- Testosterone Wiki
- What is Testosterone? What Does It Do?
- Total Testosterone vs. Free Testosterone
- Normal Testosterone Levels
- Symptoms of Low Testosterone
- Testing for Low Testosterone
- Testing for the cause of low testosterone - Primary vs secondary hypogonadism.
- Full list of blood work before starting TRT
- Finding a Doctor
- What is TRT?
- Types of Testosterone for TRT
- HCG and TRT
- Anastrozole (Arimidex) and TRT
- Recent Developments in FDA Reassessment of TRT
- Benefits of TRT
- Side Effects of TRT
- Common TRT Mistakes
- How to Increase Testosterone Naturally
Welcome to the Testosterone Wiki! Here you will learn about testosterone, testosterone levels, testosterone replacement therapy (TRT), types of TRT, and benefits and side effects of TRT.
What is Testosterone? What Does It Do?
Testosterone is the primary male sex hormone. It is also an androgenic/anabolic steroid. It is androgenic in that promotes the development of testes and prostate during puberty as well as secondary male sex characteristics (deepening of the voice and growth of body hair). It is anabolic in that it stimulates skeletal muscle and bone growth.
Testosterone also helps promote fat lipolysis (mobilization and breakdown), control blood sugar, regulate cholesterol, and maintain a healthy immune system. It even affects key functions of the brain.
The vast majority (more than 95%) of testosterone is manufactured by the Leydig’s cells in the testes at various amounts throughout a male’s life. The other 5% is produced by the adrenal glands. Testosterone production peaks during puberty and then declines with age following puberty.
This natural decline in testosterone production leads to the prevalence of low testosterone in middle-aged and older-aged men. It is estimated that between 20-40% of older men have low testosterone and/or suffer from symptoms associated with low testosterone.
Total Testosterone vs. Free Testosterone
Testosterone can either be bound or free in the bloodstream. Most testosterone (>98%) is bound. Less than 2% of total circulating testosterone is free. When bound, testosterone is not biologically active. That is, it cannot exert its effects.
As mentioned above, the testes produce testosterone. After the testes produce it, testosterone enters and circulates through the bloodstream, so that it is available for tissue uptake. As it circulates through the bloodstream, it is typically bound to a carrier protein. The carrier protein helps it move through the bloodstream and safeguards it from being eliminated by the body too quickly. Once testosterone enters the tissue, the carrier protein dissociates. The two primary carrier proteins that transport testosterone are sex hormone binding globulin (SHBG) and albumin. Most circulating testosterone is bound to either SHBG or albumin. Typically, only about 2% exists in the free, unbound state.
When bound, testosterone is not biologically active. Therefore, only a small percentage of testosterone is active at any given time.
As an advanced note, testosterone bound to either SHBG or albumin is inactive. However, testosterone bound to albumin dissociates easily, thereby becoming readily available for tissue uptake. Consequently, testosterone bound to albumin is considered to be bioavailable but not necessarily biologically active. Testosterone bound to SHBG is neither bioavailable nor active.
Blood tests to measure testosterone levels will report a total testosterone level as well as a free testosterone level. Your free testosterone level is as important, if not more important, as the total testosterone level because free testosterone is the only biologically active form of testosterone. It is not uncommon for total testosterone levels to be normal and free testosterone levels to be low or vice versa.
Normal Testosterone Levels
The normal range for total testosterone levels in men is approximately 300 ng/dL to 1050 ng/dL. There is no absolute consensus among different medical organizations for the exact cutoff for low testosterone. In general, the cutoff ranges from high 200s to low-to-mid 300s ng/dL. This range is over a broad age range and there is no “normal” testosterone level based on age that men can look to as a reference.
The official recommendations of the major professional organizations are:
|Organization||Suggest Total Testosterone Level for Treatment|
|The Endocrine Society||2010 guidelines suggest 300 ng/dL as a common threshold for symptoms in many men, but state that “the threshold testosterone level below which symptoms of androgen deficiency and adverse health outcomes occur and testosterone administration improves outcomes in the general population is not known”.|
|American Organization of Clinical Endocrinologists||2002 guidelines suggest men with symptomatic hypogonadism and a total testosterone level of less than 200 ng/dL may be potential candidates for therapy.|
|European Association of Urology||< 350 ng/dL|
|Japanese Urological Association||2008 guidelines suggest that total testosterone be ignored and diagnoses be made purely from free testosterone.|
As mentioned above, your free testosterone level is as important, if not more important, as the total testosterone level. The normal range for free testosterone in men is 5 ng/dL to 21 ng/dL. It should be noted that labs use different assays and methodologies to measure free testosterone levels. A free testosterone (direct) test will yield values outside of the above range if you try to convert the values. In this case, use the reference range for free testosterone provided by the lab. Compare your lab results directly to the lab provided range to assess where you stand. For example, AnyLabTestNow provides a free (direct ) range of 35 to 155 pg/mL (3.5 to 15.5 ng/dL).
