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.
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.pdfCompounded transdermal testosterone cream in a Topi-Click container
The removal of blood for health purposes has been practiced for several thousand years. Across many societies the act of “bloodletting”, or removal of blood, was thought to cure a multitude of ailments. Ancient Egyptians (circa 1000 BC) believed that occasionally self- sacrificing some blood improved spirituality and cured the body of any illness present. Other ancient societies like the Myan’s encouraged bloodletting for religious purposes.
Throughout the advancement of our understanding of how the human body works we slowly realized that getting rid of blood does not cure all illnesses, however there is a benefit from this procedure under specific circumstances.
Today we call the procedure of removing excess red blood cells Therapeutic Phlebotomy, which is the treatment of choice for blood disorders in which the removal of red blood cells and/or iron is needed to manage disease symptoms and reduce complications.
‘Polycythemia’ is one of the more common conditions effectively treated using therapeutic phlebotomy. Polycythemia is an excessive production of red blood cells. With polycythemia the blood becomes very viscous or "sticky," making it harder for the heart to pump. High blood pressure, strokes and heart attacks can occur in left untreated. People with polycythemia usually experience fatigue, weakness, headaches, and hypertension. Polycythemia is a symptom which occurs with a variety of known and sometimes unknown origins.
Here are just some examples of known origins of polycythemia;
• Heavy smoking • Dehydration • High levels of stress • Lung diseases or disorder • Certain medications and drugs • Exposure to high altitudes • Too much Testosterone (see below) • ObesityTestosterone (TRT) & Elevated Red Blood Cell Production- Polycythemia
Some men and woman are genetically prone to getting polycythemia, and more commonly people have poor lifestyle choices which result in too many blood cells (smoking, for example). The association between testosterone replacement therapy (TRT) and polycythemia has been reported for the past few years as the use of testosterone replacement has become more common. In addition to increasing muscle and sex drive, testosterone can increase the body's production of red blood cells. This hematopoietic (blood-building) effect could be a good thing for those with mild anemia.
Most men on Testosterone Replacement Therapy who are being properly monitored by an experienced TRT doctor do not experience polycythemia. Women taking testosterone typically do not have to worry about polycythemia resulting from the testosterone itself due to being prescribed a much lower dosage of testosterone than men (Read more about Testosterone in Women-make clickable to: http://defymedical.com/blog/item/18-testosterone-replacement-for-women-too ) For those patients who do experience elevated red blood cells it can be effectively reversed with a therapeutic phlebotomy where typically one pint or blood is removed and discarded. This could also be done by volunteering for a blood donation in which one pint is usually taken. Doctors may prescribe a therapeutic phlebotomy every 8-12 weeks for patients with persistent polycythemia, or more frequently until the red blood cells return to normal.
Once the phlebotomy (or donation) is complete many patients immediately feel better and high blood pressure returns to normal. People who suffer from chronic polycythemia may need routine therapeutic phlebotomies to keep red blood cells within a consistent healthy range.Testing Hematocrit Is Important for Patients on TRT
Follow up blood testing is required at least twice per year for any patient receiving hormone and testosterone medications. One of the reasons follow up testing is important is to monitor red blood cells including one of its primary components called hematocrit. The test that measures your blood cells including hematocrit is called the Complete Blood Count or CBC.
An experienced TRT doctor will make sure blood cells and hematocrit are maintained within a healthy normal range and will correlate test results with your testosterone levels and lifestyle factors, making adjustments to medications if needed along with ordering a Therapeutic phlebotomy if hematocrit becomes too high.
Here is a very informative article which explains polycythemia caused by TRT and how to effectively manage it.
How to Manage High Red Blood Cells Caused By TRThttp://www.defymedical.com/resources/health-articles/308-how-to-manage-polycythemia-caused-by-testosterone-replacement-therapy
Other Possible Health Benefits
Therapeutic Phlebotomy can be an important new method of treatment for some patients, especially for people who suffer from hypertension (high blood pressure). A small study conducted by Immanuel Hospital in Berlin found that therapeutic phlebotomy caused a marked decrease in both blood pressure and “bad” cholesterol levels. This latest study was prompted by earlier research which suggested regular blood donors have lower cholesterol and reduced risk of heart problems and stroke.
Defy Medical patients who receive therapeutic phlebotomy for the treatment of high hematocrit and high blood pressure have been observed to have an immediate decrease of blood pressure, returning to a normal range. Other studies show that diabetics had better blood sugar control when they had blood regularly removed.
