metabolizes so quickly, and needs to be administered frequently, it is easy to stabilize levels and optimizes blood-testosterone-levels quickly. On the downside IM injections must be given frequently which can keep patients from remaining compliant. Also, since the levels peak faster there is also an increased chance of aromatizing the testosterone into estrogen and increased DHT conversion which can cause side effects. 100mg of Propionate yields ~93mg of testosterone.

Other Esters found in TRT medicine may include;

Aqueous Testosterone Suspension: No-Ester. Requires frequent IM injections since it remains in the body only for a few hours. (Very painful injection). The risks outweigh the benefits when it comes to Testosterone Suspension and we do not recommend prescribing this particular ester.
Published in Defy Medical Blog