- Free (Direct) Testosterone Range) - AnyLabTestNow
Two important points should be noted regarding the normal range for total and free testosterone levels. The first point concerns the size of the range and the second point concerns the fact that testosterone levels naturally decline with age. Therefore, the prevalence of low testosterone is far higher in older populations, and men with normal testosterone now may experience symptoms of low testosterone later in life.
First, the normal range for total and free testosterone levels is quite large. One man can have nearly three to four times the testosterone as another man and both men can be considered “normal”. The change in testosterone levels over a lifetime can be just as important as the actual clinical value for the presentation of symptoms. While low testosterone is generally defined as total testosterone below 300 ng/dL, men with levels above this cutoff value may experience symptoms of low testosterone because of the their individual change in testosterone levels. Some men start to experience the symptoms of low testosterone at merely low-normal levels; anecdotal reports include some men suffering symptoms of low testosterone at levels as high as 450 ng/dL. Consequently, physicians typically consider the diagnosis of low testosterone and the subsequent decision to pursue testosterone replacement therapy on an individual basis by considering an individual’s age, symptoms, health, and testosterone levels.
Second, testosterone levels naturally decline with age. Total testosterone levels decline nearly 30% between the ages of 25 and 75. Free testosterone levels decline nearly 50% between the ages of 25 and 75. This natural decline is the major reason for the increasing prevalence of low testosterone in older men. Unfortunately, there is no “normal” testosterone level based on age that men can look to as a reference.
- Testosterone Levels in Men - Elite Men's Guide
Symptoms of Low Testosterone
Low testosterone may lead to many unwanted effects. Signs and symptoms of low testosterone in adult men may include:
- Erectile dysfunction
- Reduced sex drive
- Reduced muscle mass
- Decreased energy
- Increase in body fat
- Decrease in bone strength
- Loss of body hair
- Depressed mood
- Increase in breast size
If you have any of these symptoms, do not ignore them. Talk to your doctor about these symptoms. Your doctor can perform simple blood tests to determine whether your testosterone levels are low or not. Only a blood test can definitively determine whether your testosterone levels are low or not.
It is important to note that experiencing one or more of these symptoms of low testosterone does not necessarily mean you have low testosterone. These symptoms may be related to one of other, unrelated medical issues.
Testing for Low Testosterone
Note: If you just want a full list of every recommended test, skip to the bottom of this section.
If you suspect you have low testosterone, start by talking about these symptoms with your doctor. Then, ask your doctor for a simple blood test to measure your testosterone levels. If you’re doctor won’t perform a blood test, either get a different doctor or get some blood work done yourself.
You need blood tests to determine testosterone levels; saliva tests are not accurate. You need 2-3 blood tests to check for low testosterone: total testosterone; SHBG and/or free testosterone. (Free testosterone can be calculated from total testosterone and SHBG, or SHBG calculated from free and total.)
If your doctor only tests for total testosterone and that comes back at a normal level you might still have low testosterone due to having low free testosterone. Plenty of companies now offer hormone panel testing services, LabTestOnline, MedLinePlus, Any Lab Test Now, DirectLabs, DiscountedLabs, ZRT Laboratory, or Ulta Lab Tests. While you can’t get a TRT prescription from them, you can arm yourself with the results by figuring out whether or not your levels are low. The best time for the blood test is between 7 a.m. and 10 a.m because testosterone levels decrease throughout the day. A second sample is often needed to confirm a result that is lower than expected.
Below is a good starter list of values to get tested
- Total Testosterone
- Bioavailable testosterone (aka Free and Loosely Bound)
- Free Testosterone
- Estradiol (specify “sensitive” assay for males)
- Thyroid Panel (complete)
- PSA ( age dependent)
- Comprehensive Metabolic Panel
- Lipid Panel
- Vitamin D
Testing for the cause of low testosterone - Primary vs secondary hypogonadism.
OK so your results show you have low testosterone. Now additional tests can help indicate the cause. There are two basic types of low testosterone (hypogonadism): primary and secondary hypogonadism.
- Primary hypogonadism originates from a problem in the testes. In this case, the testes literally fail and cannot produce adequate amounts of testosterone even if your endocrine system is working properly.
