Introduction
‘I’ve lost my mojo baby’ (Austin Powers)
Testosterone is the major male sex hormone. It plays a defining and critical role in the sexual characteristics of being male; including muscle bulk and strength, sexual behaviour, assertiveness and even aggression. It also has a long list of other impacts all over the body that are surprising and sometimes forgotten.
Males develop significant testosterone levels around the time of puberty. This sees the development of male sexual characteristics. Levels peak in the 20s and then decline gradually from then.
Testosterone is not just about muscles and sex. It plays a major role in mood, metabolism, bone strength and the function of cells in many parts of the body. Women have testosterone as well, although at a much lower level. Whilst testosterone is the main male sex hormone, it sits alongside other male hormones called ‘androgens’ which all play a role.
Androgens go up and down like many other hormones; when we are healthy and physically active, our body creates higher levels of them. When we are eating poorly, inactive, malnourished or eating a poor diet, inactive or run down, we will generally make less of them.
Testosterone levels have been declining in the developed world for over 50 years. Many put this down to major changes in lifestyle and more chemicals in our food and environment. Gone are the days that we would roam the earth under the natural sun using our bodies and not our computers; is it any wonder that testosterone is vanishing?
For many, the symptoms of testosterone deficiency are sneaky and slow to emerge. The subtle hints of taking longer to recover from a workout, decreased happiness and energy, a lack of mental sharpness and a sexual and general slow down can be endlessly put down to the ups and downs of life. However, many men and women derive significant benefit from testing for and addressing low testosterone rather than skirting around it. Is testosterone replacement such a dirty phrase?
Particularly during the 1980s and 90s, testosterone therapy got a bad reputation due to excessive abuses in the bodybuilding community; toxic muscle heads starting fights and starring in The Expendables left a sour taste for many. Like any drug, too much is bad for you. However, a healthy and natural testosterone can have a profound impact on a person’s total health. The restoration of vitality itself can be life changing; more energy, stronger muscles, a sharper mind and a better libido can redefine a person’s quality of life.
Ultimately, testosterone replacement remains taboo in the medical community. In my experience, men will turn to the black market and seek a solution to their problems if they cannot get it via their doctor. This article aims to discuss as much as possible about testosterone and its replacement as a starting point on safely navigating testosterone. This is not a replacement for medical advice, but it is a starting point for those wanting to know more.
What is Testosterone and what does it do?
Testosterone is the male sex hormone. It is produced in the testicles (and to a small degree, the adrenal glands in both women and men). Production is regulated by the brain in the pituitary gland. The pituitary gland is a stalk-like gland in the brain that tells the testicles to make testosterone and is also involved in stabilising its levels.
Functionally, testosterone plays a vital role in multiple bodily functions including:
- sperm production,
- body hair growth,
- male sexual behaviour,
- muscle growth and maintenance of muscle strength,
- mood,
- vitality & energy and
- sexual desire.
- moderating inflammation,
- suppressing high insulin levels
- Weight loss
- Fat burning
Medically, doctors use it in burns victims to stimulate muscle growth; in the sporting world, bodybuilders often use it to gain large amounts of muscle.
How is testosterone produced?
The production of testosterone starts in puberty and has naturally fluctuating levels until puberty ends. It is made in the testicles after signalling from the brain.
From the mid 30s onwards, testosterone naturally declines at about 1% per year; however it is unclear whether this causes any symptoms in most men.
Testosterone is not just about one hormone. The process of testosterone synthesis involves the production of multiple hormones known as ‘upstream’ or associated hormones. These include pregnenolone, DHEA, Luteinising Hormone, Androstadienole, DHT to name a few.
These hormones all play a role in brain health, anxiety, sleep, pheromones and sexual attraction, bone health, sperm production and many more that are poorly understood.
What causes low testosterone?
The causes of low testosterone fall into three broad categories.
- Damage or disease to the testicles or pituitary glands
In this case, the brain still tells the testicles to make testosterone but they are damaged and so they can’t. Causes include:
Undescended testicle (especially bilateral) , a childhood surgical condition where the testicles remain in the abdomen and can become damaged
Radiation or chemotherapy to the testicles or pituitary (in the brain) from cancer treatment
Trauma or surgery to the testicles or pituitary, such as a car accident
- Significant illnesses or body wide illnesses that are known to lower testosterone
In this case, the illness sends inflammation signals to the brain and this slows down or stops the brain’s messaging to the testicles to make testosterone. Examples include:
- Diabetes
- Cancer
- Malnutrition
- Some medications
- Obesity (fat tissue contains enzymes which convert testosterone to oestrogen)
- Environmental causes that are still poorly understood
Similar to the above, certain stimuli and environmental exposures interrupt the production of testosterone at all levels.
Fluorescent lights
Processed foods with potential plastic or oestrogen derivatives
Environmental pollution such as pesticide or other chemical exposures
Sleep deprivation
How can low testosterone be diagnosed?
