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"
One of the most frustrating things for a guy on testosterone replacement therapy is when the pharmacy cannot refill medication due to it being on "back order". Back-order can of course mean many things, and since pharmacies sometimes fail to explain to the patient what is happening I thought I would post my understanding of what may be occurring, what to expect, and what to do. Things change rapidly within the US pharmaceutical pipeline resulting in limited access to some medications. This article is meant to provide a better understanding of the situation when specific medications are temporarily not available at the pharmacy.
One might wonder how a common medication like "testosterone cypionate" can all of a sudden be unavailable at the pharmacy.
Medication shortages can indeed happen even with common medications. The shortage can occur at different levels within the pipeline that delivers medications from the supplier to the pharmacy shelf. Where this shortage occurs will determine how many people are affected. I will briefly explain how the pipeline works. Drug manufacturers who make "brand name" drugs and compounding pharmacies who create customized generic drugs both purchase drugs in raw form from an FDA approved supplier. Once a drug is made into a finished product by the manufacture or compounder, it then must pass a series of regulatory protocols which include testing before becoming available to patients through a pharmacy.
So when it comes to raw material suppliers, if just one large supplier has a problem leading to a shortage of a specific raw material than it will certainly affect many pharmacies across the US who will be unable to obtain it from that supplier. Sometimes the shortage can affect all suppliers who carry that drug, or sometimes there is only one (or few) supplier who carries a particular drug- like testosterone esters. This can result in a nationwide shortage of a medication.
For example, there could be a delay with the supplier of the raw materials needed to make test cypionate which would mean that no pharmacy or manufacturer could obtain the needed ingredient to make a finished product. A delay can occur for a variety of reasons, including inability to pass an FDA inspection resulting in temporary or even permanent suspension. Usually there is enough stock left on the pharmacy shelf to be used while the shortage is resolved. Smaller pharmacies may not have stock and will be out completely so you would need to call around to see if another pharmacy may have your medication available.
Shortages can also occur down the chain at the pharmacy level- maybe the pharmacy simply forgot to order their supply or they underestimated the amount needed. Usually this level of shortage can be resolved in a day or two. Also at the pharmacy level, particularly compounders, there are different regulations including USP 797 which governs how injectable testosterone (and all injectables) are made. USP 800 which requires HCG and testosterone to be made in a separate negative flow "clean room" which some compounding pharmacies do not have. If the drug does not pass every test while being compounded or manufactured then it will be discarded instead of dispensed, causing a temporary delay as another batch is made. Another delay that may occur when obtaining your medication is the result of the additional steps needed to procure and fill a controlled substance. Dont forget that testosterone (and HCG in many states) is considered a controlled substance. All of these regulations are controlled by state and federal agencies who can pass legislation that limits access to certain medications. Any of this can cause a delay or lead to a shortage of testosterone or hcg.
I have wintessed an entire batch of test cypionate thrown out because it's potency was higher than the strength listed on the label. This caused the pharmacy to place test cyp on back order for 48 hours until they catch up on making more. The worst I have experienced while working at the pharmacy in 2009 is when compounded testosterone enanthate was on back order for 6 months before becoming available for most pharmacies to dispense again. In this case the shortage occurred at the supplier, reason unknown. I dont see this happening with cypionate as its very common in the US, but shortages may still occur for various reasons.
Brand name HCG is commonly in shortage at retail pharmacies as of 2015. Due to lack of insurance coverage and high price, men are much better off obtaining their HCG from a compounding pharmacy. Compounded HCG is less than half the price and rarely on back order at compounding pharmacies.
Suppliers and pharmacies usually work fast to resolve any delay unless it has to do with policy change or regulatory violation
What to do if your pharmacy is out of testosterone cypionate?
Contact other local pharmacies first to see if they have any in stock. Do not hesitate to ask them why there may be a shortage, but don't expect an answer because often they may not even know
Contact compounding pharmacies who supply injectable testosterones. Even if the compounder does not take insurance, they will charge you an affordable price. Paying for it is much better than missing your injection.
If the issue is related to a specific type of testosterone, like 'cypionate', you can then ask if another ester like 'enanthate' is available. Enanthate is close enough to cyp that you could substitute it if needed. Remember, you will have to get your doctor to 'okay' the change to enanthate first. Testosterone enanthate is usually available at retail pharmacies in 200mg/ml X 5ml bottles. It is also compounded at some pharmacies.
