Testosterone in TRT and Benefits of TRT in treating suboptimal testosterone levels

Testosterone is the hormone that gives men their manliness. Produced by the testicles, it is responsible for male characteristics like a deep voice, muscular build, and facial hair. Testosterone also fosters the production of red blood cells, and increases bone density. Levels peak by early adulthood and drop as you age—up to 2% per year beginning around age 40. Normal levels are between 300 and 1,000 ng/dL. Low testosterone produces several symptoms, such as:

-impotence or changes in sexual desire -depression or anxiety -less energy -reduced muscle mass -weight gain -anemia -hot flashes.

The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed mood, anaemia, loss of muscle and bone mass, by increasing serum testosterone levels to physiologic range. TRT has been used in the last 70 years, and overtime, numerous preparations and formulations have been developed to improve pharmacokinetics (PKs) and patient compliance. The routes of delivery approved for use in the Western world include subcutaneous, buccal, nasal, subdermal, transdermal and intramuscular (IM).

Testosterone replacement therapy (TRT) has surged in popularity over the past decade. Millions of older men have turned to TRT to restore hormone levels in hopes of refueling energy and reigniting their sex drive.

If you just heard of TRT, its natural to be a little sceptical.

At first glance the benefits look too good to be true, improved physique, better mood, better sex, more confident and better health…

Are these benefits real or are they overblown? How likely are you to really notice everything on this list and how long does it take for the benefits to be seen?

The answers aren’t straightforward and there are differences between individuals that will impact how many benefits you see, and how long it will take for you to see benefits.

Testosterone replacement therapy, what is it?

Testosterone replacement therapy is the administration of the testosterone hormone into the body, to replace low levels of natural production.

It is called replacement because the natural production of the body reduces with the addition of exogenous testosterone (from outside the body) and is eventually replaced (this can be avoided by the use of HCG).

But what about those rumours that Trt correlated with a increase chance of heart attack

Dr. Frances Hayes, a reproductive endocrinologist with Harvard-affiliated Massachusetts General Hospital, points out that some of these studies had limitations. "For instance, in one study, TRT doses were much higher than what would usually be prescribed, and the subjects tended to be more frail, with other health problems," she says. "Other studies showed no evidence of increased risk."

The latest findings

Recent research has supported this position. A study reported at the 2015 American Heart Association Scientific Sessions involved 1,472 men ages 52 to 63 with low testosterone levels and no history of heart disease. Researchers found that healthy men who received TRT did not have a higher risk of heart attack, stroke, or death. Furthermore a more recent study published in Canada showed 300% decrease in heart attack rates with long term (3+year) therapy. Having low testosterone and a a sedimentry lifestyle makes one much more prone to heart attack than having high normal levels combined with a active lifestyle.

Furthermore, a study in the August 2015 Mayo Clinic Proceedings showed no link between TRT and blood clots in veins among 30,000 men.

TRT's relationship with other health issues is also mixed. For instance, TRT has previously been tied to a higher incidence of prostate cancer, but a study published in the December 2015 Journal of Urology found that exposure to TRT over a five-year period was not linked to a greater risk of aggressive prostate cancer. Testosterone levels decline by around 1% per year after the age of 30. As well as this SHBG increases in the body with age, leading to lower free testosterone levels.

In some men this leads to low testosterone symptoms. Other young men have conditions such as damage to the testicles from cancer or varicoceles, pituitary issues, genetic problems that lead to incomplete sexual development or have low testosterone for unknown reasons.

What are the benefits of TRT?

· Improved mood – reduced anxiety · Improved libido (sex drive) · Improved assertiveness · Improved confidence · Better erection quality · Better sleep quality · Increased muscle mass and strength · Improved beard growth · Better vascularity and blood supply (which reduces risk of diabetes and can even reverse mild type 2 diabetes). · Deeper and more stable voice · Improved bone density · Improved cognition including memory and mental acuity · Reduced all-cause mortality (deaths over a time period compared to men not on testosterone replacement therapy)

Improved mood and cognition Jung and Shin (2016) demonstrated that the benefits of testosterone replacement therapy improved various aspects of mental health in men with testosterone deficiency.

They noted improvements in memory, mental acuity and mood.

In this study there were very few side effects, and none were serious. It is common for men who start treatment to notice a return to normal levels of brain function, where before they suffered from ‘brain fog’. Brain fog is when men struggle to perform simple mental arithmetic, remember things that happened recently, and find concentrating difficult.