There is a blood test to check for testosterone however it can be difficult to interpret. Testosterone is highest in the morning and is impacted by food; the best test is 8am in a fasted state (no food from midnight).
There is no concrete guide on what ‘number’ constitutes a low testosterone. Some men can have a low number and still seem to have plenty of testosterone for their needs; vice versa, some men have high numbers but either the testosterone is being blocked or interrupted or it’s not enough for their body.
It is important to only test for testosterone in conjunction with taking a thorough history by your doctor to make sure the blood tests add up to the real life experience. Questionnaires looking at the presence of symptoms of low testosterone help to understand the context and give a more accurate picture.
If a man has symptoms suggestive of low testosterone (or a medical history putting him at risk), blood tests can proceed.
How is testosterone tested in blood tests?
Testosterone exists in two forms in the blood. Most testosterone (98%) is bound to other molecules in the blood called Serum Binding Hormone Globulin or SHBG or albumin. The other ~2% is free and available for tissue activity and is called Free Testosterone.
It is customary to test for Free Testosterone, Total Testosterone, SHBG and a few other health blood tests when assessing testosterone.
This may or may not include cholesterol, sugar/insulin/HbA1c to check for diabetes, general check up for liver, kidneys, heart, full blood count, vitamins etc. as may apply.
The reason here is to get a total picture to understand why a man might have symptoms of low testosterone.
What is more important, free testosterone or total testosterone?
It is important to test for Free Testosterone, Total Testosterone and SHBG on the first visit to understand the different factors at play.
For example, SHBG levels are low in men with obesity and metabolic syndrome; this often means that less testosterone is carried around the body. Addressing this with weight loss, exercise and insulin management can really help the delivery of testosterone
Correction of this with an effort to lose weight, exercise and lower insulin and the inflammation associated with metabolic syndrome are just as critical to treating the symptoms of testosterone deficiency. This opportunity should not be missed.
Furthermore, a full health check can help identify a large prostate, cardiovascular risk factors or vitamin deficiencies; all of which will impact energy, erections and the ability to exercise and generate healthy testosterone levels.
In daily practice, Total Testosterone is more useful for the diagnosis of low testosterone. There is no accepted cut off level for low testosterone however, a level near 300 ng/dL needs to be considered alongside the symptoms to make a judgement on whether additional testosterone should be used. Men at 400 or 500 may warrant treatment based on the symptoms. Treat the patient, not the number!
Bioavailable testosterone describes the testosterone not bound to SHBG and either free or bound to albumin. It is increasingly being used by doctors to reflect non-SHBG testosterone activity. The testosterone blood test should be taken in the morning in the fasted state; food intake can decrease testosterone by up to 25%.
What are the symptoms of testosterone deficiency?
The symptoms of low testosterone mimic many other conditions and include: fatigue, lack of muscle gain or maintenance, low sexual desire, growth of breast tissue or hip fat, depression, thin bones (low testosterone can lead to osteopenia or thin bones). Questionnaires are available online. As emphasised earlier, the full health picture should always be evaluated to ensure no serious diseases in other parts of the body are missed.
How can testosterone be replaced?
Testosterone can be replaced directly in three ways:
By mouth (tablets),
Through the skin (patches, creams, gels, sprays) or
injection (into muscle or subcutaneous tissue).
Each method involves a testosterone molecule being delivered to the body and being used, prior to being broken down by the liver. Several forces are at play. The absorption of the drug will impact how quickly and reliably the full dose works day in day out. All molecules are unstable but some will last a lot longer than others and this creates uncertainty as to when they are broken down. Finally, oral testosterone has to go through the liver which creates problems.
What this means is that each form of testosterone delivery will last a different length of time, require a different dose and may absorb differently. There are pros and cons to which form to use. Finally, testosterone products are not generally interchangeable with each other. If you are switching from a cream to an injection, the dose and experience will be different for most men.
Creams and gels are popular, dosed daily, and are reasonably convenient but have variable absorption and come off if you swim or shower in 6 hours. Using a very routine dose, a tube or packet of sachets may only last half a month. Results can vary widely. There is also the risk of transferring it to the skin of children or women; this is problematic.
The following table is just an example of some brands on the market; brands of topical testosterone differ in each country.
Product | Method of Delivery | Item | Total Dose | How long it lasts | Ingredient | Similar products in other countries |
Androgel 1% | Gel | 50mg sachet | 1/1.5/2 Sachets (50- 100) | 30 sachets (15-30 days) | 17-beta hydroxyandrost-4-en-3-one | Testogel. Testim |
AndroForte 5 | Cream | 1mL= 50mg | 1-2mL 50mg/ 100mg | 50mL tube (25-50 days) | 17-beta hydroxyandrost-4-en-3-one |
Tablets are rarely used as historical formulations were known to cause liver inflammation. New brands may come on the market but are not commonly used at present. These are mostly available on the black market and not recommended as they can be damaging for your liver.