Although anecdotal, almost every patient who completes a therapeutic phlebotomy at Defy Medical has reported an increase in energy and well-being during the days following the treatment.Defy Medical Offers Therapeutic Phlebotomy at our Tampa Clinic
During your treatment you will receive:
• Hematocrit test administered before treatment- Immediate results • Blood pressure and examination before and after treatment • Therapeutic Phlebotomy performed by our Registered Nurse • Q&A discussion during treatment with experienced clinician • No wait time • One-on-one care during treatment • Appointment Reminders when routine treatments are needed • Average time for treatment: 1 hour
How to Manage Polycythemia Caused by Testosterone Replacement Therapy (TRT) by Nelson Vergel: http://www.defymedical.com/resources/health-articles/308-how-to-manage-polycythemia-caused-by-testosterone-replacement-therapy
Elevated E2 During TRT: To Treat or Not To Treat?
TRT may lead to elevations in serum estradiol (E2) and in some cases to levels above the upper limit of normal. The development of nipple or breast tenderness or frank gynecomastia has been reported in association with TRT, and in these cases there is a clear indication for the use of aromatase inhibitors to reduce E2. Some authors recommend with- drawal ﬁrst of TRT with subsequent resolution of symptoms, followed by the use of aromatase inhibitors together with reinitiation of TRT . Some clinicians, particularly in the antiaging com- munity, advocate the routine use of aromatase inhibitors with TRT even in the absence of symp- toms of estrogen excess. These clinicians believe that maintaining a relatively low estrogen concentration improves male health and the efﬁcacy of TRT.
However, the basis for this belief is uncertain. In one randomized controlled trial, treatment of men with low T with anastrazole normalized T levels, but there was no improvement in symptoms of low T or changes in body composition, muscle strength, or hematocrit . Further studies of this nature are needed. Furthermore, E2 levels in some men treated with aromatase inhibitors decreased below 40 pmol/L, considered the threshold at which there is increased risk of developing osteoporotic changes. Additionally, case reports of men with congenital aromatase deﬁciency suggest that aromatase inhibition may risk decreasing insulin sensitivity, potentially worsened by TRT [44,45].
The only trials identiﬁed in this review that compared the use of TRT with and without an aromatase inhibitor were conducted in men with hyposexuality and seizure disorders. One trial showed a signiﬁcant beneﬁt in sexual interest from the addition of testolactone therapy . A second trial involving 40 men reported a trend toward improved libido in men treated with T and anastrazole over T alone, although this did not reach statistical signiﬁcance. Some men in the T-only group reported improvement in libido despite increases in E2 with TRT .
The results of these studies should be interpreted with caution as it is not clear how this group compares with the larger group of T-deﬁcient men. These men were all treated with antiepileptic drugs such as phenytoin and carbemazapime, which increase SHBG, likely through induction of hepatic synthesis, and may therefore impact androgen and estrogen concentrations and metabolism. Impotence, decreased libido, and infertility are common and associated with a deﬁciency in free T despite normal total T levels . E2 levels are increased in hyposexual men with epilepsy compared with men with normal sexual function and with healthy controls .
We therefore ﬁnd no evidence to support the contention that relative reductions in E2 via the use of aromatase inhibitors or other agents in conjunction with TRT offer beneﬁts beyond that offered by TRT alone. Anecdotally, in our practice, there have been rare cases of men who failed to experience symptomatic beneﬁts from TRT and were found to have elevated E2 concentrations. Some of these men have responded to steps to lower E2 concentrations, either by reduction in T dosage or by addition of aromatase. However, these cases are anecdotal, and even if treatment was beneﬁcial, the rarity of such occurrences does not justify the routine use of aromatase inhibitors together with TRT. Moreover, aromatase inhibitors may reduce E2 levels below a crucial threshold for bone health, and dual-energy X-ray absorptiometry (DXA) monitoring should therefore be considered for individuals receiving such therapy.
Nelson Vergel www.ExcelMale.com
www.ExcelMale.comSource: Estrogens in Men: Clinical Implications for Sexual Function and the Treatment of Testosterone Deficiency Ravi Kacker, MD,* Abdulmaged M. Traish, PhD,† and Abraham Morgentaler, MD* *Beth Israel Deaconess Medical Center, Harvard Medical School, Urology, Boston, MA, USA; †Laboratory for Sexual Medicine Research, Boston University, Boston, MA, USA International Society for Sexual Medicine
Sarcopenia is defined as the loss of muscle, fat free mass (FFM), and loss of strength experienced by men and women as they age. This is usually coupled with an increase in body fat. This change in our body resulting partly from a decline in testosterone and GH levels results in an increased risk for injury and also metabolic disease. Testosterone plays a role in restoring glycogen and increasing nitrogen in muscle tissue; both processes are important for the maintenance of muscle. When testosterone declines so does the ability to support muscle.