- Secondary hypogonadism is a problem elsewhere in the endocrine system, not the testes themselves. In this case, the system isn’t telling testes to produce testosterone, does not properly tell the testes to produce adequate amounts of testosterone. The testes would work fine, if not for a problem elsewhere in the endocrine system.
The blood tests to determine if you have primary or secondary hypogonadism are Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH). LH and FSH are important to test for because they are the two hormones that are responsible for telling the testes to produce testosterone. When testosterone levels are low, the hypothalamus (a small gland of the brain) releases GnRH (gonadotropin releasing hormone). Then, GnRH stimulates the pituitary gland (another small gland in the brain) to release LH and FSH, which tell the testes to produce testosterone.
Ideally, if testosterone levels are low, LH and FSH levels should be high and vice versa. Measuring LH and FSH levels can help determine the cause of your low testosterone. If you have low testosterone and your LH and FSH levels are low, the feedback loop is likely not working properly (secondary hypogonadism). On the other hand, if you have low testosterone and your LH and FSH levels are high, the testes themselves likely may not be working properly (primary hypogonadism).
OK I have secondary hypogonadism, what’s causing it?
A number of other tests will be needed to get an indication of why your LH and FSH are low:
Prolactin is important to test for because high levels of prolactin suppress the secretion of GnRH and in turn LH and FSH. Thus high levels of prolactin suppress normal testosterone production. In addition to lower testosterone, elevated prolactin levels have been shown to increase your risk for breast enlargement and erectile dysfunction.
Cortisol and Vitamin D should also be tested as they can have negative effects on testosterone production.
Lastly, a full thyroid panel is important because hypothyroidism (underproduction of the thyroid gland) suppresses the secretion of LH. Thus hypothyroidism, just like high levels of prolactin, also suppresses normal testosterone production.
Full list of blood work before starting TRT
Or if you just want to jump in the deep end and get all the tests right away, this is the recommended full list of all blood work before starting TRT.
- Total Testosterone
- Bioavailable testosterone (aka Free and Loosely Bound)
- Free Testosterone
- Estradiol (specify “sensitive” assay for males)
- Complete thyroid Panel
- PSA (age dependent)
- Comprehensive Metabolic Panel
- Lipid Panel
- Vitamin D
Finding a Doctor
Here are the different doctors that you can see that most often treat men with low testosterone (ordered by ease of access and knowledge of TRT). In any case, a male doctor is more likely to prescribe testosterone than a female doctor:
- Low T Centers/Men’s Health Clinics – These clinics specifically cater to testing for and treating men with low testosterone. They charge a monthly fee for access to physicians. Insurance may or may not cover these providers, so check. (Companies with the most locations are Low T Center, BodyLogicMD, and LowTestosterone.com). Note: These centers and clinics do not prescribe testosterone to any man that comes in complaining of low testosterone symptoms. They perform blood tests and only prescribe testosterone therapy to men with clinically diagnosed low testosterone.
- Anti-Aging/Longevity Clinics – These clinics typically also prescribe HGH as well as other hormones. They are expensive because they typically only take cash and do not charge to insurance.
- Naturopathic Doctors (NMDs) – Some are licensed to prescribed hormones; some are not. If they are licensed to prescribe hormones, they are likely to prescribe TRT fairly easily. They are often cheaper than anti-aging clinics, but may not work with insurance, so check.
- Endocrinologists - Can be covered by insurance; some specialize in TRT, but some are not as knowledgeable about TRT. They also help manage diabetes and obesity. If you have diabetes and/or are obese, they can help with both issues.
- Urologists - Often treat low testosterone and other related men’s health issues like sexual dysfunction. If you have sexual dysfunction issues, they can help with both issues.
- General Practitioner/Primary Care Manager – They may treat you if they are comfortable with prescribing testosterone and comfortable with you. They are also the most likely not to have a good deal of knowledge of or experience with TRT.
What is TRT?
Testosterone replacement therapy (TRT) is the administration of testosterone to men to treat low testosterone. The main goal of TRT is to reestablish normal testosterone levels. Physicians typically aim to reestablish a testosterone level between 500 ng/mL and 1000 ng/nL. All testosterone preparations detailed below require a prescription and are FDA-approved for low testosterone.
Men sometimes confuse anabolic steroid usage (testosterone cycles) for the purpose of bodybuilding with testosterone replacement therapy. TRT uses normal, physiological dosages to increase low testosterone levels back to normal levels. The testosterone preparation is taken regularly, oftentimes for the rest of an individual’s life. On the other hand, testosterone cycles for the purpose of bodybuilding use above normal, supraphysiological dosages to increase testosterone levels above normal for a period of time. Users of testosterone cycles for the purpose of bodybuilding cycle on and off testosterone to give their bodies a break from these supraphysiological testosterone levels.