Injections deliver the most effective and reliable method of testosterone delivery. The benefits hinge on reliable drug absorption and the ability to ensure steady levels if injected regularly. (all molecules are unstable over time, however less so once reliably inside the body rather than on the skin).
Injectable Formulations: which is best?
Unique to injectable testosterones is the ability of the manufacturer to modify the molecule to make it stay in the body for longer. Some injections are manufactured to provide enough testosterone for 3 months; the objective from the manufacturer is to achieve less frequent injections.
In general, frequently dosed testosterone provides more stable levels. Because testosterone is converted to estrogen by aromatase, an enzyme in our fat tissues, high doses of long acting testosterones tend to have more estrogenic side effects than smaller, more frequent doses. It also results in an unpredictable testosterone level towards the end of the dose that results in resumption of the testosterone deficiency symptoms described before.
The purest way to deliver efficient, active testosterone with minimum estrogenic side effects and a reliable concentration is by daily injections. This is not often practical and so a commonly used regimen is for twice weekly injections of intermediate acting injectables such as Testosterone Enanthate or Cypionate.
Testosterone Type | Brand | Dose | Regimen | How long it lasts | Similar products in other countries |
T Propionate |
|
|
|
| Testoviron, Testovis |
T Cypionate | Depo Testosterone | 200-400mg q2weeks | 0.2mL IM 5 times per fortnight of 200mg per mL (40mg) or variant OR 0.5mL per week | 10mL vial 200mg per 1mL 20 weeks |
|
T Enanthate |
| 200-400mg q2weeks | 0.2mL IM 5 times per fortnight of 200mg per mL (40mg) or variant OR 0.5mL per week | 5mL vial 200mg per 1mL 10 weeks | Delatestryl |
T Undecanoate(Injection) | Nebido | 1000mg/4mL | 4mL injection once every 3 months | 3 months | Reandron, Andriol, Nebido |
T Undecanoate(Oral) |
| NA | Twice daily | Monthly | Jatenza, Andriol |
Generally speaking, testosterone products are not interchangeable with each other.
What is Sustanon?
Sustanon is a mixture of a range of testosterone esters (the name given to molecules adjusted for different halflives or durations of action in the body). It was designed to give steady testosterone activity after injection.
Sustanon remains a popular choice of testosterone for many men as it provides multiple durations of testosterone; however it still requires frequent dosing adjustments to keep testosterone levels steady.
How can Testosterone be Indirectly Replaced?
Not all testosterone replacement therapy requires testosterone itself.
One of the problems with directly giving testosterone is that there is suppression of the hypothalamic pituitary axis. This means that testosterone from the outside world tells the brain to stop telling the testicles to make your own testosterone and sperm. This can also cause the testicles to shrink which can bother some men.
If you only use medical replacement doses for one year, studies suggest strongly that this will reverse however it is another factor to consider.
This very same process can also lower the amount of other hormones that the brain tells other glands to make. These include
- DHEA
- Progesterone
- Androstadienone
These hormones play a role in nerve function, brain health, sexual attraction and many others.
When using testosterone, studies have shown that using medications that avoid the suppression of the hypothalamic-pituitary axis (the brain stelling the testicles and other glands to keep making hormones) can help maintain testicular function and the production of all of these other hormones.
There are a few ways to do it.
To understand what these drugs do, it is worth explaining how the brain and testicles regulate how much testosterone is made.
In normal circumstances, the hypothalamus (hormone HQ of the brain) will release Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH), which are the signals that travel to the testicles (or ovaries) to trigger the creation of sperm and testosterone.
If this process went forever then there would be ever high FSH and LH and far too much testosterone and sperm! So, to regulate the supply, estrogen and testosterone reach the hypothalamus and tell the brain ‘hey we have enough hormones for today thanks, no need for more’ and shut down the production pathway for a while.
This is called a negative feedback cycle and keeps the system in check.
Men who take testosterone will have suppressed FSH/LH due to the extra testosterone and estrogen (remember that the aromatase enzyme in fat turns excess testosterone into estrogen) acting in the brain saying ‘hey we have enough’.
There are ways to manipulate this signalling using medications that either trick the brain into making more FSH and LH, or to mimic these hormones directly. In this way, we can either trick the brain or the testicles or both into making more testosterone.
Clomiphene is a medication that blocks estrogen from binding to receptors in the hypothalamus in the brain. By doing this, the brain will either keep making more FSH and LH (if a person is using testosterone) or make a bit more compared with normal circumstances.
Studies have shown clomiphene to provide a modest increase in testosterone levels in men with reduced LH/FSH (who may have low testosterone from disease or lifestyle factors) levels as well as maintaining sperm levels in men who are taking testosterone.
It has been used for fertility in men however that is beyond the scope of this article. It is mostly useful in men with reduced LH/FSH or who want to preserve sperm output whilst on direct testosterone therapy.
