Background

Testosterone is one of the most universally well-known, but also commonly misunderstood hormones out there. It has captured the imagination of men since its discovery, entering popular imagination as a do-it-all hormone that’s universally responsible for “dude stuff.” Many people think that taking testosterone will be the cure-all to what ails them, and will turn every guy into a lean, trim, athletic, energetic horn-dog with the sexual prowess of an 18-year-old and the energy of a triathlete. We all wish that was true, but reality is a bit more complex. Here we’ll try to explore some of the details behind this popular hormone.

Understanding Testosterone

Testosterone is a hormone, primarily produced in the testicles, that has numerous effects on both male and female physiology (yes, women have a need for testosterone too!). It governs many well-known processes such as libido (sex drive), muscle mass, energy, mental alacrity – the list goes on. Having normal levels of testosterone, defined as roughly between 400-600, but up to 1000 or so in some men, is critical for normal emotional and sexual well-being.

What Causes Low T?

What causes a men’s testosterone to decline? For a long time we though it was aging, and although there is a mild gradual decline in T levels over time, there are very healthy men with T levels still rock solid well into their 70s. The real culprit is the accumulation of comorbid conditions. Basically, a healthy body makes good T levels, and an unhealthy body does not. Thus, the most common causes of low T are:

  • Poor Sleep
  • Stress
  • Obesity
  • Sedentary Lifestyle
  • Poor Diet

Just fixing these will go a long way to help return testosterone levels to normal.

400-600

Normal range levels of total testosterone in men. 1000 is necessary for some men.

10-15%

Body weight reduction can increase your testosterone by 150-200 points.

Signs and Symptoms of Low Testosterone

Being deficient in testosterone, a condition called male hypogonadism, can lead to all of these bad things listed below. In addition, emerging data shows that having prolonged hypogonadism can also increase the risk of diabetes, bone density loss, and even cardiac death. Thus, restoring men who are hypogonadal to the normal state can be a huge part of ensuring optimal health.

Reduced sex drive

erectile dysfunction

fatigue and lack of energy

loss of muscle mass

increase in body fat

decreased bone density

Mood Changes

concentration/memory difficulties

If you are experiencing any of these symptoms, testosterone could be a potential cause. The next step is to evaluate your hormone system with labs and then decide on a treatment plan, if appropriate.

How Testosterone is Normally Made

The real long-term “win” for any Men’s Health advocate is to encourage men to make the lifestyle modifications needed to increase their own testosterone, enabling them to live happier, healthier, and more fulfilling lives. While the answer to increasing your testosterone can certainly be found in a bottle of testosterone cypionate, for most men, this will only ever be a compensatory solution, and does not get to the heart of the issue. The fundamental key to hormone health, and all health in general, is eating well, moving your body, and ensuring that you get good sleep. In patients with sleep apnea, getting on a mask can raise testosterone levels by 150-200 points alone! In obese men, losing 10-15% of your body weight can increase your testosterone by 100-150 points! These are the things we always start with, but for many men it’s not enough. That’s when we start using some pharmacological aids to get us there.

Treatment Options for Low Testosterone

Now that we understand the physiology, how do we increase testosterone levels? Here we break things down into two approaches. The first is the commonly known Testosterone Replacement Therapy, or TRT. This truly means replacing the body’s testosterone with external testosterone. The second approach doesn’t have a formal name, so let’s call it Internal Testosterone Boosting, or ITB for short. These two therapy paradigms have very different philosophies, so let’s explore them below.

The real long-term “win” for any Men’s Health advocate is to encourage men to make the lifestyle modifications needed to increase their own testosterone, enabling them to live happier, healthier, and more fulfilling lives. While the answer to increasing your testosterone can certainly be found in a bottle of testosterone cypionate, for most men, this will only ever be a compensatory solution, and does not get to the heart of the issue. The fundamental key to hormone health, and all health in general, is eating well, moving your body, and ensuring that you get good sleep. In patients with sleep apnea, getting on a mask can raise testosterone levels by 150-200 points alone! In obese men, losing 10-15% of your body weight can increase your testosterone by 100-150 points! These are the things we always start with, but for many men it’s not enough. That’s when we start using some pharmacological aids to get us there.