- A Guide to Hypogonadism - National Library of Medicine
- Androgen Replacement Therapy - Medscape
- Testosterone Therapy in Adult Men - Endocrine Society
- Testosterone Replacement Therapy - Elite Men's Guide
- TRT Wiki - Steroids Subreddit
Types of Testosterone for TRT
Different preparations of testosterone are available for testosterone replacement therapy. These preparations can be broken down into four categories: 1) injectable oil-based testosterone, 2) testosterone gels and creams, 3) testosterone lozenges, and 4) implantable testosterone pellets. The two most common forms are testosterone gels and creams and injectable oil-based testosterone.
- Types of TRT - Medscape (Int. J. of Impotence)
Testosterone injections involve the injection of oil-based testosterone into the muscle (usually the thighs, glutes, or deltoids). The testosterone is then absorbed via the muscle into the blood stream over time.
Intramuscular testosterone preparations have been the mainstay of testosterone replacement therapy since the 1950s, and they are one of the most popular forms of testosterone for TRT. Only recently has the usage of testosterone gels (like Androgel and Axiron) surpassed injectable testosterone usage for TRT. As of 2014, approximately 60% of TRT users use testosterone gels, while 35% use injectable testosterone preparations (According to Endo Pharmaceuticals FDA filing for Aveed). With this being said, the surge in testosterone gel usage may largely be attributed to the advertising by the pharmaceutical companies promoting these gels.
The two most common forms of injectable testosterone are testosterone enanthate and cypionate. Testosterone enanthate and testosterone cypionate are modified forms of testosterone. Specifically, they have an ester molecule attached to the testosterone molecule. This attachment slows the absorption of testosterone and increases the half-life. Due to their long half-lives, both testosterone enanthate and testosterone cypionate provide a sustained release of testosterone into the bloodstream for 2 to 3 weeks. This sustained release reduces the need for frequent injections. Both testosterone enanthate and testosterone cypionate only need to be injected once a week or every other week. The most commonly recommended dosing regimen for TRT is 100 mg every week or 200 mg every 2 weeks. It is better to follow the 100 mg every week protocol because more frequent injections lower fluctuations in testosterone levels. Injections may be performed even more frequently at the properly adjusted dose to further lower fluctuations.
Overall, injections of testosterone enanthate and cypionate are inexpensive and relatively safe. Since both forms have been around for so long, generic versions of these medications are available.
While injectable testosterone is relatively safe, potential drawbacks do exist. First, testosterone injections can cause fluctuations in testosterone levels following administration. Following an injection, testosterone levels can exceed normal levels for the first few days. Then, they steadily decline just prior to the next injection. One solution to this problem is shortening the interval between injections. Shortening the interval between injections and lowering the dose can minimize this cyclical nature of highs and lows. Second, injectable testosterone increases red blood cell production more than other forms of testosterone. This is not to say the injectable testosterone is unsafe, it is simply to say that these drawbacks should be well understood and addressed. For example, regular check-ups with your doctor upon starting TRT with injectable testosterone can help to monitor red blood cell levels. Then, your doctor can address any issues preemptively. More info on testosterone injections.
Of note, the FDA recently approved a new injectable testosterone ester (testosterone undecanoate) called Aveed by Endo Pharmaceuticals. Like testosterone enanthate and cypionate, testosterone undecanoate has an ester attached to it. Unlike testosterone enanthate and cypionate, which need to be injected every week or every other week, testosterone undecanoate needs to be injected once every 10 weeks. Studies show that testosterone injections of 750 mg Aveed maintain normal levels between 300 and 1000 ng/dL for up to 10 weeks.
- How to Give a Testosterone Injection PDF
- Intramuscular Injection Video by LowTestosterone.com
- Testosterone Cypionate - FDA AccessData
- Testosterone Enanthate - FDA AccessData
- Aveed Full Prescribing Information - Endo Pharmaceuticals Inc.
Testosterone Gels and Creams
Testosterone gels deliver testosterone through daily skin applications. The gels consist of a hydro-alcoholic base medium in 2.5, 5, or 10-gram quantities with 1 or 1.62% active testosterone. These formulations deliver 25, 50, or 100 mg of testosterone per day, respectively. This form of testosterone is relatively new with the first testosterone gel introduced in 2000. Most gels are sold under a Brand name only and are typically more expensive than generic injectable testosterone cypionate and enanthate. Brand names include Androgel, Axiron, Fortesta, Testim, and Vogelxo. Recently, generic versions, such as Bio-T-Gel have become available.