Clomiphene is started as a dose of 25mg every other day and increased as tolerated to 50mg every other day. Rarely Clomiphene can cause visual changes or breast enlargement due to changes in the pituitary gland in the brain. If this occurs it is recommended to stop Clomiphene therapy and these side effects should resolve. Some people may have mild nausea, bloating or headaches.
Human Chorionic Gonadotropin is a molecule similar to Luteinising Hormone and is able to stimulate the Leydig cells of the testicles to create testosterone. Similar to clomiphene, it has the ability to keep the testicles productive, avoid testicular shrinkage and preserve sperm output for men who are taking testosterone.
Unlike clomiphene, HCG does not lead to higher luteinising hormone levels. Studies have shown that it is effective in preserving sperm output in men who are taking testosterone when used at 500 units twice per week. Like clomiphene, HCG can be used as monotherapy to stimulate testosterone production with perhaps greater effect than clomiphene. It is the preferred option for men who want to avoid any risk to fertility whilst addressing low testosterone.
HCG needs to be injected twice or three times per week subcutaneously or in the fat layer underneath the skin. Similar to testosterone therapy, the increase in downstream hormones such as oestrogen from excess testosterone need to be monitored with blood tests.
The side effects of HCG include those of testosterone:
An increase in Estradiol
An increase in red blood cells
Derangement in cholesterol
Hair loss
Change in mood, weight or libido
Pain or irritation at the injection site
HCG has not been studied long term in humans to assess for cancer risk however experiments on cells have not shown chromosomal abnormalities. HCG must not be given to women unless under the supervision of a doctor.
Finally, HCG must be injected and has to be stored in the fridge.
Arimidex
Arimidex is an aromatase inhibitor. It stops the enzyme in our fat cells turning excess testosterone into estradiol (the main form of estrogen). The point of using it is to shift the dial slightly into leaving a bit more testosterone in the body compared with estrogen.
It also plays a role in blocking one of the side effects that may come from using testosterone; extra estrogen. This guide will talk later about the common side effects of taking testosterone.
Men need estradiol too and so taking arimidex or similar medications regularly is not recommended; low estradiol can cause a profound loss of libido. Arimidex should only be used if blood tests indicate high estradiol.
Longer term, arimidex use is associated with thin bones. Using testosterone replacement in smaller doses, more frequently, may help reduce the need for arimidex. Men on arimidex should have regular bone density scans and have their Vitamin D checked regularly.
Nonetheless, it can be used if somebody clearly has high estrogen as their main problem.
What are the side effects and risks of using testosterone?
Testosterone used in small replacement doses is largely very safe. There are a range of physiological responses that have to be monitored. You need to be aware of the following:
Sperm Production: ToT will shut down your own sperm production by telling your brain to lower Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH). These hormones normally tell the testicles to produce testosterone and sperm. With outside testosterone being used, the pituitary ‘shuts down’ these messengers and sperm production ceased. Men who have not had their children should NOT use testosterone unless they have consulted a specialist or had their sperm frozen.
Estrogen: Excess testosterone is converted into estradiol (the main form of estrogen) by the enzyme aromatase, which is found in fat tissues. A blood test should be done at 6-8 weeks and the aim is for oestradiol to be between 20-40pg/mL . Lower causes aggression and higher causes breast tissue, female pattern fat deposition, lower muscle growth, mood changes. If the oestradiol is high, a medication called arimidex and/or nolvadex can be used for a few weeks. Your doctor will discuss this with you
Too many red blood cells: Very high doses of testosterone will cause an increase in red blood cells. This is more common in excessive doses used in bodybuilding. A regular blood check can be used to detect and avoid this. If you have too many red blood cells, this can cause stroke and heart disease or spleen damage.
High Cholesterol: Similar to red blood cells, excessive testosterone can cause an increase in testosterone. In mild doses used in ToT (testosterone optimisation therapy) this is less likely however it should be checked.
Liver damage: This is rare when using testosterone however can result from high cholesterol or the use of arimidex.
Hair Loss: Taking high levels of testosterone can lead to high levels of Free Testosterone. Free testosterone is converted to DHT or Dihydrotestosterone in the scalp. This potent form of testosterone causes hair to stop growing. In my experience, if a man is using medical or physiological doses of testosterone (that is, just replacing the testosterone towards normal high end levels), then this is unlikely. However, all men should watch out for hair thinning and have a chat about using finasteride. Finasteride is a medication that blocks DHT in the scalp and has been proven to prevent testosterone or male related hair loss.
Shrinking of Testicles: When we take testosterone, the extra testosterone will tell the brain to stop releasing the FSH and LH, which in turn tell the testicles to make testosterone and sperm. When this happens, the testicles will often shrink. This is fairly rare but may bother some men.
This can be dealt with by using HCG or clomid during therapy.
It should be pointed out that testosterone use does not shrink the penis.