They noted that men may also find that their motivation and drive is reduced:

‘The effect of testosterone administration on cognitive function and depression in hypogonadal men is believed to be related to the enhancement of brain perfusion, which is supported by the fact that there are androgen receptors in the brain, suggesting that steroid hormones play a role in neural function.’

Interestingly they go on to hypothesis the potential benefits this could have on men with other mental health conditions. In particular, they refer to a study on men with mild alzheimer’s.

‘The effects of TRT in men with mild cognitive impairment or Alzheimer’s disease have been evaluated in small placebo-controlled trials. For example, Cherrier et al (2005) evaluated a sample of 32 subjects, which included 17 men with mild cognitive impairment and 15 with Alzheimer’s disease. At the 6-week follow-up, patients who received TRT showed significantly better scores regarding spatial memory, constructional abilities, and verbal memory compared to those noted in the placebo group. Taken together, these results suggest that TRT has a beneficial effect on cognitive function.’

This is clearly a very interesting finding and something that needs further research. There is some evidence that low testosterone reduces perfusion (supply of blood to tissues) in various areas of the body. Improving testosterone levels often provides relief from conditions such as diabetes that have the side effect of reducing blood supply to regions.

Improved libido (sex drive) Hackett et al. (2017) found that men with type 2 diabetes and low testosterone saw large improvements in sexual desire and erection quality after starting testosterone replacement therapy. This is a common benefit we see in our patients within the first 6 months of TRT. Khera et al. (2011) showed that TRT with a testosterone gel significantly improved sexual function including libido in a large study of 840 men.

There are many medical treatments for erectile dysfunction. Most very effective for men who have mechanical issues preventing an erection.

However, in some men, the issue isn’t as much an inability to get an erection, which can be a mechanical or biochemical issue but more of a combination of a lack of desire and willingness to engage in sexual activity. This can often be a cause of erectile dysfunction which stems from low testosterone. In men with low testosterone, improving these levels to normal often results in a return to normal erectile function.

Does TRT improve your lifespan and prevent aging?

Regardless of the potential side effects listed previously, if taken properly, TRT can improve your health and lifespan.

In a recent, large study, TRT was shown to reduce the number of men who died from all causes compared to controls who weren’t taking TRT and had low testosterone. Evidence shows that testosterone is cardioprotective and good for heart health. Goodale et al even state that ‘ there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not.’

They go on to talk about the various benefits of that TRT has been demonstrated to have on the heart and general health:

‘Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes.’

Testosterone is also converted into estrogen in men. If men have low testosterone they often also have low estrogen. estrogen is really important in men, it is protects the cardiovascular system, joints and other connective tissue, whilst helping with healing. It is also well established that men with low testosterone are at greater risk from cardiovascular issues than those with normal testosterone levels.

Increased muscle mass, strength and reduced body fat There are lots of studies which demonstrate the impressive effects of testosterone on men’s muscle mass, strength and body fat levels.

It is something that most men who start testosterone notice – a dramatic change in their physique. Testosterone is an effective muscle mass builder by increasing the protein synthesis required for growth. It also improves neuromuscular function which results in strength increases. This is part of the androgenic effect of testosterone and includes the effects of DHT (dihydrotestosterone).

Men with higher testosterone levels tend to have lower overall visceral and abdominal body fat levels. Both of these things (when raised) are bad for overall health and lead to increased mortality rates.

Men with higher testosterone levels tend to have lower overall visceral and abdominal body fat levels. Both of these things (when raised) are bad for overall health and lead to increased mortality rates.

Does TRT improve bone density?

A common effect of low testosterone is reduced bone density. This is partly due to low testosterone and partly due to the reduction in estrogen that results (as estrogen is converted from testosterone in men). Increasing testosterone levels improves bone density, particularly in the spine where older men often suffer from compression fractures.

The main effect on bone density is most likely driven by estradiol levels, however this is mainly a by-product of testosterone in men as it is converted by the aromatase enzyme.

As a result, men with low testosterone will have lower bone density, and increasing testosterone will improve estrogen levels.

How long does it take for TRT to start working?

In most patients, the benefits of TRT take from 3 to 6 months to be fully realised. Some benefits, such as bone density, fat loss and muscle mass increases, will continue to improve for longer than 6 months.