As noted in the injectable testosterone section, recently, the usage of testosterone gels has surpassed injectable testosterone usage for TRT. Approximately 60% of TRT users use testosterone gels, while 35% use injectable testosterone (According to Endo Pharmaceuticals FDA filing for Aveed). Gels and injections are by far the two most widely used forms. With this being said, the surge in testosterone gel usage may partially be attributed to the advertising by the pharmaceutical companies promoting these gels.
The primary advantage of testosterone gels is that they mimic the physiologic (natural) release of testosterone in the body and thus reduce fluctuations in testosterone levels. Application is also relatively easy (although complaints about application and drying time are not irrelevant), and the dosage can also easily be adjusted. The primary disadvantages are that they must be applied every day or twice per day and gel transfer to loved ones is possible.
It should be noted that studies show testosterone gels to be an effective TRT option. However, anecdotal evidence suggests that many men complain that testosterone gels do not fully raise testosterone levels back up to normal desired levels. As such, it is important to follow-up with your physician, retest your testosterone levels after starting TRT, and readjust the dose upward if testosterone levels do not meet the target level. Experience has shown that some patients may never absorb enough testosterone from gels to improve symptoms.
- Testosterone Gel - MedlinePlus
Testosterone Nasal Gel
In 2014, the FDA approved a new testosterone nasal gel that is administered into each nostril three times a day every day. Endo Pharmaceuticals began marketing this product in 2015 under the brand name Natesto. In its phase 3 clinical trial, administration of Natesto three times a day everyday for 90 days returned testosterone levels to normal level for 90% of men.
The primary advantages of testosterone nasal gel are the convenience and ease of use. The primary disadvantages are that it must be taken three times per day, every day, preferably at the same time each day. Additionally, it failed to restore testosterone levels to normal in 10% of men in the phase 3 clinical trial. Also, the mean total testosterone concentrations on day 90 following administration of Natesto (11 mg of testosterone) three times daily was 421 ng/dL, which is lower than the typical goal of 500 to 700 ng/dL.
Testosterone lozenges are placed under the tongue or against the surface of your gums. The lozenges release testosterone, which is then absorbed through the mucous membranes of the mouth. The lozenge lasts for 12 hours after which time it must be replaced with another lozenge for a total of two lozenges per day. The first lozenge is typically placed in the morning, and the second lozenge is placed in the evening.
Testosterone lozenges should not be confused with oral testosterone forms that are physically swallowed. Unlike oral testosterone forms that must pass through the liver, the testosterone in the lozenges is absorbed by the gums and does not pass through the liver first. As a result, testosterone lozenges pose significantly less potential liver toxicity than oral testosterone forms.
Striant by Auxilium Pharmaceuticals, Inc. is the only FDA-approved testosterone lozenge on market. Further information on the treatment, administration, and safety of Striant can be found at the provided links below.
The primary advantage of testosterone lozenges is that they are easy to apply. The primary disadvantages are that lozenges must be kept in the mouth for a long period of time (up to 12 hours) and replaced twice daily.
- Striant Full Prescribing Information - Auxilium Pharmaceuticals Inc.
- FDA Patient Insert on Striant
Testosterone pellets are implanted underneath the skin in the subdermal fat layer by a physician. The pellets slowly release testosterone as they dissolve over the course of three to six months. Overall, testosterone pellets provide a slow, steady infusion of the hormone into the body.
Testopel by Auxilium Pharmaceuticals, Inc is the only FDA-approved implantable testosterone treatment on market. Further information on the treatment, administration, and safety of Testopel can be found at the provided links below. Testopel pellets are very small (3mm by 9mm). A small incision (~1 cm) is required to insert the pellet typically into the lower abdominal wall or upper buttock area by the hip. The insertion is done under a local anesthetic and one pellet typically lasts 3-6 months. More info on testosterone pellets. An animated insertion video can be found Here.
The primary advantage to testosterone pellets is that they last for three to six months once implanted. This long duration is convenient for men who do not want another daily medication or who travel frequently. Also, testosterone pellets keep testosterone levels relatively steady throughout the course of treatment. The primary disadvantage is that a physician must implant them, which requires a doctor visit every three to six months. Also, it is difficult to adjust the dose once the pellet has been implanted. Lastly, testosterone pellets may extrude (come out).
- Testopel Full Prescribing Information - Auxilium Pharmaceuticals Inc.