Low testosterone after stopping testosterone: As we know, our brain decides to stop telling the testicles to make our own testosterone when we are on therapy. Once we stop taking the testosterone, it can take a while for this system to fire back up again. Sometimes HCG and clomid can be used for 6-8 weeks to help things get back to normal.
Aggression, high libido, mood changes: These are rare on small doses of testosterone but please tell your doctor if these emerge.
Will I be on testosterone optimisation therapy forever?
The goal of testosterone optimisation therapy is to restore testosterone levels to a youthful norm and improve the quality of life. At the same time, we aim to clean up general health in the background to see if we can restore natural testosterone production. This means exercising, losing weight, sleeping well, replacing missing vitamins (and other herbal medications) and eating clean.
In some cases, the improvement in general health means that the downward pressure on natural testosterone production from poor health is relieved and we can think about going off the testosterone and relying on natural testosterone levels.
In my clinical experience, this is extremely rare.
By the time a man clearly has low testosterone, a fair bit of damage has been done to the brain to testicle hormone system and a full recovery just is not possible. Remember, as we age, damage builds up and our cells do not live as long and die off.
The challenge here is managing long term testosterone.
88% of men on testosterone therapy will not produce sperm and almost all will have suppressed testosterone levels. (Hsieh et al). Studies generally show that recovery of both sperm and testosterone is pretty good when the duration of testosterone is 12 months or less and the doses have been medical rather than bodybuilding doses.
Other studies show that men who have taken very high doses of testosterone over many years were much less likely to ever recover sperm or testosterone making capacity.
The magic moment here is 12 months.
Many of my patients are over 45 and have already finished their patients. For these men, the ‘shop is closed’ and preserving sperm is not a goal. Many of these men have put up with low testosterone for years and are not keen to go off it; they understand that if they want to keep using it without a break then the day will arise that even if we go off it and use clomiphene and buckets of HCG, their testicles may never wake up and produce testosterone again.
In my experience, most are ok with this and are willing to keep going for life.
The difficulty is in younger men or men who have the desire to go off it some day.
In these cases, we need to do two things. The first is to use HCG alongside the testosterone. This can be done in the same syringe with a bit of training and practice and so can be convenient. Dosing testosterone alongside 500-1000 units of HCG twice per week is usually the recommended regimen. Some will also use clomiphene.
The other thing we need to do is the one yearly break. The studies show that most men, even after a year of testosterone therapy, will recover full testicular function both in terms of sperm and testosterone.
For men who want to preserve testicular function, it is best to take a break from testosterone for 3 months every 12 months. During this time, we can use additional HCG or clomid, or even growth hormone, to maintain an anabolic effect.
However, by resting the testicles every 12 months and allowing them to function naturally, we can aim to put a stop gap in the process whereby testosterone use can put the testicles to sleep long enough that they never wake up.
At the same time, I prefer my patients to get a sperm test once a year. This way, we are taking breaks from testosterone, using medications to keep the testicular function going and keeping an eye on sperm production.
Preserving fertility whilst on TrT?
What tests should I have whilst on ToT?
Every man is unique and should ideally have ToT with their regular doctor. It cannot be emphasised enough that ToT should take place with a whole health approach so that other diseases are not missed. The following tests represent what men on ToT should have tested in addition to annual checkups, examinations and blood pressure checks.
ITEM | HOW OFTEN | UNITS | RANGES |
Total testosterone | *Baseline *6 weeks after new dose of T started *Every 4 months | ng/dL | >600ng/dL 645 |
Patient Handout: Testosterone Optimisation Therapy 11
ITEM | HOW OFTEN | UNITS | RANGES |
Free testosterone | *Baseline *6 weeks after new dose of T started *Every 4 months | ng/dL | ~ 2% of total |
SHBGSerum hormone binding globulin | *Baseline *6 weeks after new dose of T started *Every 4 months | nmol/L | 18.3-54.1 |
CBCComplete blood count | *Baseline *6 weeks after new dose of T started *Every 4 months | Haematocrit < 52% Haemoglobin <20 | <52% Hb: 13.3-17.5 |
Estradiol E2 | *Baseline *6 weeks after new dose of T started *Every 4 months | pg/mL | 20-40 ideally |
LFTs | Baseline Every 6 months | Within range | Within range |
DHEA | Every 6 months | mcg/dL | 95-530 |
Pregnenolone | Every 6 months | ng/dL | 80-180 |
Thyroid Function | Baseline Every 6 months | Discuss with doctor | Discuss with doctor |
PSAProstate Specific Antigen | Baseline Every 6 months | Discuss with doctor | Discuss with doctor |
Lipid Panel | Baseline Every 6 months | Discuss with doctor | Discuss with doctor |
Renal Function Tests | Baseline Every 6 months | Within range | Within range |
HbA1c | Baseline Every 6 months | 5.0% | 5.0% |
Prolactin | Annually | ng/dL | <30 |
What else should be monitored whilst on testosterone?