If there is ever an injectable testosterone apocalypse and no injectable versions are available (which should never happen), you can always temporarily change to a topical gel + HCG to maintain. Again, there many different brands/generics injectable testosterones that such a full shortage would be rare. At least there are options
If you ever find HCG on backorder at compounding pharmacies just sit tight, it will become available again soon. As stated before, I have never seen HCG in short supply on the compounding side and if there ever was a shortage it was only for a day or so.
Part of the high level of service Defy Medical strives towards for our patients includes maintaining communication with our pharmacies in order to prepare for any upcoming changes and requirements. This ensures that we can continue providing affordable access to these medications to our patients no matter where they happen to live.
Article commentary by Jasen Bruce
Men and women on testosterone replacement therapy who previously suffered from low testosterone and depression already understand the positive effect that testosterone has on their mood. A study led by Rupert Lanzenberger from the Vienna Medical University Department of Psychiatry and Psychotherapy has demonstrated for the first time worldwide that testosterone increases the number of serotonin transporters (proteins) in the human brain. Serotonin is a neurotransmitter that plays an important role in maintaining positive mood and emotional well-being. There are many more studies which demonstrate the relationship between the sex hormone testosterone, depression, and positive mood. Maintaining adequate levels of testosterone is shown to reduce the occurrence of depression. The presentation titled “Testosterone needs Estrogen's help to inhibit Depression “by Professor Mohamed Kabbaj interestingly shows that both estrogen and testosterone work together to alleviate depression and anxiety. In both men and women, some testosterone converts to estrogen. In men, this is the primary source of estrogen. In women, estrogen is also produced in the ovaries. The article indicates that the actual conversion of testosterone to estrogen in the brain is necessary for anti-depressant and anti-anxiety effects. This research will hopefully help patients suffering from depression obtain better access to hormone testing and proper treatments when certain hormones are found to be too lowThe only statement I do not agree with is regarding the “need” to synthesize a drug which acts like testosterone due to the fear of “numerous side effects” associated with testosterone. Of course those of us who read the latest evidence know that the “numerous side effects” result from improper prescribing of testosterone and the lack of proper monitoring. Testosterone replacement therapy correctly administered and monitored by an experienced doctor has very low risk and long term health benefits. Why take a hormone already identical to what the body produces and alter it to produce a drug? I believe the efforts would be better spent educating more doctors on how to properly monitor testosterone replacement therapy after diagnosing low testosterone. Although this study is done on men, we know the effects are equally beneficial in women. Article excerpt: “Maybe in the future, when we are trying to develop an antidepressant that works in low-testosterone males, we can target some of the mechanisms by which testosterone acts, since it has numerous side effects,” he said. Testosterone acts on many receptors and pathways in the brain, so the challenge is to come up with a drug that provides only the effect you want.” Referenced: http://www.defymedical.com/video-education...-rfp69hrv-dpuf
"...the male sex hormone testosterone also affects our mood and emotions, as well as our libido -- and in a positive way."
A recent study of a male population explores the relationship between testosterone and erectile function. As suspected, higher levels of testosterone equals a better erection and improved sex drive. This study also helps to explain the different types of blood tests used to check testosterone, and why it is important for men and women to have more than just the total testosterone checked (also known as serum testosterone).
The study observed over 700 men from a specific population (population-based study) and established a correlation between a man’s testosterone level and his erectile function. The men in the study were followed for a period of 4 years and were selected to participate after receiving a comprehensive survey and baseline examination designed to narrow down the participants. Erectile function was determined by having each participant complete the widely used IIEF erectile function questionnaire in addition to blood testing. The men had to have been “in a stable sexual relationship for at least 6 months” at the time of the study. Their IIEF results helped to quantify their level of erectile dysfunction (ED) into three categories; none, mild, and moderate to severe (ED).
You can take the IIEF erectile function questionnaire used in this study by clicking the link below. What is your IIEF erectile function score? http://defymedical.com/services/sexual-health/326 Results will generate a score that can be used to recommend the next clinical step towards treatment.