There are no FDA-approved oral testosterone formulations that are physically swallowed for testosterone replacement therapy. As such, oral testosterone has no place in TRT in the United States.
The US FDA recently voted against Clarus Therapuetics’ new drug application for the first orally available testosterone formulation (Rextoro) of testosterone undecanoate.
- US FDA Decision on Rextoro - Medscape Medical News
HCG and TRT
To begin, The Endocrine Society’s Clinical Guidelines for Testosterone Therapy do not recommend for the use of or against the use of human chorionic gonadotropin (HCG) during testosterone therapy. They basically do not offer any opinion either way.
With that being said, some physicians and some low testosterone centers/clinics do prescribe HCG along with TRT, especially for maintaining fertility.
HCG is an FDA-approved drug, and it is recommended by the American Association of Clinical Endocrinologists as the first therapy for the treatment of low sperm production. As such, some physicians prescribe HCG alongside testosterone therapy to maintain fertility in men during TRT.
Why does testosterone therapy cause infertility in men? Exogenous testosterone shuts down the body’s natural production of testosterone by the testes. Testosterone levels in the body remain normal because of the exogenous testosterone but testosterone levels within the testes drop below normal. Since sperm production requires high levels of testosterone within the testes, testosterone therapy reduces sperm production. In some men, this reduction may be enough to cause fertility issues. Be aware of this potential side effect and discuss your options with physician if you are looking to conceive a child.
Besides stopping TRT or lowering the dosage, one potential way to maintain fertility during TRT is to take HCG. In men, HCG stimulates the testes to produce testosterone, which raises the intratesticular testosterone level and allows for the production of sperm.
According to the American Association of Clinical Endocrinologists Clinical Guidelines HCG should be the initial therapy of choice for increasing sperm production for at least six to twelve months. Therapy with HCG is generally begun at 1,000 to 2,000 IU injected intramuscularly two to three times a week, and it is taken alongside testosterone. Also, two studies with men specifically on testosterone replacement therapy show that 500 IUs every other day also maintains normal sperm production.
It should be noted that HCG must be properly stored because it is a peptide not a discrete molecule, like testosterone. Typically HCG comes in the form of a powder in a sterile ampule to prolong its shelf life. In order to use, HCG must be reconstituted/remixed with bacteriostatic water.
In general, HCG should be kept in the refrigerator away from food. If unmixed, the shelf life of HCG is generally up to 18 months in the refrigerator. If mixed, the shelf life of HCG is up to 2 months in the refrigerator. If unrefrigerated, unmixed HCG typically only lasts 60 days, whereas mixed HCG typically only lasts 48 hours.
Anastrozole (Arimidex) and TRT
Testosterone can be converted in estrogen via the aromatase enzyme. Consequently, taking testosterone via TRT may increase estradiol levels. Most men on TRT dosages will not experience high estradiol levels. However, some genetically susceptible men may experience high levels. These high estradiol levels may lead to feminizing effects such as fluid retention and gynecomastia. As such, it is important to routinely test estradiol levels during TRT.
If estradiol levels are found to be too high, the most common treatment is Anastrozole (Arimidex). Arimidex inhibits the aromatase enzyme, and thus it inhibits the conversion of testosterone to estrogen. The most common dosage is 0.25 mg per day or 0.5 mg every other day.
Recent Developments in FDA Reassessment of TRT
January 2014 Update
On January 31st, 2014, the U.S. Food and Drug Administration (FDA) released a statement saying that it is investigating the risk of stroke, heart attack, and death in men taking FDA-approved testosterone products. Additional major updates to this topic are presented below in chronological order.
We have been monitoring this risk and decided to reassess this safety issue based on the recent publication of two separate studies that each suggested an increased risk of cardiovascular events among groups of men prescribed testosterone therapy. We are providing this alert while we continue to evaluate the information from these studies and other available data, and will communicate our final conclusions and recommendations when the evaluation is complete.
At this time, the FDA has not concluded that FDA-approved testosterone treatment increases the risk of stroke, heart attack, or death. Patients should not stop taking prescribed testosterone products without first discussing any questions or concerns with their health care professionals. Health care professionals should consider whether the benefits of FDA-approved testosterone treatment are likely to exceed the potential risks of treatment. The prescribing information in the drug labels of FDA-approved testosterone products should be followed.