At a minimum the Free/Total Testosterone, CBC, Estradiol and SHBG should be done after 6-8 weeks of first starting ToT to ensure no problems and then this can be stretched to every 3 months. Some patients may have other tests completed in health care packages.
In addition to the aforementioned blood tests specifically designed to monitor testosterone, a discussion should take place about lifestyle measures to improve health in relation to hormone function. This includes diet, exercise, vitamins and supplements, optimisation of sleep and wellbeing as well.
If there is a deficiency of vitamins, such as vitamin D, or interruptions to sleep, a lack of weight loaded exercise or poor dietary intake, this will act against the body’s attempts to synthesis testosterone. The development of diabetes or obesity will also hinder the effect of testosterone.
When is the best time to have a testosterone blood test?
If you are on testosterone treatment, the best time to have a blood test is before your next testosterone shot is due. The goal is to measure the testosterone at its lowest ebb or trough. If you take the blood test after an injection or dose of testosterone, you will only be measuring the testosterone you have just put into the body rather than what is usually there.
The exception to this is the creams; the time to take the blood test depends on the type of cream. Generally, the best test is taken 2 hours after applying the cream.
For all blood tests generally, a morning fasting test is better. This means no eating from midnight and only water in the morning. You may brush your teeth.
How long does testosterone take to work?
The impacts of testosterone start at different times for different people. In general, the following have been reported:
Sexual interest seems to improve from weeks 3 until 6 and then remain at this level.
Erections and ejaculations seem to improve from weeks 12 until 26 and then remain at this level.
Depressive symptoms seem to improve from weeks 3 until 6 and gains in this regard remain peaked as of this stage
Body composition gains start at week 12 until 16 and continue until 52 weeks Bone mineral density improvements begin at week 26
Glycaemic control improvements begin at week 12 until 52
These effects will generally vary widely amongst different men of different ages. In general, it will take 6 months of effective, therapeutic testosterone therapy with lifestyle measures, weight loss and management of other contributory health conditions before a benefit can be established.
A quick guide on taking ToT medications.
Before taking any form of testosterone, you should discuss how to do it with a pharmacist, nurse or doctor. For topical or cream/gel testosterone, it is pretty straight forward. Injections are however a bit more of a learning curve.
Over time, men on testosterone by needle will require regular frequent injections. It is not practical to come into the doctor’s office twice per week forever for this; you will have to learn how to do it yourself.
The best way to do this is to book some training with your doctor or their nurse. Some general tips on injecting will be given here and please refer to another article called ‘Self Injecting’ for more information.
AndroGel
Each sachet contains 50mg of testosterone in 5g of gel. Tear open the packet onto clean hands. Rub into a clean area of skin on the shoulder or abdomen. Wait until the area is completely dry before replacing your clothing. Wash your hands with soap and water and ensure you discard the packet safely, away from children. Do not come into contact skin to skin with women or children. The starting dose is one sachet per day. Do not swim or shower for at least a few hours so that it soaks in.
Depo Testosterone (Testosterone Cypionate)
Each vial of 10mL size or 1mL size generally contains 200mg per mL. The starting dose is 100mg per week delivered in two doses. Each 3.5 days, or twice per week, give 0.25mL. Some men may start a bit higher to ‘front load’ the dose at 0.5mL twice per week; have this discussion with your doctor
Basic Injecting steps
First, take the plastic cap off the vial.
Use an alcohol swab to wipe the rubber top.
Unwrap and then uncap your brand new small insulin needle.
Using the needle, draw up 0.5mL (about half way).
Use another alcohol over the area of skin you will inject.
Use a different area of thigh or shoulder than last time.
Pinch the area, careful not to touch the clean area with your fingers,
drive the needle in and deliver the dose.
Place a cotton bud over the area and discard the needle carefully.
What kind of needle and syringe to use?
- 1mL syringe with luer lock screw top
- 21g needle to draw up testosterone
- 25g needle to inject it
For injecting a thick liquid like testosterone, you want a luer lock syringe. This is a type of syringe end that has to be screwed on rather than just pushed on.
The reason is that if you have a push-on syringe, the testosterone liquid is so thick that the pressure from pressing the plunger might translate into the needle blowing off and spraying liquid testosterone all over your arse. It’s not a pretty site and it won’t help testosterone get into the bloodstream. You won’t have this problem with a screw top.
For all injections, aim to use a Luer Lock syringe; especially after a few doses of testosterone you might not anticipate how strong your muscles are on your syringe trigger arm.
How do I store testosterone; especially an open glass vial?
Testosterone can be stored at room temperature but must be stored out of the light. Some men will keep the vial in the cupboard.
You may note that Testosterone Cypionate may come in a 10mL volume or a 1mL volume. Sustanon generally comes in a 1mL glass vial.
The 10mL packet has a rubber stopper on the top that means you can put a clean needle in and the vial remains sterile and sealed. This is one of the reasons I prefer the 10mL bottle.