The blood tests performed in the study include measurements of total testosterone, free testosterone, bio-available testosterone, and a protein called sex hormone binding globulin (SHBG). Many men (and women) along with their primary care doctors focus on just total testosterone, which measures the total sum of both bound and unbound testosterone. There is a difference between bound and unbound testosterone. Your body cannot use all of the testosterone measured in a total testosterone test. SHBG is a protein which can attach to testosterone very tightly which prevents testosterone from entering your cells. Any testosterone attached to SHBG would be considered bound, which the body cannot use. The level of SHBG was tested along with testosterone in this study. There are other proteins which can also bind to the testosterone molecule, such as albumin. Albumin does not bind as tightly as SHBG and therefore can quickly become unbound so that testosterone can be used by your cells. Free testosterone describes the testosterone which is not bound by any proteins and is available to be immediately used. Bio-available testosterone is a measurement of both free testosterone and also testosterone bound to albumin which, as mentioned, is easily separated so that the testosterone becomes available for use (free) when needed. Your body can use bio-available testosterone but it cannot use testosterone bound by SHBG.
This study explored the relationship between testosterone, our primary sex hormone, and erectile function. The conclusion showed a clear cause-effect relationship between the two. This is important to know since erectile dysfunction (ED) “is a worldwide disorder that affects millions of men” and has a negative influence on quality of life. If this relationship is not understood then ED treatments can fail for many men without understanding why. For example, PDE-5 inhibitors (Viagra, Cialis, Levitra) are commonly prescribed medications to treat ED. They work by inhibiting the enzyme (PDE-5) that prevents nitric oxide from relaxing the spongy erectile tissue in the penis (corpus cavernosum). Nitric oxide is released in the penis when a man is sexually aroused. Studies show that PDE-5 inhibitors like Viagra work more efficiently when there is a sufficient amount of testosterone present. These medications are more likely to fail if a man has low testosterone. Interestingly there is a positive relationship between testosterone and nitric oxide. Aging men who are experiencing ED should request to have a testosterone blood test to see if low testosterone, or more specifically low free-testosterone is the cause. The study came to the conclusion that “men with low free testosterone and high SHBG were at the highest risk of ED”. Remember, free testosterone is not bound by proteins and can be immediately used to support an erection and improve overall sexual performance.
This study emphasizes why it is important to always blood test both total and free testosterone. It can be additionally beneficial for some men experiencing poor erectile function to also blood test sex hormone binding globulin (SHBG), and Dihydrotestosterone (DHT)-an androgenic byproduct of testosterone. Androgens are shown to help maintain healthy erectile function in aging men (Testosterone is also an androgen). Testosterone in a younger man plays a role in the development of sex organs and male characteristics, such as the voice deepening and increase in body hair. After these tasks have been completed testosterone continues to play a role in the maintenance of erectile function and sex drive in aging men.
There can be many factors leading to erectile dysfunction but amongst all the causes it was common to find a deficiency or insufficiency of testosterone. It is important to first check testosterone levels when experiencing ED. Testosterone replacement therapy can be prescribed by a trained doctor to help restore low levels but first you must determine if your low testosterone may be caused by lifestyle habits, such as alcohol or drug use, or by disease. Restoring testosterone to a good level can help improve your erectile performance and libido.
To download the full study as a PDF for free please visit our clinical study library by clicking on the link below. The study is listed under the title “Sex Hormones Predict the Incidence of Erectile Dysfunction: From a Population-Based Prospective Cohort Study (FAMHES)”. You can also email jasen@defymedical to request a PDF copy.
Clinical study library: http://defymedical.com/resources/clinical-studies/24-testosterone-replacement-therapyReference: Luo, Y., Zhang, H., Liao, M., Tang, Q., Huang, Y., Xie, J., Tang, Y., Tan, A., Gao, Y., Lu, Z., Yao, Z., Jiang, Y., Lin, X., Wu, C., Yang, X. and Mo, Z. (2015), Sex Hormones Predict the Incidence of Erectile Dysfunction: From a Population-Based Prospective Cohort Study (FAMHES). Journal of Sexual Medicine. doi: 10.1111/jsm.12854
Other references used:
The role of testosterone in erectile function and dysfunction. L. Gooren, MD, PhD, Available online 7 September 2006
Combining Testosterone and PDE5 Inhibitors in Erectile Dysfunction: Basic Rationale and Clinical Evidences. Emanuela A. Greco, Giovanni Spera, Antonio Aversa. Department of Medical Pathophysiology, University of Rome “La Sapienza”, 00161 Rome, Italy. Available online 13 July 2006
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.
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.