Whilst most men notice some improvements early on in their TRT journey, there are lots of factors which affect the rate of progress.

Firstly, and most importantly, TRT is a process. Optimising testosterone replacement therapy takes time and you should work with your doctor to monitor blood results and adjust dosages. Often the dose you start on will cause testosterone and estrogen levels to rise. This will dampen any benefits and may feel like testosterone is still low. Occasionally (much more rarely) the dose is too low and patients need to increase it further to get levels into the optimal range. In both situations, a blood test is important to ensure careful adjustment of your dose by a specialist doctor.

Secondly, the type of testosterone preparation will cause variations in the time it takes for men to notice improvements. A testosterone ester like propionate will have a faster effect than something like Nebido which takes longer to act in the body due to a longer ester attachment.

Doctors primarily recommend medium acting esters such as testosterone cypionate and testosterone enanthate which can take around 6 weeks to build up to their full testosterone levels in the blood. However, the benefits of testosterone replacement therapy for men who have lower levels may be seen before this build up happens.

Thirdly, some of these improvements take a while to be seen in the body. Usually mood and libido improvements take a few weeks to a couple of months to appear if the dosage is optimised and estrogen levels are good. Other physique changes can take a bit longer.

Saad et al. (2011) researched the timescales for the effects of testosterone replacement therapy and found that:

· Effects on sexual interest appear after 3 weeks plateauing at 6 weeks, with no further increments expected beyond. · Changes in erections/ejaculations may require up to 6 months. · Effects on quality of life manifest within 3–4 weeks, but maximum benefits take longer. · Effects on depressive mood become detectable after 3–6 weeks with a maximum after 18–30 weeks.

Finally, there are individual factors which influence how long it takes for testosterone to show benefits. The individual’s testosterone levels before starting treatment. If very low then the impact of adding testosterone may be felt more quickly.

Androgen receptor differences. Some men have less sensitive androgen receptors, often due to previous steroid abuse. Others naturally have more androgen receptors which will improve the response rate to testosterone levels increasing. Differences can be seen in CAG length,

Unknown factors. Some men are more sensitive to increases in testosterone and estrogen. Others are genetically more susceptible to converting testosterone into estrogen as they have more aromatase in their bodies. This can mean that the benefits of testosterone replacement therapy are less obvious.

You need to have both low levels of testosterone—less than 300 nanograms per deciliter (ng/dL)—and several symptoms (see page 7) to get a prescription for TRT. "It is possible to have low levels and not experience symptoms," says Dr. Hayes. The normal testosterone reference range for men is 300-1000ng/dl, which means one man can have triple the testosterone level as another and both be considered “Normal” but I would bring into question, which man would have more of an advantage in athletics and mental focus and drive. I think the answer is a given in this case. Normal doesn’t nessasarily

mean “optimal”. Many HRT clinics in the US have already adopted this priciple by givin their clients slightly over what canadian Mds would prescribe in a normal case. The general starting dose for trt in canada is 100mg test cypionate once a week. While american HRT clinics commonly prescribe 150-200mg a week administered subQ frequently to maintain stable blood serum testosterone.

For instance, the No. 1 contributor to falling levels is weight gain. "Weight has a bigger impact on testosterone levels than aging. As weight goes up, testosterone levels go down," she says. A five-point increase on the body mass index scale—for instance, going from 30 to 35—is equivalent to adding 10 years to your age in terms of testosterone levels.

"Your doctor should also review any other factors that might influence levels, like medication or medical conditions," says Dr. Hayes. In these instances, your doctor may treat the underlying condition or change your medication or dosage to one that would not affect testosterone levels.

Men also need to understand the limits of TRT, as many envision it as a type of fountain of youth. "Its impact is less than what many men would expect," says Dr. Hayes.

For example, two often-touted benefits of TRT are sexual health and vitality. A double-blind study in the Feb. 18, 2016 issue of The New England Journal of Medicine reviewed the effects of TRT on 790 men ages 65 and older. Those who received TRT for one year, versus those on placebo, saw improvements in sexual function, including activity, desire, and erectile function. However, the group experienced only a slight improvement in mood and saw no changes in walking speed, which was used to measure TRT's effect on vitality.

Using TRT

TRT is often given by either gel application or injection. With a gel, you spread the daily dose—often the size of a ketchup package—over both upper arms, shoulders, or thighs. Injections are typically given into the buttocks once every two weeks.