The 1mL glass vials are tricker to play with. Many people will cut themselves opening it. The best way to open it is to use a piece of cloth or rubber and snap the top off confidently.
Once opened, you are generally only going to use 0.25-5mL of a mL at a time. This means that the glass vial remains sitting in the open for a few days if not a week!
There are a few approaches. The easiest is to draw up your remaining doses of testosterone, add a clean needle still in the protector as a stopper, and place them in a cupboard away from light or a fridge. You can then inject at will.
Some men will store the testosterone in the fridge too. Whilst testosterone is ok to be stored at room temperature, generally it helps keep injections clean to be in a fridge.
This can be done, but remember to take your testosterone out of the fridge for a good half hour before you want to inject it. Testosterone is already a thick liquid. If it is cold, it will be especially thick and potentially impossible to inject.
HCG
HCG tends to come in packets of 5000-6000 units. These need to be made up into smaller batches of 500 units or 1000 units to be injected twice per week for the duration of therapy.
The best way to do this is to divide the packet of 5000-6000 units into smaller doses in 1mL syringes.
Steps to do this
- Prepare 10-12 syringes (10 for 5000 units, 12 for 6000 units)
- Each syringe needs 0.2mL normal saline 0.9% (NS) or bacteriostatic water (most people use normal saline which is generally sterile for 6 weeks of storage in a fridge)
- Calculate the total amount of NS 0.9% you will need; E.g 10 syringes x 0.2mL = 2mL, 12 syringes is 2.4mL
- Round up for waste and error. E.g. 10 syringes – 2mL (add 2.2-2.4mL), 12 syringes = 2.4mL (round up to 2.6mL etc.)
- If the 5000 or 6000 units of HCG in the packet are a liquid, inject that whole dose into a 3mL syringe and add additional NS 0.9% to make up the desire quantity. E.g 5000 units of HCG in 1mL of fluid in the commercial packet syringe needs to be made up to 2.2mL= simply add 1.2mL of normal saline syringe to make the total of 2.2mL
- If the 5000 or 6000 units of HCG are a powder, simply add the amount of NS 0.9% you want (2.2mL, 2.6mL etc.) , give it a good shake, and withdraw it into the syringe
- Take your target syringes to be filled up: aka, 10 or 12 x 1mL syringes
- Using your made up total volume of HCG in the 3mL syringe, carefully inject 0.2mL of volume into each of your target 1mL syringes. Remember to withdraw the plunger to see the water line at the top of the marker on the syringe, NOT the top of the syringe. Only the lines matter.
- You may have some leftover or not; this can be added as a booster dose without any harm
- Add a 25g needle still in the packet to the end of your 1mL syringes as a stopper and place them promptly in the fridge.
This is how you make up your HCG batch. I have another guide on how to do this HERE (link to be provided later).
How to inject HCG
HCG is injected into the subcutaneous fat not the muscle; this is the layer of fat immediately under the skin but above the muscle or any other structure.
The best way to inject HCG is to choose an area of fatty skin (over the buttocks seems to hurt less but you can do it anywhere), pinch the fat, drive the needle in perpendicular and inject as you withdraw. Remember to stop injecting before the needle is too close to the surface of the skin; if you are too superficial then the liquid may leak out.
The reason to inject as you withdraw is so that there is enough space for the liquid to go; if you drive the needle into the fat and inject the whole liquid in one go, there may not be enough space; this can cause a bit of pain and if there really isn’t space, the pressure of your injection can blow the needle off the syringe resulting in your HCG spraying on you and the room rather than into your fat.
Can I combine HCG and Sustanon/Cypionate into the same injection?
HCG and Testosterone cypionate or sustanon are both injected twice per week; so why not put them in the same syringe and save some effort?
This can be done. However, remember to take your testosterone out of the fridge first to warm it up before injection; otherwise it will be too thick to handle and get into the syringe, or your muscles.
The way to do this is to take your pre-made HCG syringe out of the fridge. You then put a larger needle on it; remember that testosterone is a very thick liquid and will not travel up a small syringe (especially if recently cold). You then draw up the amount of testosterone you want (e.g. 0.25mL or 50mg, or 0.5mL if you’re riding higher) into the same syringe as the HCG on TOP of the HCG. HCG is water soluble and testosterone is fat soluble; the two liquids will not mix.
At this stage, you change to a smaller needle but nothing smaller than a 25g. Testosterone will not go through anything too small and you’ll blow the syringe off and spray the medicine all over the place.
Now, you may recall that testosterone needs to be injected into the muscle and HCG into fat. A common compromise here is to inject into the deep subcutaneous fat. This means deep enough to almost reach muscle but still in fat. Studies have shown that testosterone will still be absorbed from the subcutaneous fat.
You give the injection in the same fashion as outlined and then safely dispose of your sharps into a sharp bin.
Clomiphene
Start clomiphene at 25mg or half a tablet every other day. If you do not experience side effects, move up to 50mg tablets every other day. It is used continuously or periodically in 2-4 weeks blocks as per your physician.