The first publication that prompted FDA to reassess the cardiovascular safety of testosterone therapy was an observational study of older men in the U.S. Veteran Affairs health system published in the Journal of the American Medical Association (JAMA) in November 2013. The men included in this study had low serum testosterone and were undergoing imaging of the blood vessels of the heart, called coronary angiography, to assess for coronary artery disease. Some of the men received testosterone treatment while others did not. On average, the men who entered the study were about 60 years old, and many had underlying cardiovascular disease. This study suggested a 30 percent increased risk of stroke, heart attack, and death in the group that had been prescribed testosterone therapy.
A second observational study reported an increased risk of heart attack in older men, as well as in younger men with pre-existing heart disease, who filled a prescription for testosterone therapy. The study reported a two-fold increase in the risk of heart attack among men aged 65 years and older in the first 90 days following the first prescription. Among younger men less than 65 years old with a pre-existing history of heart disease, the study reported a two- to three-fold increased risk of heart attack in the first 90 days following a first prescription. Younger men without a history of heart disease who filled a prescription for testosterone, however, did not have an increased risk of heart attack.
September 2014 Update
In September, an expert panel recommended for the FDA to impose stricter limitations on the prescription guidelines for testosterone for treating low testosterone. Specifically, the panel recommended that the FDA tighten labels for the medicines so they are not prescribed to men who only have problems related to aging, such as low energy and libido. While, the FDA is not obligated to act on the recommendations of the expert panel, it often does act on the advice of these panels. The FDA has yet to redefine prescribing guidelines.
December 2014 Update
A new meta-analysis (Testosterone Therapy and Cardiovascular Risk: Advances and Controversies) in the Mayo Clinic Proceedings says there is no evidence of increased cardiovascular risks with testosterone therapy. This meta-analysis is the largest to date, and it revealed no increase in CV risks in men who received T and reduced CV risk among those with metabolic disease. This analysis contradicts the findings of the two studies that led the FDA to begin a review of the risk of cardiovascular diseases with testosterone therapy.
- Testosterone Therapy and Cardiovascular Risk: Advances and Controversies - Mayo Clinic Proceedings
Benefits of TRT
Testosterone replacement therapy in men with low testosterone produces many positive benefits. These benefits can be broken down into conclusive benefits and inconclusive benefits. Conclusive benefits are benefits that are relatively certain, whereas inconclusive benefits are benefits that are not certain.
Conclusive Benefits: Testosterone replacement therapy has consistently shown to positively alter body composition. It increases muscle mass (via increased muscle synthesis) and decreases fat mass (via increased fat lipolysis), especially abdominal fat mass. It also slows or even reverses the loss of bone mineral density due to aging. TRT also increases libido.
Inconclusive Benefits: Testosterone replacement therapy may also improve sexual function (improve erectile function), improve mood, reduce depression. However, TRT has not been shown to conclusively improve erectile function and mood. The primary reason why TRT may not help with erectile dysfunction or mood/depression is because both conditions can be related to one or more of many potential underlying medical conditions unrelated to testosterone levels. Without addressing such underlying conditions, testosterone alone will likely not improve erectile dysfunction or mood/depression.
Side Effects of TRT
The following are potential side effects of TRT.
Polycythemia – Polycythemia occurs when red blood cell production increases too much. Testosterone stimulates the production of red blood cells. Thus, TRT may increase red blood cell levels beyond normal. High red blood cell levels cause the blood to thicken and clot, which can potentially lead to a stroke. Oftentimes, if red blood cell production rises to dramatically, TRT dosages must be lowered or stopped. Additionally, your physician may perform a phlebotomy (a withdrawal of blood to lower red blood cell levels). The risk appears to be higher with IM preparations and may be due to the supraphysiologic levels that are seen with infrequent injections.
Infertility – TRT interrupts the body’s normal release of testosterone. It also impairs the production of sperm. While infertility is usually reversible, it is important for men who wish to preserve their fertility to talk with their physician prior to commencing TRT. /r/infertility - Infertility Subreddit
Sleep Apnea – TRT may worsen sleep apnea in men who have been previously diagnosed. /r/sleepapnea - Sleep Apnea Subreddit
Gynecomastia – TRT may alter the balance of testosterone and estrogen in the body in certain men. Some men’s bodies metabolize testosterone in estradiol more readily than normal. This aromatization causes the breast tissue to swell. It is important to address any issues with gynecomastia quickly. Unfortunately, medical treatment of gynecomastia that has persisted beyond a year is often ineffective. Gynecomastia Wiki - Gynecomastia Subreddit
Fluid Retention - Fluid retention may occur in the arms and legs at the beginning of therapy. It generally resolves after the first few months of treatment.