If men want to try to naturally boost their testosterone, there are 3 prescription medications we can use to help this process. Clomiphene citrate (Clomid) is a medication originally developed to help women get pregnant but has been used off label in men for many years. Clomid upregulates pituitary LH and FSH production, increasing the brain signals to the testicles and promoting more testosterone production. Anastrozole is an aromatase inhibitor – it blocks the conversion of testosterone to estrogen, thereby increasing testosterone and decreasing estrogen.  HCG is an injection that is essentially LH in a bottle – this can be useful for testicular size preservation, jump-starting the testicles for post-testosterone fertility recovery, or as an adjunct to other treatments. One specific group of men that we usually recommend these therapies to are men who are actively trying to father a child, or who have plans of doing so in the future. That’s because these hormones increase sperm production as well.

Pros

Cons

Preserves Fertility

Works 50% of time

Boosts your own system

May cause mood swings

Clomid / Anastrozole – easy pills

Just doesn’t work for some people

No ball shrinkage

Testosterone replacement therapy (TRT) is a treatment for men diagnosed with low testosterone. TRT can help restore testosterone levels to a normal range and improve symptoms. The goal is to raise testosterone levels back to normal and restore sexual function and energy levels. All forms of TRT do just that – replace testosterone – they do not do anything to raise your body’s natural production. These methods are certainly effective and are widely prescribed if patients understand the risks and benefits of TRT. Each form has a few considerations – generally there is a trade off between of often something has to be taken and how invasive that option is. Then there are pharmacokinetic differences, side effect differences, and of course, price and access differences. Let’s go through each individually so you can pick the right option for you.

The oldest and most widely used version of TRT, consisting of a weekly injection of Testosterone Cypionate or Testosterone Enanthate into the Muscle or Subcutaneous fat. There are variations in dose amount and frequency, but generally most patients do one injection per week. Overall the cheapest form of TRT but also the most suppressive to the internal system because the T is on-board all the time.

Pros

Cons

Cheap ~ $50 per month

Very suppressive to the pituitary

Highest peak levels possible

Testis shrinkage and no sperm

Very customizable dosing

High peak = estrogen excess

Highest rate of polycythemia (thick blood)

Injections can be painful – big needles

Prior versions of oral testosterone were unfriendly to the liver, and for many years we did not have oral T available in the USA (it was available in Europe and Asia since the 1970s).  New formulations have been developed but have only been out since 2019, but have revolutionized the landscape in a short time. Oral T offers numerous advantages besides the fact that it’s by far the easiest to take including customized dosing and potentially less suppressive effects on the testes. This form of TRT mimics the natural daily variation of testosterone secreted by the body and so better simulates the natural body compared to long-acting TRT formulations. For the Men’s clinic at UPNT, oral testosterone is the new gold standard of TRT therapy.

Pros

Cons

Lowers SHBG = Higher Free T, patients feel great

Twice a day dosing

Convenient pills

Must be taken with food

Best side effect profile of any TRT

$159 per month

May not fully suppress the pituitary

No estrogen excess

Xyosted is testosterone enanthate placed in an epi-pen style auto-injector pen. It is very convenient and easy for patients to inject, dosing at once per week. It is a great injection option for those who cannot do regular injections.

Pros

Cons

Easy to use once a week

Max dose 100mg per week

Good peak levels

Hard to get insurance coverage

Moderate side effect profile

$150 per month

Long-acting and slow-absorbing, subcutaneous testosterone pellets can be implanted into the fat under the buttocks through a quick office-based procedure. Usually this is done every 3-4 months, allowing for a set-it-and-forget-it way of doing TRT. However, it does so in a very unphysiological way that creates a big difference between the peak and trough levels.

Pros

Cons

Only done every 3-4 months

Large peek-tough ratio

Good peak levels

Only covered for Medicare, cash option available

No at-home therapy

Pellet complications (extrusion, infection)

$550 every 304 months

Skin creams and gels were the first line therapy for a long time, and while they are non-invasive, they have to be applied every day. Absorption can vary widely, dose titration is tough and there is a real risk of transferring the product onto others since it is on the skin. For the UPNT Center for Men’s Health, these have fallen out of favor, though some patients still like it.

Pros

Cons

Easy to apply

Not very effective / weak levels

Non-invasive

Transference risk to others

Low side effect profile

Skin irritation possible

~ $80 per month

Natesto is a nasal testosterone gel that is administered 3x per day, one squirt in each nostril. While far from the most convenient administration method, it does offer the advantage of being very rapid on and very rapid off. This form of TRT also does not seem to fully suppress endogenous T production and spermatogenesis, making it an option to consider in younger men with future fertility potential. However, it can be quite annoying to use and cause nasal irritation which can be bothersome.

Pros

Cons

Rapid on / off

3x a day is a lot

Does not shut down the internal pathway

Nasal irritation

Preserves sperm production

Poor symptomatic control long term

$140 per month

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