Men and women start Testosterone Replacement Therapy (TRT) for different reasons, all commonly diagnosed as having some degree of hypogonadism with symptoms. One thing is certain, TRT will help slow down (prevent) sarcopenia during the aging process. When low testosterone is properly restored in older men and women with existing sarcopenia they can experience a reversal of symptoms and improved quality of life. Incorporating strength training and a high protein/low glycemic diet will result in the opposite of sacropenia- a decrease in body fat with an increase in muscle and strength.
A paper titled "Anabolic Interventions for Age-Associated Sarcopenia" discusses how sarcopenia is influenced by hormones, nutrition, and excersise. The authors examine some clinical data regarding specific hormones, nutritional supplements and their effect on body composition. The full paper in PDF is available for free in the Defy Medical clinical study archive- Contact us to receive access. The paper was written in 1999 and since then there has been more data collected regarding the anabolic effects of testosterone on body composition.
Preventing and Reversing Sarcopenia can prolong lifespan
Interestingly, another paper shows that people who have more muscle and less fat live longer lives. Not to mention a better quality of life. The study is titled "Muscle Mass Index As a Predictor of Longevity in Older Adults" and is also available for free by requesting a copy.
" Aging is associated with significant reductions in fat free mass, and an increase in adiposity. The principal component of the decline in fat free mass is a decrease in muscle mass due to a reduction in muscle protein content and synthesis rates. The loss of FFM is associated with loss of muscle strength and function and with increased disability and mortality (6). The body composition changes in old age are multifactorial and may be related to the concomitant changes in hormone production, protein turnover, and disuse atrophy. The evidence to support the use of testosterone or GH supplementation in age-related sarcopenia is only beginning to be presented"
"The age-associated changes in body composition result from lower levels of anabolic hormones, neuromuscular alterations, and a general decline in muscle protein turnover (1–3). The frailty of old age has emerged as an important public health problem because it impairs mobility and quality of life and increases the risk of falls and the use of health care resources (4–6). Therefore, recent years have witnessed a growing interest in the use of anabolic interventions for augmenting muscle mass and function in older men"
Testosterone is often mistakenly defined as a hormone that is important for men only. Studies and practical obervation has shown that testosterone is a very important hormone for women too.
Women experience a rapid decline in sex hormones such as estradiol and testosterone while aging. Other important hormones that can decline with age or illness include those produced by the adrenal and thyroid glands. Although women produce a much lower amount of testosterone than men, this decline is noticed throughout the whole body. Research has shown that testosterone is responsible for a women’s sexual desire and responsiveness, mood, sense of well-being and mental acuity. The Women’s Health Institute at the University of New Jersey suggests that androgens (testosterone) play a significant role in affecting pre-menopausal and post-menopausal symptoms and quality of life
As it does in men, testosterone supports bone density and muscle tissue. Increased bone density is critical because of the increased risk of osteoporosis women face as they age. Women produce their testosterone in the ovaries and adrenal glands and typically lose 70 percent of the hormone by the age of 40. This decrease can cause most, if not all the effects listed above. Some other effects of low testosterone in women include increased risk of cardiovascular disease (Med. Suisse Romande2003 Mar) and increased risk of Alzheimer’s (Cell mol Life Sci. 2005 Feb). A simple blood test through a physician can determine the level of testosterone in the body and therefore can detect a deficiency.
The best testosterone range for men to maintain health and quality of life has been established. Men appear to respond optimally when the total testsoterone level is greater than 550ng/dl. Improvments can be experienced when testosterone is maintained in the upper-end of the established range, roughly between 650ng/dl-1100ng/dl. Just like men, women have testosterone level that should be maintained within a specific range in order for the hormone to support the functions in which it is reponsible. Clinical focus on testosterone in women has been lacking therefore we must rely on the data that is presently available. In addition to clinical studies, we also have years of observing clinical practice within the emerging feild of "hormone replacement therapies" in which re-trained doctors provide compounded bio-identical hormone medications to treat women for hormone deficiencies inclduing testosterone. Many of the most experienced doctors have established the best range for Total Testosterone levels in women to be between 45ng/dl-120ng/dl, depending on other factors including symptom response and other hormone biomarkers. I have no doubt that women can experience the same health and physical benefits as men by maintaining optimal testosterone levels with the assistance of a trained doctor.
Supplementing with the adrenal hormone ''DHEA' can be useful for improving testosterone levels in women. If this does not work, there are other methods of testosterone administration. The therapy of choice is a topical cream applied in a very small amount to the skin. The hormone is absorbed through the skin and into the blood stream. Injections and pellets are also available to restore deficient testosterone. Just a small amount of this hormone will make a big impact on women’s quality of life.For more information: www.defymedical.com
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.
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.