Each method has its advantages. With gels, there is less variability in levels of testosterone. "However, you have to be careful to avoid close skin contact for a few hours, especially with women, as the testosterone could cause acne or hair growth," says Dr. Hayes.

With injections, testosterone levels can rise to high levels for a few days after the injection and then slowly come down. This can cause a roller-coaster effect, where mood and energy levels spike before trailing off.

Most men feel improvement in symptoms within four to six weeks, although changes like increases in muscle mass may take from three to six months.

TRT may not always need to be taken for life. "If the issue that caused your testosterone levels to drop in the first place resolves, you should have a trial off treatment and be re-evaluated by your doctor," says Dr. Hayes

Conclusion

This is a brief overview of some of the main benefits of TRT. To really notice these benefits you have to find specialist treatment using the correct medications.

In North America these medications are often hard to come by, and aren’t readily provided by the public health system.

We at Cytech uses the Gold Standard of TRT which is adapted to your individual circumstances and physiology to provide the best treatment options with the least possible side effects.

This includes the use of HCG for maintenance of fertility, natural production and the regulation of hormonal by-products which are lost when using TRT on its own.

If you’d like to discuss treatment with us then please contact for more information and expert advice.

References · Cherrier MM, Matsumoto AM, Amory JK, Asthana S, Bremner W, Peskind ER, et al. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology. 2005;64:2063–2068. · Jung HJ, Shin HS. Effect of Testosterone Replacement Therapy on Cognitive Performance and Depression in Men with Testosterone Deficiency Syndrome. World J Mens Health. 2016;34(3):194-199. doi:10.5534/wjmh.2016.34.3.194 · Loo SY, Azoulay L, Nie R, Dell’Aniello S, Yu OHY, Renoux C. Cardiovascular and Cerebrovascular Safety of Testosterone Replacement Therapy Among Aging Men with Low Testosterone Levels: A Cohort Study. Am J Med. 2019 Sep;132(9):1069-1077.e4. doi: 10.1016/j.amjmed.2019.03.022. Epub 2019 Apr 3. PMID: 30953635. · Hackett G, Cole N, Saghir A, Jones P, Strange RC, Ramachandran S. Testosterone replacement therapy: improved sexual desire and erectile function in men with type 2 diabetes following a 30-week randomized placebo-controlled study. Andrology. 2017 Sep;5(5):905-913. doi: 10.1111/andr.12399. Epub 2017 Aug 3. PMID: 28771964. · Khera M, Bhattacharya RK, Blick G, Kushner H, Nguyen D, Miner MM. Improved sexual function with testosterone replacement therapy in hypogonadal men: real-world data from the Testim Registry in the United States (TRiUS). J Sex Med. 2011 Nov;8(11):3204-13. doi: 10.1111/j.1743-6109.2011.02436.x. Epub 2011 Aug 11. PMID: 21834870. · Goodale T, Sadhu A, Petak S, Robbins R. Testosterone and the Heart. Methodist Debakey Cardiovasc J. 2017;13(2):68-72. doi:10.14797/mdcj-13-2-68 · Rajfer J. Relationship between testosterone and erectile dysfunction. Rev Urol. 2000;2(2):122-128. · Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, Ellenberg SS, Cauley JA, Ensrud KE, Lewis CE, Barrett-Connor E, Schwartz AV, Lee DC, Bhasin S, Cunningham GR, Gill TM, Matsumoto AM, Swerdloff RS, Basaria S, Diem SJ, Wang C, Hou X, Cifelli D, Dougar D, Zeldow B, Bauer DC, Keaveny TM. Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone: A Controlled Clinical Trial. JAMA Intern Med. 2017 Apr 1;177(4):471-479. doi: 10.1001/jamainternmed.2016.9539. Erratum in: JAMA Intern Med. 2017 Apr 1;177(4):600. Erratum in: JAMA Intern Med. · Saad F, Aversa A, Isidori AM, Zafalon L, Zitzmann M, Gooren L. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol. 2011;165(5):675-685. doi:10.1530/EJE-11-0221 · A. Ferlin, L. Bartoloni, G. Rizzo, A. Roverato, A. Garolla, C. Foresta, Androgen receptor gene CAG and GGC repeat lengths in idiopathic male infertility, Molecular Human Reproduction, Volume 10, Issue 6, July 2004, Pages 417–421