What is Testosterone Resistance?

What is Testosterone Resistance?

A wide range of physical and mental issues in men can be attributed to a low testosterone level. As a major anabolic and sexual hormone in men, a deficiency in testosterone can cause premature ageing with regressing signs of virilization and male characteristics.

Symptoms of testosterone deficiency (TD) are as follows.

  • Reduced sex drive
  • Reduced erectile function
  • Loss of hair
  • Decreased beard growth
  • Decreased muscle mass and strength
  • Persistent fatigue and lassitude
  • Nervousness and irritability, loss of interest
  • Poor concentration and memory, cognitive function
  • Lack of mental firmness, motivational drive 
  • Symptoms of depression.
  • Obesity 

Testosterone deficiency compromises the quality of men’s lives as well as shortening their lifespan. Nowadays there is a heightened awareness of problems associated with low testosterone and many people enquire about how the level can be boosted. As a result, there is a huge commercial interest in testosterone replacement therapy (TRT).


The Paradox in the diagnosis of testosterone deficiency syndrome (TDS)

However, it is a well-known fact that a much lower than expected proportion of men benefit from testosterone replacement therapy. In this article, I have written about the effect of aromatase activity in turning testosterone into oestrogen regardless of the amount of testosterone supplemented.

The concept of supplementing testosterone to tackle the problem of testosterone deficiency is far too simplistic considering the fact that hormones never act in isolation as they continuously and sensitively interact with the totality of one’s internal chemistry. Sex hormone levels are kept closely in check by the negative feedback control of the brain and gonad and Testosterone is one downstream component of this intricate feedback loop. I wrote how testosterone replacement can actually undermine male fertility and why it is not safe for sperm production here.  

Studies show that those characteristic symptoms of testosterone deficiency are very poorly correlated with the total testosterone (TT) level in the blood. So there is a dichotomy between clinical and laboratory findings: men can have symptoms of testosterone deficiency which are unsubstantiated by laboratory tests. There is no relationship between blood levels of testosterone and the typical symptomatology of testosterone deficiency. Furthermore, each person seems to have his own testosterone threshold for deficiency symptoms that differs markedly between individuals. Therefore, the absolute number in a blood test is of little diagnostic value and the symptoms should be treated, not the numbers.


Do you have Receptor Sensitivity?

Even if the man has the expected level of testosterone for his age, symptoms of testosterone deficiency can persist. This is because, like insulin resistance in diabetes, there are varying degrees of testosterone resistance in a man’s body causing a relative rather than absolute insufficiency of the hormone. 

Hormones bind to receptors, much like a lock and key, and exert their intracellular effects.

The fault causing the relative deficiency of testosterone is not in the compromised function of the testes, but in the cellular testosterone receptors, that have become insensitive or resistant to the actions of the hormone. 

If the man has resistance at a cellular level, the testosterone levels seen in a lab test are irrelevant as his receptor would not respond appropriately to any amount of testosterone. 


How receptors become insensitive to hormone signal

It is a multifaceted problem. The ageing process, general health status and environmental effects all influence testosterone production and regulation.


There are many ways in which advancing years take their toll on the brain, the major sex organ in the body. With age, blood flow decreases to many tissues which also reduces the supply of testosterone to the cells.  A wide range of degenerative changes have been reported in the ageing testis such as a decrease in the number of Leydig cells, increased fibrosis (thickening and scarring of the tissue), decreased circulation and changes in hormone synthesis. Sexual stimuli tend to be less frequent and less intense and feedback of sensory impulses from the wrinkled skin and flaccid penis creating arousal is similarly reduced. Androgens exert a direct effect on penile tissue making it sensitive and helping maintain erectile function. Neurovascular changes are particularly prominent in diabetics, which further reduce tissue responsiveness. Reduction in muscle mass and accumulation of visceral fat seen in diabetes and metabolic syndrome can be reversed by improved testosterone synthesis and regulation, with a consequent improvement in erectile function.

Vegetarian/vegan Diet

Strict low-cholesterol diets have been shown to lower Total Testosterone (TT) and Free Testosterone (FT) levels by 14 per cent. Vegetarian diets, especially if low in protein, can increase SHBG, further reducing FT. Men placed on a low-fat, high-fibre vegetarian diet show an 18 per cent reduction in both TT and FT, which is reversed when they resume a normal diet. Conversely, a high-protein, low-carbohydrate diets raises TT and lowers SHBG. 

low testosterone Agnes Ryu

Decrease of serum total and free testosterone during a low-fat high-fibre diet.

Low-fat high-fibre diet decreased serum and urine androgens in men.

Homo Sapiens’ dietary strategy should be based on millions of years of human evolution, not current ideology.

Metabolic Changes 

Androgen deficiency has been shown to decrease lipid oxidation and resting energy expenditure, raising triglycerides and increasing insulin resistance. Data indicate that low serum testosterone levels are associated with an adverse metabolic profile, erectile dysfunction, and increased cardiovascular risk in men. 


Insulin resistance and testosterone resistance go hand in hand 

There are many parallels and interactions between adult-onset diabetes and Testosterone Deficiency Syndrome. In diabetes, if the beta cells have been stimulated for a prolonged period of time, they become depleted and unable to secrete pulses of insulin and then become ‘blind’ to changes in glucose concentration. In the same way, as beta cells fail in diabetes, in patients with testicular atrophy and androgen insensitivity syndrome, Leydig cell hyperplasia in the testis is often found. 

Prediabetes, insulin resistance is an epidemic. Low testosterone, both in absolute or relative terms is an epidemic.

Insulin is the master growth hormone controlling the levels and activities of other hormones in the body including other sex hormones and stress hormones. Adding testosterone molecules when the body is in the state of insulin resistance is futile. 

In the insulin resistance state, your brain, the biggest sexual organ cannot access the energy that it needs to operate effectively and your cells starve although they are swimming in the sea of glucose in the blood.

Because of this association between insulin resistance and low testosterone, I always recommend that each patient has their hormone levels including insulin and glucose checked.

Lifestyle factors contributing to diabetes, metabolic syndrome and alcoholism cause fibrosis and damage to both pancreatic islets and Leydig cells but can be modified beneficially for both conditions. 



Dr Ryu’s articles:

Belly Fat, the enemy of manhood

How man is oestrogenised

Insulin Resistance: The critical piece of the puzzle