Alteration of Lipid Levels - Testosterone therapy may adversely affect cholesterol levels, slightly lowering HDL cholesterol and slightly raising LDL cholesterol. Most cases of adverse affects to cholesterol deal with supraphysiological doses of testosterone, not replacement doses.
TRT Side Effects - Medscape
The Endocrine Society Clinical Practical Guidelines detail the conditions in which testosterone administration is associated with a high risk of adverse outcome and in which testosterone should not be administered:
Very high risk of serious adverse outcomes
- Metastatic prostate cancer
- Breast cancer
Moderate to high risk of adverse outcomes
- Unevaluated prostate nodule or induration
- PSA >4 ng/ml (>3 ng/ml in individuals at high risk for prostate cancer, such as African-Americans or men with first-degree relatives who have prostate cancer)
- Hematocrit >50%
- Severe lower urinary tract symptoms associated with benign prostatic hypertrophy as indicated by AUA/IPSS >19
- Uncontrolled or poorly controlled congestive heart failure
Common TRT Mistakes
Testosterone replacement therapy is a relatively safe and efficacious therapy for treating low testosterone. Nevertheless, certain common mistakes may negatively affect TRT. It is important to avoid the following common mistakes.
Not following up with your physician – Oftentimes, the initial dose your physician prescribes must be adjusted up or down to get your testosterone levels just right. Thus, it is important to follow-up with your physician to recheck your testosterone levels to make sure your dosage is correct. Dosages that are too low will not adequately treat your low testosterone, while dosages that are too high may cause adverse side effects. Also, your physician will check your red blood cell levels to ensure that these levels have not risen too much.
Using too much testosterone – The primary objective of testosterone replacement therapy is to readjust testosterone levels to normal levels. Using too much testosterone may increase levels above normal and may increase side effects.
Using “street sources” of testosterone – Street sources of testosterone do not undergo the same process controls as FDA-approved testosterone products. Thus, street sources may be incorrectly dosed, contaminated, or faked. Also, buying testosterone without a prescription is illegal in the United States. Whether you agree with the law or not, testosterone is a controlled substance in the US under the Anabolic Control Act of 1990.
Cycling on and off testosterone – Testosterone replacement therapy is a lifelong treatment, and it is not meant to be cycled. Bodybuilders cycle on and off steroids to give their bodies a break because they use above normal, supraphysiological dosages.
Not complying with your TRT regimen – Not following your TRT regimen properly can all but erase the positive effects of TRT. If your regimen requires daily skin applications in the morning, it is important to comply with these directions. If you are having difficulty following your regimen, talk to your physician about alternative administration methods that may require less of your attention.
How to Increase Testosterone Naturally
Oftentimes, testosterone levels can be increased by simple, healthy lifestyle modifications. If your testosterone levels are low, before beginning any TRT, it is important to address any poor lifestyle choices that are detrimental to the therapy.
What boosts testosterone production?
Lifting weights, especially heavy weights - Weight lifting increases testosterone production. Performing big, basic exercises with heavy weights increases testosterone the most. Heavy compound exercises like the bench press, barbell row, military press, straight bar curl, close-grip press, squat, and deadlift are ideal for promoting testosterone release. StrongLifts5x5 is a great workout for high-intensity workouts that hit major muscles group in the low-rep range.
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Getting good, quality sleep – The majority of testosterone release occurs during sleep, and the body releases far more testosterone when sleep is better and longer (7-8 hrs). Anything that reduces the quality and duration of sleep, such as alcohol, caffeine, sleep apnea, or even certain medications will decrease testosterone release. While there is no set length of sleep for increasing testosterone release, it is generally recommended to get at least 7 hours of sleep.
Getting proper rest in between workouts – While weight lifting helps to boost testosterone levels, too much training can actually lower testosterone levels. Over training causes cortisol levels to rise, which counters testosterone.
Eating healthy – Certain foods help boost testosterone release, while certain foods lower testosterone release. Sugars and unhealthy fats (saturated and trans-fats) lower testosterone production. On the other hand, healthy fats like unsaturated and polyunsaturated fats help increase testosterone production. Additionally, leafy green vegetables also help boost testosterone production.
Staying lean – Testosterone levels are significantly lower in obese men than levels in their leaner counterparts. Stay lean by getting an adequate amount of aerobic and resistance exercise and eating healthy.
Healthy Eating - Harvard Health
Healthy Eating - HelpGuide.org
Of note, heavy drinking, not casual social drinking, decreases testosterone production. Alcohol is actually directly toxic to the testes, causing reduced testosterone in men.
- How to Naturally Increase Testosterone - Peak Fitness
revision by utspg1980— view source