Arimidex
Arimidex is a medication to block the conversion of testosterone to oestrogen by our fat cells. It is started at 0.5mg (half a tablet) once every 10 days and the dose will be adjusted by your doctor based on your Estradiol blood test results. You should not use too much arimidex as it can affect your bone density.
Tamoxifen
Tamoxifen is a Selective Estrogen Receptor Modulator or SERM. It is sometimes used to prevent the activity of excess Estrogen on certain tissues in the body, notably the formation of male breast tissue. It is generally safe to take for a trial of 6-12 weeks for this under supervision. Side effects include nausea, rashes, hot flushes, fatigue and loss of libido. It is taken daily.
Finasteride
Finasteride is a 5 alpha reductase inhibitor; it blocks the conversion of testosterone to dihydrotestosterone, a more powerful testosterone, in the tissues. It is used in small doses to prevent DHT related hair loss in men. Side effects are rare but include loss of libido, lower ejaculation amount and potential finasteride syndrome which is a rare depressive and
concentration illness thought to be related to blockade of neurohormones. It is taken as 1mg at night.
Topical DHT
Topical DHT is being developed for use in potential beard growth. At present it is used as a form of testosterone delivery in children with specific hormonal needs. DHT absorption would directly mimic testosterone replacement therapy at high doses and so at this stage, is not available routinely. DHT would be expected to rise from testosterone replacement therapy.
How do I track my testosterone?
There are many apps to track your testosterone.
https://www.steroidplotter.com/ is helpful to look at doses from different formulations.
What are the other health issues for men who take too much testosterone?
The use of testosterone beyond doctor recommended doses is strictly not recommended. There is a risk of
An enlarged heart: Testosterone causes the heart to remodel and lay down collagen. If the user is also using estrogen blockers such as arimidex, then this risk is increased and can lead to permanent heart disease and death
Raised Angiotensin II: this hormone is involved in causing the heart to enlarge as well as causing high blood pressure. Some men may take blood pressure tablets to block this but it is not clear how well they work.
Estrogen blockage has significant mood, brain, cognitive, heart and libido impairments. It is not recommended
Testosterone abuse and the heart
Sadly, every year I encounter a new testosterone patient who has injected substantial amounts of testosterone over the years without medical help and now has heart disease.
The first step to avoid this is to always seek the input of an experienced doctor in your testosterone therapy. It is not wise to just follow your coach; they may help you look big, but a doctor they are not.
Men who abuse steroids should have regular echocardiogram (an ultrasound of the heart to check it is the normal size) and consider an angiotensin II Blocker like telmisartan or olmesartan; this is a blood pressure pill that helps protect the heart from stress. This is due to the higher incidence of heart disease in body builders; typically seen as larger hearts with collagen deposition.
Some studies have shown that body builders using supraphysiological testosterone levels with suppressed estrogen due to aromatase inhibitors have more collagen in their hearts. Often this goes unnoticed until they drop dead.
This is reflected in studies showing that in the heart, testosterone encourages fibroblastic activity and collagen deposition which is blocked by estrogen in the heart; this underlies the
danger of self treating with these medications.
Furthermore, a higher adrenalin release is stimulated by anabolic steroids; a high adrenaline increases the afterload (the stiffness of the arteries such that the heart has to ‘push’ harder to get blood out of the heart) which encourages an enlarged heart. Some body builders will use
nebivolol twice per day 5mg and telmisartan 20mg in the evening to prevent these inflammatory consequences for the heart.
Once again, this highlights the heart dangers of using anabolics and aromatase inhibitors and the potential for death; any cardiac issues should see a cardiologist for review of beta blockers, angiotenson II blockers etc. to mitigate risk.
Related Topics
- Human Growth Hormone
- Sports Supplementation
- Insulin Resistance
- Sleep and the Brain
- Nutritional and Environmental Medicine
- How to make up HCG
- Self injecting guide
REFERENCES
Crosnoe-Shipley LE, Elkelany OO, Rahnema CD, Kim ED. Treatment of hypogonadotropic male hypogonadism: Case-based scenarios. World J Nephrol. 2015;4(2):245-253. doi:10.5527/wjn.v4.i2.245
Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. J Urol. 2013;189(2):647-650. doi:10.1016/j.juro.2012.09.043
Lee JA, Ramasamy R. Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men. Transl Androl Urol. 2018;7(Suppl 3):S348-S352. doi:10.21037/tau.2018.04.11
Rabijewski M. Leczenie hipogonadyzmu a zachowanie płodności u mężczyzn [The treatment of hypogonadism and maintenance of fertility in men]. Pol Merkur Lekarski. 2016;40(237):198-201.
Wenker EP, Dupree JM, Langille GM, et al. The Use of HCG-Based Combination Therapy for Recovery of Spermatogenesis after Testosterone Use. J Sex Med. 2015;12(6):1334-1337. doi:10.1111/jsm.12890